Kirin-Amgen v TKT

Lack of Enablement, “Biogen” Insufficiency and Claim Ambiguity

On 31 July 2002, the UK Court of Appeal (Kirin-Amgen v Hoechst and Transkaryotic Therapies, unreported), ruled that Transkaryotic Therapies (TKT) does not infringe Amgen's patent for the protein erythropoietin (EPO), reversing the earlier decision of the Patents Court (Kirin-Amgen v Roche and Transkaryotic Therapies [2002] RPC 1). The decision of the Patents Court is exceptionally lengthy and covers many interesting issues and a summary of the decision and the Court of Appeal’s review can be found on the Jenkins website. In “Court of Appeal gets to Grips with the Protocol” we look at the issue of purposive construction on which the case ultimately turned. Here we focus on the issue of insufficiency.

We can list three grounds for insufficiency under the Patents Act 1977 Section 72(1)(c):

i) a patent claims results which it does not enable;

ii) a patent claims every way of achieving a result when it enables only one way and it is possible to envisage other ways of achieving that result which make no use of the invention; or

iii) the claims are ambiguous to the point where it is not possible to determine whether there is infringement.

Amgen (not very helpfully) tells us that the first and second grounds are not separate grounds, and (much more helpfully) gives us a set of five guidelines to follow for claims that include potentially ambiguous comparative tests.

 

A “Principle of General Application”

In Biogen v Medeva the inventor (Professor Sir Kenneth Murray) was the first to succeed in producing hepatitis B virus antigen by recombinant DNA techniques, but he did not identify the DNA sequence of the antigen. His contribution to the art was seen by the House of Lords as no more than the disclosure of one method of achieving the known goal. The House of Lords held the broad claims of the Biogen patent to be invalid for insufficiency of disclosure (Biogen v Medeva [1997] RPC 1 HL). A summary of Biogen can be found on the Jenkins website. In Kirin-Amgen v Roche and Transkaryotic Therapies (which we shall refer to as “Amgen”) the defendants attempted to argue that the inventor (Dr Lin) had contributed no more to the art of manufacture of EPO than Professor Murray had contributed to the art of hepatitis B, i.e. that he did no more than "to decide to [attempt the goal] and succeed.”

The judge at trial (Mr Justice Neuberger) saw a similarity with Biogen in terms of an inventive way of achieving something which everyone was looking to do, but concluded that Dr Lin contributed much more. Dr Lin set out a table (Table VI) of the amino acid sequence of EPO, the identity and location of the nucleotide sequences of the exons and the introns and he determined the upstream and downstream sequences. Although he succeeded only in transfecting certain hamster cells (which would be an achievement comparable to that of Biogen’s Professor Murray), he contributed sufficient new information to the art to enable others to design methods of producing EPO through expression in other cells. Neuberger J considered this to be a contribution of general application and the Court of Appeal agreed.

One of the several grounds of insufficiency alleged was that the disclosure was not enabling in respect of analogues of the disclosed DNA sequence (i.e. variations where amino acid residues have been changed or removed without the effectiveness of the protein being lost). Amgen's claims (see below) encompassed innumerable analogues. The evidence showed that it might take an entire lifetime to identify what the possible analogues might be, but there was no evidence of any specific analogue that would not work to express EPO. Because the specification disclosed a principal of general application, Amgen should be entitled to a claim of correspondingly general terms. They did not need to show that they had proved its application in every individual instance. Support for the claim (as opposed to insufficiency of the disclosure) was a pre-grant matter for the patent office (in this case the European Patent Office).

Neuberger J had separately used the terms "classic" insufficiency and “Biogen” insufficiency for the two scenarios set out by Lord Hoffman in Biogen, viz. (i) the patent claims results which it does not enable and (ii) the patent claims every way of achieving a result when it enables only one way and it is possible to envisage other ways of achieving that result which make no use of the invention. But he applied a two-stage analysis. He first addressed those possible forms of insufficiency and found there to be “classic” insufficiency. He then considered Biogen and concluded that there was no insufficiency at all. The Court of Appeal said this was incorrect and said that Section 72(1)(c) provides just one ground of invalidity, which, broadly stated, is that the specification must enable the invention to be performed. But the Court of Appeal did not find any claims to be insufficiently supported. To the contrary, in agreeing that the invention disclosed a principal of general application (albeit a principal defined in somewhat narrower terms that that identified by the Patents Court), the Court of Appeal held all the claims to be sufficiently supported.

 

Claim Ambiguity

Another significant ground for insufficiency that was considered at length was the ruling of the Patents Court that one of the claims (claim 19) was insufficiently enabled (and therefore invalid) because of the indeterminate terms of a comparative test in the claim. The claim called for a recombinant polypeptide which had “higher molecular weight” than EPO isolated from urinary sources.

Neuberger J believed there were too many extrinsic factors upon which infringement would depend. But the Court of Appeal said

Section 72(1)(c) (insufficiency) is concerned with enablement. . . . In our view TKT's allegation is not a ground of insufficiency, it is an attack of lack of clarity dressed up to look like insufficiency. We can see no reason to stretch 72(1)(c) to seek to cover issues of lack of clarity of claiming, as patentees will not be able to establish infringement of unclear claims.

In this case, the test (an SDS-PAGE test) could be carried out without undue effort. The claim was enabled across its width.

Referring to the many tests produced in evidence using different urinary sources purified to different degrees, some post-dating the date of the patent application, all showing different results with regard to whether the resulting DNA sequence had "higher molecular weight [than] EPO isolated from urinary sources", the Court considered an oft-quoted speech of Lord Shaw in British Thomson-Houston Company v Corona Lamp Works [1922] 39 RPC 49

It is easy, whenever language of generality and relativity applicable to size, measure, weight or the like have been employed, to put puzzles which might indicate that, at certain points, you are at that thin strip of mechanical territory in which, on the one side, there might be failure, and, on the other, success. But the reply to such criticism is that that is not how practical men work. They work to achieve success, and if, adopting the broad lines laid down in a specification, they do not find any real difficulty in achieving success, this may not conclude the matter, but it goes far to show that the vagueness of the specification has not mislead them – practical people who were not seeking for failure but for success – had not caused the invention to fail to reach their mind, but has, on the contrary, for all practical purposes, guided them, and that without difficulty, towards the success which prior to that no experiment nor invention had achieved.

Drawing from this passage, the Court of Appeal set out some clear rules for considering whether a comparative test in a claim is insufficient:

i) the onus is upon the defendant to establish that the test is insufficient;

ii) the question of insufficiency has to be judged as of the filing date;

iii) it has to be decided by the court through the eyes of the skilled person;

iv) the skilled person is deemed to be seeking success rather than failure; and

v) lawyers can often think up puzzles at the edge of a claim, but skilled persons are concerned with practicalities not puzzles.

Donning the mantle of the skilled person at the filing date who is always seeking success, the Court of Appeal found the claim with the comparative test (claim 19) to be sufficiently enabled.

 

Comment

"Classic insufficiency" and "Biogen insufficiency"

The Court of Appeal appears to have been somewhat harsh on Neuberger J in describing his categorization of "classic insufficiency" and "Biogen insufficiency" as erroneous, as the two forms of insufficiency he identified seem to come directly from Lord Hoffman's speech in Biogen. But even Neuberger J recognized that neither of his ennumerated approaches gave a complete analysis. The first steps in the analysis must be "what is the inventive concept?" and "is it a principal of general application?" These are difficult questions and (as we see from Biogen) even the greatest minds can take different views, but all other conclusions flow from these initial enquiries.

The effect of Biogen is not solely to expand the validity attack of insufficiency to over-broad claims. The decision links the permissible breadth of a claim to the contribution the invention makes to the art. It recognizes that there are inventions that disclose a principle capable of general application and there are those that do not. The former are entitled to be claimed more broadly. An analysis of the scope of the technical contribution to the art must be the starting point for the analysis of sufficiency of disclosure.

Comparative tests in claims – claim ambiguity

Under Section 32(1)(i) of the Patents Act of 1949 (now obsolete), ambiguity in a claim used to be a specific ground of revocation. An example of a patent being revoked under that Act on account of a comparative test can be found in Proctor and Gamble v Peaudouce [1989] FSR 180. The patent was for a disposable diaper having flexible side flaps of a certain stiffness defined with reference to a “Taber” stiffness test used in the paper board industry. The test was problematic when applied to an absorbent material. One problem was that the Taber test called for sampling of five samples and “neither more nor less”, whereas many more samples would be required to achieve the accuracy required by the patent claim. The Court of Appeal ruled:

A claim must be sufficient and clear so as to define the monopoly upon which there could be no intrusion. If there was no clarity, intrusion could not arise. It was fundamental that a producer of a product must know where he could not intrude. If, after applying the test in the patent, he could not determine whether or not his product would infringe the claims, there was an insufficiency of definition.

Although ambiguity is no longer a ground of revocation, the new five-point guidelines for a comparative test do permit the “ambiguity” grounds for insufficiency to continue, but surely Proctor and Gamble would have been decided differently under the “seeking success” element of the test? Surely a skilled reader seeking success could have modified the test to sample more samples?

Claiming analogues in Biotech cases

It is common in the biotech field to draft claims to DNA sequences coding for a protein and sequences coding for analogues to the protein. There is always a danger that such claims will be held invalid for insufficiency (see American Home Products v Novartis [2001] RPC 8). Amgen were perhaps fortunate that no evidence was produced of any specific analogue that would not work to express EPO. It would surely not have been difficult to find one such analogue. By contrast, in American Home Products the judge at first instance found on the evidence that it was almost certain that many of the analogues would not exhibit the immunosuppressant activity upon which that invention was based.

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The Amgen Patent Claims Amgen’s patent had thirty-one claims, three of which are summarized here for discussion in this newsletter. Claim 1 was directed to a product:- 1. A DNA sequence for use in securing expression in a prokaryotic or eukaryotic host cell of a polypeptide product having at least part of the [structure of EPO to allow ...haemoglobin synthesis] selected from the group consisting of: (a) [certain DNA sequences set out in certain tables] or their complementary strands (b) DNA sequences which hybridise under stringent conditions to the protein coding regions of the DNA sequences defined in (a) or fragments thereof; and (c) DNA sequences which, but for the degeneracy of the genetic code, would hybridise to the DNA sequences in (a) and (b). Claim 19 was a product-by-process claim:- 19. A recombinant polypeptide having part or all of the primary structural conformation of human or monkey EPO [as set forth in certain tables] or any allelic variant or derivative thereof possessing the biological property of [causing bone marrow cells to.... increase haemoglobin synthesis...] characterised by being the product of eukaryotic expression of an exogenous DNA sequence and which has higher molecular weight... from EPO isolated from urinary sources. Claim 26 was also a product-by-process claim:- 26. A polypeptide product of the expression in a eukaryotic host cell of a DNA sequence according to any one of claims 1,2,3,5,6 and 7. In each case, omitted words do not further define the product itself, only its function.