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Biogen Inc v. Medeva Plc

1. I have had the advantage of reading in draft the speech prepared by my noble and learned friend Lord
Hoffmann. For the reasons he gives I would dismiss the appeal.

2. I wish to express the gratitude of the Appellate Committee to our two expert advisers, Professor D. Glover of
the University of Dundee and Professor J. Neil of the University of Glasgow, who provided the Committee with
invaluable assistance both before and during the hearing.

LORD BROWNE-WILKINSONMy Lords,

3. For the reasons given in the speech prepared by my noble and learned friend Lord Hoffmann I too would
dismiss the appeal.

LORD MUSTILL

4. I have had the opportunity to read in draft the speech of my noble and learned friend Lord Hoffmann, and
agree both with the conclusion that the appeal should be dismissed and with the reasons for that conclusion. In
particular I am glad to adopt the proposed reconciliation of sections 14(5) and 72(1) of the Patents Act 1977,
which eliminates a difficulty expressed by the Court of Appeal in Genentech Inc.'s Patent [1989] R.P.C. 147.

5. There is however one matter which I should mention: namely, the necessity or otherwise for a valid patent to
concern an invention, as well as satisfying the conditions expressed in paragraphs (a) to (b) of Section 1(1) of the
Act. This question was not contested before the House, although some reference was made to it in debate, for it
was agreed (rightly in my opinion) that it has no bearing on the present appeal. My reason for referring to it is
simply to make clear that in concurring with all your Lordships in the reasons for dismissing the appeal I should
not be taken to accept, without full argument, that the need for an invention would always be academic, or that
no such need is expressed by the words of section 1(1): nor indeed do I understand my noble and learned friend
as advancing any conclusion to that effect. Certainly, in the great majority of cases, there will be no need to
complicate the enquiry by looking outside the four conditions. The traditional law of patents is, however, in the
course of adapting itself to new technologies, beyond contemplation when the foundations of that law were
established. This process is not without strain, and I believe that in some instances a close conceptual analysis of
the nature of patentability will not be a waste of time. Such a case was Genentech Inc.'s Patent where the claim
was for a product already existing in nature, a subject far distant from the mechanical and chemical inventions to
which so much of traditional patent law relates. There may well be others in the future.

6. My Lords, my purpose in adding this footnote to the speech of my noble and learned friend is not of course to
express any opinion, one way or the other, on the correctness of the reasoning outlined at pp. 261-266 of the
report of Genentech Inc.'s Patent. The intention is only to emphasise that when a dispute does arise on which this
question may have a bearing it will merit study leading to a definitive answer.

LORD SLYNN OF HADLEYMy Lords,

7. I have had the advantage of reading in draft the speech prepared by my noble and learned friend Lord
Hoffmann. For the reasons he gives I too would dismiss the appeal.

LORD HOFFMANNMy Lords, 1. Genetic Engineering.

8. In this appeal your Lordships' House has for the first time to consider the validity of a patent for products of
genetic engineering. This is a technology which has developed only during the last 25 years, in consequence of
the great advances which have been made in our knowledge of the genetic code contained in every living cell.
The code is embodied in a molecule of deoxyribonucleic acid ("DNA") which directs the cell to make the
proteins which the organism requires. Genetic engineering or "recombinant DNA technology" consists of
altering the DNA of a suitable cell so that it produces a protein which in nature occurs in another organism. In
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this way it has been possible to manufacture products of great medical importance which could not have been
made by orthodox chemical synthesis.

2. The patent in suit.

9. The principal claim of the patent in suit is for an artificially constructed molecule of DNA carrying a genetic
code which, when introduced into a suitable host cell, will cause that cell to make antigens of the virus hepatitis
B ("HBV"). I shall have to describe in much greater detail what antigens are and how the invention enables them
to be made. Suffice it for the moment to say that HBV is a widespread human virus, often causing fatal diseases
of the liver, and that its antigens can be used both to test for whether someone has the virus and to make a
vaccine which can give immunity against infection.

3. Biogen and Professor Murray.

10. The patent is based upon experimental work done in 1978 by Professor Sir Kenneth Murray of Edinburgh
University. Recombinant DNA technology was then in its promising infancy. In February 1978 Professor Murray
and a number of other molecular biologists of international repute, together with financial backers, met in
Geneva and decided to found Biogen Inc, the patentee company ("Biogen"), for the purpose of exploiting the
technology for commercial purposes. One of the first projects upon which they agreed was to try to make the
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.

4. History of the proceedings and legal issues.

11. On 22 December 1978 Biogen filed a U.K. patent application describing what Professor Murray had done.
This application, known in the proceedings as "Biogen 1" forms the basis of a claim to priority in respect of a
later application filed with the European Patent Office ("EPO") in Munich on 21 December 1979. The European
Patent was granted on 11 July 1990 and opposition proceedings were dismissed on appeal by the EPO on 28 July
1994.

12. Meanwhile, in 1992 Biogen began infringement proceedings against the respondent, Medeva plc, which was
proposing to market what it described as a third-generation hepatitis B vaccine made by recombinant DNA
technology in colonies of mammalian cells. Medeva counterclaimed for revocation. It alleged that the patent was
invalid on a number of grounds. I shall briefly mention those which are still relied upon without at this stage
making any comment or doing more than to refer to the sections of the Patents Act 1977 on which the objections
are based. They are, first, that the claimed invention was obvious (sections l(l)(b) and 3), both at the date of
application for the patent in suit and at the date of Biogen 1. Secondly, that Biogen was not entitled to the
priority date of Biogen 1 because it did not "support" the invention claimed in the patent (section 5(2)(a)).
Thirdly, that the claimed invention was not an invention (section 1(1)), and fourthly, that the description in the
specification was insufficient (section 72(l)(c)). Biogen concedes that the claimed invention was obvious at the
date when the application for the European patent was filed but not that it was on the date of Biogen 1.

13. Aldous J. held that the claims in the patent were supported by the matter disclosed in Biogen 1 and that it
was accordingly entitled to the earlier priority date. He dismissed all the objections and held the patent valid and
infringed. The Court of Appeal (Nourse, Peter Gibson and Hobhouse [Link].) allowed an appeal. Hobhouse L.J.
gave the judgment of the court. He held that Biogen 1 did not support the claimed invention and that in any case
it was obvious at the earlier date. He would have been inclined, but for Medeva's counsel's lack of enthusiasm
for the point, to hold that it was not an invention at all. He also held the description in the specification to be
insufficient. From this comprehensive reverse Biogen appeals to your Lordships' House.

5. The state of the art in 1978.

14. In this appeal much turns upon identifying the inventive step, if any, in what Professor Murray did. There is
no doubt that he was the first person to make HBV antigens by recombinant DNA technology. It does not
however follow that he was inventive. The technology was developing very fast and recent developments might
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have made its use for that purpose obvious. Even if it was not, it does not follow that "making HBV antigens by
recombinant DNA technology" would be the right way to describe his inventive step. Whenever anything
inventive is done for the first time it is the result of the addition of a new idea to the existing stock of knowledge.
Sometimes, it is the idea of using established techniques to do something which no one had previously thought
of doing. In that case, the inventive idea will be doing the new thing. Sometimes, it is finding a way of doing
something which people had wanted to do but could not think how. The inventive idea would be the way of
achieving the goal. In yet other cases, many people may have a general idea of how they might achieve a goal
but not know how to solve a particular problem which stands in their way. If someone devises a way of solving
the problem, his inventive step will be that solution, but not the goal itself or the general method of achieving it.
To discover precisely what constituted the inventive step, one must therefore examine the state of the art of
molecular biology in 1978. Would it have been a new idea to think of making HBV antigens at all ? Or would
that have been a goal which people had thought about but did not know how to achieve ? If the latter, would it
have been inventive to think in general terms of using recombinant DNA technology ? Or would that also have
been something which many molecular biologists would have wanted to do if only they could think of how to
overcome particular difficulties which stood in their way ? To answer these questions, I must try to describe, as
briefly as the nature of the subject will permit, what was the state of knowledge in December 1978, firstly, about
the DNA of HBV, and, secondly, about the techniques of recombinant DNA technology. Both branches of
knowledge were then advancing at a considerable pace. It is not altogether easy to present a snapshot of the state
of the art on the precise date when Biogen 1 was filed. As one would expect, some of the expert witnesses at the
trial thought that the next steps were clear and obvious and others thought that they were difficult and doubtful.
The judge made findings of fact on these questions to which I shall in due course return. For the moment, I can
confine myself to matters which were not in dispute.

(a) HBV in 1978.

15. A paper published in 1970 by D.S. Dane and others ((1970) Lancet, i, 695-698) had made the suggestion,
which by 1978 was generally accepted, that the infective agent of hepatitis B was a certain particle about 42
nanometres in diameter which had been found in the blood of infected people. ("Nano-" means one thousand
millionth or 10"9. A nanosecond is to a second what a second is to 30 years). The "Dane particle" appeared to
include a circular molecule of DNA in a protein core and to be surrounded by a protein surface.

16. Proteins are complex molecules (their main elements are carbon, hydrogen, oxygen and nitrogen) formed
from chains of amino acids linked to each other by peptide bonds (hence also known as "polypeptides") and
folded into three-dimensional structures. There are twenty different amino acids and the order of amino acids in
the chain will determine the geometric shape and chemical characteristics of the polypeptide.

17. The chemical structure of a viral protein may enable it to recognise a complementary structure on the surface
of a suitable cell in its host organism, attach itself to that cell, introduce its own genetic material and thereby use
the resources of the host cell to replicate itself. But similar processes of recognition may stimulate the immune
system of the host organism to produce "antibodies," proteins which attach themselves to the virus and render it
noninfectious. The proteins in the virus which cause the production of antibodies are called "antigens." An
antibody recognises its corresponding antigen by a specific region of the latter's chemical structure known as its
"epitope." The antibody will attach itself to the epitope which complements a region in its own molecular
structure.

18. The relationship between antibody and antigen provides the means of both diagnosing and vaccinating
against infection by the virus. If a patient has been infected with the virus, his blood will contain the
corresponding antibodies. If the antigen can be purified or artificially made and introduced into a sample of the
patient's blood, tests can show whether the blood contains any antibodies. This will indicate prior infection. A
polypeptide which, by reason of having the right epitope, complements a particular antigen is said to display
"antigen specificity" in respect of that antigen. Antigens can also be used for vaccination because once the
immune system has been exposed to the antigen it will produce the relevant antibodies. Upon subsequent
challenge by the antigen, it will produce the same antibodies much more quickly and copiously. A polypeptide
which causes the immune system to produce an antibody is said to display "antigenicity." If a protein with the

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relevant antigenicity is introduced into the blood stream, it will put the immune system on alert. Thus the
immune response will prevent or reduce the severity of infection on a subsequent exposure to the virus.

19. The Dane particle appeared to have at least two antigens, one at its core (hepatitis B core antigen or HBcAg)
and one upon its surface (hepatitis B surface antigen or HBsAg). One way to obtain these antigens was to purify
them from Dane particles taken from the blood of people infected by the virus. This had been done with some
success. But there were concerns about the safety of such vaccines and supplies were limited by the number of
donors. They could not be greatly enhanced by using infected laboratory animals because the virus infects only
human beings and a few higher primates like chimpanzees.

20. Another theoretical possibility was to make the antigens artificially by orthodox chemical synthesis. But this
required knowledge of the sequence and structure of the amino acids. In 1978, however, little was known about
them. It appeared that there might be different strains of virus with surface antigens of different shapes. In April
1977 Darrell L. Peterson and others had published a paper (Proc. Natl. Acad. Sci. USA Vol. 74, pp. 1530-1534)
in which they described HBsAg as "a group of morphologically heterogenous, complex, macromolecular
structures." They did identify a sequence of nine amino acids at the end of the polypeptide chain and ended by
saying that complete information about the amino acid composition of HBsAg could achieve the goal of the
synthetic vaccine.

21. A promising alternative method was recombinant DNA technology. For this purpose it was necessary to find
the genes which coded for the antigens and insert these into a host cell which could express them in recoverable
form. This involved two problems. The first was to find the genes. The most likely guess was that they were
somewhere in the DNA of the Dane particle. But no one knew for certain. Secondly, there was much doubt about
how one inserted them into a host cell and whether there was any available type of host cell in which they could
be expressed. I shall enlarge upon these problems in the next section.

(b) Recombinant DNA technology in 1978.

22. Crick and Watson had discovered the structure of the DNA molecule in 1953. It consists of two strands of
nucleic acid wound about each other in the form of a double helix. Each strand consists of a chain of nucleotides
with a phosphate backbone. The nucleotides are distinguished only by their chemical bases, which consist of one
of four chemicals: adenine (A), guanine (G), cytosine (C) and thymine (T). The bases in each strand are linked
by hydrogen bonds to their complementary bases in the other strand, C pairing with G and T with A. The
sequence of the bases in the nucleic acid strand constitutes a universal code, using four letters arranged in groups
or "codons" of three, which determines the chemical processes in every living cell. A single complement of the
DNA in an organism is called the "genome" and it includes, in complex organisms, many genes which code for
the manufacture of different proteins.

23. The manufacture of a protein in a cell is preceded by a chemical reaction in which the two strands of DNA
are separated. One strand is then copied or "transcribed" into a complementary sequence of bases in a single
strand of nucleic acid called messenger ribonucleic acid ("mRNA"). By a series of complex chemical reactions,
the sequence of bases is "translated" in its groups of three (or codons) into a defined sequence of amino-acids in
a protein. Each of the 20 amino acids from which proteins are made is encoded by one or more codons. Thus the
individual genes within the DNA, by the processes of transcription and translation, direct the synthesis of a
sequence of amino acids which comprise a polypeptide. The reading process is initiated by a codon which
constitutes a "start" or initiation signal and it is terminated, when the polypeptide is complete, by one of several
codons which constitutes a "stop" or termination signal. The "start" sequence will also ensure that the protein
synthesising machinery is in the right "reading frame," that is, that it reads each codon beginning with its first
nucleotide rather than the second or third.

24. Recombinant DNA technology involves introducing a foreign DNA molecule, coding for a protein which is
natural to a different organism, into a host cell in such a way that the artificially introduced gene is correctly
transcribed and translated into the protein for which it codes. This requires coupling that DNA on to a "vector"
DNA molecule so that the hybrid has the ability, first, to replicate within the host cell; secondly, to provide the
correct signals to control transcription and translation; and thirdly, to provide a suitable marker function to
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enable host cells carrying the hybrid DNA molecule to be recognised. Two broad categories of DNA molecules
will, on introduction into bacterial cells, either integrate themselves with the existing DNA of the cell or operate
independently. In either case, they cause the cell to make the proteins encoded by their DNA. These are circular
DNA molecules called plasmids and the DNA of viruses which infect bacteria ("bacteriophages" or "phages"). In
the early 1970s techniques were developed whereby bacterial plasmid and bacteriophage DNA could be cut up
and combined with fragments of DNA from other sources. It was therefore possible to take a sequence of foreign
DNA which might encode a protein, introduce it into the DNA of a plasmid or phage and use the latter as a
vehicle or "vector" to insert the DNA into a bacterial cell. In the late 1970s, these techniques were extended to
permit the expression of foreign genes, but, just as it had previously been uncertain whether the foreign genes
would survive in the bacteria, so there was uncertainty over the requirements for regulating expression.

25. Cutting up the DNA strands was achieved with the aid of enzymes called "restriction endonucleases." These
digest specific sequences of nucleotides and therefore cut the DNA at a point called a "restriction site." The
majority of restriction sites consist of four or six base sequences. For example, the enzyme called BamHI cuts
DNA at the sequence GGATCC. As it happens, 1978 was the year in which the Nobel Prize was awarded to the
discoverers of restriction endonucleases. When a strand of DNA has been cut with a restriction endonuclease,
another fragment can be joined at that point with an enzyme called a DNA ligase. It is thus possible to
"recombine" DNA from different sources to produce an artificial molecule.

26. By 1978 there were several ready-made vectors available which could be used to introduce chosen fragments
of DNA into bacteria in order that they would replicate and provide large quantities of the foreign gene. One of
the most popular was a recombinant plasmid known as pBR322 (its makers were Bolivar and Rodriguez). It was
a circular molecule of DNA which had been put together from fragments of the DNA of several natural plasmids.
It included restriction sites which enabled it to be cut at predetermined points with various enzymes. Although
not widely used for expression studies, it contained suitable "start" and "stop" codes (called "expression control
sequences") between which the foreign gene could be inserted. These expression control sequences regulate the
expression of bacterial genes carried by the plasmid that serve as "markers;" genes which confer upon the host
bacteria resistance to different antibiotics. This enabled one to test in the laboratory whether a bacterial cell had
been "transformed" by the plasmid, that is, whether it had been taken up as part of the cell's genetic code, by
seeing whether it survived contact with a given antibiotic. By 1978, a small number of experiments had shown
that in certain cases foreign DNA could be expressed when the hybrid plasmid was introduced into the well-
known bacterium called Escherichia coli ("E. coli").

27. Bacteria are extremely simple organisms classified as "prokaryotic" because they consist of single cells
without nuclei. More complex ("eukaryotic") organisms have ceils with nuclear membranes. Until 1978 it was
by no means clear that the protein-making equipment of a bacterial cell was up to the task of expressing the
genes which coded for the proteins of eukaryotic cells. But that summer an important paper was published by Dr.
Lydia Villa-Komaroff and others (Proc. Natl. Acad. Sci. USA Vol. 75, pp. 3727-3731). This proved conclusively
that it was possible to express the DNA for the production of a eukaryotic cell protein (in that case, rat
preproinsulin) by inserting it into pBR322 and transforming E. coli.

28. This discovery was highly relevant to the project for making the antigens of hepatitis B. Since the virus
infects only higher organisms its proteins are necessarily eukaryotic. In 1978 vectors for transforming a
eukaryotic host cell were still under development. The Biogen project for making the HBV antigens therefore
required that they should be capable of being made in bacteria.

29. Professor Walter Gilbert of Harvard University, who had been the leader of the team doing the experiments
which led to the Villa-Komaroff paper, was present at the Biogen founding meeting in Geneva. He was
optimistic that any eukaryotic gene could be expressed in a foreign host. Others were more doubtful. The
expression of rat preproinsulin had worked but there remained uncertainty about why it had worked. It did not
follow that one could by similar means express all, or indeed any, other eukaryotic proteins.

30. Professor Murray also faced a difficulty which Dr Villa-Komaroff had been able to avoid. Eukaryotic DNA
had been found to contain sequences of nucleotides which did not seem to code for anything. They were called
"introns" or junk code. Eukaryotic cells had a mechanism for stripping out introns as part of the process of
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transcribing the DNA into mRNA. The mRNA which the cell's ribosomes translated into polypeptides was
cleaned up and free of introns. However, no introns had been found in prokaryotic DNA. It was therefore
assumed that prokaryotic organisms like E. coli had no mechanism for removing introns. This meant that the
expression mechanism of a prokaryotic cell might be unable to cope with natural or "genomic" DNA coding for
a eukaryotic protein and containing introns. A sequence of introns in the middle of the relevant gene could cause
it to make the wrong amino acids, or shift the protein-synthesising machinery into the wrong reading frame, or
be read as a "stop" sequence and bring expression to a halt.

31. Dr Villa-Komaroff had been able to side-step this problem by using an artificial DNA ("cDNA") made by
reverse transcription from natural mRNA which had been obtained from rats. This was an artificially cloned
double copy of the mRNA from which the introns had already been removed. But Professor Murray had no
source of mRNA from which he could make cDNA. All that he could obtain was genomic DNA from Dane
particles.

32. One way to determine whether or not introns presented a problem would have been to "sequence" the HBV
genome, that is, to identify the order of each base in the viral DNA molecule. It should then have been possible
to discover where the relevant gene was and whether it contained introns or not. There was considerable
uncertainty about the coding capacity of the viral DNA. There did not seem to be enough DNA, even without
introns, to code for all the polypeptides which the virus contained. However, other explanations had been put
forward. Some thought that the virus might use some of the host cell's DNA to encode some of the virion
proteins. In 1978, however, the HBV genome had not yet been sequenced. A reliable technique for sequencing
had been invented by Professor Gilbert, but it was laborious and slow. It was not until six months after the filing
of Biogen 1 that the whole genome was sequenced by Valenzuela and others in the University of California at
San Francisco {Nature, Vol. 280, 815-819). The genes which coded for the antigens were found to have no
introns. It is because of this discovery and other advances in the state of the art that Biogen conceded that, by the
date of its European filing, the method by which HBV antigens could be made was obvious. But the information
was not available in 1978.

6. Biogen 1: Professor Murray's success.

33. I must now summarise what Biogen 1 discloses. Professor Murray purified some DNA from Dane particles
and cut it into fragments with restriction enzymes chosen to digest the DNA at as few sites as possible. The
object was to produce the largest possible fragments. There were two reasons for wanting large fragments. One
was that screening large numbers of small fragments would be time-consuming. The other was to have the best
chance of not cutting within the relevant gene, or, at any rate, within the part which coded for a relevant epitope.
As Biogen 1 put it:

"To be useful in the process a restriction enzyme should not cleave the HBV DNA within an
essential part of the gene for antigenic specificity"

34. "Within an essential part of the gene" may mean that fragments of the antigenic polypeptide would do,
provided that they displayed HBV antigen specificity. By the time of the EPO patent application, the claims
make it clear that they cover not only the polypeptide but also fragments which exhibit the relevant properties.
But Biogen 1 does not make anything of this point.

35. Professor Murray therefore chose the restriction enzymes Kpn I, Bg1II, Bam HI, Ava I and Eco RI all of
which cut at six-nucleotide sites, these being mathematically less likely to occur than four-nucleotide sites.

36. Having obtained his large fragments, Professor Murray then employed established techniques of recombinant
DNA technology to ligate the HBV DNA to pBR322 and introduce this into E. coli. In so doing, he followed
almost exactly what Dr Villa-Komaroff had done to make rat prepro insulin. The antibiotic tests for ascertaining
whether the bacterial cultures had been transformed by the plasmids and thus acquired antibiotic resistance were
standard. The hybridisation tests which demonstrated that the colonies contained HBV DNA had been published
in 1975. Professor Murray used a test for detecting antigen specificity which had been published by Broome and
Gilbert earlier in 1978. Some of the cultures containing fragments cut with Kpn I and Bam HI tested positive.
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Biogen 1 does not say whether they were positive for HBcAg or HBsAg but Professor Murray's evidence at the
trial was that they were positive for both.

37. Biogen 1 describes the invention as based upon the discovery that HBV DNA, "when appropriately cleaved"
and inserted into a vector such as a plasmid or phage, can be used to transform a micro-organism so that it
produces polypeptides with HBV antigen specificity. It identifies as a "particularly surprising" feature of the
invention the fact that genes from eukaryotic organisms "would not normally be expressed in bacteria."

38. Although, as I have said, Biogen 1 does not make separate reference to HBcAg and HBsAG, it plainly treats
the invention as capable of being used to make both antigens. It says that depending upon the structure of the
HBV DNA used and the means used to cleave it, the fragment may contain DNA which codes for one or more
different antigens. It says that vectors other than pBR322 and host organisms other than E. coli (including yeasts
or fungi) may be used. Finally it points out that known methods may be used to amplify production of the DNA
and increase productivity of the host cells, thereby enabling large quantities of the antigens to be made.

7. The claims of the patent in suit.

39. I now set out the principal claims of the patent in suit, which Biogen 1 is said to support. Claim 1 reads as
follows:

1. 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.

40. The claim is to a product, a molecule identified partly by the way in which it has been made ("recombinant
DNA") and partly by what it does (the words following "characterised by"). It generalises what Professor
Murray had done in two ways. First, as to the results he had achieved. He had made a particular form of
recombinant plasmid (pBR322 with fragments of Dane particle DNA) which had transformed E. coli and, he
said, caused it to express the genes of HBcAg and HBsAg. The claim was for any recombinant DNA molecule
which expressed the genes of any HBV antigen in any host cell. Secondly, there was generalisation of the
method which he had used. He had made his DNA molecule from a standard pBR322 plasmid and large
fragments from Dane particle DNA, chosen simply on the basis that they should be large. This was a technique
imposed upon him by lack of information about the coding sequences. Thereafter, he employed conventional
means to express the DNA in a conventional bacterial host. The claim was for any method of making a DNA
molecule which would achieve the necessary expression.

41. Claims 2 to 4 are based upon claim 1:

2. The recombinant DNA molecule according to claim 1, characterized in that the polypeptide
displaying HBV antigen specificity also displays HBV antigenicity.

3. 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.

4. 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.

Claim 6 (as amended) is to:

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6. A polypeptide free of any human 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.

Claims 7 and 8 are to polypeptides displaying respectively HBcAg and HBsAg specificity, produced by host
cells transformed in accordance with claims 1, 2 or 3 or 1, 2 or 4 respectively.

8. Patentable Inventions.

42. Section 1(1) of the 1977 Act defines "patentable inventions." It says:

1(1) A patent may be granted only for an invention in respect of which the following conditions are
satisfied, that is to say -

(a) the invention is new;(b) it involves an inventive step;(c) it is capable of industrial application;(d) the
grant of a patent for it is not excluded by subsections (2) and (3) below;

and references in this Act to a patentable invention shall be construed accordingly.

9. What is an invention ?

43. The Act thus lays down various conditions, both positive (in paragraphs (a) to (c)) and negative (in paragraph
(d)) which an invention must satisfy in order to be a "patentable invention." This scheme might suggest that
logically one should first decide whether the claimed invention can properly be described as an invention at all.
Only if this question receives an affirmative answer would it be necessary to go on to consider whether the
invention satisfies the prescribed conditions for being "patentable." In practice, however, I have no doubt that in
most cases this would be a mistake and cause unnecessary difficulty.

44. The Act does not define the concept of an invention. Section 1(1) was intended to reflect, "as nearly as
practicable," Article 52 of the European Patent Convention ("EPC"): see section 130(7) of the 1977 Act. Article
52 also has no definition of an invention. It seems that the parties to the EPC were unable to agree upon one: see
Singer and Singer, The European Patent Convention (English edn. 1995 by Ralph Lunzer), para. 52.04). But the
reason why the parties were content to do without a definition was that they recognised that the question would
almost invariably be academic. The four conditions in section 1(1) do a great deal more than restrict the class of
"inventions" which may be patented. They probably also contain every element of the concept of an invention in
ordinary speech. I say probably, because in the absence of a definition one cannot say with certainty that one
might not come across something which satisfied all the conditions but could not be described as an invention.
But the draftsmen of the Convention and the Act, as well as counsel at the bar, were unable to think of any
examples. Just in case one should appear, section 1(5) gives the Secretary of State power to vary the list of
matters excluded by paragraph (d) to "for the purpose of maintaining them in conformity with developments in
science and technology."

45. As the four conditions are relatively familiar ground, elucidated by definitions in the Act and the
jurisprudence of the courts and the EPO, it will normally be more convenient to start by deciding whether they
are satisfied. In virtually every case this will be the end of the inquiry. There may one day be a case in which it is
necessary to decide whether something which satisfies the conditions can be called an invention, but that
question can wait until it arises.

46. One can of course imagine cases in which the alleged subject-matter is so obviously not an invention that it
is tempting to take an axe to the problem by dismissing the claim without inquiring too closely into which of the
conditions has not been satisfied. So in Genentech Inc's Patent [1989] R.P.C. 147, 264 Mustill L.J. said, by
reference to the ordinary speech meaning of "invention":

"You cannot invent water, although you certainly can invent ways in which it may be distilled or
synthesised."

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This is obviously right and in such a case it may seem pedantic to say that water fails the condition in paragraph
(a) of section 1(1) because it is not new. Unfortunately, most cases which come before the courts are more
difficult. Judges would therefore be well advised to put on one side their intuitive sense of what constitutes an
invention until they have considered the questions of novelty, inventiveness and so forth. In the present case, I
think that Medeva's counsel was right to resist the invitation of the Court of Appeal to make submissions on
whether the claims constituted an invention.

10. Inventive Step

47. I will therefore first consider the question of whether what Professor Murray did in 1978 involved, as at the
date of Biogen 1, an inventive step. Section 3 says:

"An invention shall be taken to involve an inventive step if it is not obvious to a person skilled in the
art, having regard to any matter which forms part of the state of the art by virtue only of section 2(2)
above . . ."

Section 2(2) defines the state of the art:

"The state of the art in the case of an invention shall be taken to comprise all matter (whether a
product, a process, information about either or anything else) which has at any time before the
priority date of that invention been made available to the public (whether in the United Kingdom or
elsewhere) by written or oral description, by use or in any other way."

48. The question is therefore whether what Professor Murray did was obvious having regard to all matter which
had been made available to the public before 22 December 1978. Aldous J., after hearing expert evidence about
what people skilled in the art of recombinant DNA technology would have thought and done at the time, held
that it was not. I will summarise his reasoning. He followed the procedure suggested by Oliver L.J. in
Windsurfing International Inc v. Tabur Marine (Great Britain) Ltd [1985] R.P.C. 59, 73-74 by dividing the
inquiry into four steps:

"The first is to identify the inventive concept embodied in the patent in suit. Thereafter, the court has
to assume the mantle of the normally skilled but unimaginative addressee in the art at the priority
date and impute to him what was, at that date, common general knowledge in the art in question.
The third step is to identify what, if any, differences exist between the matter cited as being "known
or used" and the alleged invention. Finally, the court has to ask itself whether, viewed without any
knowledge of the alleged invention, those differences constitute steps which would have been
obvious to the skilled man or whether they require any degree of invention."

49. Aldous J. identified the inventive concept as "the idea or decision to express a polypeptide displaying HBV
antigen specificity in a suitable host." The identification of the inventive concept is, as I have said, critical to this
case and I shall have more to say about it later. At this stage I only observe that as formulated by Aldous J., the
inventive concept means, in effect, having the idea of making HBV antigens by recombinant DNA technology.
But that seems to me to be putting the matter far too wide. The idea of making HBV antigens by recombinant
DNA technology was shared by everyone at the Geneva meeting of Biogen in February 1978 and no doubt by
others working in the field, just as the idea of flying in an heavier-than-air machine had existed for centuries
before the Wright brothers. The problem which required invention was to find a way of doing it.

50. Aldous J. then considered what would have been known to the man skilled in the art. I have already
summarised what relevant information would have been available to the public in 1978. In particular, Aldous J.
considered the importance of the Villa-Komaroff paper and said:

"It is accepted that once a decision [had] been made to try expression of the HBV genome, the
technique set out in Villa-Komaroff would have been sufficient to enable it to be carried out. Thus
the difference between the prior art and the inventive concept is the idea or decision to express a
polypeptide displaying HBV antigen specificity in a suitable host."
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Again, I think that this is not a sufficiently specific way of stating the inventive concept. The general idea of
expressing the gene for a polypeptide displaying HBV antigen specificity in a suitable host was, as I have said,
fairly widely entertained. The inventive concept was the notion that Professor Murray's method of achieving the
goal - creating large fragments of genomic DNA, ligating them to pBR322 and introducing the hybrid molecule
into E. coli - would work.

51. Aldous J. then considered what strategies would have been available in 1978 to a skilled man who wanted to
achieve the goal of making HBV antigens by recombinant DNA technology. One (strategy A) was to try to find
out more about HBV and its DNA. In particular, one would sequence the genome. This would provide the
information upon which a decision could be made as to whether and if so how to express the relevant genes. The
alternative (strategy B) was, as Professor Murray had done, to take the genomic DNA and try to express it in E.
coli. Biogen's case, as recorded by the judge, was that -

"it was not until the sequence had been obtained, with the knowledge that introns would not be a
problem, that the skilled man would seriously consider expression of HBV antigens."

The judge accepted this submission and held that Strategy B would not have been obvious in 1978. He said:

"In the present case, there is no evidence to suggest that anyone, other than Biogen, contemplated
expression of the HBV antigen in December 1978, despite the fact that the skilled man must have
read the Villa-Komaroff paper and there was an incentive to do so. The reason may well be that
stated in the patent, namely the skilled man was put off by introns."

He also rejected the argument that Strategy A was an obvious way of making the antigens. The evidence showed
only that sequencing might show that there were no introns and that the gene could be expressed in bacteria but
there was no ground for assuming that it would.

52. In the Court of Appeal, Hobhouse L.J. held that strategy B was obvious. The decision to adopt it was a
"matter of business judgment," a "mere commercial decision." Biogen had made a decision "to pursue an
identified goal by known means." I think, with all respect to the closely-reasoned judgment of Hobhouse L.J.,
that the reference to a commercial decision is an irrelevancy. The fact that a given experimental strategy was
adopted for commercial reasons, because the anticipated rewards seemed to justify the necessary expenditure, is
no reason why that strategy should not involve an inventive step. An inventor need not pursue his experiments
untouched by thoughts of gain. Most patents are the result of research programmes undertaken on the basis of
hard-headed cost-benefit analysis. Nor do I think that the analogy of a bet is particularly helpful. In Genentech
Inc's Patent [1989] R.P.C. 147, 281, Mustill L.J. said, in my opinion rightly, that "it cannot ... be assumed that
inventiveness must have been involved somewhere, just because a wager on success could have been placed at
long odds." The question is not what the odds were but whether there was an inventive step.

53. Having said this, I do think that Hobhouse L.J. was substantially correct in saying that Professor Murray had
chosen to pursue an identified goal by known means. The goal of obtaining HBV antigens by recombinant DNA
technology was obvious and the Villa-Komaroff method was by then part of the state of the art. If, therefore, the
inventive concept was simply, as Aldous J. said, "the idea or decision to express a polypeptide displaying HBV
antigen specificity in a suitable host," I would agree with Hobhouse L. J. that, so stated, the concept was
obvious. It is however clear from the reasoning of Aldous J. that in order to explain why he regarded the decision
as involving an inventive step it is necessary to describe it with rather more particularity. A proper statement of
the inventive concept needs to include some express or implied reference to the problem which it required
invention to overcome. The reasons why the expert witnesses thought it was not obvious to try the expression of
genomic HBV DNA in E. coli were for the most part concerned with the uncertainties, in the absence of
sequence information, about the presence of the HBV antigen genes in the Dane particle DNA, the perceived
difficulties of expressing genomic eukaryotic DNA in a prokaryotic host, and, specifically, the problem of
introns. It seems to me, therefore, that a more accurate way of stating the inventive concept as it appeared to
Aldous J. is to say that it was the idea of trying to express unsequenced eukaryotic DNA in a prokaryotic host.

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54. The question of whether an invention was obvious has been called "a kind of jury question" (see Jenkins L.J.
in Allmanna Svenska Elektriska A/B v. The Burntisland Shipbuilding Co. Ltd (1952) 69 R.P.C. 63, 70) and
should be treated with appropriate respect by an appellate court. It is true that in Benmax v. Austin Motor Co.
Ltd [1955] A.C. 370 this House decided that, while the judge's findings of primary fact, particularly if founded
upon an assessment of the credibility of witnesses, were virtually unassailable, an appellate court would be more
ready to differ from the judge's evaluation of those facts by reference to some legal standard such as negligence
or obviousness. In drawing this distinction, however, Viscount Simonds went on to observe, at p. 374, that it was
"subject only to the weight which should, as a matter of course, be given to the opinion of the learned judge."
The need for appellate caution in reversing the judge's evaluation of the facts is based upon much more solid
grounds than professional courtesy. It is because specific findings of fact, even by the most meticulous judge, are
inherently an incomplete statement of the impression which was made upon him by the primary evidence. His
expressed findings are always surrounded by a penumbra of imprecision as to emphasis, relative weight, minor
qualification and nuance (as Renan said, la v rit est dans une nuance), of which time and language do not permit
exact expression, but which may play an important part in the judge's overall evaluation. It would in my view be
wrong to treat Benmax as authorising or requiring an appellate court to undertake a de novo evaluation of the
facts in all cases in which no question of the credibility of witnesses is involved. Where the application of a legal
standard such as negligence or obviousness involves no question of principle but is simply a matter of degree, an
appellate court should be very cautious in differing from the judge's evaluation.

55. In the present case I think that the reason why Hobhouse L.J. differed from the judge on the question of
obviousness was not because of any failure to give sufficient weight to the judge's evaluation of the evidence but
because he took at face value the judge's statement of the inventive concept. On the other hand, if the concept is
reformulated in accordance with the judge's reasoning as I have suggested, the argument for the existence of an
inventive step is much stronger. If no question of principle were involved, I think it would be wrong to interfere
with the judge's assessment. But the inventiveness alleged in this case is of a very unusual kind. It is said to
consist in attempting something which a man less skilled in the art might have regarded as obvious, but which
the expert would have thought so beset by obstacles as not to be worth trying. In The Raleigh Cycle Co. v. H.
Miller & Co. (1946) 63 R.P.C. 113 the Court of Appeal was prepared to assume that it could be inventive to
realise that a bicycle hub dynamo of conventional design could function satisfactorily even though it rotated at a
lower speed than was previously thought essential. There may be a question of principle here but, like the Court
of Appeal in that case, I shall not pursue the question of whether this amounts to an inventive step for the
purposes of patent law because I am content to assume, without deciding, that what Professor Murray did was
not obvious.

11. Priority date

56. The next question is whether, given that Biogen 1 disclosed what would at the time have been a patentable
invention, it "supports" the invention actually claimed in the patent in suit. This question must be answered in
the affirmative if Biogen is to be able to rely on the date of Biogen 1 as its priority date in accordance with
section 5(2)(a). The relevant provisions are as follows:

5(1) For the purposes of this Act the priority date of an invention to which an application for a
patent relates and also of any matter (whether or not the same as the invention) contained in any
such application is, except as provided by the following provisions of this Act, the date of filing the
application.

(2) If in or in connection with an application for a patent (the application in suit) a declaration is
made, whether by the applicant or any predecessor in title of his, complying with the relevant
requirements of rules and specifying one or more earlier relevant applications for the purposes of
this section made by the applicant or a predecessor in title of his and each having a date of filing
during the period of twelve months immediately preceding the date of filing the application in suit,
then -

(a) if an invention to which the application in suit relates is supported by matter disclosed in the earlier
relevant application or applications, the priority date of that invention shall instead of being the date of
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filing the application in suit be the date of filing the relevant application in which that matter was
disclosed or, if it was disclosed in more than one relevant application, the earliest of them;

57. In Asahi Kasei Kogyo KK's Application [1991] R.P.C. 485 this House decided that for matter to be capable
of supporting an invention within the meaning of section 5(2)(a) it must contain an "enabling disclosure," that is
to say, it must disclose the invention in a way which will enable it to be performed by a person skilled in the art.
This construction has not been challenged by the appellants before your Lordships' House. It is however
important to notice the relationship between the requirement of "support" in section 5(2)(a) and certain other
provisions of the Act which share the concept of an enabling disclosure.

58. The concept of an enabling disclosure is central to the law of patents. For present purposes, it touches the
matters in issue at three different points. First, as we have seen, it forms part of the requirement of "support" in
section 5(2)(a). Secondly, it is one of the requirements of a valid application in section 14. And thirdly, it is
essential to one of the grounds for the revocation of a patent in section 72. I shall start with section 14.
Subsection (3) says:

"The specification of an application shall disclose the invention in a manner which is clear enough
and complete enough for the invention to be performed by a person skilled in the art."

This is plainly a requirement of an "enabling disclosure." In addition, subsection (5)(c) says that the claim or
claims shall be "supported by the description." It was by reference to subsection (3) that Lord Oliver of
Aylmerton, who gave the leading speech in Asahi, reasoned, at p. 536 that a description would not "support" the
claims for the purpose of subsection (5)(c) unless it contained sufficient material to enable the specification to
constitute the enabling disclosure which subsection (3) required: "the Act can hardly have contemplated a
complete application for a patent lacking some of the material necessary to sustain the claims made." By parity
of reasoning, he said that "support" must have the same meaning in section 5(2)(a).

59. The absence of an enabling disclosure is likewise one of the grounds for the revocation of a patent specified
in section 72(1). Paragraph (c) says that one such ground is that -

"the specification of the patent does not disclose the invention clearly enough and completely
enough for it to be performed by a person skilled in the art."

This is entirely in accordance with what one would expect. The requirement of an enabling disclosure in a patent
application is a matter of substance and not form. Its absence should therefore be a ground not only for refusal of
the application but also for revocation of the patent after grant. Similarly, the same concept is involved in the
question of whether the patent is entitled to priority from an earlier application. This is not to say that the
question in each case is the same. The purposes for which the question is being asked are different. But the
underlying concept is the same.

60. The explanation of section 14(5)(c) in Asahi seems to me to provide an answer to a point which puzzled the
Court of Appeal in Genentech Inc's Patent [1989] R.P.C. 147. The court noted that although section 14(5)(c) is a
statutory requirement for a valid patent application, non-compliance is not a ground for revocation of a patent
which has been granted. Section 72(1) states exhaustively the grounds upon which a patent may be revoked.
These grounds do not, as such, include non-compliance with section 14(5). But the substantive effect of section
14(5)(c), namely that the description should, together with the rest of the specification, constitute an enabling
disclosure, is given effect by section 72(1)(c). There is accordingly no gap or illogicality in the scheme of the
Act.

61. The need for an enabling disclosure to satisfy the requirements of support under section 5(2)(a), valid
application under section 14 and sufficiency under section 72(1)(c) has, I think, been plain and undisputed since
the decision in Asahi. What has been less clear is what the concept of an enabling disclosure means. Part of the
difficulty has been caused by a misinterpretation of what the Technical Board of Appeal of the EPO said in
Genentech I/Polypeptide expression (T 292/85) [1989] OJEPO 275. This was a patent for an plasmid suitable
for transforming a bacterial host which included an expression control sequence or "regulon" which could enable
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the expression of foreign DNA as a recoverable polypeptide. The Examining Division was willing to grant a
patent only in respect of the plasmids, bacteria and polypeptides known at the date of application. The Technical
Board of Appeal allowed the appeal, saying that the Examining Division had taken too narrow a view of the
requirement of enabling disclosure:

"What is also important in the present case is the irrelevancy of the particular choice of a variant
within the functional terms 'bacteria,' 'regulon' or 'plasmid.' It is not just that some result within the
range of polypeptides is obtained in each case but it is the same polypeptide which is expressed,
independent of the choice of these means. . . . Unless variants of components are also embraced in
the claims, which are, now or later on, equally suitable to achieve the same effect in a manner which
could not have been envisaged without the invention, the protection provided by the patent would be
ineffectual . . . The character of the invention this time is one of general methodology which is fully
applicable with any starting material, and is, as it was already stated, also independent from the
known, trivial, or inventive character of the end-products."

In other words, the applicants had invented a general principle for enabling plasmids to control the expression of
polypeptides in bacteria and there was no reason to believe that it would not work equally well with any plasmid,
bacterium or polypeptide. The patent was therefore granted in general terms.

62. In Molnlycke AB v. Procter & Gamble Ltd [1992] FSR 549, however, Morritt J. interpreted this decision
to mean that it was a general rule of European patent law that an invention was sufficiently disclosed if the
skilled man could make a single embodiment. This interpretation was followed by Aldous J. in Chiron
Corporation v. Organon Teknika Ltd [1994] FSR 202, although I think I detect in his judgment some surprise
that the EPO should have adopted such a mechanistic and impoverished approach to the concept of enabling
disclosure. As we shall see, he applied the same rule in the present case.

63. In fact the Board in Genentech I/Polypeptide expression was doing no more than apply a principle of patent
law which has long been established in the United Kingdom, namely, that the specification must enable the
invention to be performed to the full extent of the monopoly claimed. If the invention discloses a principle
capable of general application, the claims may be in correspondingly general terms. 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.

64. 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: see May & Baker Ltd v. Boots Pure Drug Co Ltd (1950) 67 R.P.C. 23, 50. On the other
hand, if he has disclosed a beneficial property which is common to the class, he will be entitled to a patent for all
products of that class (assuming them to be new) even though he has not himself made more than one or two of
them.

65. Since Genentech I/Polypeptide expression the EPO has several times reasserted the well established
principles for what amounts to sufficiency of disclosure. In particular, in Exxon/Fuel Oils (T 409/91) [1994]
OJEPO 653, para. 3.3., the Technical Board of Appeal said of the provision in the European Patent Convention
equivalent to section 14(5)(c) of the Act:

"Furthermore, Article 84 EPC also requires that the claims must be supported by the description, in
other words, it is the definition of the invention in the claims that needs support. In the Board's
judgment, this requirement reflects 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."

12. Support for the claims

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66. I come therefore to the question of whether Biogen 1 contained an enabling disclosure which supported the
claims in the patent in suit. The argument before Aldous J. seems to have concentrated on the questions of
whether it had been shown that Professor Murray's method was capable of making both HBcAg and HBsAg and
whether it would work in eukaryotic as well as bacterial hosts. The judge, following his earlier decision in
Chiron Corporation v. Organon Teknika Ltd [1994] FSR 202, said that it would be enough if the
specification enabled one embodiment to be made. As there was no doubt that Professor Murray had made
HBcAg in cultures of E. coli, that was an end of the matter. In case it was considered that the claims really
amounted to two inventions, one for making HBcAg and another for HBsAg, he found that the skilled man
would also have been able to make HBsAg. Having heard the evidence of Professor Murray and others, he said:

"Upon the evidence, I conclude that Biogen did express and demonstrate expression of the surface
antigen using the techniques described in the specification."

The disclosure was therefore sufficient in respect of both inventions.

67. In the opposition proceedings in the EPO, the argument proceeded upon similar lines. The only issue on
sufficiency seems to have been whether the invention could produce HBsAg as well as HBcAg. The Technical
Board, like Aldous J., found as a fact that it could. The question of whether the method could be used in other
hosts was not argued, the opponents thinking (probably rightly) that this point was concluded against them by
the EPO decision in Genentech I/Polypeptide expression. In fact, if Professor Murray's method worked in a
prokaryotic host, despite the possibility that such a host might not be able to cope with introns, it was even more
likely to work in a eukaryotic host, which was better equipped for dealing with them. For my part, therefore, I
would not differ from the findings of either Aldous J. or the Technical Board in rejecting both these grounds of
opposition.

68. In the Court of Appeal, Hobhouse L.J. began his judgment by saying that he did not believe that the court
was differing from Aldous J. "on any question of the acceptance of the evidence of witnesses or primary
scientific fact." He nevertheless made a thorough re-examination of the evidence on whether the method
disclosed in Biogen 1 had enabled the making of HBsAg and came to the conclusion that it had not. He said:

"The outcome of this evidence is that whatever results the plaintiff obtained in 1978 did not amount
to evidence justifying a claim to have produced a recombinant DNA molecule which enabled the
expression of HBsAg in E. coli (or any other host)."

69. I am bound to say that I regret the decision of the Court of Appeal to revisit the evidence upon which the
judge made his finding of fact. For the reasons given earlier in relation to the issue of obviousness, I think that
this was a question on which greater respect should have been paid to the judge's findings. The Court of Appeal's
reversal of the judge on this issue greatly lengthened the hearing before your Lordships' House, as no doubt it
had done in the Court of Appeal. The House was invited to undertake a minute examination of the facts with a
view to restoring the findings of the judge. It was even offered inspection of the autoradiographs claimed to
show the positive results upon which Professor Murray had based his claim to success -an offer which your
Lordships felt able to decline. But I think that your Lordships learned enough of the detailed facts to form the
view that the judge's decision was one which was open to him upon the evidence and should not have been
disturbed.

70. But the fact that the skilled man following the teaching of Biogen 1 would have been able to make HBcAg
and HBsAg in bacterial cells, or indeed in any cells, does not conclude the matter. I think that in concentrating
upon the question of whether Professor Murray's invention could, so to speak, deliver the goods across the full
width of the patent or priority document, the courts and the EPO allowed their attention to be diverted from what
seems to me in this particular case the critical issue. It is not whether the claimed invention could deliver the
goods, but whether the claims cover other ways in which they might be delivered: ways which owe nothing to
the teaching of the patent or any principle which it disclosed.

71. It will be remembered that in Genentech I/Polypeptide expression the Technical Board spoke of the need for
the patent to give protection against other ways of achieving the same effect "in a manner which could not have
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been envisaged without the invention." This shows that there is more than one way in which the breadth of a
claim may exceed the technical contribution to the art embodied in the invention. The patent may claim results
which it does not enable, such as making a wide class of products when it enables only one of those products and
discloses no principle which would enable others to be made. Or it may claim 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.

72. One example of an excessive claim of the latter kind is the famous case of O'Reilly v. Morse (1854) 56 U.S.
(15 How.) 62 in the Supreme Court of the United States. Samuel Morse was the first person to discover a
practical method of electric telegraphy and took out a patent in which he claimed any use of electricity for
"making or printing intelligible characters, signs, or letter, at any distances." The Supreme Court rejected the
claim as too broad. Professor Chisum, in his book on Patents (vol. 1, 1.03[2] summarises the decision as follows:

"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."

73. A similar English case is British United Shoe Machinery Co Ltd v. Simon Collier Ltd (1908) 26 R.P.C.
21. The patentee invented a piece of machinery for automatically trimming the soles of boots and shoes by
means of a cam. One of the claims was in general terms for automatic means of trimming soles. Parker J. said, at
pp. 49-50:

"... [T]he problem was simply how to do automatically what could already be done by the skill of
the workman. On the other hand, the principle which the inventor applies for the solution of the
problem is the capacity of a cam to vary the relative positions of two parts of a machine while the
machine is running. Assuming this principle to be new, it might be possible for the inventor, having
shown one method of applying it to the solution of the problem, to protect himself during the life of
his Patent from any other method of applying it for the same purpose, but I do not think that the
novelty of the principle applied would enable him to make a valid claim for all means of solving the
problem whether the same or a different principle were applied to its solution."

74. I return therefore to consider the technical contribution to the art which Professor Murray made in 1978 and
disclosed in Biogen 1. As it seems to me, it consisted in showing that despite the uncertainties which then existed
over the DNA of the Dane particle - in particular, whether it included the antigen genes and whether it had
introns - known recombinant techniques could nevertheless be used to make the antigens in a prokaryotic host
cell. As I have said, I accept the judge's findings that the method was shown to be capable of making both
antigens and I am willing to accept that it would work in any otherwise suitable host cell. Does this contribution
justify a claim to a monopoly of any recombinant method of making the antigens? In my view it does not. The
claimed invention is too broad. Its excessive breadth is 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. Professor Murray
had won a brilliant Napoleonic victory in cutting through the uncertainties which existed in his day to achieve
the desired result. But his success did not in my view establish any new principle which his successors had to
follow if they were to achieve the same results. The inventive step, as I have said, was the idea of trying to
express unsequenced eukaryotic DNA in a prokaryotic host. Biogen 1 discloses that the way to do it is to choose
the restriction enzymes likely to cleave the Dane particle DNA into the largest fragments. This, if anything, was
the original element in what Professor Murray did. But once the DNA had been sequenced, no one would choose
restriction enzymes on this basis. They would choose those which digested the sites closest to the relevant gene
or the part of the gene which expressed an antigenic fragment of the polypeptide. The metaphor used by one of
the witnesses was that before the genome had been sequenced everyone was working in the dark. Professor
Murray invented a way of working with the genome in the dark. But he did not switch on the light and once the
light was on his method was no longer needed. Nor, once they could use vectors for mammalian cells, would
they be concerned with the same problem of introns which had so exercised those skilled in the art in 1978. Of
course there might be other problems, but Biogen 1 did not teach how to solve them. The respondents Medeva,
who use restriction enzymes based on knowledge of the HBV genome and mammalian host cells, owe nothing to
Professor Murray's invention.
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75. It is said that what Professor Murray showed by his invention was that it could be done. HBV antigens could
be produced by expressing Dane particle DNA in a host cell. Those who followed, even by different routes,
could have greater confidence by reason of his success. I do not think that this is enough to justify a monopoly of
the whole field. I suppose it could be said that Samuel Morse had shown that electric telegraphy could be done.
The Wright Brothers showed that heavier-than-air flight was possible, but that did not entitle them to a monopoly
of heavier-than-air flying machines. It is inevitable in a young science, like electricity in the early nineteenth
century or flying at the turn of the last century or recombinant DNA technology in the 1970s, that dramatically
new things will be done for the first time. The technical contribution made in such cases deserves to be
recognised. But care is needed not to stifle further research and healthy competition by allowing the first person
who has found a way of achieving an obviously desirable goal to monopolise every other way of doing so. (See
Merges and Nelson, On the Complex Economics of Patent Scope (1990) 90 Columbia Law Review 839.)

76. I would therefore hold that Biogen 1 did not support the invention as claimed in the European Patent and that
it is therefore not entitled to the priority date of Biogen 1. As it is conceded that the invention was obvious when
the patent application was filed, it is invalid.

13. The EPO decision.

77. I must at this point say something about the decision of the Technical Board of the EPO, which dismissed
opposition proceedings and held the patent valid. Decisions of the EPO on questions of law are, as this House
said in Merrell Dow Pharmaceuticals Inc v. H.N. Norton & Co. Ltd [1996] RPC 76, 82, of considerable
persuasive authority. But the decision of the EPO in this case did not, as it seems to me, proceed on any principle
different from those I have endeavoured to apply. The Board held, as I have been willing to assume, that the
invention described in Biogen 1 was not obvious at the priority date. On the other hand it held that the disclosure
in Biogen 1 was in respect of the same invention as that claimed in the patent and, contrary to my view hereafter
expressed, that such disclosure was sufficient to enable the invention to be performed to the full extent of the
claims. But in arriving at this conclusion, the Board 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.
Nothing was said about whether the claims were too broad because expression could also be achieved without
the use of the teaching which it contained, by a method of which it could not be said, in the words of the
Technical Board in Genentech I, that it was "in a manner which could not have been envisaged without the
invention." But the principle upon which I have come to the conclusion that on this ground the patent is invalid
is also, as I have said, clearly stated in decisions of the EPO such as Genentech I and Exxon. I would not
therefore regard the outcome of this appeal as suggesting any divergence between the jurisprudence of this court
and that of the EPO.

14. Sufficiency

78. If your Lordships are agreed that, lacking the support of an earlier priority date, the patent is invalid for
obviousness, it is unnecessary to consider whether it was also invalid for insufficiency and therefore liable to be
revoked under section 72(1)(c). But the reasoning by which I have come to the conclusion that the patent was
not entitled to the earlier priority also, in my view, leads to the conclusion that it was insufficient. I should
however mention one point of some general importance concerning the construction of this provision which
arose in the course of argument. This is the question of the date on which the specification must "disclose the
invention clearly enough and completely enough for it to be performed by a person skilled in the art." The Court
of Appeal thought it was the date of filing of the application, which in this case was 21 December 1979. Aldous
J. said it was the date upon which the application was published, which was 28 May 1986. On the latter view, a
specification may be insufficient when the application is filed but satisfy section 72(1)(c) because of advances in
the art made between then and the date of publication. I do not think that the point arises in this case, because,
whatever date one chooses, the patent did not disclose any method for making the antigens other than that
disclosed in Biogen 1. It therefore remained insufficient for the purpose of sustaining a claim to every
recombinant DNA method. Nevertheless, since the point was argued and there was a difference of view in the
courts below, I shall shortly express my own opinion.

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79. Aldous J. followed a number of authorities which held that the date of publication was the date for deciding
the question of sufficiency under the Patents Act 1949. The reasoning was that the purpose of requiring a
specification was to allow the public to work the invention after the expiry of the monopoly. This in itself might
suggest that it was enough if the disclosure was sufficient when the patent expired. But, as Buckley L.J. said in
Standard Brands Inc.'s Patent (No. 2) [1981] R.P.C. 499, 529, the public was also entitled to know as soon as the
patent is published whether it was valid or not. This pointed to the date of publication. He also drew attention to
the fact that the specification might have been amended after filing. Such amendments would be treated as
relating back to the date of filing and it would therefore be inappropriate to test sufficiency by reference to the
specification originally filed.

80. In my view, however, there is an important difference between the 1949 and 1977 Acts which make decisions
on the earlier Act an unsafe guide. Section 72(1)(c) of the 1977 is not only intended to ensure that the public can
work the invention after expiration of the monopoly. It is also intended to give the court in revocation
proceedings a jurisdiction which mirrors that of the Patent Office under section 14(3) or the EPO under Article
83 of the EPC, namely, to hold a patent invalid on the substantive ground that, as the EPO said in Exxon/Fuel
Oils (T 409/91) [1994] OJEPO 653, para. 3.3., the extent of the monopoly claimed exceeds the technical
contribution to the art made by the invention as described in the specification. In the 1949 Act, this function was
performed by another ground for revocation, namely that the claim was not "fairly based on the matter disclosed
in the specification" (section 32(l)(i)). The requirement of sufficiency was therefore regarded as serving a
narrower purpose. But the disappearance of "lack of fair basis" as an express ground for revocation does not in
my view mean that general principle which it expressed has been abandoned. The jurisprudence of the EPO
shows that it is still in full vigour and embodied in articles 83 and 84 of the EPC, of which the equivalents in the
1977 Act are section 14(3) and (5) and section 72(l)(c).

81. Section 72(l)(c) can only give effect to this principle if the relevant date for compliance is the date of
application. It would be illogical if a patent which ought to have been rejected under section 14(3) is rendered
immune from revocation under section 72(1)(c) by advances in the art between the date of application and the
publication of the specification. The provisions for amendment, so far from detracting from this view, seem to
me to support it. Section 76(2) says that the amended application shall not disclose matter which extends beyond
that previously disclosed. In other words, the application may not add new matter to make an insufficient
application sufficient. It seems to me in accordance with this scheme that an insufficient application should also
not become sufficient because of general developments in the state of the art after the filing date. I therefore
agree on this point with the Court of Appeal.

82. I would dismiss the appeal.

Upon Report from the Appellate Committee to whom was referred the Cause Biogen Inc. against
Medeva plc, That the Committee had heard Counsel as well on the 29th and 30th days of April as on
the 1st, 2nd, 7th, 9th, 13th, 14th, 15th, 16th, 20th, 21st, 22nd and 23rd days of May last upon the
Petition and Appeal of Biogen Inc., of 14 Cambridge Center, Cambridge, Massachusetts, United
States of America, praying that the matter of the Order set forth in the Schedule thereto, namely an
Order of Her Majesty's Court of Appeal of the 3rd day of November 1994, might be reviewed before
Her Majesty the Queen in Her Court of Parliament and that the said Order might be reversed, varied
or altered or that the Petitioners might have such other relief in the premises as to Her Majesty the
Queen in Her Court of Parliament might seem meet; as upon the case of Medeva plc lodged in
answer to the said Appeal; and due consideration had this day of what was offered on either side in
this Cause:

It is Ordered and Adjudged, by the Lords Spiritual and Temporal in the Court of Parliament of Her
Majesty the Queen assembled, That the said Order of Her Majesty's Court of Appeal of the 3rd day
of November 1994 complained of in the said Appeal be, and the same is hereby, Affirmed and that
the said Petition and Appeal be, and the same is hereby, dismissed this House: And it is further
Ordered, That the Appellants do pay or cause to be paid to the said Respondents the Costs incurred
by them in respect of the said Appeal to this House, the amount thereof to be certified by the Clerk
of the Parliaments if not agreed between the parties: And it is also further Ordered, That the fees and
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expenses payable to the Specialist Advisers appointed under Standing Order XIV be paid by both
parties in equal shares.

Cler: Parliamentor:

Contains public sector information licensed under the Open Justice Licence v1.0.

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