T 2046/19 - Combining in vivo and in vitro diagnostics

Key points

• Claim 1 reads as follows: ""1. A method for the prognosis .... of patients with COPD the method comprising the steps of:

  i) providing a sample of a bodily fluid from said patient, ii) determining in said sample the level of at least one biomarker, selected from the group consisting of proadrenomedullin (proADM), pro-natriuretic peptide, pro-Vasopressin (proAVP) and Procalcitonin (PCT) or fragments thereof of at least 12 amino acids in length, [and]

  iii) determining the BODE-index parameters according to one of the following steps:

  iii-a) determining the BODE-index parameters body-mass index (BMI, parameter B), degree of airflow obstruction (FEV1, parameter O), and dyspnea (parameter D), omitting the BODE-index parameter exercise capacity (parameter E);

  iii-b) determining the BODE-index parameters body-mass index (BMI, parameter B) and dyspnea (parameter D), omitting the BODE-index parameters exercise capacity (parameter E) and degree of airflow obstruction (FEV1, parameter O);

  iv) correlating said level of said at least one biomarker determined in step ii), in combination with said BODE-index parameters determined in step iii-a) or in step iii-b) to the prognosis and/or risk assessment and/or monitoring of therapy and/or management of patients with COPD."'

• The patent was opposed. The Board considers the claim to be insufficiently disclosed.
• However, my question initially was, how is a claim reciting 'determining dyspnea' (shortness of breath) not a diagnostic method under G 1/04? 
• The answer is probably r.9 of G1/04: "The grant of a European patent in respect of a diagnostic method which includes preceding method steps of a technical nature carried out by a device (cf. point 6.4.3 above) does not contravene [Article 53(c) EPC 2000] because the performance of the respective method steps does not satisfy the criterion "practised on the human or animal body". However, in the event of patent protection, it will normally be sufficient to purchase the device in question in order to be entitled to carry out such a method [*]. In cases where the same diagnostic conclusions can be attained by a method not including the use of the device, those carrying it out will not be inhibited by the patent. Therefore, the medical or veterinary practitioners cannot be considered to be hampered by the existence of such a patent."
• [*] - the Enlarged Board refers to the national case law and rules about exhaustion and implied licenses. 
• Hence, according to this decision, it seems that a method of in vitro diagnosis is still patentable even if combined with an in vivo diagnostic test.
• "the so-called "BODE index" was known as a tool for the prognosis of mortality and hospitalisation for COPD in patients with COPD."
• 
  

EPO 

The link to the decision is provided after the jump, as well as (an extract of) the decision text.

https://www.epo.org/en/boards-of-appeal/decisions/t192046eu1

1. Sufficiency of disclosure - main request

1.1 The requirement of sufficiency of disclosure must be satisfied at the effective date of the patent, i.e. on the basis of the information provided in the patent application as filed, together with the common general knowledge then available to the person skilled in the art. In the following analysis, where the board refers to passages of the opposed patent, the same content is also found in the text of the application as filed.

Technical background

1.2 The opposed patent relates to the individual risk-assessment of patients with COPD (chronic obstructive pulmonary disease). A patient diagnosed with COPD may be in a stable or unstable (acute exacerbated) state of the disease (see also dependent claim 5). The goals of COPD assessment are to determine the severity of the disease, its impact on a patient's health status, and the risk of future events (exacerbations, hospital admission, death) in order to guide therapy (see paragraph [0004] of the opposed patent).

1.3 As set out in the opposed patent (see paragraphs [0006] and [0029]), the so-called "BODE index" was known as a tool for the prognosis of mortality and hospitalisation for COPD in patients with COPD. It combines four variables into a single score. These parameters are:

B: body-mass index

O: degree of airflow obstruction, measured by lung-function testing (FEV1)

D: dyspnea

E: exercise capacity, measured by the six-minute walk test

Depending on the respective measurement results, scores are assigned to the patient for each parameter (see table 2 in the opposed patent). The sum of these scores is the BODE index. It reflects the impact of both pulmonary and extrapulmonary factors on prognosis and survival in COPD, with higher scores indicating greater risk.

1.4 However, determination of the BODE index is cumbersome as it requires a 6-minute walk test in the stable state of the disease, and it is not suitable for acute exacerbations (see paragraph [0006] of the opposed patent).

1.5 Thus, there had been increasing interest in using other parameters, including pulmonary biomarkers, to monitor disease severity in patients with COPD (see paragraphs [0006] to [0008]). It was known, for instance, that certain biomarkers, such as procalcitonin, are increased during exacerbations. Systemic biomarkers were also known to be of interest as a means of determining disease severity and prognosis in stable COPD. However, information was still scarce as to the prognostic value of these biomarkers.

Objective and claimed subject-matter

1.6 The opposed patent (see paragraph [0009]) seeks to provide a method for easy and reliable prognosis and/or risk assessment and/or monitoring of therapy and/or management of patients with COPD, with minimum inconvenience for the patient.

1.7 More specifically, it is suggested that such a method should replace part of the conventional determination of the BODE-index parameters, with a view to reducing the burden on the patient.

1.8 To this aim, and as defined in claim 1 as granted (see point I. above), several predictor parameters are to be determined:

- the level of at least one biomarker, selected from a specified group of eligible biomarkers, in a sample of a bodily fluid of a patient with COPD (claim 1, steps i) and ii))

- selected parameters of the BODE index (claim 1, step iii), namely:

(a) either three parameters (BOD) are to be determined, omitting parameter E

(b) or two parameters (BD) are to be determined, omitting both parameters O and E

These parameter values determined for the individual patient are to be combined and "correlated to" the prognosis and/or risk assessment and/or monitoring of therapy and/or patient management, which is both the purpose and the effect of the method (claim 1, step iv); see also paragraphs [0001] and [0009] to [0012] of the opposed patent).

1.9 The board understands this to mean that the assessment made for an individual patient (which is the claimed method's stated purpose), on the basis of this patient's parameter values obtained according to steps i) to iii), will be based on a known relationship (i.e. a correlation) between a combination of the specific parameters chosen and a relevant clinical outcome that is to be considered for the analysis. Hence, this general correlation, which will be applied in step iv) to the patient's individual parameter values, must of necessity have been established before carrying out the claimed method on individual patients. Otherwise it would not be possible to determine which parameters should be measured according to steps i) to iii).

1.10 The claimed method is defined functionally by its result. This result is defined only indirectly, in a general and rather broad manner, in that the method must enable prognosis, risk-assessment, therapy monitoring and/or management of patients with COPD. The crucial step for achieving this purpose is step iv).

1.11 While there is no doubt that the person skilled in the art would know how to collect parameter values according to steps i) to iii), claim 1 does not say how step iv) is to be put into practice. In particular, the claim does not specify how to choose the contributing parameters in the first place, how to combine the parameter values in practice and how to establish and use a correlation of these combined values to a particular outcome to achieve the defined purposes of prognosis, risk assessment, monitoring of therapy and patient management.

1.12 The prognosis or risk assessment addressed in claim 1 has to relate to a specific clinical outcome. On the basis of this prognosis or assessment, measures for therapy monitoring (such as testing for particular parameters, increasing or reducing the frequency of tests) or patient management (such as decisions about medication or hospitalisation) can then be determined.