The patent provides novel polynucleotides encoding PCSK9b and PCSK9c polypeptides, fragments and homologues thereof.
Brief outline of the case
The proprietor and the opponents 1 and 2 appealed the decision of maintenance by the OD according to AR1.
The MR in opposition corresponds to the claims as granted with claims 8 and 11 deleted. This MR did not allow maintenance as claim 10 of the MR was infringing Art 123(2). Claim 10 related to “A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject…”
Claim 5 of the MR and of AR1 corresponds to claim 5 as granted.
Claim 5 as granted reads
- “An isolated antibody that binds specifically to the isolated polypeptide of SEQ ID NO:2 or SEQ ID NO:4.”
The board held that claim 5 was lacking N over D3=Rashid et al. 2005, Proc. Natl. Acad. Sci 102(15), 5374-5379, not mentioned in the ISR.
The patent was revoked.
The assessment of Novelty
The OD’s position
The OD decided that, in line with T 2101/09, the expression “antibody that binds specifically to” a polypeptide used in the claim limited the claimed subject-matter to antibodies that bound to epitopes which are unique for this polypeptide.
Therefore, the claimed subject-matter was limited to antibodies “reactive with those epitopes of PCSK9b or PCSK9c that discriminate PCSK9b or PCSK9c from other structurally related sequences in the art”.
In this respect, the OD decided that none of the 12 documents cited by the opponents would deprive claim 5 from N, i.e. also not D3.
The board’s position
The board held that the subject-matter of claim 5 encompasses antibodies that bind to epitopes shared by the isolated polypeptide of SEQ ID NO:2 (PCSK9b) or SEQ ID NO:4 (PCSK9c) and the PCSK9 protein.
The board made a distinction between two standards:
- The standard of disclosure to apply when assessing the legal question of novelty, which is the standard of a direct and unambiguous disclosure.
- The standard of proof to apply when assessing evidence and factual questions, which is the standard of “balance of probabilities”.
For the board those two standards are distinct, unrelated and should not be mixed
The board added that the fact that the standard of disclosure required for a finding of lack of novelty, or for allowing an amendment to the application under Art 123(2) is immaterial to the question of which standard of proof applies when considering evidence and factual issues in the context of novelty or inventive step.
Going more into the details of the case the board also explained what should be understood under “binds specifically to” and under an “isolated polypeptide“.
Meaning of “binds specifically to”
The board noted that in the case underlying T 2101/09, the patent did not define the meaning of an antibody “specifically reactive with” a (novel) polypeptide and no evidence was available for a commonly accepted meaning of this term either. For the board, the case at hand was different from that underlying T 2101/09.
The board held that the subject-matter of claim 5 encompasses antibodies that bind to epitopes shared by the isolated polypeptide of SEQ ID NO:2 (PCSK9b) or SEQ ID NO:4 (PCSK9c) and the PCSK9 protein.
Meaning of “isolated polypeptide”
For the board, the expression “isolated polypeptide“, as commonly understood in the art, refers to a polypeptide removed from its original environment, i.e. a polypeptide which is, to some extent, purified.
The “isolated polypeptide” referred to in claim 5 does not need to be in its active native form, but could also be in a denatured or linearised form provided that it has been isolated from its natural environment.
The board added that claim 8 as granted concerns an “isolated polypeptide” for use in preventing, treating, or ameliorating a medical condition, i.e. contains an additional functional limitation of the recited “isolated polypeptide” which is absent from claim 5 and therefore cannot be used to restrict the subject-matter of this claim.
The board’s conclusion
The board concludes that the subject-matter of claim 5 encompasses antibodies binding to an epitope shared by the full-length or mature PCSK9 protein and one or both of the PCSK9b and PCSK9c polypeptides, including linear epitopes and epitopes accessible only in denatured forms of the polypeptides.
The application of those notions in the present case.
The question of whether or not a given known antibody binds to a particular polypeptide is a question of fact.
The board noted that in the case at hand, the burden to prove that the antibody disclosed in document D3 binds to the PCSK9b and/or PCSK9c polypeptides lay with the opponents.
However, the standard of proof generally applied at the EPO for deciding on an issue of fact is the balance of probabilities.
The board was however not persuaded by the arguments of the OD that, by way of exception, a higher standard must apply in the present case. For the OD, it was “reasonable to assume” or “highly likely” that they also recognize the protein, was not sufficient to argue that the prior art directly and unambiguously discloses an antibody binding to the antigens of SEQ ID NOs: 2 or 4.”
The board was also not persuaded by the proprietor’s argument that, inter alia, decisions T 943/93 and T 464/94 supported the notion that a higher standard of proof than that of the balance of probabilities applied when examining N.
The factual question to be decided upon in the present case is whether it is more likely than not that a known PCSK9 antibody would bind specifically to the PCSK9b and/or the PCSK9c polypeptide. In assessing this question, any evidence submitted by the parties is considered by the board and such evidence does not necessarily have to be in the form of “wet lab” experiments, as argued by the patent proprietor.
D3 discloses a polyclonal antibody raised against two short murine PCSK9 peptides. It is also demonstrated in D3 that the polyclonal antibody binds to full-length and mature murine PCSK9 in an immunoblot after denaturing gel electrophoresis (“SDS-PAGE”), i.e. it binds to the peptide in a denatured form.
The polyclonal antibody disclosed in D3 recognises an epitope determined by the linear sequence of a peptide, which is fully contained within the PCSK9b and PCSK9c polypeptides.
In view of this factual assessment, the board considered that it is more likely than not that this antibody, the availability of which had not been questioned, also specifically binds to the PCSK9b or PCSK9c polypeptides, at least in a so-called “Western blot”, i.e. an immunoblot of proteins separated by denaturing gel electrophoresis.
Consequently, the board concluded that, based on the applicable standard of proof, the polyclonal antibody disclosed in D3 also specifically binds to the PCSK9b and PCSK9c polypeptides comprising the same peptide.
Hence claim 5 lacked N over the disclosure of D3.
Comments
The distinction made by the board between two standards might a priori look somehow artificial. This is not necessarily the case.
The notion of “balance of probabilities” applies when a decision about facts has to be taken. This is nothing new
For the board, the legal standard for N appears to be that of a direct and unambiguous disclosure.
The factual standard to assess N is that of “balance of probabilities”.
The number of cases in which a deciding body will have to resort to “balance of probabilities” to actually decide whether the disclosure is novelty destroying will most probably be rather low.
In the present case “balance of probabilities” was about the substance of what has been disclosed.
However, “balance of probabilities” can also play a role when deciding whether a piece of prior art, like a leaflet or an oral statement during a conference, belongs to the prior art under Art 54(2).
The distinction made in the present decision does thus not appear as a new definition of what has to be understood under N, but a kind of tool to better define what has actually been disclosed.
It is noticeable that the board found it necessary to add a comment about extension of object under Art 123(2).
I am looking forward to see a first decision of a board where the notion of “balance of probabilities” is used in factually assessing added subject-matter or identity of invention when it comes to validity of the priority.
https://www.epo.org/law-practice/case-law-appeals/recent/t181708eu1.html
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