CASRIP Newsletter - Spring/Summer 1997, Volume 4, Issue 2

Highly Anticipated UK Decision of Biogen v. Medeva about Validity of Biotechnology Patents

On October 31, 1996, the House of Lords handed down a long-awaited decision regarding the patentability of a biotechnology invention in Biogen v. Medeva.¹ Because the unanimous decision revoking the patent is the first consideration by the House of Lords of a genetically engineered product, it will significantly impact the validity of biotechnology patents in the futures. Particularly, its approach to the assessment of broad claims will be of immense significance.

This landmark decision was an appeal from the October 27, 1994 Court of Appeal Decision² which held that Biogen’s patent was invalid due to insufficiency, obviousness and failure to pertain to an "invention." Although the House of Lords upheld the Court of Appeal’s judgment, it followed a significantly different route and sharply disagreed with various aspects of the Court of Appeals’ decision.

Instead the House of Lords reinstated the trial judge’s finding of fact and admonished the Court of Appeal to exercise appellate caution in reversing the trial judge’s evaluation of the facts, as even the most specific findings of fact were inherently an incomplete statement of the impression which was made upon the judge by the primary evidence. The House of Lords’ opinion, delivered by Lord Hoffmann, embraced a clear and well reasoned analysis, which carefully balanced the interests of the patentee against those of the public.

In addition, the House of Lords’ decision is worthy of praise because it reflects the global convergence of patent law and the corresponding awareness of foreign patent doctrine (Lord Hoffmann cites Professor Chisum’s treatise, as well as Merges’ and Nelson’s influential article on patent scope) by investing the decisions of the EPO with considerable persuasive authority in accordance with the requirements of Section 91(1)³ and 130(7).⁴

Biogen v. Medeva concerned Biogen Inc.’s patent relating to the exploitation of Hepatitis B virus (HBV) using recombinant DNA (rDNA) technology. The patent was based upon experimental work done in 1978 by Professor Sir Kenneth Murray of Edinburgh University. At that time, recombinant DNA technology was in its promising infancy. In February of that year, Professor Murray and a number of other molecular biologists of international repute founded Biogen, Inc. to exploit the new recombinant DNA technology for commercial purposes. One of the first projects undertaken by the company was the production of antigens of HBV. Professor Murray began work in the spring of that year and in November, reported that he had produced two of the known HBV antigens in colonies of cultured bacteria.

On December 22, 1978, Biogen filed a UK patent application (hereinafter referred to as "Biogen 1") based on Professor Murray’s work. The UK application formed the basis for a priority claim for a later application filed at the European Patent Office (EPO) on December 21, 1979 (EP B-1 182 442). The European patent was finally granted on July 11, 1990. Subsequently, it was subject to an extensive opposition action, which was dismissed on appeal by the EPO on July 28, 1994⁵, the last day of the Court of Appeal hearing.

At the time of filing the first patent application, the genome for HBV had not been sequenced. However, many details of HBV had been ascertained during the 1970s. In 1970, the infective agent of Hepatitis B was discovered. This so-called "Dane particle" appeared to include a circular molecule of DNA in a protein core and to be surrounded by a protein surface. Correspondingly, it seemed to have at least two antigens, one at the core (HBcAg) and one at the surface (HBsAg). One way to obtain these antigens was to purify them from the Dane particles taken from the blood of people infected with the virus. But there were concerns about the safety of such derived vaccines and supplies were obviously limited by the number of donors. Alternatively, antigens could be made artificially by chemical synthesis, but this required knowledge of the sequence and structure of the amino acids. However, in 1978 little was known about them.

A promising third approach was recombinant DNA technology. At the claimed priority date, two experimental rDNA strategies were available. One way was to sequence the HBV genome, i.e. to identify the order of each base of the viral DNA molecule. A second, high-risk strategy involved randomly cutting the HBV DNA into large fragments and to then clone and express them. Biogen chose the latter "shotgun" approach. Contrary to any expectations, the technique had been successful. However, six months after filing Biogen 1 and three months before EP ‘442, the genome was sequenced by researchers at the University of California at San Francisco. Biogen therefore conceded that the claimed invention was obvious at the filing date of EP ‘442. It was thus vital for Biogen to convince the court that Biogen 1 indeed supported the invention in the later EP ‘442.

In 1992, Biogen instigated infringement proceedings against the respondent, Medeva^PLC, which was proposing to market what it described as a third-generation Hepatitis B vaccine (HEPAGENE) made by rDNA technology in colonies of mammalian cells. Medeva counterclaimed, alleging that the Biogen patent was invalid under the UK Patents Act on four grounds: (1) lack of invention under sec. 1(1)⁶; (2) lack of inventive step under sec. 1(1)(b) and 3; (3) nonentitlement to the priority date of Biogen 1, because it did not support the claimed invention under section 5(2)(a); (4) insufficient description in the specification under sec. 72(1)(c).

The principal claim for the appeal concerned a product claim in which the molecule was identified partly by the way in which it had been made (rDNA techniques) and partly by the way it was expressed to produce HBV antigens.⁷ Subsequent claims, based on the principal claim, covered both the distinct HBV "surface" and "core" antigens and their expression in bacterial, yeast and mammalian host cells.⁸

In addressing whether the Biogen claims constituted an "invention" as required by sec. 1(1), Lord Hoffmann rejected the approach of the Court of Appeal, which first required an examination of whether or not the claims constituted an invention before assessing whether the requirements for patentability had been satisfied. He reasoned that such an approach would cause unnecessary difficulty and would almost invariably be academic. Recognizing that the four conditions of patentability in section 1(1) not only restrict the class of inventions which may be patented but also comprise every element of the concept of invention in ordinary speech, Lord Hoffmann recommended that courts first consider the conditions for patentability such as novelty, inventiveness, industrial application, as well as the excluded categories, before tackling the question of whether the claims satisfy the definition of invention.

A caveat was voiced in a short opinion by Lord Mustill, who had been a member of the Court of Appeal in the infamous Genentech v. Wellcome⁹ decision. Though he agreed with Lord Hoffmann that in the great majority of cases there would be no need to complicate the enquiry by looking outside the conditions of patentability, he espoused that some instances may require a closer conceptual analysis. Apparently, he continued to entertain the same concern expressed in Genentech: that products, such as proteins existing in nature, ought not to be granted patent protection.

With regard to inventive step, he sidestepped the ultimate issue by accepting the judgment of the first instance court on this point. Perhaps the most interesting comment on inventive step was Lord Hoffmann’s acknowledgment that commercial reasoning in itself could not justify lack of inventive step. Previously, the Court of Appeal had determined that Professor Murray’s "shotgun" approach lacked an inventive step because it was "a mere commercial decision" and "a matter of business judgment." This pronouncement distressed the patent and biotechnology community at the time, and many thought it heralded disaster for the research and development programs of biotechnology companies, since any decision to pursue the expression of a particular gene and the recombinant production of a particular protein was commenced after precise calculation of the potential payoff.

However, as the House of Lords correctly observed, a given experimental strategy is usually adopted for commercial reasons because the anticipated rewards seemed to justify the necessary expenditure. Therefore, commercial reasoning in itself should not justify lack of inventive step. Moreover, as Lord Hoffmann correctly concluded, it runs counter to the very function of inventive step to suggest that an inventor needs to pursue his experiments untouched by thoughts of gain. Indeed, the sole question is whether there was an inventive step, irrespective of the inventor’s reasons for pursuing the respective invention.

The crux of the decision hinged on whether Biogen 1 supported the invention claimed in EP ‘442, as the House of Lords assumed that the invention was not obvious at its first priority date. In reference to the earlier House of Lords decision in Asahi Kasei Kogyo KK’s Application¹⁰, Lord Hoffmann explained that for matter to support an invention under sec. 5(2)(a) of the Patent Act of 1977, it must disclose the invention in a manner which enables it to be performed by a person skilled in the art. The same principle applies to the relationship between sec. 14(3) and 14(5)(c). That is, a description does not "support" the claims for the purpose of sec. 14(5)(c), unless it contained sufficient material to qualify the specification as an "enabling disclosure" within the meaning of sec. 14(3).

This correspondence between these two patent principles resolves the problem that has irked the British patent community since the inception of the 1977 Patent Act, namely that lack of support or "fair basis," as it was previously called, was not a separate ground of revocation¹¹. The substantive effect of section 14(5)(c), that the description should, together with the rest of the specification, constitute an enabling disclosure, is given effect by sec. 72(1)(c). Accordingly, Lord Hoffmann held "enabling disclosure" to be central to the law of patents, as the underlying concept relates to sec. 5(2)(a), 14 and 72(1)(c).

He then considered the meaning of the concept of enabling disclosure. He referred to the Technical Board of Appeal decision in GENENTECH I/Polypeptide Expression,¹² which has, on numerous occasions, been misinterpreted as supporting the proposition that one example of, or one way of carrying out, the invention is sufficient to meet the disclosure requirement of Art. 83 EPC. Lord Hoffmann rectified this misconstruction by indicating that the applicants had invented a general principle and was therefore entitled to claims in general terms.

He asserted that the Board in GENENTECH I/Polypeptide Expression had done no more than apply a principle long established in British patent law, namely, that a specification must enable the invention to be performed to the full extent of the monopoly claimed. This was affirmed several times by the Technical Boards of Appeal, particularly in EXXON/Fuel Oils¹³. Some see the latter decision as reversing the liberal trend set in GENENTECH I.

However, as Lord Hoffmann pointed out, these decisions are not inconsistent but are actually easily reconcilable on their respective facts. Both endorse the general legal principle that the extent of the patent monopoly, as defined by the claims, should correspond to the technical contribution to the art in order for it to be supported, or justified.

According to this postulate, if the invention discloses a principle capable of general application, the claim may be in correspondingly general terms. In that case, the patentee need not show that he has proved its application in every individual instance. On the other hand, if the claims include a number of discrete methods or products, the patentee must enable the invention to be performed in respect of each of them.

Thus if the patentee has hit upon a new product which has a beneficial effect but cannot demonstrate that there is a common principle by which that effect will be shared by other products of the same class, he will be entitled to a patent for that product but not for the class, even though some may subsequently turn out to have the same beneficial effect. On the other hand, if he disclosed a beneficial property which is common to the class, he will be entitled to a patent for all products of that class even though he has not himself made more than one or two of them.

But the fact that the skilled man following the teaching of Biogen 1 would have been able to make HBcAg and HBsAg in any cell does not conclude the matter. The critical issue in this case is not whether Professor Murray’s invention could deliver the goods across the full width of the patent or priority document, but whether the claims covered other ways in which they might have been delivered: ways which owe nothing to the teaching of the patent or any principle disclosed. The breadth of claim may thus exceed the technical contribution to the art, not only by the results which it does not enable, but also by claiming ways of achieving a result, when it enables only one way.

In that context, the House of Lords cited the famous US Supreme Court decision in O’Reilly v. Morse¹⁴ as an example of a case concerning excessively broad patents. To elucidate the significance of this case, Lord Hoffmann cited Professor Chisum’s Treatise: "Before Morse’s invention, the scientific community saw the possibility of achieving communication by the ‘galvanic’ current but did not know any means of achieving that result. Morse discovered one means and attempted to claim all others."¹⁵

In a similar vein, Lord Hoffmann held the patent in suit to be too broad. Its excessive breadth was due, not to the inability of the teaching to produce all the promised results, but to the fact that the same results could be produced by different means. Despite Professor Murray’s brilliant Napoleonic victory in cutting through the uncertainties which existed in his day to achieve the desired result, his success did not establish any new principle which his successors had to follow if they were to achieve the same results. Once the DNA had been sequenced, none would choose the restriction enzymes Professor Murray had employed.

Similarly, it was not enough that Professor Murray had shown by his invention that it could in fact be done, and that this would provide those who followed by different routes with greater confidence. To grant a monopoly to the first person who has found a way of achieving an obviously desirable goal for every way of doing so would, in the words of Merges and Nelson¹⁶, stifle further research and healthy competition in the post grant phase.

Lord Hoffmann was aware of the fact that the patent in suit had survived an opposition before a Specialist Technical Board of Appeals of the EPO. Similar to his earlier leading judgment in Merrell Dow Pharmaceuticals Inc. v. H.N. Norton & Co. Ltd.¹⁷, he took pains to emphasize the considerable persuasive authority of EPO decisions. He distinguished the contrary judgment of the Technical Boards of Appeal on the ground that it directed its attention solely to the question of whether the teaching in Biogen 1 would enable the man skilled in the art to achieve expression of HBsAg as well as HBcAg. It did not concern itself with the issue whether the claims were too broad because expression could also be achieved without the use of the teaching which it contained. This same principle was also clearly stated in GENENTECH I and EXXON so that in Lord Hoffmann’s opinion no divergence between the jurisprudence of this court and that of the EPO is suggested.

Although the statements on insufficiency are strictly obiter, as the House had already concluded that the patent was not entitled to an earlier priority date and therefore obvious, Lord Hoffmann pointed out that the same reasoning applied in relation to support would also lead to the conclusion that it was insufficient. In this context, he referred to the vexed question of the date on which the specification must disclose the invention, so as to enable a person skilled in the art to perform it. In the lower courts there had been a conflict as to whether the relevant date was the date of publication or application. On this issue the House of Lords sided with the Court of Appeal and held the date of application to be relevant. Lord Hoffmann reasoned that it would be illogical if a patent which ought to have been rejected under section 14(3) is rendered immune from revocation under sec. 72(1)(c) by intervening advances in the art. An insufficient application cannot become sufficient in light of developments in the state of the art after the filing date.

The primary significance of the House of Lords decision is founded on providing a mode for reasserting the need for congruence between patent scope and the disclosed contribution to the art. Lord Hoffmann thereby astutely affirmed the time honored patent law principle that the effective disclosure is the quid pro quo for the grant of a patent. By the same token, the House of Lords has shown a way how to rectify the current imbalance in Europe between the conditions of grant, which include the description’s support of the claims, and the grounds of revocation. Under the guise of insufficient disclosure, the House of Lords has introduced the patent law principle of "lack of support" as a ground of revocation, whereby the claims of a complete specification may not extend beyond what the patentee disclosed as his invention.

-- Michael Kern

¹[1997] RPC 1.
²Biogen v. Medeva, [1995] FSR 4; [1995] RPC 25.
³According to sec. 91(1), judicial notice shall be taken among others of the EPC and any decisions of, or expression of opinion by, the relevant Convention court on any question arising under or in connection with the relevant Convention.
⁴Sec. 130(7) declares that various sections, including sec. 1(1) to (4), 2 to 6, 14(3), (5) and 72(1) and (2) are so framed as to have, as nearly as practicable, the same effects in the United Kingdom as the corresponding provisions of the EPC.
⁵T296/93, [1995] EPOR 1 – "BIOGEN/HBV antigen production."
⁶This ground of revocation was later dropped by Medeva. Nonetheless, the House of Lords addressed the issue.
⁷Claim 1 read as follows:

A recombinant DNA molecule characterized by a DNA sequence coding for a polypeptide or a fragment thereof displaying HBV antigen specificity, said DNA sequence being operatively linked to an expression control sequence in the recombinant DNA molecule and being expressed to produce a polypeptide displaying HBV antigen specificity when a suitable host cell transformed with said recombinant DNA molecule is cultured, the transformed host cell not producing any human serum proteins and any primate serum proteins other than the polypeptide displaying HBV antigen specificity.

⁸Claims 2 to 4 are based upon claim 1 and state:

A polypeptide free of any humThe recombinant DNA molecule according to claim 1, characterized in that the polypeptide displaying HBV antigen specificity also displays HBV antigenicity.
The recombinant DNA molecule according to claim 1 or 2, characterized in that the DNA sequence codes for a polypeptide or a fragment thereof displaying the HBV antigen specificity of a hepatitis B virus core antigen.
The recombinant DNA molecule according to claim 1 or 2, characterized in that the DNA sequence codes for a polypeptide or a fragment thereof displaying the HBV antigen specificity of a hepatitis B virus surface antigen.
an serum proteins and any primate serum proteins which displays HBV antigen specificity, said polypeptide being produced by a host cell transformed with a recombinant DNA molecule according to claim 1 or 2.

⁹[1989] RPC 147.
¹⁰[1991] RPC 445, 24 IIC 247 [1993}.
¹¹Similarly, the EPC does not provide for a ground of opposition that corresponds to the application requirement of "support" under Art. 84.
¹²T 292/85, [1989] O.J. EPO 275.
¹³T 409/91, [1994] O.J. EPO 653.
¹⁴56 U.S. (15 How.) 62 (1854).
¹⁵Vol. 1, § 1.03[2]. See also Vol. 2, § 7.03[1].
¹⁶Robert Merges and Richard Nelson, On the Complex Economics of Patent Scope, 90 Colum. L. Rev. 839 (1990).
¹⁷[1996] RPC 76, 82.

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