T 1957/14 - QTL's unclear

Key points

• In what appears to be an important decision for patents relating to plants and seeds, the Board decides that the claim at issue is unclear because it relies on QTL's (quantitative trait locus).
• The claim is directed to a maize plant having at least 14 QTL's, each QTL is defined by a pair or markers and by a position on a chromosome, each marker is essentially a DNA sequence which is given in the claim (SEQ ID), but the markers are not themselves the genes giving the advantageous properties (if I understand the technology correctly). More importantly is that QTL's are the most commonly used way to define conventionally bred plants in patent claims.
• "In the board's view, the skilled person may well understand the terms used in the claim and how to use the technology related to these terms in practice. Yet this understanding and these practical skills do not, in the present case, convey to the skilled person the structural features necessary to unambiguously characterise the alleles referred to in the claim."
•  "The alleles are moreover defined in claim 1 by further definitions in relation to the QTLs, i.e. the QTLs' supposed location on a chromosome, the QTLs' linkage to marker loci which in turn are defined by PCR primers identified by their sequence and the size of the amplification product " (as I tried to summarize above).
•  "In the board's opinion it is evident that none of these definitions provides the skilled person with any information about the structural features of the alleles themselves. Thus, the sequence of an allele is neither derivable from the QTL's supposed location on the chromosome nor from a characterisation of the markers linked to it, regardless of how extensive that characterisation is."
•  'Hence, the physical parameters of the alleles (see point 4 above), their structures, are not defined by the definitions in the claim. Consequently, the essential features characterising the claimed plant, the alleles (see point 3 above), are also not defined by the claim. For the above reasons, the board concludes that claim 1 lacks clarity."
• Added: The particular QTL's at issue were also defined by a reference to a deposited material. "in the board's opinion, the reliance on deposited inbred line material for the definition of the essential features of the invention and by requiring it to be analysed in order to identify the relevant alleles is at odds with the principle that, generally, the meaning of a claim, including its essential features, should be clear, for the person skilled in the art, from the wording of the claim alone "
• The  oral decision was given on 17 January 2018 so the written decision has taken some time to issue (on 30.11.2018). The claims in case T 1063/18 for which oral proceedings are publicly announced for 5 December 2018 also rely on QTL features. See here for a 2016 paper on patent claims and QTL's. See in particular pages 21 and 23 and in particular page 31. 

EPO T 1957/14 - link




Claim 1 of the main request reads:
"1. A maize plant characterized by a set of at least
14 QTLs each of which contributes to the phenotypic trait of grain yield as measured by quintals per hectare, wherein each of said QTLs is characterized by the presence of an allele of that QTL that contributes in a positive way to the phenotypic trait of grain yield, wherein each QTL is genetically linked to at least one marker locus selected from the group of loci characterized by at least one pair of linked markers each of which can be identified by a pair of PCR oligonucleotide primers consisting of a forward primer and a reverse primer exhibiting a nucleotide sequence as given in
(1) SEQ ID NO: 59/60 with an amplification product in a PCR reaction having a molecular weight of 120 bp and SEQ ID NO: 77/78 with an amplification product in a PCR reaction having a molecular weight of 85 bp, respectively, identifying a marker pair linked to QTLl, wherein QTL1 is located on chromosome 1 at a supposed position at 115.6 cM and is obtained from inbred line M3047/2 (NCIMB 41460); ...

Reasons for the Decision

Introduction and explanation of terms

1. The present invention relates to a maize plant "with a genome comprising a unique allele profile associated with the corresponding QTLs [quantitative trait loci] contributing to the expression of a variety of phenotypic traits of economic interest selected from the group of grain yield (...)" (see application, page 1, first paragraph). "The term "quantitative trait" has been used to describe a phenotype that exhibits continuous variability in expression and is the net result of multiple genetic loci presumably interacting with each other and/or the environment" (see application, page 1, fourth paragraph). The term "quantitative trait locus" (QTL) refers "to an association between a genetic marker and a chromosomal region and/or gene that affects the phenotype of a trait of interest" (see application, page 4, first full paragraph). A "genetic marker" is a "feature of an individual's genome (e.g., a nucleotide or a polynucleotide sequence that is present in an individual's genome) that is associated with one or more loci of interest" (see application page 4, lines 24 to 26). An "allele is understood, within the scope of the invention, to refer to alternative forms of various genetic units associated with different forms of a gene or of any kind of identifiable genetic element" and "an allele associated with a quantitative trait may comprise a single gene or multiple genes or even a gene encoding a genetic factor contributing to the phenotype represented by said QTL" (see application, page 2, fifth and sixth paragraph).

Main request

Clarity (Article 84 EPC) - claim 1

2. Article 84 EPC provides that the claims shall define the matter for which protection is sought and that they shall be clear and concise and be supported by the description. Rule 43(1) EPC further requires that the claims shall define the matter for which protection is sought in terms of the technical features of the invention.

The technical features of the invention are the physical features which are essential to it. The technical features of a claim to a physical entity are the physical parameters of the entity. In appropriate cases technical features may be defined functionally (see G 2/88, OJ EPO 1990, 93, Reasons, point 2.5).

The meaning of the technical features essential to the invention ("essential features") should be clear for the person skilled in the art from the wording of the claim alone (see decision G 1/04, OJ EPO 2006, 334, Reasons, point 6.2).

3. Claim 1 is directed to a maize plant (see section VI for the complete wording of the claim). The plant is characterised by "a set of at least 14 QTLs" and each QTL is characterised by "the presence of an allele of that QTL that contributes in a positive way to the phenotypic trait of grain yield".

Thus, the technical features essential for the invention are the alleles present in the QTLs because they are ultimately responsible for the phenotypic trait of grain yield.

4. As set out above (see point 1), an allele, in the context of the present invention, "may comprise a single gene or multiple genes or even a gene encoding a genetic factor contributing to the phenotype represented by said QTL". Thus, an allele is a "genetic unit" (see application, page 2, line 30). A genetic unit or a gene is characterised by it being a stretch of nucleotides which have a certain order ("nucleotide sequence"), thus defining the informational content of that unit. Hence, the physical parameter of the allele - which is the essential technical feature of the claimed plant - and by which it could certainly be unambiguously characterised is its primary structure, i.e. its nucleotide sequence.

4.1 In claim 1 the alleles are defined (i) by a functional feature, i.e. their positive contribution to the phenotypic trait of grain yield and (ii) by a structural feature, i.e. their presence within a QTL.

4.2 In turn, the QTLs, in addition to the presence of an allele, are further characterised (i) in that they are genetically linked to at least one marker locus, (ii) by the chromosome on which they are found and the supposed position on that chromosome and (iii) by the inbred line they can be obtained from.

4.3 The marker locus to which the QTL is genetically linked is characterised (i) by the presence of at last one pair of linked markers, each of which can be identified by a pair of PCR oligonucleotide primers, the sequences of which are identified in the claim by SEQ ID numbers, and (ii) the size of the amplification product in a PCR reaction.

4.4 The inbred line is defined by its internal designation and its deposit number.

5. It is therefore to be decided whether this definition (see points 4.1 to 4.4) provides an unambiguous characterisation of the physical parameters of the alleles and thus of the essential feature of the claimed maize plants.

6. The appellant argues that, in the light of his general technical knowledge and the description, the person skilled in the art of plant breeding was familiar with the terms used in claim 1, in particular with the terms "QTL" or "genetically linked" (to a marker locus) and also understood what was meant by an allele contributing in a positive way to a phenotypic trait. In fact, the subject-matter of the claim, including the terminology used, reflected what was the day-to-day business of the plant breeders' work, i.e. to follow and transfer plant traits with the help of genetic information about the QTLs/marker loci which were causative for the trait.

6.1 In the board's view, the skilled person may well understand the terms used in the claim and how to use the technology related to these terms in practice. Yet this understanding and these practical skills do not, in the present case, convey to the skilled person the structural features necessary to unambiguously characterise the alleles referred to in the claim.

7. The appellant further argues that the alleles were clearly defined in claim 1 by reference to the QTLs in which they were present for the following two reasons (see below points 8 and 9).

8. The QTLs were described by reference to a deposited material. The Boards of Appeal, in the context of Article 83 EPC, had considered a reference to deposited material as a surrogate for the description of a sequence, i.e. as an alternative to structural information. An example of this case law was decision T 109/91.

8.1 As to decision T 109/91 of 15 January 1992, the sole question dealt with was the novelty of the claimed subject-matter (see Reasons, point 2.1). At issue was whether the claimed plasmid, pHM1519, was the same as plasmid pCG1, disclosed in a document (1), and made available by reference to the deposition number. The appellants had carried out an analysis of the restriction sites and the length of the respective restriction fragments of the deposited plasmid and the claimed plasmid, respectively.

In that context, the board held that "Rule 28 [EPC 1973] states the requirement of a sufficient disclosure within the meaning of Article 83 EPC [1973] as far as microorganisms are concerned which cannot be described in words such that the invention can be carried out by a skilled person.

A such disclosed plasmid, as is the case here, can be used by a skilled person without the necessity of the knowledge of the molecular structure of this plasmid. A connection of the requirements of a deposition of living material to the implicit knowledge of the molecular structure for the purposes of the judgment of novelty is not self-evident" (ibid., point 2.9).

The board concluded that the evidence provided by the appellants that plasmid pCG1 was the same as the claimed plasmid pHM1519 was convincing and that there was no necessity for the appellants to go further in its analysis of the complete DNA-molecules of both plasmids (ibid., point 2.12).

8.2 In the present board's view, as can be seen from the above summary, decision T 109/91 is not directly applicable to the present situation. Firstly, it is concerned with novelty of the claimed subject-matter and not its clarity. Secondly, the reference to the deposit is used to define the claimed subject-matter as such, i.e. all of its features and not only an essential one. The board seems to say that the so-defined subject-matter fulfils the requirements of Article 83 EPC because the plasmid "can be used by a skilled person without the necessity of the knowledge of the molecular structure of this plasmid".

However, the board also says, when considering the disclosure of the structural features of the plasmid, that "[a] connection of the requirements of a deposition of living material to the implicit knowledge of the molecular structure for the purposes of the judgment of novelty is not self-evident" (ibid., point 2.9). To this board this means that the board in case

T 109/91 was of the view that the molecular structure of the plasmid was not implicitly disclosed by depositing the material and referring to its deposit number. This understanding appears to be in line with the findings of the competent board in e.g. decision T 301/87 (OJ EPO 1990, 335, Reasons, points 6.2 to 6.4).

8.3 The present board is thus not persuaded by appellant's argument that deposited material serves "as a surrogate for the description of a sequence, i.e. as an alternative to structural information".

9. Furthermore, the appellant argues that the deposited material provided a material source of the alleles of the invention. The appellant submits that in the deposited material the markers were linked to the QTLs. The skilled person, a plant breeder, could access the deposited material. This allowed them to identify and transfer the allele contributing to the trait at issue by using the markers without undue burden in to any target maize germplasm.

9.1 However, in the board's opinion, the reliance on deposited inbred line material for the definition of the essential features of the invention and by requiring it to be analysed in order to identify the relevant alleles is at odds with the principle that, generally, the meaning of a claim, including its essential features, should be clear, for the person skilled in the art, from the wording of the claim alone (see point 2 above).

9.2 Furthermore, the fact that the plant breeder can obtain a plant having the favourable alleles by accessing the deposited inbred lines and then transferring those alleles to a progeny plant by crossing and selection using the markers, may be a consideration relevant in the context of sufficiency of disclosure. However, when it comes to clarity, the board fails to see how the fact that the breeder knows how to make a plant that falls within the claim's scope can help the clarity of the definition of the essential features in the claim.

10. The board can also not accept that the definition of the alleles in present claim 1 should be considered as clear because a skilled person can determine whether any given plant falls within the scope of claim 1 - even without knowing the structure of the alleles - by determining whether the markers as defined in the claim are present in that plant.

11. Thus, the appellant's arguments do not convince the board that claim 1 of the main request provides a clear definition of the structural features of the alleles and thus of the essential features characterising the claimed maize plant.

12. The alleles are defined in claim 1 by further features (see also points 4.1 to 4.4 above).

13. Thus, they are defined by the functional feature "that contributes in a positive way to the phenotypic trait of grain yield" (see point 4.1).

13.1 It is established case law that for functional features to be considered as clear they must not only put the skilled person in the position to be able to understand the teaching of the claim, but also must he be able to implement them. In other words, they must provide "instructions which are sufficiently clear for the expert to reduce them to practice without undue burden, if necessary with reasonable experiments" (see decision T 68/85, OJ EPO 1987, 228, Reasons, point 8.4.3 and decisions cited in section III.A.3.4 of the Case Law of the Boards of Appeal of the European Patent Office, 8th edition 2016). The present board understands this to mean that by reading the functional feature the skilled person, through his common general knowledge, should be aware of structural features corresponding to that functional definition.

13.2 In the light of this case law the board considers that the functional feature "contributes in a positive way to the phenotypic trait of grain yield" is not clear since the skilled person does not know to which structural feature or features it corresponds.

The present situation is different from e.g. the situation in which the name of a known herbicide resistance - which would be considered as a functional feature - is used to define a herbicide resistance gene and the skilled person is aware of this structure through his common general knowledge (see e.g. decision T 890/02, OJ EPO 2005, 497, Reasons, points 5 to 9).

14. The alleles are moreover defined in claim 1 by further definitions in relation to the QTLs, i.e. the QTLs' supposed location on a chromosome, the QTLs' linkage to marker loci which in turn are defined by PCR primers identified by their sequence and the size of the amplification product (see points 4.1 to 4.4).

15. In the board's opinion it is evident that none of these definitions provides the skilled person with any information about the structural features of the alleles themselves. Thus, the sequence of an allele is neither derivable from the QTL's supposed location on the chromosome nor from a characterisation of the markers linked to it, regardless of how extensive that characterisation is.

16. The appellant referred to decisions T 915/10, T 967/10 and T 1988/12, of which, in its view, the circumstances underlying the first one were comparable to the present case, whereas those underlying the two latter decisions were different.

16.1 In decision T 967/10 of 22 October 2015, the claim under consideration was for a lettuce plant showing a reduced susceptibility towards infection with Bremia lactucae, which plant was obtainable by crossing a susceptible lettuce plant with a lettuce plant grown from the seed of one of several deposited seeds. The board considered that the claimed plant was, at least partly, defined by a process for its production but that it is unknown what the genetic information present in the genome of the claimed plants, and one of the characterising technical features imparted to the claimed plants by the process, actually is. Therefore the process feature as such was considered unclear (see Reasons, points 7 to 10).

In decision T 1988/12 of 10 November 2016, the claim under consideration was to a Brassica plant characterised solely by a process by which it was obtainable. As a consequence of the process features, the subject-matter of claim 1 included Brassica plants whose phenotype was due to the presence in their genome of genetic information identical to that present in the genome of the deposited seeds. Since the skilled person could not derive from the claim per se the explicit structural or informational nature of this genetic information, the process through which the claimed plant was defined did not impart identifiable and unambiguous technical features to it and in particular, the genetic information present in the genome of the claimed plants was unknown (see Reasons, points 8 to 13).

In contrast to the appellant, the board considers the finding of this board in the present case (see point 18 below) to be in line with the findings of the boards in these two decisions since in these cases and in the present case the claimed subject-matter was considered unclear because, due to the particular definition chosen, the essential features of the claimed plants remained unknown.

16.2 Decision T 915/10 of 11 June 2015 concerned soybean plants which had been genetically modified so as to make them tolerant to the herbicide glyphosate and which contained in their genome the particular transgenic insertion event MON89788. Claim 1 was for a soybean plant "the genome thereof containing SEQ ID NO: 9, wherein the plant is obtainable by crossing a plant obtained from soybean seed deposited under ATCC accession number PTA-6708 and another plant" (emphasis added). This claim was considered to meet the clarity requirement of Article 84 EPC (see Reasons, point 7).

However, SEQ ID NO: 9 represents the entire inserted DNA present in the particular transgenic insertion event MON89788 along with some flanking soybean genomic sequences (see Reasons, point 3). The claimed plant was thus characterised by the nucleotide sequence of the insert and the exact location within the genome, which information is considered in itself a clear characterisation of an event (see also decision T 2239/08 of 10 January 2013, Reasons, point 6 and decision T 967/10, supra, Reasons, point 16).

Contrary to the appellant, the board therefore considers that the present case is not comparable to the case underlying decision T 915/10.

17. Hence, the physical parameters of the alleles (see point 4 above), their structures, are not defined by the definitions in the claim. Consequently, the essential features characterising the claimed plant, the alleles (see point 3 above), are also not defined by the claim.

18. For the above reasons, the board concludes that claim 1 lacks clarity.