“Industrial Application”: Proteins Need Purpose for Patentability

This article was included in our Summer 2010 edition of Inside IP magazine.

On 9 February 2010 the Court of Appeal in the UK ruled that the Patents Court was entirely correct to revoke the British part of a European patent because, on the filing date of the precursor patent application, the applicant had not demonstrated a practical use for the novel protein that they had identified and described.

In coming to his decision, Jacob LJ discussed the ‘industrial application’ requirement for patentability in detail.  Although the patent in question, European Patent No.  0939804, relates to subject matter of a biotechnological nature, the principles laid down in the decision are applicable to the wider field of pharmaceuticals.

Background

In August 2005 the European Patent Office (EPO) granted a European patent to Human Genome Sciences, Inc.  (“HGS”) for a previously unidentified protein called neutrokine-α.  The patent included claims to a nucleic acid molecule encoding the protein, the protein itself, anti-bodies to the protein and pharmaceutical and diagnostic compositions comprising any of the foregoing.

The patent provided the nucleotide and deduced amino acid sequences of neutrokine-α.  It also disclosed the results of a bioinformatics study, which had identified the physical and chemical properties of the amino acid sequence and revealed regions of identity with the amino acid sequences of three other proteins (TNF-α, TNF-β and FAS ligand).

These latter proteins are part of the same protein family (the TNF-ligand super-family); all are cytokines involved in the regulation of cell proliferation, activation and differentiation.  They are also, however, implicated in the pathogenesis of various immune system-related disorders and, at the filing date of the precursor patent application (October 1996), early studies had indicated that antibodies to such proteins could be useful in the treatment of such disorders.

Owing to the sequence homology that they had observed, HGS speculated that neutrokine-α had similar biological effects and activities to the cytokines in the TNF-ligand superfamily.  Thus, HGS further speculated that neutrokine-α could be used in the treatment of immune system-related disorders in a similar manner to the other proteins, and a list of putative uses, based upon those of the known members of the superfamily, was included in the patent application.  However, no data were provided to prove that neutrokine-α had such biological effects or activities, and no evidence was presented to support the claimed therapeutic effect.

Proceedings in the EPO

The granted patent was subsequently opposed at the EPO on all available grounds by three parties, including Eli Lilly and Company (“Lilly”).  HGS sought to defend their patent.  However, the Opposition Division of the EPO took the view that the patent contained subject matter which had been introduced during prosecution of the precursor application (which is not allowable under European patent law).  The Opposition Division consequently held the patent invalid.  Although HGS then sought to amend the claims as granted, their attempts were rejected on the ground that the amended claims encompassed subject matter lacking in inventive step.  The patent was hence revoked.

HGS appealed the EPO’s decision to revoke the patent.  As a result of the appeal proceedings, the Technical Board of Appeal at the EPO ordered that the decision under appeal be set aside and the patent be maintained on the basis of a restricted set of claims that HGS had filed during the appeal proceedings.

Proceedings in England

Meanwhile, in parallel proceedings, Lilly had sought revocation of the British part of the granted European patent in the Patents Court.  Lilly sought revocation on several grounds, including an allegation that the precursor patent application had failed to disclose an invention capable of industrial application.  Specifically, Lilly were of the view that HGS had filed their patent application without knowing the biological activity or function of neutrokine-α, the disorders that it causes or those that it might be able to treat.

At the court hearing, Kitchin J set out guidelines on the industrial application requirement for patentability.  The salient points are as follows:

(1) The capability of industrial exploitation must be derivable by the skilled person from the description of the patent specification read with the benefit of the common general knowledge;

(2) The description, so read, must disclose a practical way of exploiting the invention in at least one field of industrial activity (the notion of industry to be construed broadly, and to include activities not necessarily conducted for profit and therapeutics for rare diseases that are not intended for use in any trade at all);

(3) The purpose of the invention and how it can be used to solve a given technical problem must be disclosed in the specification in definite technical terms;

(4) It is not sufficient to describe merely an interesting research result that might yield a yet-to-be identified industrial application, as it should not be left to the skilled reader to find out how to exploit the invention by carrying out a research programme;

(5) If a substance is disclosed in the specification and its function 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 application is not satisfied; and

(6) It is no bar to patentability that an invention is found by homology studies using bioinformatics techniques, although this may have a bearing on how the skilled person would understand the disclosure.

Applying these principles to the claims of HGS’ patent, Kitchin J acknowledged that HGS had indeed discovered a novel protein and correctly identified it as a member of the TNF-ligand superfamily.  However, he considered HGS’ assertions concerning the therapeutic capacity of neutrokine-α to be entirely speculative.  Kitchin J stated

“…[the patent specification] contains an astonishing range of diseases and conditions which neutrokine-α and antibodies to neutrokine-α may be used to diagnose and treat and there is no data of any kind to support the claims made.  The skilled person would consider it totally far-fetched that neutrokine-α could be used in relation to them all and, as I have found, would be driven to the conclusion that the authors had no clear idea what the activities of the protein were and so included every possibility.  To have included such a range of applications was no better than to have included none at all.”

Kitchin J was also of the view that it was not possible for HGS to have predicted the function or therapeutic capacity of neutrokine-α based upon the other, known, members of the TNF-ligand superfamily, as those members had disparate, and sometimes unique, activities and, furthermore, only one such member had been found to have any therapeutic application.

In addition, Kitchin J observed that, even years after the filing date of the patent, only limited conclusions regarding the activity of neutrokine-α could be drawn. Moreover, the amount of work that remained to be done at the time of the court hearing pointed strongly to the conclusion that the therapeutic and diagnostic applications suggested in the patent were indeed speculative.

Thus, Kitchin J held that the patent fell short of many of points (1)-(6) above and, consequently, that each and every claim in the patent was invalid.

HGS, having had some success in the EPO’s Board of Appeal finding of the patent being valid on the basis of more restricted claims, appealed to the Court of Appeal.  However, the Court of Appeal dismissed the appeal, even in respect of the more restricted claims, finding that the invention was not capable of industrial application.

Seemingly conscious that this was a decision contrary to that of the EPO’s Board of Appeal, Jacob LJ explained in detail why that was justifiably so.  The crux of the matter was said to be that the Board of Appeal and the Court of Appeal were working on different evidence and using a different procedure, and this is why they had come to a different conclusion on the facts; it was not an issue of law.

Indeed, Jacob LJ explained how the Court of Appeal may, save in very exceptional circumstances, conduct a case only on the evidence and materials presented before the Patents Court.  Such evidence and materials will have undergone intensive investigation and testing, including by the process of cross-examination, before the Patents Court.

In view of this, and in view of the Court of Appeal giving very considerable deference to the findings of fact of the Patents Court, all parties make their best efforts, and lay all of their cards on the table, for the decision of the Patents Court.

The procedure in EPO proceedings is very different and much less intensive.  There is much less room for the testing of evidence before the Opposition Division and Board of Appeal, there is no cross examination and no compulsory disclosure of documents (including, most notably, those adverse to a party’s case).  Fresh material is also admissible on appeal.  In HGS’ case, the Board of Appeal had permitted a substantial amount of further evidence from HGS shortly before the oral hearing, which it expressly relied upon in its decision.  Jacob LJ, referring to the procedure involving the facts and testing of expert evidence at the EPO, described the latter as “…something of a “coarse filter”.  It cannot, need not and does not investigate matters affecting validity as profoundly as a national court can.”

Jacob LJ thus made clear that, in his view, once a patent has been granted by the EPO and survived any opposition, the ultimate arbiter of its validity in any designated Contracting State is the national court system of that Contracting State deciding the case using its own fact-finding procedures.  The Court of Appeal is not bound to follow, or even give deference to, the Board of Appeal’s findings of fact (as has previously been illustrated by several English cases, including Kirin-Amgen v TKT [2004] UKHL 46, [2005] RPC 169, Biogen v Medeva [1997] RPC 1 and Conor v Angiotech [2008] UKHL 49).

This is not the case, however, for principles of law, where the Court of Appeal will follow any principle laid down by the Board of Appeal, only reserving the right to differ if “…we are sure that the commodore is steering the fleet onto the rocks…”, as Jacob LJ so neatly said in his judgment.

Jacob LJ thus concluded that Kitchin J was right to hold that the invention described and claimed in HGS’ patent had failed to satisfy the industrial application requirement for patentability.  Revocation of the patent was thus upheld, allowing Lilly to continue in the development of their own neutrokine-α antibody.

 

Comment

This is a highly important decision for patent proprietors and applicants in the biotech field, given the commercial significance of biotech therapeutics.  Although the decision was made in an English court, other national courts (and possibly the EPO) may well begin to follow suit.  Indeed, Kitchin J made very clear in his judgment that, as far as possible, he had construed the ‘industrial application’ provision of the UK Patents Act so as to have the same effect as the corresponding provision in the European Patent Convention.

In light of this decision, it is clear that it is no longer enough for a UK or European (UK) patent application to simply state what an invention described in the specification may be used for.  Indeed, some evidence that the invention actually has the suggested capability is clearly now required.

This is not perhaps unreasonable, given that the purpose of granting a patent is to reward an inventor for his or her significant contribution to the art.  Indeed, as Kitchin J explained in his judgment, “…the purpose of granting a patent is not to reserve an unexplored field of research for the applicant nor to give the patentee unjustified control over others who are actively investigating in that area and who might eventually find ways to exploit it.” Applicants in the biotech field especially, therefore, should be careful to provide evidence of the therapeutic value of their products when their UK or European (UK) patent application is prepared.

The decision between (i) filing a patent application early, so as to obtain the earliest possible date by which the novelty and inventive step of the claimed invention will be assessed, and (ii) filing late enough to include sufficient evidence to support the claimed invention in the manner discussed above, will therefore be even harder to make.  One way of coming to a decision, however, would be to weigh up the associated risks.

Option (i) is clearly now associated with an inherent risk of your patent being found invalid for lack of industrial application.  However, this will undoubtedly be more problematic for those discovering a biological or pharmaceutical product that bears no, or only a weak, resemblance (in terms of its structure and activity) to those already known or that, on the basis of a structural similarity, appears to be a new member of a known family, but that family demonstrates disparate activities (as in the HGS case).  Indeed, in either of these situations, no effect could be assigned to the new product without relying on some experimental data.

Option (ii) remains associated with the risk of being beaten to the finish line by your competitors.  This, however, will undoubtedly be a greater problem for inventors operating in a crowded technical field.

Tanya Heare 14 Jun 2010

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