T 1759/12 (Blood sample testing/BAXALTA) 25-04-2019

1. The duly summoned appellant II did not attend the oral proceedings, which in accordance with Rule 115(2) EPC and Article 15(3) RPBA took place in its absence.

Admissibility of the opposition (Article 99 EPC, Rules 76 and 77 EPC)

2. Appellant I submitted that the opposition was not admissible because the opponent (appellant II) did not sufficiently substantiate its novelty objection therein.

3. The notice of opposition objects to the patent in suit not only on the ground of Article 100(a) EPC for lack of novelty (Article 54 EPC), but also on lack of inventive step (Article 56 EPC) and insufficiency of disclosure (Article 100(b) EPC) (see page 2, first two paragraphs). It is established case law that an opposition is admissible if at least one of the grounds of opposition is sufficiently substantiated in the notice of opposition (see Case Law of the Boards of Appeal, 2016, 8th edition (hereinafter "CLBA"), IV.D.2.2.7). Since appellant I has not objected to the opponent's (appellant II) substantiation as being insufficient with regard to all of the grounds, except for novelty, already from the outset it cannot succeed.

4. Thus, the opposition is admissible.

Admission of auxiliary request 3 into the appeal proceedings (Article 12(4) RPBA)

5. Auxiliary request 3 was filed by appellant I with its statement of grounds of appeal (see section III above). According to Article 12(1) and (4) RPBA, the request would therefore normally be, as a rule, part of the appeal proceedings. With reference to Article 12(4) RPBA, however, this rule does not apply under all circumstances, since the provision refers to the power of the boards of appeal to hold inadmissible, i.e. exclude, inter alia requests filed for the first time with the statement of grounds of appeal which could have been filed during the first instance proceedings.

6. In its communication in preparation of the oral proceedings, the board explicitly addressed the issue of admission of auxiliary request 3 into the appeal proceedings. In this context it was observed that the amendments in claims 1 and 10 of present auxiliary request 3 directly addressed an issue under Article 123(2) EPC that was raised by the opponent against the corresponding claims in auxiliary requests 1 and 4 during the first instance proceedings. This issue came up only during the oral proceedings before the opposition division, although the opponent was aware of these sets of claims from the onset of the opposition proceedings (see points 18 and 19 of the board's communication).

7. Appellant II neither provided any substantive comments or arguments in reply to the board's positive provisional opinion on the admission of auxiliary request 3, nor attended the oral proceedings (see point VII supra).

8. In these circumstances, auxiliary request 3 is admitted into the appeal proceedings.

Witness hearings (Article 117(1) EPC)

9. Appellant II requested the hearing of witnesses for providing evidence that (i) documents D2 to D4 were publicly available before the claimed priority date of the patent, and (ii) that the claimed subject-matter was anticipated by the disclosure of documents D2, D5 and D6.

10. In its communication in preparation of the oral proceedings, the board addressed the issue of witness hearings. In this context, the opinion was expressed that the disclosure of documents D2 to D6 did not add any information that went beyond the disclosure of document D1, and that in these circumstances the hearing of witnesses on the issues of the documents' public availability and disclosure was not necessary.

11. Despite the board's negative opinion on hearing witnesses, appellant II neither provided substantive comments or arguments nor attended the oral proceedings. Accordingly, for the reasons given therein, witnesses were not heard.

Main request (claims as granted)

Claim interpretation - claim 1

12. Claim 1 is directed to a method for uniquely identifying viral positive biological fluid donations, which encompasses blood donation samples. The method comprises various process steps. In other words, the claim is openly defined and allows for the presence of other process steps in addition to those explicitly recited in the claim.

12.1 The method comprises the steps of, firstly, defining an n-dimensional matrix comprising a multiplicity of elements. Each element is defined by its position at a dimensional intersection in the matrix and a notation, while the matrix itself is defined by an index for each dimension. In other words, in a 2-dimensional matrix, for example, consisting of columns (first dimension) and rows (second dimension) each element is uniquely identified at the intersection (crossing) of the column and the row to which different letters and/or numbers ("indexes") have been allocated.

12.2 In a second step, each sample from a multiplicity of fluid donations is mapped to a particular element in the matrix which allows its unique identification. Then aliquots of these samples, i.e. sub-samples are taken. Their number is defined by the number of dimensions characterising the matrix, for example, two in a 2-dimensional matrix.

12.3 In a further step, all sample aliquots belonging to a single notation and a single dimensional index of the matrix are pooled, for example, in a 2-dimensional matrix all samples of the same row and the same column.

12.4 Each of the pooled samples are then tested by PCR for detecting a potential viral contamination. In case one of the pools is tested viral positive, the unique indexing of the pools in the elements of the matrix allows the identification of the single virus-positive sample donor.

13. The term "n-dimensional matrix" referred to in claim 1 is not defined and, hence, encompasses any number of dimensions. In the board's opinion, the skilled person would construe this term to relate to an abstract concept that is mathematically defined by variables, such as integers, notations and indexes. Thus, an n-dimensional matrix according to claim 1 is not confined to the physical space of two dimensions (N=2, e.g. a microtiter plate), or three dimensions (N=3, e.g. a cube), but encompasses an undefined number of higher dimensions, such as N=4 (e.g. a row of cubes), N=5 (e.g. rows of cubes on a table), N=6 (e.g. rows of cubes on tables in different rooms) etc. The indexing of each dimension allows the unique identification of samples/elements in the matrix.

14. Furthermore, the term "multiplicity" in relation to biological fluid donations and internal matrix elements as referred to in claim 1 has a relative meaning. In the board's view, this term means at least two or more. Thus, claim 1 encompasses the provision of fluid donation samples to be tested and matrices with internal elements in any number exceeding one.

Inventive step (Article 56 EPC) - claim 1

Closest prior art

15. It is uncontested that document D1 represents the closest prior art for the method according to claim 1.

16. Document D1 discloses a PCR-based method for uniquely identifying virus-contaminated samples of blood donations, which requires that up to three separate PCR tests are performed on different pools of samples. In order to identify virus-positive blood samples, aliquots of each sample are filled in wells of three sets of identical microtiter plates containing 96 sample wells, i.e. one set of plates for each of the three PCR tests (see page 13, column 2, first and second paragraphs, Figure 1 on page 17).

16.1 In a first PCR test, a single so-called master pool sample containing aliquots from all the blood samples to be tested (maximum of 600) is examined for the presence of a potential virus contamination (see page 13, column 2, second paragraph, Figure 1, left part). In case the sample of the master pool is virus-positive, two additional PCR tests are required for identifying the contaminated donor sample(s).

16.2 The second PCR test aims at the identification of the one or more microtiter plates containing a virus-positive sample. For this purpose pools of samples derived from one microtiter plate only are generated, i.e. each pool contains a maximum of 96 samples (see page 13, column 2, last paragraph to page 14, column 1, first paragraph and Figure 1, middle part).

16.3 The third PCR test serves the identification of a single virus-positive sample. This is achieved by forming subpools of samples derived from each column (indexed as "1 - 12") and row (indexed as A to H ("A bis H")) of the microtiter plate previously tested virus-positive. All of these subpools are analysed in a single PCR test cycle at the same time. The virus-positive sample(s) is/are located in the well positioned at the crossing, i.e. the intersection, of a virus-positive "row" and "column" sample pool (see page 14, column 1, first paragraph and Figure 1, right part).

16.4 It is uncontested that the microtiter plates of Figure 1 in document D1 represent 2-dimensional matrices with 96 internal elements.

17. As set out above (see points 13 and 14), the method according to claim 1 encompasses various embodiments, including a method wherein the matrix may consist of two dimensions (N=2) and contains 96 sample elements - like the microtiter plate disclosed in document D1. This embodiment of claim 1 will be considered in the following.

18. As likewise set out above (see point 12), the method of claim 1, and accordingly the embodiment under consideration, is openly defined and allows for the presence of further unspecified process steps, for example the first and the second PCR test reported in document D1 (see above). Thus, the claimed embodiment differs from the method disclosed in Figure 1 of document D1 only in that two aliquots are taken from each sample, instead of three.

19. Appellant I argued that the technical effects ascribed to this difference were a faster and cheaper method, in particular in situations with large sample numbers. Hence the technical problem underlying the claimed method consisted in providing an improved method for uniquely identifying viral positive biological fluid donations.

20. According to established case law, only the effects actually achieved vis-à-vis the closest prior art are to be be taken into account for the determination of the technical problem. Furthermore, the effect has to be attained throughout the entire range covered by the claim (see Case Law of the Boards of Appeal, I.D.4.1, including T 1422/12 of 11 April 2013 cited therein, and I.D.4.3).

21. As set out above, the claimed method is not limited to the analysis of "large" sample numbers, due to the relative meaning of the term "multiplicity", which may encompass any number exceeding one. In the board's opinion, and contrary to appellant I's view, the same applies to the teaching of document D1 for the following reasons:

22. The board agrees with appellant I that the PCR-based assay reported in document D1 was developed to overcome technical problems and high costs associated with a PCR testing of single blood samples (see page 13, second column, line 1 et seq. which reads as follows: "Die PCR (Polymerase-Ketten-Reaktion = Virusdirektnachweis durch Suche nach Viruserbinformation) als theoretisch geeignetes Tool ist derzeit aus technischen und Kostengründen noch nicht routinemäßig für das separate Screening jeder Einzelspende bei großen Blutspendediensten einzusetzen. Um dennoch die unbestrittenen Vorteile der PCR nutzen und Erfahrungen sammeln zu können..." (emphasis added)).

23. However, since already the pooling of some samples compared to a single sample to be tested by PCR provides cost and logistic advantages, the skilled person would rather derive from this passage in document D1, that pools containing far less than the 600 samples explicitly mentioned in document D1 likewise benefit from these advantages.

24. This view is further supported by the mentioning of a pool of "maximal 600" or a "max. 600er Pool" of single samples in document D1 (see page 13, column 2, second paragraph, Figure 1, left part). The term "maximal" in this context explicitly teaches the skilled person that the assay may be used for pools of samples well below that number, because it defines solely the upper limit.

25. There are also no technical reasons indicated in document D1 that would deter the skilled person from applying the PCR test to pools of samples of lower numbers. On the contrary, the document teaches that pools of 600 samples are defined as maximum, because at this size the sensitivity of the PCR still equals that of the available commercial kits for testing single blood samples (see page 14, column 2, first and second paragraph reading as follows: "Die in der täglichen Routine erreichbare Testsensitivität (Virus-konzentration bei einem positiven Spender in einem Pool von 599 virusfreien Spenden) liegt bei [...]. Damit wird mindestens die gleiche Nachweisempfindlichkeit wie bei Testung von Einzelspenden mit den heute verfügbaren kommerziellen Testkits erreicht", emphasis added). In other words, the reliability of the PCR to detect a single virus contamination in a pool of 600 blood samples equals that of analysing samples individually, or pools containing up to 600 samples do not negatively affect the PCR sensitivity under the experimental conditions disclosed in document D1.

26. Likewise the mentioning of about "3000" blood samples as the daily workload of the German Red Cross in a specific federal state in Germany (see paragraph bridging page 14 and 15 of document D1) does not teach the skilled person that the assay cannot be used for smaller numbers of blood samples. The skilled person is aware that the number of blood donations varies since the donation is voluntary, and that a need exists for testing them quickly, irrespective of their numbers, because donated blood has a limited storage stability.

27. In view of the considerations above, the skilled person would use the PCR assay disclosed in document D1 to test for potential virus contaminations in blood samples where the total number of blood samples does not exceed 96, i.e. the number of wells found on a single microtiter plate.

28. In these circumstances, the skilled person would further derive from Figure 1 in document D1 that three separate PCR tests for identifying a virus-positive sample are not necessary - but only two, because the sample pool to be examined by the first and the second PCR test is identical. As a consequence thereof, the skilled person would recognise that there is no need for taking three sample aliquots from each sample - but only two, because the number of aliquots equals the maximum number of PCR tests in the assay.

29. Appellant I argued that the skilled person in the light of the teaching of document D1 would strictly follow the complete three-step PCR approach disclosed in Figure 1, since the overall amount of required PCR reactions was lower compared to a single or a two-step PCR test. However, as set out above in situations with up to 96 samples the first PCR test is superfluous and document D1 does solely disclose microtiter plates with 96 wells. Hence, this argument is not convincing.

30. In view of the considerations above, the board concludes that the claimed embodiment under consideration does not achieve the technical advantages asserted by appellant I when compared to the closest prior art method. Thus, in line with the case law (see above), the technical problem is defined as the provision of an alternative method for uniquely identifying viral positive biological fluid donation samples.

31. The method according to claim 1 solves this problem.

Obviousness

32. As set out above, in situations where the sample size to be pooled does not exceed the number of wells on a single microtiter plate, the skilled person starting from the closest prior art method would immediately recognise that the taking of three sample aliquots instead of two is superfluous, because the pools to be tested for a potential virus contamination by the first and the second PCR test as disclosed in Figure 1 of document D1 are identical.

33. In these circumstances, the skilled person starting from the closest prior art method and faced with the above mentioned problem, would arrive in an obvious manner at the embodiment under consideration.

34. Thus, the method according to claim 1 of the main request contravenes Article 56 EPC.

Auxiliary requests 1 to 3

Inventive step (Article 56 EPC) - claim 1

35. Claim 1 of auxiliary request 1 embraces the embodiment considered above with regard to the main request (see section X above).

36. This embodiment is also encompassed by the method of claim 1 of auxiliary request 2 which differs from that of auxiliary request 1 in that the feature "wherein the subpools are all tested at once in a single PCR testing cycle" has been added.

36.1 As set out above (see point 16.3), the third PCR test disclosed in Figure 1 of document D1 tests all subpools at the same time in a single cycle.

36.2 Furthermore, like claim 1 of the main request, claim 1 of auxiliary request 2 defines the method "openly", i.e. the claimed method may comprise further process steps in addition to the ones explicitly cited (see above). In view of these considerations, the feature "wherein the subpools are all tested at once in a single PCR testing cycle" cannot be construed to relate to all process steps that may be present in claim 1, but only to those explicitly cited. Thus, contrary to appellant I's view, claim 1 of auxiliary request 2 does not relate to a concept fundamentally different from that disclosed in document D1.

37. Claim 1 of auxiliary request 3 differs from that of auxiliary request 1 in that the feature "forming a single master pool by combining an aliquot of each sample or an aliquot of each of the subpools, the master pool containing a sample from all of the donations;

performing a PCR test for viral indication on the master pool, and if the PCR test of the master pool is positive, the following steps are carried out:

testing each subpool via a PCR test for viral indication, wherein the subpools are all tested at once in a single PCR testing cycle;" has been added.

38. This feature in claim 1 of auxiliary request 3 is identical to the formation of a master pool that contains aliquots of all samples to be examined by PCR for a potential virus contamination as disclosed in document D1 (see point 16.1, above). Thus, the reasons set out above for the embodiment under consideration of claim 1 of the main request and auxiliary request 2, likewise apply to the method according to claim 1 of auxiliary request 3.

39. Consequently, the arguments set out above for the embodiment under consideration of claim 1 of the main request likewise apply to the method of claims 1 of auxiliary requests 1 to 3, which likewise contravene Article 56 EPC.

Auxiliary request 4

Article 123(2) EPC - claims 1 and 10

40. The issue to be assessed with regard to Article 123(2) EPC in relation to the subject-matter of claims 1 and 10 of auxiliary request 4 is whether or not the feature "where n is any integer from 3 to N" can be directly and unambiguously derived by the skilled person, using common general knowledge, from the patent application as a whole.

41. Claim 2 as originally filed read as follows: "The method according to claim 1, wherein the n-dimensional grid is at least a 3-dimensional grid" (emphasis added). Moreover, page 29, line 38 to page 30, line 2 of the patent application discloses that "The method begins in block 301 by defining an N-dimensional sample matrix or grid. The matrix may be of any size and comprise any number of dimensions from 2 to N, but preferably is a 3-dimensional regular matrix, organized as a square" (emphasis added).

42. Claim 2 as originally filed discloses literally the contested feature of present claims 1 and 10, except for the term "matrix", for which the term "grid" is used. However, page 29, line 38 of the patent application discloses that the method either defines a "N-dimensional sample matrix or grid". In other words, the terms matrix and grid are used interchangeably in the patent application, i.e. a "grid" is not a specific embodiment of a "matrix". In view of these passages in the patent application, and contrary to appellant II's view, the method of claims 1 and 10 finds a direct and unambiguous basis in the patent application.

43. Accordingly, Article 123(2) EPC is complied with.

Article 84 EPC - claims 1 and 10

44. Appellant II submitted that the feature "3 to N" in present claims 1 and 10 lacked clarity and support in the patent application, because the variable "N" might relate to values smaller than three, like in a "count-down" situation.

45. The board is not convinced by this argument. In line with the opposition division's finding in the decision under appeal, the variable "N" in the range "3 to N" recited in claims 1 and 10 can only be construed to relate to values higher than three (see point 13 above). There are also no indications for a "count-down" situation derivable from the patent application as a whole, which rather on the contrary specifies, for example, in claim 2 as originally filed that the grid (i.e. the matrix) is "at least" 3-dimensional (emphasis added). In other words, the value "3" defines the lower limit of the range indicated in claims 1 and 10. Furthermore, the range "3 to N" finds support on page 30, lines 1 and 2 of the description of the patent application.

46. Thus, the subject-matter of claims 1 and 10 is clear and supported, and hence, auxiliary request 4 complies with the requirements of Article 84 EPC.

Article 83 EPC - claims 1 and 10

47. Appellant II submitted in the context of sufficiency of disclosure and inventive step that the mapping of samples to elements in the matrices exceeding three dimensions falling within the scope of claims 1 and 10 were insufficiently disclosed.

48. The board is not persuaded by this argument, since as set out in point 13 above, the term "n-dimensional matrix" in claims 1 and 10 relates to an abstract concept that is mathematically defined by variables. It is thus not confined to the physical space of two or three dimensions. Since the concept allows for a unique mapping of fluid samples to elements in matrices of any dimension including their subsequent identification, the patent application discloses the invention in a manner sufficiently clear and complete to be carried out by the skilled person.

49. The requirements of Article 83 EPC are therefore complied with.

Article 56 EPC - claims 1 and 10

Closest prior art

50. It is common ground between the parties that document D1 represents the closest prior art for the subject-matter of claims 1 and 10.

51. The claimed methods differ from that disclosed in document D1 in that the matrix has at least three dimensions instead of two, and that subpools are formed "from all samples identified by a matrix notation in which one dimensional index is fixed", i.e. from all samples along the axes of all three (or more) dimensions. The use of such a matrix has the effect that the overall number of PCR reactions required for uniquely identifying a virus-positive sample is reduced compared to the method described in document D1. This results in significant time and cost savings.

52. Appellant II submitted that the technical problem was the provision of a method for identifying viral positive blood donations wherein the samples are arranged in an alternative manner. However, as set out above, since the use of an at least 3-dimensional matrix instead of a 2-dimensional improves the claimed method vis-à-vis that of the closest prior art, the board does not concur with appellant II's view.

53. Thus, the technical problem underlying the subject-matter of claims 1 and 10 is defined as the provision of an improved method for uniquely identifying virus-positive biological fluid donations.

54. The methods according to claims 1 and 10 solve this problem across the whole scope of the claims for the reasons set out above in the context of sufficiency of disclosure.

Obviousness

55. It remains to be assessed whether or not the skilled person starting from the closest prior art method and faced with the problem defined above, would have arrived at the methods of claims 1 and 10 in an obvious manner.

56. Document D1 discloses solely the mapping of potentially viral-positive blood donations by pooling samples in 2 dimensions. Since the teaching of document D1 is limited to the use of microtiter plates, and subpools are only formed from samples from the columns and rows of individual plates, the document provides no suggestions how to further reduce the number of PCR reactions required for identifying potentially virus contaminated blood sample(s), let alone by pooling samples along the axes of further dimensions.

57. Appellant II submitted that the skilled person in the light of the teaching of document D1 merely had to stack the microtiter plates disclosed therein on top of each other to arrive at the methods according to claims 1 and 10 in an obvious manner.

58. The board does not share this view because document D1 neither mentions the stacking of microtiter plates nor solves the mere stacking of microtiter plates alone the underlying technical problem. Document D1 provides no suggestions or hints that such a stacking could be used for the formation of further subpools along the axes of the third or any higher dimension thereby reducing the number of PCR tests required for identifying virus-positive blood samples. Nor is the formation of additional subpools rendered obvious by any of the other prior art documents on file, either alone or in combination with document D1.

59. Hence, auxiliary request 4 meets the requirements of Article 56 EPC.

60. Since auxiliary request 4 corresponds to auxiliary request 5 upon the basis of which the opposition division decided that the patent could be maintained, both appeals have to be dismissed.