Blood, Sweat and Tears - in Vitro Diagnostic Method Claims Limited by Intended Use

Dr. C. Richter (DE)

1. Introduction to in vitro diagnostics

In vitro diagnostics (IVD) continues to be one of the fastest-growing areas in healthcare, with an expected growth of 5.1 % between 2014 and 2020 and worldwide sales of 67.3 billion dollars in 2020[1], owing to advances in the field of genomics and an increasing demand for diagnostics for age-related conditions. Therefore, it comes as no surprise that patent offices and courts are dealing with an increasing number of patents and litigation cases in this field[2].

IVD tests are usually based on the detection of a biomarker in a bodily fluid. A biomarker is an analyte the presence, absence or concentration of which relates to a disease of interest. For example, if a patient is infected by a virus, the circulating virus will trigger the production of antibodies that bind specifically to the virus and can be detected in a blood sample. A variety of biomarkers for diseases and conditions exist, from simple organic compounds to complex biomolecules including specific gene sequences or even whole cells.

2. Claims in European patent office (EPO) prosecution proceedings

R&D activities in IVD frequently culminate in the filing of patent applications. According to national case law, a method claim can only be enforced in those countries where the patent is valid and the diagnostic assay is actually performed, not in those where the service is merely advertised or where samples are collected[3]. Therefore, patent protection in a broad range of countries is desirable, which is the reason why many applicants intending to commercialize in Europe decide to file European patent applications.

Patent offices find themselves under considerable pressure not to grant unduly broad claims, in particular in the field of biotechnology. IVD related product claims often lack novelty, since reagents such as polypeptides may be described in the state of the art before their function and diagnostic usefulness is revealed. In consequence, many applicants request the grant of method claims.

In prosecution proceedings, applicants frequently incorporate the diagnosis of a specific disease as an intended use in such method claims, either voluntarily or hoping that such a limitation will render novel the subject matter of the claims over a piece of prior art disclosing the method in general or for the diagnosis of another disease.

Furthermore, in the absence of relevant case law and provisions in the Guidelines providing guidance how to examine sufficiency of disclosure of in vitro diagnostic claims, EPO Examining Divisions frequently tend to interpret Art. 83 EPC such that method claims must be limited to the diagnosis of one or few select diseases the correlation of which with the biomarker is directly corroborated by experimental evidence. In other words, if it is shown that a sample from a patient suffering from a certain disease contains the biomarker, but samples from healthy subject do not, claims relating to a method for the diagnosis of this disease (but no others) are likely to be considered allowable[4].

As a result, the vast majority of granted in vitro diagnostic method claims appear to include an intended use feature[5].

3. Claims limited to a specific disease may neither be a fair reward for the inventors nor clearly define of the scope of protection

The assumption underlying the objection according to Art. 83 EPC that a biomarker directly correlates only with one or few select diseases is far from current approaches in diagnostics and tends to underestimate the value of many IVD assays. If a patient presents, the medical doctor in charge is likely to consider his clinical picture and history and then follow a diagnostic workflow starting with methods based on unspecific biomarkers, the results of which may lead them to exclude certain diseases and consider more seriously others, leading to the performance of a select number of highly specific tests for the final diagnosis.

In other words, the result of an IVD assay may be a valuable contribution, even though it may only steer the clinician in the right direction rather than provide a conclusive diagnosis. The fact that a negative test result may be used to rule out one disease and point to another one has been acknowledged by the Enlarged Board of Appeal in G1/04[6]. Therefore, a claim limited to diagnosis of a single disease is in many cases not a fair reflection of the inventor's contribution to the art.

Moreover, the limitation of a claim to a distinct disease of condition may lead to legal uncertainty at the stage of litigation.

The result of diagnostic tests may be relevant for the diagnosis of other diseases, but the patentee may argue that the protected diagnostic method will inevitably be used if the technical steps of the method are practiced, because the diagnostically useful result is obtained, no matter whether the person carrying out the method aimed to diagnose the disease specified in the intended use feature[7].

While this may seem like a rather biased way of interpreting the scope of protection, features relating to the purpose, technical effect or function of product claims have been considered irrelevant if structural features were sufficient to define the requirements for achieving the sought-after technical effect in national infringement proceedings[8]. Similarly, the BGH ruled that indications of purpose, technical effect or function in method claims do not necessarily limit the scope of protection, but may simply help the person skilled in the art understand the background of the invention[9].

Moreover, the Guidelines, referring to T304/08, contemplate in the context of clarity that the indication of an intended use of this method may at most be seen as limiting to the extent that the method has to be suitable for that use[10]. If this was applied to in vitro diagnostic method claims, a claim limited to a novel intended use such as the diagnosis of a specific disease would be anticipated by the disclosure in the state of the art of the method in general or for the diagnosis of another disease. This new provision is in line with the national case law cited in that the intended use is not to be regarded as a limiting technical feature.

By contrast, in a more recent BGH decision regarding the validity of a patent comprising a biomarker-based diagnostic claim[11], the indication of the intended use and the reaction of the reagent and the analyte was disclosed in the prior art, but without revealing their exact chemical natures. The claims of the patent comprised a method with an intended use ("for the diagnosis or monitoring the therapy of coeliac disease"), and the BGH pointed out that neither was a method for the purpose of diagnosing coeliac disease disclosed nor clarified whether the autoantigens could be used for such a method, apparently considering the intended use an independent feature contributing to the novelty to the patented method. It was emphasized that the prior art did not disclose a method for the purpose of diagnosing or monitoring the therapy of said disease.

Likewise, many EPO examining divisions readily acknowledge novelty subject to incorporation of an intended use feature relating to the diagnosis of a second disease, apparently in a manner similar to a novel use of a previously known product[12].

If such an intended use is indeed considered a valid novelty-conferring feature, the logical consequence is that it will have to be considered as limiting the scope of protection. However, since opinion on the subject appears to be divided, it is at present unclear how a national court in infringement proceedings will interpret the scope of such claims.

In summary, limiting patents by introducing an intended use in the form of a single specific disease may not only mean that the patentee is denied a scope of protection reflecting their contribution to the art, but may also obscure the scope of protection and lead to legal uncertainty.

4. Towards a balance between a fair reward for the patentee and public interest

Novel case law and special consideration of in vitro diagnostic method claims in the Guidelines are clearly desirable to clarify how an intended use should be interpreted. In particular, attention should be given to the difference between working methods and methods of manufacture on the one hand and in vitro diagnostic method claims on the other. While the intended use may well only be a redundant feature if the properties of the product are determined by manufacturing steps, there is no implicit technical connection between the steps of the diagnostic method and the diagnostic result, meaning that an intended use feature in an in vitro diagnostic claim that is essential for the patentability should not be disregarded. In any event, it is paramount that patent offices and courts follow a uniform approach.

As far as the examination of the requirements according to Art. 83 EPC is concerned, it seems necessary to establish a minimum standard that has to be met if an in vitro diagnostic method claim is to be considered allowable.

It is of course essential that data provided by applicant should provide credible support showing that the assay provided is a valuable contribution to the diagnosis. More specifically, it should be plausible that there is a significant correlation between the detection of a biomarker and the disease, i.e. that a group of patients suffering from the disease of interest is more likely to show a specific test result that allows for distinction from another relevant group such as a group of healthy individuals or a group of patients suffering from a different conditions, but with similar symptoms. It should be borne in mind, though, that this specific test result need not necessarily be positive in the sense that the presence of the marker in the patient's sample is detected. In some cases, detecting the absence of a marker may be just as useful[13].

Furthermore, it is just as important to consider clinical symptoms of the relevant diseases as well as the diagnostic work flow. An examining approach involving an automatic limitation of an in vitro diagnostic method claim to the disease(s) mentioned in the examples may not do the inventors justice. A key consideration should be whether a clinician is in practice likely to consider the result relevant for the diagnosis. The applicant should be allowed to extend the protection to the diagnosis of further diseases which are characterized by similar symptoms, but may be distinguished using the method according to the invention, even if such diseases are unrelated in terms of their molecular mechanisms. Furthermore, extending the scope of protection this way will make it more difficult for an infringer to argue that his intention was to use the method for the diagnosis of another disease, thus adding to the clarity of the claims and streamlining infringement proceedings.

In addition, special credit should be given to inventors of assays for the diagnosis of orphan diseases, since samples and clinical data are difficult to come by and supplementary protection certificates are not available for diagnostic products and methods.

Applicants are well advised to provide arguments supporting the usefulness of their method for the diagnosis of all relevant diseases rather than just including a list of diseases of commercial interest in the application. It may be helpful to discuss the importance of the test result in the context of a diagnostic workflow and by showing how a clinician may build on the test result a diagnosis of diseases beyond those mentioned in the examples. Key clinical symptoms should be defined in the application or by reference to current text books.

The result should be a granted patent reflecting the true achievements of the inventors, from a broad method claim, with a limitation to a reasonably broad group of diseases or even no such limitation in the case of a groundbreaking diagnostic method contributing to a variety of diagnoses, to a narrow claim for the diagnosis of a specific single disease if the readout of the in vitro diagnostic method merely confirms a diagnosis strongly suggested by the clinical picture.

1. Deloitte, 2017 global life sciences outlook; https://www2.deloitte.com/hu/en/pages/life-sciences-and-healthcare/articles/global-life-sciencessector-outlook.html; downloaded on October 2, 2018.
2. For example, BGH 2016, 1027 - Zöliakiediagnoseverfahren; BGH, GRUR 2017, 475 - Rezeptortyrosinkinase II; BGH GRUR 2017, 493 - Borrelioseassay.
3. Landgericht Düsseldorf 4b O 247/09 - Hunde-Gentest; BGH, GRUR 2017, 475 - Rezeptortyrosinkinase II
4. Throughout this article, it is assumed that the claim is phrased such that it does not fall under the exception to patentability according to Art. 53 (c). A more accurate intended use feature would be "aiding in the diagnosis" rather than "for diagnosis".
5. For a rough assessment, 42 patents comprising in vitro diagnostic method claims granted and published by the EPO between 2012 and 2018 were identified using the PatBase software package (Minesoft) and the key words "method" and "diagn*" as well as IPC classes G01N33/48 and G01N33/50, followed by review of the claims. Patents relating to veterinary diagnostics, companion diagnostics, the identification of pharmacologically active compounds, general analytical or chemical methods and medical or diagnostic devices were disregarded. In 37 out of 42 patents (88.1%), claims were limited specific diseases. Only in 4 out of 42 patents (9.5 %), claims were limited to a reasonably broad generic group of diseases, in one patent there was no disease-related limitation.
6. In section 5.1 of the results of G1/04, the Enlarged Board of Appeal acknowledges that a diagnosis includes a negative finding that a particular condition can be ruled out.
7. It may in fact be difficult for a court to determine, based on technical facts, whether the intended use feature is practiced, since the disease to be diagnosed may be considered a subjective element, i.e. depend on the intention of the alleged infringer (German: subjektives Tatbestandsmerkmal). An expert witness may have to be heard before a decision can be made.
8. BGHZ 112, 140, 155f. - Befestigungsvorrichtung II.
9. BGH, GRUR 2010, 1081 - Bildunterstützung bei Katheternavigation.
10. Section F-IV 4.13 (2018), final paragraph, where there is no reference to diagnostic claims, though. T304/08 relates to a method for reducing malodor.
11. BGH 2016, 1027 - Zöliakiediagnoseverfahren.
12. G2/88, G6/88.
13. For example, it is widely accepted that the presence of an autoantibody to the protein DFS70 shows that a patient is less likely to suffer from ystemic rheumatic autoimmune disease (Showman, O., Gildburd, B., Chayat, C., Amital, H., Langevitz, P., Watad, A., Guy, A., Perez, D., Azoulay, D., Blank, M., Segal, Y., Bentow, C., Mahler, M., Shownfeld, Y. (2018) Prevalence of anti-DFS70 antibodies in patients with and without systemic autoimmune rheumatic disease. Clin. Exp. Rhematol. 36 (1):121-126.

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