UK Patents Court judgment in Eli Lilly v Human Genome Sciences

15 October 2008

Gerry Kamstra

The Patents Court (Mr Justice Kitchin) has, somewhat unusually, revoked a patent on the grounds of lack of industrial applicability. HGS owns EP(UK) 0,939,804 (“the Patent”) which 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. The claims (as proposed to be amended in the proceedings) cover the nucleic acid sequence of Neutrokine-α, recombinant vectors containing the sequence, recombinant host cells containing the sequence, a process for making Neutrokine-α, Neutrokine-α itself, antibodies to Neutrokine-α and portions thereof, pharmaceutical compositions comprising the Neutrokine-α nucleic or amino acid sequence or an antibody to Neutrokine-α or portion thereof and diagnostic compositions.

Eli Lilly challenged the claims on the grounds of lack of (i) industrial applicability (ii) sufficiency and (iii) inventive step, as well as (iv) extension of subject matter as regards certain proposed amendments to the claims. At the heart of the challenge was an assertion that the specification of the Patent fails to describe the activities of Neutrokine-α in a way that is anything more than speculative, in particular that the specification does not have any in vitro or in vivo data to support the predictions about the activities of Neutrokine-α. The predictions in the Patent are lengthy, comprising a number of lists of wide ranging (and according to the judge, even contradictory) claims to activity.

Eli Lilly argued that its own independent work on Neutrokine-α (which it called LP-40) confirmed that the therapeutic applications in the Patent were speculative; and HGS argued that its work confirmed the predictions in the specification were reasonable, both parties having focused primarily on activities on B and T cells. Having reviewed the evidence the judge concluded that from some three years (1999) after the priority date it had become increasingly clear that Neutrokine-α is expressed by peripheral blood leukocytes, and in the spleen and lymph nodes; and that Neutrokine-α plays a significant role in the proliferation and differentiation of B cells and (shown more recently) a role in T cell proliferation and activation. He also concluded that as the activities of Neutrokine-α have been elucidated it has been recognised as a target for diseases that are specifically associated with altered B cell function (eg autoimmune diseases and SLE (systemic lupus erythematosus) and B cell malignancies such as lymphoma). Summarising, the judge said that “the limited conclusions ultimately drawn and the amount of work that remains to be done point strongly to the conclusion that the therapeutic and diagnostic applications suggested in the Patent were indeed speculative”.

Dealing first with the allegation of lack of industrial applicability, the judge pointed out that although the UK implementation on 28 July 2000 of the Biotechnological Inventions Directive 98/44/EC in the Patents Act 1977 did not apply to the Patent (which was applied for in 1996) the parties agreed that this made no fundamental change to the applicable principles. Article 5 (3) of the Directive specifically requires the industrial application of a sequence or partial sequence of a gene to be disclosed in the patent specification. The judge then referred to the judgment of the Court of Appeal in Chiron Corporation v Murex and Others [1996] RPC 535 (in which it was held that a claim to any polypeptide encoded by any nucleotide sequence capable of selectively hybridising with the genomic sequence of the disclosed strain of hepatitis C virus was invalid for lack of industrial application given the failure of the specification to describe any utility for any such polypeptide). He also reviewed the European Patent Office and US decisions on the point, then summarising the applicable principles as follows:

  1. "The notion of industry must be construed broadly. It includes all manufacturing, extracting and processing activities of enterprises that are carried out continuously, independently and for commercial gain (BDP1 Phosphatase/Max-Plank). However, it need not necessarily be conducted for profit (Chiron) and a product which is shown to be useful to cure a rare or orphan disease may be considered capable of industrial application even if it is not intended for use in any trade at all (Hematopoietic cytokine receptor/Zymogenetics).

  2. The capability of industrial exploitation must be derivable by the skilled person from the description read with the benefit of the common general knowledge (PF4A receptors/Genentech).

  3. The description, so read, must disclose a practical way of exploiting the invention in at least one field of industrial activity (BDP1 Phosphatase/Max-Plank; Multimeric Receptors/Salk Institute).

  4. More recently, this has been re-formulated as an enquiry as to whether there is a sound and concrete basis for recognising that the contribution could lead to practical application in industry. Nevertheless, there remains a need to disclose in definite technical terms the purpose of the invention and how it can be used to solve a given technical problem. Moreover, there must be a real prospect of exploitation which is derivable directly from the specification, if not already obvious from the nature of the invention or the background art (Hematopoietic cytokine receptor/Zymogenetics; Serine Protease/Bayer).

  5. Conversely, the requirement will not be satisfied if what is described is merely an interesting research result that might yield a yet to be identified industrial application (Multimeric Receptors/Salk Institute). A speculative indication of possible objectives that might or might not be achievable by carrying out research is not sufficient (BDP1 Phosphatase/Max-Plank). Similarly, it should not be left to the skilled reader to find out how to exploit the invention by carrying out a research programme (Hematopoietic cytokine receptor/Zymogenetics).

  6. It follows that the purpose of granting a patent is not to reserve an unexplored field of research for the applicant (BDP1 Phosphatase/Max-Plank) nor to give the patentee unjustified control over others who are actively investigating in that area and who might eventually find ways actually to exploit it (Hematopoietic cytokine receptor/Zymogenetics).

  7. If a substance is disclosed and its function is essential for human health then the identification of the substance having that function will immediately suggest a practical application. If, on the other hand, the function of that substance is not known or is incompletely understood, and no disease has been identified which is attributable to an excess or a deficiency of it, and no other practical use is suggested for it, then the requirement of industrial applicability is not satisfied. This will be so even though the disclosure may be a scientific achievement of considerable merit (BDP1 Phosphatase/Max-Plank).

  8. Using the claimed invention to find out more about its own activities is not in itself an industrial application (BDP1 Phosphatase/Max-Plank).

  9. Finally, it is no bar to patentability that the invention has been found by homology studies using bioinformatics techniques (Hematopoietic cytokine receptor/Zymogenetics) although this may have a bearing on how the skilled person would understand the disclosure.”

Applying these principles to the claims of the Patent and the evidence the judge concluded that he was “quite satisfied that the skilled person would consider the Patent does not of itself identify any industrial application other than by way of speculation”, that it was “no answer to say that subsequent research has shown they [the claimed inventions] may be useful to treat diseases associated with particular B cell disorders” and that all the claims of the Patent are invalid.

Turning to the attack of insufficiency the judge pointed out that the key question, having construed the claims properly, was whether (following Biogen v Medeva [1997] RPC 1) the specification enabled the skilled person to perform the claimed inventions over the whole scope of the claims without undue burden. The question of the utility or activity of such claimed inventions did not enter into such considerations. On that basis the claims to nucleotide and amino acid sequences and to antibodies were held to be valid but the claims to pharmaceutical and diagnostic compositions were held to be invalid. Although having regard to the judge’s comments about the irrelevance of the question of industrial applicability to the question of sufficiency it might appear that the judgment on the pharmaceutical and diagnostic claims is inconsistent, when one remembers that such claims require a composition which is “pharmaceutical” or “diagnostic” it is clear that such considerations (of applicability) must nevertheless apply.

With regard to the attack on inventive step, the judge identified the relevant tests of obviousness from the Pozzoli v BDMO [2007] FSR 37 and Conor Medsystems v Angiotech Pharmaceuticals [2008] UKHL 49 judgments. Eli Lilly attacked inventive step on two grounds: a conventional attack alleging obviousness over certain prior art and an allegation that the claims made no contribution to the art. In rejecting the attack of obviousness over the prior art references the judge, interestingly, pointed that although the skilled person must be deemed to consider any piece of prior art properly and with interest the law does not deem him “to assume the prior art has any relevance to the problem he is addressing or require him to take it forward”. On the other hand (and perhaps inconsistently having just concluded there was an inventive step on the Pozzoli grounds) taking into consideration the approval by the House of Lords in Conor v Angiotech of the decisions of the European Patent Office in AGREVO T 0939/92 and John Hopkins University School of Medicine T 1329/04, the judge accepted that each of the claimed inventions failed to make any technical contribution (as followed logically from the finding of lack of industrial applicability) and were obvious.

Finally, with regard to the attack of extension of subject matter the judge accepted that the deletion of the words “having Neutrokine-α activity” from claim 10 (to a process for making a Neutrokine-α polypeptide) allowed denatured (ie inactive) polypeptides to fall within the scope of the claimed subject matter and that this claim was invalid. The application for leave to appeal has yet to be heard.