The appeal concerned with the validity of a patent which claimed the nucleotide sequence of the gene which encodes for a novel protein. The patent in suit was European Patent (UK) 0,939,804. It describe the encoding nucleotide, the amino acid sequence, and certain antibodies, of a novel human protein, which it call Neutrokine-α, and include contentions as to its biological properties and therapeutic activities, as well as those of its antibodies. These contentions were predictions, which were substantially based on the proposition that Neutrokine-α is a member of the TNF ligand superfamily.
The application for the Patent was filed by Human Genome Sciences Ltd (“HGS”) on 25 October 1996, and it was granted by the Examining Division of the European Patent Office (“the EPO”) to HGS on 17 August 2005. Accordingly, the Patent’s validity was to be judged as at October 1996.
In very summary terms, the disclosure of the Patent included the following features: (i) the existence and amino acid sequence of Neutrokine-α, (ii) the nucleotide sequence of the gene encoding for Neutrokine-α, (iii) the tissue distribution of Neutrokine-α, (iv) the expression of Neutrokine-α by its mRNA (the encoding gene) in T-cell and B-cell lymphomas, and (v) the information that Neutrokine-α is a member of the TNF ligand superfamily.
The central issue both in the High Court proceedings and in the opposition proceedings before the EPO was whether, in the light of the common general knowledge at October 1996, by disclosing the facts namely the existence and structure of Neutrokine-α, the sequence of its encoding DNA, its tissue distribution, its expression, and its membership of the TNF ligand superfamily, the Patent satisfied Articles 52 and 57 of the EPC so as to enable HGS to claim the encoding gene for Neutrokine-α.
After the grant of the Patent to HGS, it was the subject of opposition proceedings brought in the EPO by Eli Lilly and Company (“Eli Lilly”). Following an oral hearing before the Opposition Division of the EPO (“the OD”) in June 2008, the Patent was revoked on the basis that the claimed invention constituted, as the Judge put it, a claim to an arbitrary member of the TNF ligand superfamily without a known function. HGS appealed against the OD’s decision to the Board which allowed the appeal. Meanwhile, Eli Lilly brought parallel proceedings in the High Court for revocation of the Patent in this jurisdiction. The High Court revoked the Patent. The decision was given on 31 July 2008, after the decision of the OD, but before HGS had appealed to the Board. HGS appealed against the High Court’s decision to the Court of Appeal which dismissed the appeal.
The essence of the Board’s approach in relation to the requirements of Article 57 in relation to biological material was summarised in the following points:
The general principles are:
(i) The patent must disclose “a practical application” and “some profitable use” for the claimed substance, so that the ensuing monopoly “can be expected [to lead to] some … commercial benefit”;
(ii) A “concrete benefit”, namely the invention’s “use … in industrial practice” must be “derivable directly from the description”, coupled with common general knowledge;
(iii) A merely “speculative” use will not suffice, so “a vague and speculative indication of possible objectives that might or might not be achievable” will not do;
(iv) The patent and common general knowledge must enable the skilled person “to reproduce” or “exploit” the claimed invention without “undue burden”, or having to carry out “a research programme”;
Where a patent discloses a new protein and its encoding gene:
(v) The patent, when taken with common general knowledge, must demonstrate “a real as opposed to a purely theoretical possibility of exploitation”;
(vi) Merely identifying the structure of a protein, without attributing to it a “clear role”, or “suggest[ing]” any “practical use” for it, or suggesting “a vague and speculative indication of possible objectives that might be achieved”, is not enough;
(vii) The absence of any experimental or wet lab evidence of activity of the claimed protein is not fatal;
(viii) A “plausible” or “reasonably credible” claimed use, or an “educated guess”, can suffice;
(ix) Such plausibility can be assisted by being confirmed by “later evidence”, although later evidence on its own will not do;
(x) The requirements of a plausible and specific possibility of exploitation can be at the biochemical, the cellular or the biological level;
Where the protein is said to be a family or superfamily member:
(xi) If all known members have a “role in the proliferation, differentiation and/or activation of immune cells” or “function in controlling physiology, development and differentiation of mammalian cells”, assigning a similar role to the protein may suffice;
(xii) So “the problem to be solved” in such a case can be “isolating a further member of the [family]”;
(xiii) If the disclosure is “important to the pharmaceutical industry”, the disclosure of the sequences of the protein and its gene may suffice, even though its role has not “been clearly defined”;
(xiv) The position may be different if there is evidence, either in the patent or elsewhere, which calls the claimed role or membership of the family into question;
(xv) The position may also be different if the known members have different activities, although they need not always be “precisely interchangeable in terms of their biological action”, and it may be acceptable if “most” of them have a common role.
The High Court had concluded that (a) the Patent discloses Neutrokine-α as a new member of the TNF ligand superfamily; (b) all known members of the superfamily had pleiotropic effects, (c) there were some features which all those known members shared, such as expression by T-cells and a role in the regulation of T-cell proliferation and T-cell mediated responses; (d) however, there were other features which some family members had, but others did not; (e) it would be anticipated that the activities of Neutrokine-α “might relate to T-cells and, in particular, be expressed on T-cells and be a co-stimulant of B-cell production; that it might play a role in the immune response and in the control of tumours and malignant disease; that it might have an effect on B-cell proliferation”; (f) subsequent research has confirmed that was indeed the case; (g) there was a search for new members of the family as they were of interest to the pharmaceutical industry.
The Supreme Court after discussing the law as well as the facts on the aspect concluded that HGS’s appeal on the Article 57 issue should be allowed, Eli Lilly’s cross-appeal on the insufficiency issue should be dismissed, and the case should be remitted to the Court of Appeal to deal with the outstanding issues.