Court of Appeal finds remaining claims of Neutrokine patent valid

Practical Law UK Legal Update 4-521-2716 (Approx. 6 pages)

Court of Appeal finds remaining claims of Neutrokine patent valid

by PLC IPIT & Communications

Background

Article 83 of the European Patent Convention (EPC) provides:

The European patent application shall disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.

Section 72(1)(c) of the Patents Act 1977 makes failure to meet this requirement a ground for revocation.

Article 123(3) of the EPC provides that:

The European patent may not be amended in such a way as to extend the protection it confers.

Section 72(1)(e) of the Patents Act 1977 provides for a ground of revocation on that basis.

Facts

Eli Lilly and Company (Lilly) brought an action to revoke European Patent (UK) 0,939,804 (the Patent) held by Human Genome Sciences Inc (HGS) on the grounds, among others, of lack of industrial applicability, insufficiency and obviousness. HGS applied to amend the Patent. The Patent disclosed the nucleotide and amino-acid sequence of a novel member, called Neutrokine-α, of a family of proteins known as "the TNF ligand superfamily" (TNF family). These are cytokines, proteins which act as inter-cellular mediators in inflammation and immune responses. HGS had discovered Neutrokine-α using bioinformatics and filed the Patent shortly afterwards, before any practical use had been identified. Instead, the Patent identified the protein as a member of the TNF family and included a long list of activities and uses based solely upon what was known about other members of the family. Kitchin J held that the entire patent was invalid for lack of industrial applicability and also for obviousness as there was no contribution to the art, while the claims to pharmaceutical and diagnostic compositions were invalid for insufficiency (see, Legal update, High Court finds biotechnology patent invalid as claimed invention not susceptible of industrial application).

Before this decision, in opposition proceedings in the European Patent Office (EPO) brought by Lilly, the opposition division had revoked the European patent on the ground that the claimed invention lacked any inventive step. Both decisions were appealed.

The Court of Appeal requested the EPO appeals board to accelerate its proceedings, and arrangements were made for the EPO appeal to be heard before the hearing in the Court of Appeal (see Legal update, Court of Appeal delays appeal hearing until EPO appeal completed). The EPO Technical Board of Appeal (TBA) allowed the appeal and held the European patent as amended in the proceedings to be valid (see Legal update, EPO appeal board finds Neutrokine patent valid).

The Court of Appeal then heard the appeal and decided to uphold Kitchin J's decision rather than following the TBA (see Legal update, Court of Appeal disagrees with EPO over validity of Neutrokine patent). HGS were given leave to appeal to the Supreme Court and Lilly cross-appealed on the basis that, even if the patent satisfied the industrial application requirement, it was still insufficient. The Supreme Court unanimously decided to allow the appeal and dismiss the cross-appeal. On the basis of their analysis of EPO case law, they held that Kitchin J and the Court of Appeal had not properly applied the relevant principles.

The case was remitted to the Court of Appeal to deal with the outstanding issues, the validity of three claims, two of which (claims 18 and 19) had been held invalid by Kitchin J as being insufficient and one which (claim 13) he had held to be valid over an objection of insufficiency.

Decision

The Court of Appeal, in concurring judgments given by Sir Robin Jacob and Lewison LJ, held that all three claims were valid, for the following reasons:

Sufficiency of claim 13

Claim 13 was the commercially important one. At the time of the patent, neither the patentees, nor anyone else, knew whether Neutrokine-α or any of its antibodies or both would actually be valuable products. But further research work by HGS and others led to identification of specific antibodies to Neutrokine-α, which were promising. HGS in association with GSK had an antibody product for the treatment of lupus, Lilly an antibody product for the treatment of rheumatoid arthritis and multiple myeloma, and Biogen and Genentech also had potential antibody products. All these products have their own patents. Commercially what was at stake was whether the inventors and developers of these "downstream" products had to pay royalties to HGS because it had the master claim to all Neutrokine-α antibodies.

Lilly did not challenge a crucial finding of fact by Kitchin J that it did not require undue effort to make and identify specific antibodies to Neutrokine-α at the priority date. This meant that, while there would be many, probably millions, of antibodies to Neutrokine-α, some binding well, others less so, they could all be made and isolated.

Given that, Lilly advanced a more sophisticated insufficiency attack than simply saying the products of the claim could not be made. It is summarised as follows:

Even though individual antibodies could be isolated and made, the patent gave no clue as to which, if any, actually had any practical use. Nearly all would, if investigated, prove to have had none.
It would take undue effort to find out which of the millions had any use.
The patent was aimed at products which had a valuable use, particularly as a pharmaceutical or diagnostic.
So claim 13 should be read as confined to such products. Because it required undue effort to find them, the claim was insufficient.

These arguments were rejected for the following reasons:

At the level of generality of this patent, all the antibodies have a "use". Each member was susceptible of industrial application and that was enough. All the claim called for was an antibody which specifically binds to Neutrokine-α: that in itself was its potential utility. It did not matter that discerning any particular specific utility might involve undue effort, nor that one product might well be useless or much less so than other members of the class.
Construing the claim, it did not contain any limitation to "useful". Words must not be read into patent claims unless the context compellingly so required. The context here did not. The skilled reader would know that the patentees had discovered Neutrokine-α, that it had some biological function similar to other members of the TNF ligand superfamily and that it or its antibodies might be useful. There was no reason why the skilled reader would read the claim as having a limitation to "useful" antibodies.
The argument that claim 13 was not enabling across its breadth, because it included within it antibodies which could not be identified without undue effort, failed because of the fundamental fact that all the antibodies of claim 13 could be made.
In Pharmacia v Merck [2001] EWCA Civ 1610, Aldous LJ held that a wide class claim was insufficient because it included compounds which did not have the promised activity, so it was not enabled across its scope even though all the compounds could be made. Lilly's argument that the same applied here was not accepted because:
- the invention of this patent at its level of generality was not limited in the same way as it was in Pharmacia to a specific activity. The skilled reader was not led to expect any specific activity, only a host of possibilities which may or may not in fact be.
- it was not clear that Pharmacia would be decided for the same reasons today. The objection was of an AgrEvo (T-0939/92) type, that the claim included within it many compounds as to which there was no technical contribution at all. This case was different because HGS had made a technical contribution – claim 13 was for products susceptible of industrial application.

The court rejected on the facts Lilly's argument that the amendments made to claim 13 in the Opposition proceedings had extended the protection, so the claim was not invalid on that ground.

Sufficiency of claims 18 and 19

In finding that these claims were invalid for insufficiency, Kitchin J was not invited to construe the claims and did not expressly do so. He simply proceeded on the basis that they were limited to the pharmaceutical or diagnostic equivalent of a "workable prototype". If that were right, then the claims would indeed be insufficient on his findings of fact. However, HGS contended that the judge had proceeded on an erroneous construction because, read in the context of the specification as a whole, the skilled reader would not have expected the patentee to have intended these claims to be directed to compositions with immediate practical use as a pharmaceutical or diagnostic. It followed that all he must have meant was compositions which could be formulated as suitable for administration as a pharmaceutical or suitable for use as a diagnostic. That could be done and so the claims were sufficient.

This submission was correct, and in accordance with the principles of claim construction laid down in Kirin-Amgen (see Legal update, House of Lords gives guidance on claim construction in Amgen case). The contrary view was not, involving as it did the skilled reader in ignoring the very general high level nature of this invention. Claims 18 and 19 were therefore valid.

Additional comments of Lewison LJ

In this case the Supreme Court answered the questions about the patent: what is it for and what are the chances that it will work? They said that there was a good enough chance that it would work. Therefore, the only remaining question was: can you make it? Of course, you had to decide what "it" was that the patent had to teach you how to make. As Lord Hoffmann pointed out in Kirin-Amgen, an argument about sufficiency was often an argument about what the invention really was. We find out what the invention was by looking at the claim in question, and by interpreting it in the context of the description.

Lilly submitted that these claims should be limited to useful products either:

As a question of construction.
Because as a matter of policy a patent had to teach you how to make products that had a plausibly useful therapeutic application.
Because the extent of patent protection had to be commensurate with the technical contribution.

So far as the policy questions were concerned, they were the subject of the debate in the Supreme Court. Having lost the policy argument there, Lilly was entitled to resurrect it in dealing with sufficiency. Accordingly it is a question of identifying the invention as a matter of construction of the claims.

The real question was: what significance, if any, is to be attributed to the adjectives "pharmaceutical" and "diagnostic"? Lilly argued that the claims are not merely claims to compositions but to "pharmaceutical" and "diagnostic" compositions. One could not describe a composition as a "pharmaceutical composition" unless it had some utility as such. In this context "pharmaceutical" meant suitable for use as a medicine for the treatment of a disorder. A similar approach applied to a "diagnostic composition". These adjectives required the compositions to "be of use as such". You could not call something "diagnostic" unless you knew what it was that you want to diagnose.

Claims 18 and 19 claimed products, not uses. There was no difficulty in making the products. The difficulty was in knowing which of the products would be worthwhile introducing into a human or animal body; and in what circumstances. That was part of the question: was there a good enough chance that it will work? That question has been answered affirmatively by the Supreme Court. The phrase "a pharmaceutical composition" was the common way of claiming ingredient X in packaged form. It did not promise any particular effect. The same was true for "a diagnostic composition" although there was, perhaps, more room for argument. This construction gained added force from a reading of the specification as a whole. It was clear from the specification that the patentee had no real idea what Neutrokine-α or its antibodies would do if introduced into a living creature. It is highly improbable that by using the words "pharmaceutical" and "diagnostic" in that context the patentee would have been understood to mean that the products claimed by these claims had an identifiable therapeutic use.

Comment

The decision that the remaining claims in dispute were valid was almost inevitable, given the interpretation the Supreme Court put on the industrial applicability requirement. However, Sir Robin Jacob made an interesting comment on the commercial issue of what those who have expended time and effort in developing individual members of the claimed Neutrokine-α proteins for therapeutic use might have to pay to HGS under this patent:

I say no more than that if it were to be determined pursuant to an application for a compulsory licence pursuant to section 47 of the Patents Act 1977 the question would be what is a "reasonable term" fixing the amount payable and that the assessment of that might well include the degree of risk, expense and work incurred by the respective parties.

This seems to be a warning to HGS that it should be very careful in how it sets royalty rates for this patent which, although the Supreme Court held it was entitled to have, did not involve the enormous trouble and expense that developing a useable, licensed pharmaceutical involves.

Case

Human Genome Sciences Inc v Eli Lilly and Co [2012] EWCA Civ 1185, 5 September 2012 (Hooper and Lewison LJJ and Sir Robin Jacob; Andrew Waugh QC and Miles Copeland (instructed by Field Fisher Waterhouse LLP) for Lilly and Simon Thorley QC and Michael Tappin QC (instructed by Powell Gilbert LLP) for HGS.

Court of Appeal finds remaining claims of Neutrokine patent valid | Practical Law