Divergent patent pathways Dr. Joachim Wachenfeld and Oswin Ridderbusch Vossius & Partner, Munich, Germany

Differences between the EPO and the USPTO in the assessment of patentable subject-matter in the life sciences This article was originally published in the Life Sciences Intellectual Property Review in April 2015 (in edited form).

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 designates all contracting states. Only later does the applicant have to decide in which jurisdictions patent protection is actually desired. PCT filings thus 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 biotech 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 United States, i.e., prosecution before the EPO and the 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 the 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 illustrative examples in the following. One decision that caused major concerns for those engaged in the patenting of diagnostic tools was Mayo v. Prometheus [1] decided by the US Supreme Court in March 2012. In its decision, the Court embarked on assessing patentability of claims protecting a method of optimizing 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).

[1] US Supreme Court: Mayo Collaborative Services et al. v. Prometheus Laboratories Inc.

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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. Although this decision is often argued to have resulted from poor claim drafting, it 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.” In other words, the steps or combination of

steps applying of the laws of nature must be based on an inventive concept. The EPO has a fundamentally different approach to assessing the patentability of diagnostic methods. By virtue of law (previously Article 52(4) EPC 1973, now Article 53(c) EPC 2000), diagnostic methods practiced on the human or animal body are excluded from patentability. Ten years ago, the Enlarged Board of Appeal of the EPO clarified in its opinion G 1/04 that diagnostic methods are excluded from patentability only if they comprise all of the following steps: - the steps preceding the diagnosis itself which is a “purely intellectual exercise”, specifically the collection of data, the comparison of this data with standard reference values and the determination of any deviation from the reference values, where those steps that are of technical nature must reflect an interaction with the living human or animal body; and - the step of making the actual diagnosis, i.e., attributing a particular clinical picture to the determined deviation [2]. Diagnostic methods may therefore be patenteligible before the EPO if they are practiced in vitro using a patient sample, such as a body fluid or tissue sample [3]. 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 [2] Enlarged Board of Appeal: opinion G 1/04 of 16 December 2005 [3] Examples of Technical Board of Appeal decisions confirming that in vitro diagnostic methods are amenable to patentability include T 666/05 of 13 November 2008, T 80/05 of 19 November 2008, and T 1328/08 of 10 May 2012.

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practiced on the living human or animal body, provided that they do not also claim the making of an actual diagnosis [4], and provided that they do not fall under the statutory exclusion of surgical methods [5]. 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 [6]. 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

[4] Enlarged Board of Appeal: opinion G 1/04 of 16 December 2005; applied and confirmed, e.g., in the Technical Board of Appeal decisions T 330/03 of 7 February 2006, T 619/03 of 19 June 2006, T 9/04 of 8 September 2006, T 990/03 of 19 October 2006, T 1255/06 of 23 September 2008, and T 663/02 of 17 March 2011 [5] Under Article 53(c) EPC 2000 (essentially identical to the previously applicable Article 52(4) EPC 1973), European patents shall not be granted in respect of “methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practiced on the human or animal body”. These three alternative exclusions are cumulative requirements, as confirmed by the Enlarged Board of Appeal in its decision G 1/07 of 15 February 2010. Claims directed to a method of data collection must therefore neither fall under the exclusion of diagnostic methods practiced on the human or animal body nor under the exclusion of surgical methods. A corresponding detailed assessment was made, e.g., in the Technical Board of Appeal decision T 663/02 of 17 March 2011. [6] Technical Board of Appeal: decision T 143/04 of 12 September 2006

diagnostic methods rely on laws of nature, provided that the claimed methods contain technical features [7]. Whether the claimed combination of features, as long as it satisfies the requirements established by the Enlarged Board of Appeal of the EPO in G 1/04, 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 purposelimited product claims directed to a substance or composition for use in a diagnostic method practiced on the human or animal body, including the use in any specific diagnostic method, i.e., so-called “second diagnostic use claims” [8]. In June 2013, the US Supreme Court handed down the Myriad decision [9] 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.

[7] For example, in decision T 80/05 of 19 November 2008 the Technical Board of Appeal rejected the argument that the diagnostic method claims at issue should be excluded from patentability because they were based on the discovery of a relationship existing in nature between a specific mutation in the human genome and a specific disease and on the purely mental act of associating the mutation with a predisposition for the disease, stressing instead that the claimed methods contain features that require working steps of technical nature. [8] Second diagnostic use claims in the Swiss-type format were accepted, e.g., in the Technical Board of Appeal decision T 34/95 of 26 February 1999. [9] US Supreme Court: Association for Molecular Pathology et al. v. Myriad Genetics et al.

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Essentially, 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 35 U.S.C. §101. The characterization of the claimed nucleic acid as “isolated”, i.e. 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 as such does not occur in nature. In a subsequent decision issued in December 2014, the US Court of Appeals for the Federal Circuit (CAFC) again dealt with different patents of the BRCA gene patent family [10]. The claims at issue related to single-stranded primers hybridizing 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 singlestranded 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 singlestranded – 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, i.e., to hybridize 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 hybridization 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, absent any further action, relates only to an abstract idea, constituting another implicit exclusion from patent-eligibility derivable from 35 U.S.C. §101. As the remaining claim features were considered to reflect routine measures only, there was no further inventive concept to take the claim into patent-eligibility.

[10] CAFC: University of Utah Research Foundation et al. v. Ambry Genetics Corporation

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A further decision that came to essentially the same result as the Supreme Court in Myriad was issued by the US District Court of Delaware in October 2014 [11]. One of the patents in the case at bar 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 characterized by the Court as constituting natural phenomena. Again, the remaining 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 [12]. 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 thus constituted isolated elements of the human body that are patentable in accordance with Rule 23e(2) EPC 1973 (now Rule 29(2) EPC 2000) [13].

[11] United States District Court for the District of Delaware: Genetic Technologies Ltd. v. Bristol-Myers Squibb et al. [12] Technical Board of Appeal: decision T 1213/05 of 27 September 2007; confirmed and applied to diagnostic method claims in decision T 80/05 of 19 November 2008 [13] Rule 29(2) EPC 2000 (which is identical to the previously applicable Rule 23e(2) EPC 1973) reads: “An element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element.” In a broader context, Rule 27(a) EPC 2000 stipulates that biotechnological inventions shall also be patentable if they concern “biological material which is isolated from its natural environment or produced by

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 as such 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 Technology [14], 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 contained in the material does not perform its function (as disclosed in the patent) at the time of the alleged infringement [15].

means of a technical process even if it previously occurred in nature”. [14] Court of Justice of the European Union: Judgment of the Court (Grand Chamber) of 6 July 2010 in Case C-428/08, Monsanto Technology LLC v. Cefetra BV et al. [15] In response to the first question referred to the CJEU, the Court ruled that: “Article 9 of Directive 98/44/EC (…) is to be interpreted as not conferring patent right protection in circumstances such as those of the case in the main proceedings, in which the patented product is contained in the soy meal, where it

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Thus, while the EPO does allow product claims directed to isolated nucleic acids as such, 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 at the USPTO. A prime example is the exclusion from patentability of human embryonic stem cells that we have dealt with previously [16]. A Technical Board of Appeal of the EPO has just recently confirmed that human embryonic stem cells are not patentable under the EPC [17]. In contrast, there is no exception from patentability for embryonic stem cells according to US patent law and practice. For example, in the most well known series of cases generally relating to the culture of primate embryonic stem cells, the organization Consumer Watchdog has repeatedly (and unsuccessfully) attacked the

does not perform the function for which it is patented, but did perform that function previously in the soy plant, of which the meal is a processed product, or would possibly again be able to perform that function after it had been extracted from the soy meal and inserted into the cell of a living organism.” In reaching this conclusion, the Court provided the following reasoning: “Since the Directive thus makes the patentability of a DNA sequence subject to indication of the function it performs, it must be regarded as not according any protection to a patented DNA sequence which is not able to perform the specific function for which it was patented. (…) An interpretation to the effect that, under the Directive, a patented DNA sequence could enjoy absolute protection as such, irrespective of whether or not the sequence was performing its function, would deprive that provision of its effectiveness.” [16] Patenting stem cells: filing date is the key, from the Life Sciences Intellectual Property Review newsletter, June 2014 [17] Technical Board of Appeal: decision T 1808/13 of 26 February 2015

patentability of a family of patents held by Wisconsin Alumni Research Foundation (WARF), including US Patent Nos. 5,843,780 (December 1, 1998), 6,200,806 (March 13, 2001), and 7,029,913 (April 18, 2006). However, their attacks have been limited to the alleged obviousness of the claimed methods because in the US there is no prohibition against the patenting of stem cells per se. 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 [18]. Likewise, when interpreting the scope of exclusion applicable to essentially biological processes for the production of plants, the Enlarged Board of Appeal of the EPO has taken a rather strict stance [19], in contrast to the common practice of the USPTO. In summary, there are important differences between the EPO and the USPTO in the assessment of patentable subject-matter in the 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 [18] US Supreme Court: Bowman v. Monsanto Co et al., also citing J.E.M. Ag Supply, Inc. v. Pioneer HiBred, Int’l Inc. [19] Enlarged Board of Appeal: decisions G 2/07 and G 1/08, both of 9 December 2010

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polymorphisms (SNPs) 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.

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