T 0231/13 01-08-2017

I. The applicants have appealed the Examining Division's decision, dispatched on 7 August 2012, to refuse European patent application No. 05 764 574.9.

II. The Examining Division held that claim 1 of the main request did not comply with Articles 84 and 83 EPC, because its subject-matter was neither clear nor sufficiently disclosed. More particularly, the defined "sample size" and its determination according to the claim were objected to. Claim 1 of the auxiliary request contained subject-matter extending beyond the content of the application as originally filed, in contravention of Article 123(2) EPC.

III. Notice of appeal was received on 1 October 2012. The appeal fee was paid on the same day. The statement setting out the grounds of appeal was received on 7 December 2012.

IV. The Board summoned the appellant to oral proceedings. In the communication accompanying the summons the Board set out its preliminary opinion. It raised objections of lack of clarity of the subject-matter of claim 1 of the main request and auxiliary request 2, in particular in relation to steps concerning the determination of a "sample size and calculated relative error", and lack of inventive step of the subject-matter of claim 1 of auxiliary request 1 as then pending.

V. Oral proceedings took place on 1 August 2017.

The appellant requested that the decision under appeal be set aside and that a patent be granted on the basis of the main request, filed during the oral proceedings or, in the alternative, of one of auxiliary requests 2 and 1, filed with letter dated 7 December 2012, in that order.

The previous main request, consisting of the claims of the application as originally filed, was withdrawn.

At the opening of the oral proceedings the appellant requested their postponement, due to serious illness of one of the inventors who wished to attend.

VI. Claim 1 as originally filed, which corresponds to claim 1 of the main request on which the impugned decision is based, reads as follows:

"'PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSED SAMPLES', realized by dedicated software specially developed for accomplishment of the Process from the statistical data obtained in corneal specular microscopy devices currently available in the market, characterized by, having integration among referred devices and the Process, being the software conjugated or not conjugated to the referred devices, the process taking in account patient age and accomplished from the data obtained in the referred devices, in the following sequence:

Initially, data of the clinic, examiner doctor, requesting doctor, and corneal specular microscope used in image acquisition are configured;

b. Patient data are identified: name, date of birth and age;

c. Routine to be accomplished is requested: to guide an exam being realized or to validate an already realized, past exam (needed to inform past exam date);

d. Data supplied by the specular microscopy exam are entered: endothelial density, average cellular area, number of counted cells, variation coefficient, cells with less than six, with six, and with more than six sides, and shape factor (they can be one or more than one);

e. The sampling type is selected: Standard for specular microscopes that do not calculate the variation coefficient, or Personalized in case the variation coefficient is known, when the specular microscope supplies the variation coefficient the user can choose between the Standard or Personalized sampling type;

f. Statistical power of the sample to be calculated is determined: 90% to 99% for confidence level and 10% to 1% for relative error;

g. Sample size and calculated relative error are determined;

h. Graphic and numeric demonstrations of the sample size are shown:

- Graphic and numeric demonstration of the quantity of counted cells and of the number of cells that composes the Standard Sample;

- Graphic and numeric demonstration of the quantity of counted cells and of the number of cells that composes the Personalized Sample;

- Graphic and numeric demonstration of the quantity of counted cells and, of the number of cells that composes the Standard Sample and of the number of cells that composes the Personalized Sample (simultaneously);

i. Numeric visualization of the calculated relative error determined for the number of cells that composes the chosen sample;

j. Graphic Visualization of the values found for the studied variables: endothelial density, average cellular area, number of counted cells, variation coefficient, cells with less than six, six and more than six sides, and shape factor, presented in statistical-analytic rulers in a rectangular format with stripes (areas) positioned side by side in any direction (from A to D or from D to A), where:

A. Area indicating values above that expected for the age (located in the side opposite to degradée color);

B. Area indicating values expected for the age;

C. Area indicating values lower than expected for the age, however within the biological reserve compatible with a normal function;

D. area indicating values considered critical for the age; the intensity of the color increases as the evaluated data becomes more critical

E. Arrow indicating the mean of the studied variable;

F. Indicates the inferior limit of the reliability interval (RI) for the studied variable;

G. Indicates the superior limit of the reliability interval (RI) for the studied variable; and

F-G segment: represents the reliability interval (RI) which is calculated as follows: RI = mean +/- relative error calculated for the total sample, assuming variable length, accompanying in the used scale, the value of the calculated reliability interval, F-G segment and can be positioned below, within, or above the stripes that define the areas; is the

k. An area is generated for written considerations about endothelial cells morphometry, endothelial analysis and final conclusions and another clear area is created for optional description of analyzed data (endothelial density, average cellular area, number of counted cells, variation coefficient, cells with less than six, six and more than six sides, and shape factor);

l. An clear area is generated for input of diagnosis found in the endothelial and morphometric analysis of the cornea, and another clear area is created for the optional description of the conclusion based on results evidenced by the Process, where the doctor makes considerations relative to the clinical-surgical historic; and

m. The reports are printed;

For exams accomplished under the orientation of the Process:

- Graphics: statistical-analytical rulers for each one of the studied variables (endothelial density, average cellular area, variation coefficient, percentage of cells with less than six, six and more than six sides and shape factor), individually issued for each eye;

- Sampling: Type of selected sample: standard or personalized with respective statistical power (confidence level and relative error), individually issued for each eye;

- Descriptive (mean for the studied variables and, if available, standard deviation), where the data for each eye are presented in comparative form);

- Final analysis: descriptive report at choice of the doctor responsible for the Process; or

- Complete: compounded by all four reports above described; or

To validate already accomplished exams:

- Sample analyzed with respective statistical power, individually issued for each eye; or

- Descriptive (mean of the studied variables), where data for each eye are presented in comparative form."

Claim 1 of the present main request reads as follows:

"Corneal specular microscope configured to implement a process of statistic validation of corneal endothelial cells analysed samples, said microscope being programmed with a dedicated computer program implemented in computational means, such computer program implementing said process and having as input statistical data obtained for a single patient from a corneal specular microscope, characterized by said computer program being integrated in said corneal specular microscope, the process further taking in account patient age and having as input data for a single patient obtained in said corneal specular microscope,

the process comprising the following steps in the following sequence:

a. configuring data of the clinic, examiner doctor, requesting doctor, and corneal specular microscope used in image acquisition;

b. Identifying patient data are, such data comprising: name, date of birth and age;

c. Requesting a routine to be accomplished, such routine comprising indication of: to guide an exam being realized or to validate an already realized, past exam (needed to inform past exam date);

d. entering data supplied by the corneal specular microscope exam, such data comprising one or more of: endothelial density, average cellular area, number of counted cells in said sample, variation coefficient, cells with less than six, with six, and with more than six sides, and shape factor

e. selection by a user of sampling type, such sampling type consisting of:

- standard type, in case of said specular microscope consisting of a specular microscope that does not calculate the variation coefficient, or

- personalized type, in case a variation coefficient is known through said specular microscope supplying the variation coefficient, wherein in such case the user can choose between the standard or personalized sampling type;

f. determination by a user of desired statistical power of said sample to be calculated: 90% to 99% for confidence level and 10% to 1% for relative error;

g. determination of the size of said sample, thus the sample size, obtained through:

- taking into account patient data and epidemiologic corneal data to define a total sample, designated standard sample; or

- taking into account the endothelial data referring to the eye of patient under analysis, defining a feedback such that, based in such values, an ideal sampling of said eye corresponding to said corneal endothelial cells analyzed samples is defined by the user, designated personalized sample;

and a calculated relative error associated with said sample and

obtaining a set of images of the corneal endothelium of said single patient thereby meeting said relative error;

h. presentation of graphic and numeric demonstrations of the sample size, such demonstrations consisting of:

- graphic and numeric demonstration of the quantity of counted cells and of the number of cells that composes said standard sample;

- graphic and numeric demonstration of the quantity of counted cells and of the number of cells that composes said personalized sample;

- graphic and numeric demonstration of the quantity of counted cells and, of the number of cells that composes the standard sample and of the number of cells that composes the personalized sample, simultaneously;

i. Numeric visualization of the calculated relative error determined for the number of cells that composes the chosen sample;

j. Graphic visualization of the values found for the studied variables: endothelial density, average cellular area, number of counted cells, variation coefficient, cells with less than six, six and more than six sides, and shape factor, presented in statistical-analytic rulers in a rectangular format with stripes (areas) positioned side by side in any direction (from A to D or from D to A), where:

A. Area indicating values above that expected for the age (located in the side opposite to degrade color);

B. Area indicating values expected for the age;

C. Area indicating values lower than expected for the age, however within the biological reserve compatible with a normal function;

D. Area indicating values considered critical for the age; the intensity of the color increases as the evaluated data becomes more critical

E. Arrow indicating the mean of the studied variable;

F. Indicates the inferior limit of the reliability interval (RI) for the studied variable;

G. Indicates the superior limit of the reliability interval (Rl) for the studied variable; and

F-G segment: represents the reliability interval (Rl) which is calculated as follows: RI = mean +/- relative error calculated for the total sample, assuming variable length, accompanying in the used scale, the value of the calculated reliability interval, F-G segment and can be positioned below, within, or above the stripes that define the areas; is the

k. A area is generated for written considerations about endothelial cells morphometry, endothelial analysis and final conclusions and another clear area is created for optional description of analyzed data, such analyzed data comprising endothelial density, average cellular area, number of counted cells, variation coefficient, cells with less than six, six and more than six sides, and shape factor;

l. A clear area is generated for input of diagnosis found in the endothelial and morphometric analysis of the cornea, and another clear area is created for the optional description of the conclusion based on results evidenced by the process, where the doctor makes considerations relative to the clinical-surgical historic; and

m. printing of a plurality of reports, such reports comprising:

- statistical-analytical rulers for each one of the studied variables (endothelial density, average cellular area, variation coefficient, percentage of cells with less than six, six and more than six sides and shape factor), individually issued for each eye;

- type of selected sample: standard or personalized with respective statistical power (confidence level and relative error), individually issued for each eye;

- mean for the studied variables and, if available, standard deviation, where the data for each eye are presented in comparative form;

- descriptive report at choice of the doctor responsible for the process; or

- compounded by all four reports above described; or

validation of already accomplished exams:

- sample analyzed with respective statistical power, individually issued for each eye; or

- mean of the studied variables, where data for each eye are presented in comparative form."

Apart from a few irrelevant editorial changes, claim 1 of auxiliary request 2 corresponds to claim 1 as originally filed, except that point g of the list after the first column in the claim has been modified and further points g.1 and g.2 have been added, now reading:

"g. Sample size and calculated relative error are determined by two ways:

g.1 - By the first way it taken in account patient data and epidemiologic corneal data to define the total sample, this method is denominated of Standard Sample;

g.2 - By the secon way, it is taken in account patient's endothelial data to make a feedback in the Process so that, based in these values, will be defined the ideal sampling for the eye in analysis, this method is denominated of Personalized Sample in order to accomplish the cornea endotelium sampling calculation;".

Claim 1 of auxiliary request 1 reads as follows:

"A process operatively coupled to a microscope device, the device configured to calculate values for variables wherein the variables comprise members selected from a group consisting of median and/or mean and standard deviation for corneal cellular density; average cellular area; variation coefficient; percentage of corneal cells with less than six sides; percentage of corneal cells with six sides; percentage of corneal cells with more than six sides; and shape factor, the process comprising: generating using the device a statistical-analytic ruler graphic for a variable wherein the ruler graphic comprises areas A, B, C and D wherein area A indicates values of the variable above that expected for age of a corneal cell sample, area B indicates values of the variable expected for age of the corneal cell sample, area C indicates values of the variable lower than expected for age of the corneal cell sample and within a biological reserve compatible with normal corneal function, and area D indicates values of the variable considered critical for age of the corneal cell sample; generating an arrow graphic E that indicates mean of the variable for the corneal cell sample; generating a segment graphic F-G wherein an F end of the segment indicates an inferior limit of a reliability interval for the variable, wherein a G end of the segment indicates a superior limit of the reliability interval for the variable, and wherein the segment length from F to G represents a reliability interval calculated according to a mean plus and minus a relative error calculated for the corneal cell sample; and generating a report graphic that comprises at least the ruler graphic for the variable."

VII. The appellant's arguments may be summarised as follows:

Request for postponement of the oral proceedings

At the opening of the oral proceedings their postponement was requested, because one of the inventors, who wished to accompany the professional representative, could not be present due to serious illness that required medical intervention. This was proven by a medical certificate dated 28 July 2017 and filed during the oral proceedings. The request for postponement could not have been made before because the need for medical intervention had been sudden and the representative had been informed of it only the evening before the oral proceedings.

Admissibility of the main request

The main request was only filed during the oral proceedings because an important aspect of the invention had come to light in a recent discussion with the inventor. More particularly, claim 1 of the main request had been directed to a corneal specular microscope with additional inventive features specified in steps f and g. It had been made clear that those steps were performed by the claimed microscope, which performed a process of statistic validation of analysed samples of corneal endothelial cells and provided an enhanced presentation of the results of the process.

Clarity and sufficiency of disclosure of auxiliary request 2

It was surprising that the application had been refused by the EPO, when it had not been refused in countries such as China, Japan and the United States of America.

All the terms employed in claim 1 of auxiliary request 2 were usual terms in ophthalmology or statistics. The defined sample size and relative error related to a sample of cells of the corneal endothelium. The sample size represented the number of cells contained in different images obtained by specular microscopes. Newly introduced paragraphs g.1 and g.2 specified better how sample size and relative error were determined. By performing the claimed process, an operator would set the sample size and relative error and would then obtain information indicating whether the results obtained up to a certain stage of the examination of the corneal endothelium, based on the samples analysed up to that point, could already be trusted or whether other samples were needed to reach the desired level of reliability as set by means of the sample size and relative error.

Inventive step of auxiliary request 1

Auxiliary request 1 consisted of the claims granted in the US. Claim 1 was directed to a process operatively coupled to a microscope device. The process made it possible to effectively present the variables determined by the microscope to a user. More particularly, by means of the technical features of the claimed process, graphics were produced and displayed on a single screen, which had the technical effect of enhancing the conveying of information to the user. The displaying of those graphics was therefore a technical feature to be duly considered in the assessment of inventive step.