UK Court of Appeal judgment in Eli Lilly v Human Genome Sciences

02 March 2010

Gerry Kamstra

In its unanimous judgment delivered by Lord Justice Jacob on 9 February 2010, the Court of Appeal upheld the finding in the Patents Court by Mr Justice Kitchin that the UK designation of Human Genome Sciences (“HGS”) EP 0,939,804 (“the Patent”) is invalid on the grounds of lack of industrial applicability (reported in our Update of December 2008).  The judgment is noteworthy not only because of its importance to bioinformatics companies but also because its conclusion is the opposite of that reached by the European Patent Office (“EPO”) Technical Board of Appeal (“TBA”) on the same patent a few months earlier.  Because of this, Lord Justice Jacob’s judgment addresses at some length not only the substantive question of industrial applicability, but also key differences in approach between the English Courts and the EPO.

The Patent discloses the nucleotide and amino acid sequences of a novel member of TNF (tissue necrosis factor) ligand superfamily (a class of proteins which mediate in the immune response and the function each of which is the subject of much investigation) which HGS calls Neutrokine-α. By analysing the nucleotide sequence of a cDNA clone using bioinformatics (sequence homology and comparison algorithms) HGS identified the sequence as corresponding to a new TNF ligand. Eli Lilly opposed the grant of the Patent in the European Patent Office and sought revocation of the UK designation in the Patents Court. In the Patents Court Mr Justice Kitchin held on 31 July 2008 that the Patent is invalid on the grounds of lack of industrial applicability (Article 57 European Patent Convention) as well as lack of inventive step (Article 56 EPC) since each of the claimed inventions failed to make any technical contribution (as followed logically from the finding of lack of industrial applicability). The EPO Opposition Division held on 3 December 2008 that the Patent should be revoked on the grounds of extension of subject matter (Article 123(2) EPC) and lack of inventive step (Article 56 EPC).

Given the fact that the appeal from the EPO Opposition Division to the TBA could also dispose of the appeal from the Patents Court, the Court of Appeal was keen to ensure that the appeal to the TBA be dealt with before the hearing of the appeal pending before it.  Because of this the Court of Appeal sought, and was accorded, acceleration of the appeal to the TBA. Both the decision of the TBA and the judgment of the Court of Appeal refer to this cooperation.

In the appeal to the TBA, HGS put forward slightly amended claims in their main request, limiting claim 1 to an “isolated” polynucleotide (selected from a more limited group of sequences than in the Patent as granted) which encodes a Neutrokine-α polypeptide. Similar amendments were made to the claims covering recombinant vectors and to antibodies that bind to Neutrokine-α polypeptides. The TBA reviewed the disclosure of the Patent and previous decisions of the TBA in relation to Article 57 EPC.  The TBA noted that the parties accepted that Neutrokine-α had been correctly identified as a new member of the TNF ligand superfamily in the Patent and that the key question was “whether this in itself suffices to suggest a practical way to exploit the claimed invention which is centred on Neutrokine-α, thereby providing “an immediate concrete benefit” in accordance with TBA decision T 898/05 (Zymogenetics).  The TBA noted in particular a statement in the Patent that “(l)ike other members of TNF family, Neutrokine-α exhibits activity on leukocytes including for example monocytes, lymphocytes and neutrophils. For this reason Neutrokine-α is active in directing the proliferation, differentiation and migration of these cell types”.  The TBA decided that this information should not be taken as a mere theoretical or hypothetical assumption because “it is plausible and, secondly, there is ample post-published evidence on file confirming both the presence of Neutrokine-α on activated T-cells and its ability to co-stimulate T-cell proliferation (cf inter alia Tables 1 and 2 of the second declaration of Dr Kelsoe III…)”.  This, together with other considerations, led the TBA to conclude that the Patent “provides a concrete technical basis for the skilled person to recognise a practical exploitation of the claimed invention in industry” and accordingly that the Patent fulfils the requirements of Article 57 EPC.  In relation to the objections by Eli Lilly under (Article 123(2) EPC) and (Article 56 EPC), the TBA reversed the decision of the Opposition Division, thereby upholding the Patent and remitting it to the Opposition Division on the basis of the amended claims.

The English Court of Appeal, which heard the appeal just under two months after the hearing before the TBA, dealt only with the questions arising under Article 57 EPC as these were (as it turned out) dispositive of the appeal. As indicated above, because of the difference in its conclusion from that of the TBA, the Court was at pains to explain the differences in procedure in the English Courts and the EPO, mentioning differences in approaches to evidence and the final nature of Court proceedings in contrast to the “administrative” nature of EPO proceedings.  The Court also commended the cooperation between the Court and the EPO that led to the TBA decision being made available before the English appeal.

In his judgment Lord Justice Jacob reviewed essentially the same disclosures in the Patent and the same TBA decisions relating to Article 57 EPC as the TBA. Although the same “plausibility” test was applied to each of the postulated uses of Neutrokine-α (some of which as noted earlier by Mr Justice Kitchin contradicted others) Lord Justice Jacob concluded on the evidence before him (note that this included evidence given at first instance under cross-examination) that although the postulated uses were “plausible” this was “miles away from being able to say that any particular use was plausible in the sense of being taken, by the reader, to be reasonably so. In reality one was faced with a research program to see which, if any, of the possible uses of  the Neutrokine-α or its antagonists was real”.

Importantly, and as noted by Lord Justice Jacob, the Court did not consider any of the “post-published evidence” put forward by HGS before the TBA.  He said “ (i)t is surely axiomatic that whatever the standard for susceptibility to industrial application may be, the information about it must be in the patent (supplemented if necessary by the common general knowledge of the time). Otherwise you could satisfy the Art. 57 requirement by just identifying a compound in the patent and finding a use for it later. That would contravene, for example Art. 5(3) of the [Biotechnological Inventions] Directive [which requires the industrial application of a gene sequence to be disclosed]. You cannot have a patent for an invention when only years later you or someone else finds out what it is for. The same principle as applied in Johns Hopkins [T 1329/04] concerning obviousness must apply also to Art. 57.”.  For this reason the Court did not consider the post-published Kelsoe evidence that so clearly influenced the TBA – in particular Table 1 of Kelsoe identified seven post-published scientific publications that confirm that Neutrokine-α is expressed in activated T-cells and Table 2 identified nine publications that confirmed that Neutrokine-α co-stimulates T-cells.

The decisions of the TBA and Court of Appeal, apart from reflecting differences in procedure, also perhaps reflect differences of legal approach: The TBA regarded the post-published scientific literature identified in the Kelsoe declaration as confirmatory of the postulated uses in the Patent whereas the Court of Appeal considered that such evidence was not relevant at all. Second, the Court of Appeal appears to have applied the same standard of disclosure to Article 57 as that which applies to obviousness under Article 56, whereas the TBA is quite clear that the standard of disclosure required under Article 57 is the same as that which applies to sufficiency under Article 83.  It remains to be seen whether the English case will go to the Supreme Court.