JUDGMENT
Human Genome Sciences Inc (Appellant) v Eli Lilly
and Company (Respondent)
before
Lord Hope, Deputy President
Lord Walker
Lord Neuberger
Lord Clarke
Lord Collins
JUDGMENT GIVEN ON
2 November 2011
Heard on 18, 19 and 20 July 2011
Appellant Respondent
Simon Thorley QC Andrew Waugh QC
Michael Tappin QC Thomas Mitcheson
(Instructed by Powell
Gilbert LLP)
(Instructed by Field Fisher
Waterhouse LLP)
Page 2
LORD NEUBERGER
Introduction
1. This appeal is concerned with the validity of a patent which claims the
nucleotide sequence of the gene which encodes for a novel protein (and which has
further associated claims). Although there is an insufficiency issue, which I will
consider at the end of this judgment, the primary issue on this appeal raises a
difficult question, namely the way in which the requirement of industrial
applicability in Articles 52 and 57 of the European Patent Convention (“the EPC”)
extends to a patent for biological material.
2. While this issue can be said to raise an important question of principle, its
resolution is inevitably fact-sensitive, and therefore any answer may be of limited
value in other cases. Further, the issue arises in the context of a fast-developing
field, which requires a court to approach it with caution. The need for caution is
reinforced by the fact that the answer may give rise to potentially far-reaching
consequences for scientific research, the biotech industry, and human health. On
the other hand, for those very reasons, it is particularly important that the law in
this area is as clear, consistent and certain as possible.
The patent in suit
3. The patent in suit (“the Patent”) is European Patent (UK) 0,939,804. It
describes the encoding nucleotide, the amino acid sequence, and certain
antibodies, of a novel human protein, which it calls Neutrokine-α, and includes
contentions as to its biological properties and therapeutic activities, as well as
those of its antibodies. These contentions are predictions, which are substantially
based on the proposition that Neutrokine-α is a member of the TNF ligand
superfamily.
4. The application for the Patent was filed by Human Genome Sciences Ltd
(“HGS”) on 25 October 1996, and it was granted by the Examining Division of the
European Patent Office (“the EPO”) to HGS on 17 August 2005. Accordingly, the
Patent’s validity is to be judged as at October 1996.
5. For present purposes, it is unnecessary to go into the claims or the
description of the Patent in much detail. The claims, although not in their final
Page 3
form as allowed by the Technical Board of Appeal of the European Patent Office,
are set out in an appendix to the judgment of Kitchin J at first instance, [2008]
EWHC 1903 (Pat), [2008] RPC 29. The centrally important claim for present
purposes is Claim 1, which essentially extends to the encoding nucleotides of the
gene of Neutrokine-α.
6. The specification, or description, of the Patent is well summarised by
Kitchin J at [2008] RPC 29, paras 100-133. It is confusingly long, diffuse, and
widely expressed, running to over 25 closely typed pages, and nearly 200
paragraphs of descriptive text, and a further twelve pages of sequences of
polypeptide amino acids and DNA nucleotides. Also, as Kitchin J said, the
specification “contains extravagant and sometimes contradictory claims” – [2008]
RPC 29, para 134. Perhaps rather more tolerantly, the Technical Board of Appeal
of the European Patent Office (“the Board”) referred to the Patent as having been
drafted on a “boiler-plate” basis, which it described as “a practice used by
patentees”- T 0018/09 Neutrokine/Human Genome Sciences, para 27.
7. The specification begins by explaining that Neutrokine-α is a new protein,
and a member of the TNF ligand superfamily of cytokines, which are proteins
which act as inter-cellular mediators in inflammation and other immune responses.
It states that all the known members of that superfamily “are involved in regulation
of cell proliferation, activation and differentiation, including control of cell
survival or death by apoptosis or cytotoxicity…”. The specification also explains
that the first identified member of the superfamily is known as TNF-α, which was
isolated in 1975 and whose encoding gene was sequenced in 1985. By 1996, it was
clear that TNF-α had a variety of effects on different cell types, which the
specification describes as including “immunoregulatory actions including
activation of T-cells, B-cells, monocytes, [and] thymocytes …”. Accordingly, it is
claimed, “there is a need to provide cytokines similar to [TNF-α] that are involved
in pathological conditions”.
8. The specification goes on to reveal the existence and structure of
Neutrokine-α, to claim it as a member of the superfamily, and to explain that it is
“expressed … in neutrophils … in kidney, lung, peripheral leukocyte, bone
marrow, T-cell lymphoma, B-cell lymphoma, activated T-cells, stomach cancer,
smooth muscle, macrophages and cord blood tissue.” The specification then
describes the claimed invention as potentially useful for the diagnosis, prevention,
or treatment of an extraordinarily large and disparate number of, sometimes widely
expressed, categories of disorders of the immune system, and other conditions and
actions, either through Neutrokine-α itself or through its antagonists. However,
nowhere in the Patent is there any data or any suggestion of in vitro or in vivo
studies, so there is no experimental evidence to support any of those suggestions.
Page 4
9. Among its many contentions, the specification states that, “[l]ike other
members of TNF family, Neutrokine-α exhibits activity on leukocytes including
for example monocytes, lymphocytes and neutrophils”, and so “is active in
directing the proliferation, differentiation and migration of these cell types”. These
activities are said to be “useful for immune enhancement or suppression,
myeloprotection, stem cell mobilization … and treatment of leukemia”. The
specification also discusses the tissues in which Neutrokine-α is expressed, and
goes on to state that, because Neutrokine-α belongs to the TNF superfamily, “it
will have a wide range of anti-inflammatory activities” and “may be suitable to be
employed as an anti-neovascularizing agent to treat solid tumors by stimulating the
invasion and activation of host defense cells, e.g., cytotoxic T-cells …”. It is also
said that Neutrokine-α may be “suitable to be employed to enhance host defenses
against resistant chronic and acute infections” and also “to inhibit T-cell
proliferation” or “for the treatment of T-cell mediated auto-immune diseases and
lymphocytic leukemias”.
10. In very summary terms, the disclosure of the Patent thus includes the
following features: (i) the existence and amino acid sequence of Neutrokine-α, (ii)
the nucleotide sequence of the gene encoding for Neutrokine-α, (iii) the tissue
distribution of Neutrokine-α, (iv) the expression of Neutrokine-α by its mRNA (the
encoding gene) in T-cell and B-cell lymphomas, and (v) the information that
Neutrokine-α is a member of the TNF ligand superfamily.
Technical background to the Patent
11. The teaching in the specification must, of course, be read through the eyes
of the notional addressee (or “the person skilled in the art”), an appropriately
skilled person or group of persons, as at October 1996. In that connection, the
Judge said this at [2008] RPC 29, paras 30 and 32:
“30. The Patent is directed to a team of people with about two years
of post doctoral experience. It would include a molecular biologist
familiar with routine techniques of cloning, expression and
sequencing of genes and proteins; a biochemist to make and purify
recombinant proteins; and a biologist or immunologist with
experience of the TNF superfamily and with the skills necessary to
generate and test antibodies. I am also satisfied that any team
interested in identifying a new member of the TNF superfamily
would carry out a literature search to gather as much knowledge as
possible about the existing members.
…
Page 5
32. … [T]he skilled team looking for a new member of the TNF
superfamily would have been aware that the science of
bioinformatics could provide assistance in the search and, if a
bioinformaticist was not already a member of the team, would have
considered it worthwhile to consult such a person.”
12. Accordingly, particularly in the light of the last sentence of the first of those
two paragraphs, recourse must be had not only to the common general knowledge
as at October 1996, but also to the results of any research into the literature which
such notional addressees could be expected to carry out as at that time.
13. While a fuller explanation of the background and technique of
bioinformatics, referred to in the passage quoted in para 11 above, was provided
by the Judge at [2008] RPC 29, paras 78-99, I shall attempt a very brief
explanation in the ensuing five paragraphs.
14. DNA molecules are found in virtually every human and mammalian cell.
They consist of a long chain of units called nucleotides, many of which encode, via
a related molecule called RNA, for proteins through specific regions known as
genes. A gene is a stretch of DNA, which normally includes non-coding regions as
well as protein-encoding regions. RNA is made from DNA, and the non-coding
regions are removed as the RNA is processed into mature messenger RNA
(mRNA). mRNA thus contains the protein encoding regions of a gene. mRNA is
unstable outside the cell so it is copied in the laboratory to produce the more stable
cDNA.
15. Proteins consist of a chain (or sometimes linked chains) of amino acids,
and, in mammals, they perform many essential functions in the body; they include,
for instance, insulin and erythropoietin. There are four different nucleotides, and
contiguous groups of three specific nucleotides in DNA encode either for a
specific amino acid or to indicate the end of a particular encoding exercise (known
as protein translation). The result of the translation process is often a linear strand
of amino acids, which is called a polypeptide, and which folds up to form a
functional protein. The sequence of nucleotides in DNA which encodes the amino
acid sequence of a particular protein is the encoding gene of that protein.
16. Part of the relevant art is to identify the gene of a particular protein, and to
discover in which body tissues that gene is “switched on” so as to “express” the
protein. Traditional “wet lab” experiments as at 1996 included the use of
Expressed Sequence Tags (“ESTs”), which are usually relatively small pieces of
cDNA, in attempts to identify novel protein encoding genes. However, EST
cDNAs normally do not encompass the entire sequence of the original mRNA, and
Page 6
consequently do not give complete DNA sequence information. Therefore, it was
often very difficult to derive the correct or complete protein amino acid sequence
(and hence to the identity of the protein) from such experimental strategies.
17. In the early 1990s, a new technique, known as bioinformatics, was
developed. It relies upon what Kitchin J described as “the considerable increase in
the amount of DNA and amino acid sequence data created and stored in publicly
accessible databases and a parallel increase in the power of computers” – [2008]
RPC 29, para 6. Bioinformatics enables researchers to identify genes (and the
proteins for which they encode) by comparing their sequences with previously
identified and characterised genes.
18. However, it is not possible to determine, at least conclusively, the actual
activity of any gene or protein identified by this technique until after the gene has
been cloned and the resultant protein has been subjected to in vitro and in vivo
assays. As the Judge explained at [2008] RPC 29, para 75, “Assays are essential to
determine the activities and functions of a cytokine. They are also necessary to
determine whether any putative therapeutic is effective.”
19. The immune system is the body’s defence mechanism against infection,
which, in technical terms, involves the body being attacked by foreign bodies
known as pathogens (bacteria, viruses, fungi, parasites). The system is based on
white blood cells (or leukocytes), of which there are various types, including
lymphocytes. Lymphocytes recognise and interact with structures on, or derived
from, pathogens known as antigens. Two types of lymphocyte-based mechanism
are relevant for present purposes; they are:
(i) The development (in the bone marrow, in the case of adults) of type B
lymphocytes (“B-cells”), which produce antibodies, which are molecules
which bind to specific antigen sites (or epitopes) on the surface of specific
pathogens, in order to clear those pathogens from the body, and
(ii) The development (in the thymus) of type T lymphocytes (“T-cells”),
which directly react with epitopes derived from specific pathogens, again in
order to clear those pathogens from the body.
20. Once a new protein is found and identified, it is relatively easy for those
skilled in the art to generate antibodies (or antagonists, which for present purposes
can be treated as being the same thing), but it can be much more difficult to
produce useful pharmaceuticals as a result. The production of a useful
pharmaceutical from an antibody can be seen as initially involving three steps,
namely (i) finding a murine antibody which is derived from a single B-cell and
which neutralises a particular antigen, (ii) ensuring that that antibody does not bind
Page 7
to other antigens, (iii) conversion of the murine antibody so that it can be effective
in humans. This often involves engineering it so that it is not recognised and
eliminated by the human immune system. Further to this, extensive clinical trials
are required to confirm its efficacy in human disease.
21. A more detailed explanation of the immunology may be found in Kitchin
J’s judgment, [2008] RPC 29, paras 34-50.
22. A family or superfamily of proteins is a group of proteins, all of which
enjoy a significant degree of homology, i.e. they all have certain specified
structural characteristics. Although the distinction is not always observed,
members of a particular family will normally have close structural similarity and
similar functions, whereas members of a particular superfamily, while retaining
related structural characteristics, will often be more distantly related and will
include members which have similar functions but also may include members with
different functions. However, even that is an over-simplification, as, in some cases,
proteins will have pleiotropic functions, “that is to say a multitude of different
effects on different cell types, driving multiple biological processes” – per Kitchin
J at [2008] RPC 29, para 71. Accordingly, there will be cases where members of a
family or superfamily have some functions which are common to all (or a
majority) of the members, and other characteristics which are unique to one
member (or a few members).
23. The TNF superfamily is sufficiently described for present purposes as
consisting of certain cytokines with common structural molecular characteristics.
The nature of those characteristics need not be particularised for present purposes
(they are described by Kitchin J at [2008] RPC 29, paras 53-56). As the Patent
records, the founding member of the superfamily was TNF-α, which, by 1996, had
long been known as a cytokine with a significant role in regulating immune cells;
at least eight other members of the family had been found, including one called
TNF-ß.
24. At [2008] RPC 29, para 71, Kitchin J stated that the following features
would have been appreciated by the notional addressee of the Patent about
members of the TNF ligand superfamily as at October 1996:
“i) They were all expressed by activated T-cells and some by other
[types of cell].
ii) Their activities were mediated by binding to receptors, of which a
number had been identified.
Page 8
iii) They were known to have pleiotropic actions …. Some of those
activities were understood to be unique to particular TNF ligands and
others were understood to be shared by some or all the other TNF
ligands.
iv) They all played a role in the regulation of T-cell proliferation and
T-cell mediated immune responses [and they all co-stimulated T-cell
proliferation – [2008] RPC 29, para 65].
v) Some of the ligands played a role in the regulation of B-cell
proliferation and antibody secretion and some took part in T-celldependent regulation of B-cells.
vi) Some of the ligands had an ability to induce cell death by
necrosis or apoptosis.
vii) TNF-α and TNF-ß were functionally linked as primary mediators
of immune regulation and inflammatory response.
viii) It had been suggested that various ligands were associated with
a very wide range of particular disease states …. But no disease had
been identified in which all the ligands were involved.
ix) TNF-α was the only ligand shown to have a therapeutic
application; that being for the treatment of rheumatoid arthritis
through the use of a specific monoclonal antibody. …”
25. Earlier in his judgment, at [2008] RPC 29, paras 62-68, the Judge had
described what a person skilled in the art would have been expected of a new
member of the TNF ligand superfamily as at October 1996. Such a person would
have “anticipated that one of the activities of any new member [of the TNF ligand
family] would relate to T-cells”. Such a new member would also have been
expected to “have the same roles, to some degree, as” existing members, roles
which included “involve[ment] during lymphoid or thymic development, T-cell
mediated immune responses, T-cell dependent help for B-cells or humoral B-cell
activity”, and being a “co-stimul[ant] of T-cell proliferation”. It was also clear that
an effect on B-cell proliferation and “involve[ment] with distinct human diseases”
would also have been anticipated as a “possible property” of a new member of the
TNF ligand superfamily.
Page 9
26. The Judge also said this:
“72. [I]t was appreciated that further studies were both needed and
desirable to identify further ligands in the TNF superfamily and, in
relation to each ligand, to seek to identify its unique and redundant
biological functions. There was undoubtedly an incentive to do so,
because of their apparent roles in the regulation of the immune
system and inflammatory response, their possible involvement in
various different diseases and so also, in due course, their potential
as therapeutic agents. The rewards were potentially very great. …
74 … [T]he reality [was] that pharmaceutical companies and
academic institutions were indeed looking for further members of the
TNF ligand and receptor superfamilies and seeking to elucidate their
various biological functions and roles in disease states, ultimately
with a view to developing a therapeutic or diagnostic product, if
possible.”
The proceedings in the EPO and in the English courts
27. The central issue both in the High Court proceedings before Kitchin J and
in the opposition proceedings before the EPO was whether, in the light of the
common general knowledge at October 1996, by disclosing the facts summarised
in para 10 above (namely the existence and structure of Neutrokine-α, the
sequence of its encoding DNA, its tissue distribution, its expression, and its
membership of the TNF ligand superfamily), the Patent satisfied Articles 52 and
57 of the EPC so as to enable HGS to claim the encoding gene for Neutrokine-α.
28. Article 52 of the EPC provides that an invention cannot be patented unless
it is “susceptible of industrial application”. Article 57 of the EPC (“Article 57”)
goes on to state that an invention is susceptible of industrial application “if it can
be made or used in any kind of industry, including agriculture.” In its various
decisions discussed below, the Board always refers to Article 57 alone, and I will
adopt the same approach.
29. After the grant of the Patent to HGS, it was the subject of opposition
proceedings brought in the EPO by Eli Lilly and Company (“Eli Lilly”). Following
an oral hearing before the Opposition Division of the EPO (“the OD”) in June
2008, the Patent was revoked on the basis that the claimed invention constituted,
as the Judge put it, a claim to an arbitrary member of the TNF ligand superfamily
without a known function.
Page 10
30. HGS appealed against the OD’s decision to the Board, which, after a
hearing lasting around a day and a half, in a decision given on 21 October 2009,
allowed the appeal. The Board’s decision was, in very summary terms, based on
the ground that the notional addressee of the Patent would have appreciated that,
“in the light of the common general knowledge of the TNF ligand superfamily and
its properties”, Neutrokine-α would, as the Patent states, be “active in directing the
proliferation, differentiation, and migration of [T-cells]”, and that was a sufficient
function to vindicate the Patent under Article 57 – see T 0018/09, paras 23-24.
Accordingly, the Board referred the case back to the OD with a direction that the
Patent be maintained.
31. Meanwhile, Eli Lilly brought parallel proceedings in the High Court for
revocation of the Patent in this jurisdiction. The proceedings came before Kitchin
J, who, after a hearing held over some thirteen days, decided to revoke the Patent.
His decision was, again in very summary terms, based on the conclusion that, in
the light of the common general knowledge, the notional addressee of the Patent
would have concluded that the “functions” of Neutrokine-α “were, at best, a matter
of expectation and then at far too high a level of generality to constitute a sound or
concrete basis for anything except a research project” – see [2008] RPC 29, para
234.
32. Kitchin J’s decision was given on 31 July 2008, after the decision of the
OD, but before HGS had appealed to the Board. HGS appealed against Kitchin J’s
decision to the Court of Appeal, who, on 9 February 2010, dismissed the appeal –
[2010] EWCA Civ 33, [2010] RPC 14. The Court of Appeal’s reasoning
effectively followed and approved that of Kitchin J, although it was given after the
ruling of the Board. In his judgment, with which Hallett LJ and Lewison J agreed,
Jacob LJ discussed the reasoning of the Board in T0018/09. It is, of course, against
the decision of the Court of Appeal which HGS now appeal.
33. HGS’s case on this appeal is that, notwithstanding Kitchin J’s impressively
full and careful analysis of the law, the relevant technology, the Patent and the
expert evidence, and its affirmation by the Court of Appeal, his decision that the
Patent failed to satisfy Article 57 was wrong. That case effectively mirrors the
reasoning of the Board in T0018/09. In summary, HGS contends that the reasoning
of the Board was correct, and that it shows that Kitchin J and the Court of Appeal
set too high a standard for industrial applicability in the context of a patent for
biological material.
34. HGS and Eli Lilly each rely on the jurisprudence of the Board prior to the
decision in T 0018/09 as to the way in which the requirement of industrial
applicability extends to biological material patents, as did both Kitchin J, and the
Board itself in T 0018/09. Kitchin J also referred to some domestic jurisprudence
Page 11
and to decisions of courts in the United States. It was also suggested below that the
Biotech Directive (99/44EC) (“the Directive”) was of some assistance.
The Directive, and domestic and US jurisprudence
35. Article 5 of the Directive confirms that a naturally occurring gene is
patentable, but states that “[its] industrial application … must be disclosed in the
patent application”. As Jacob LJ put it, “However clever and inventive you may
have been in discovering a gene sequence, you cannot have a patent for it or for
the protein for which it encodes if you do not disclose how it can be used” –
[2010] RPC 14, para 57.
36. It was common ground that the Directive cannot alter the meaning of
Article 57 (both because it came into force after 1996, and because the EPC
extends to countries outside the EU). While that may not prevent the Directive
being of some assistance in a case where Article 57 is in play in relation to a patent
for biological material, it seems to me that it is not helpful in the present case, as it
begs the central question, namely how far an applicant for a patent for biological
material has to go in disclosing industrial application. Jacob LJ’s pithy formulation
at [2010] RPC 14, para 57, cited in para 35 above, applies equally to Article 57
before the Directive came into force as it does afterwards.
37. So far as the cases in this jurisdiction are concerned, as Kitchin J said at
[2008] RPC 29, para 186 “[t]here is very little authority” on the topic of industrial
applicability: only a brief and very general comment from the Court of Appeal in
Chiron Corp v Murex Diagnostics Ltd [1996] RPC 535, 607-608, and a decision in
2005 of a Divisional Director acting for the Comptroller of UK Patents, Aeomica’s
Application BL O/286/05, which analysed the issue more fully. In my view,
neither case provides any assistance to the problem raised on this appeal. The
conclusions in both Chiron [1996] RPC 535 and Aeomica BL O/286/05 appear
equally consistent with HGS’s and Eli Lilly’s contentions, the observations in the
former case are at a high level of generality, and the reasoning in the latter case
rests on the US jurisprudence.
38. As for the US courts, their approach to the question of what constitutes “any
new and useful … composition of matter” under section 101 of 35 USC was
considered by the US Supreme Court in Brenner v Manson 383 US 519 (1966)
534-536, and by the US Court of Appeals for the Federal Circuit in Fisher v
Lalgudi 421 F 3d 1365 (2005) (and both decisions are discussed and quoted from
by the Judge at [2008] RPC 29, paras 218-224).
Page 12
39. The analyses in the US cases deserve great respect, and it is interesting to
note that, in Fisher 421 F 3d 1365, the US Court of Appeals referred to a
requirement that “an invention is useful to the public as disclosed in its current
form” as opposed to “prov[ing] useful at some future date after further research”,
and that the invention “can be used to provide a well-defined and particular benefit
to the public.”
40. However, there are obvious risks in relying on US jurisprudence when
considering the precise nature of the requirements of Article 57 in relation to a
claim for a patent for biological material under the EPC. There have been moves
over the past fifty years (and more) to harmonise patent law across jurisdictions
(the EPC and TRIPS – the Trade-Related Aspects of Intellectual Property
Protection – being two important examples), and it is a laudable aim to seek to
ensure that all aspects of the law of patents are identical throughout the world.
However, the achievement of such an aim is plainly not currently practicable, and,
although they have a great deal in common, there are significant and fairly
fundamental differences (over and above the different words used in Articles 52
and 57 of the EPC and section 101 of 35 USC) between US patent law and the
EPC (two notorious examples being the first to file rule in Europe, and file
wrapper estoppel in the US).
41. Accordingly, particularly when it comes to a nice question such as the
precise delineation of boundaries between patentability and unpatentability on the
ground of industrial application, it would be unsurprising if the law was not
identical under the two jurisdictions.
42. In the event, as both parties to this appeal acknowledge, it is in the
jurisprudence of the EPO, and in particular that of the Board, that the applicable
principles are really to be found. So I now turn to that jurisprudence.
The Board’s jurisprudence on Article 57 and biological material
43. There are a number of decisions of the Board prior to its decision in relation
to the Patent, which are of importance to the present appeal. In their oral
arguments, the parties concentrated on two of them, T 0870/04 BDP1
Phosphatase/ Max-Planck, on which Eli Lilly placed reliance, and T 0898/05
Hematopoietic receptor/ZymoGenetics, from which HGS sought to derive
assistance. However, because it is important to establish the nature and ambit of
the approach which the Board has adopted to the application of Article 57 to
patents for proteins and their encoding genes, it is, in my view, necessary to
consider all the decisions to which we were referred. I also consider that it is
necessary to quote a number of passages from the decisions. As both parties
Page 13
accept, the reasoning of the Board in those decisions contains the principles
applicable to this appeal, but they disagree as to the precise nature of those
principles.
44. In T 0870/04, decided on 11 May 2005, the Board upheld the rejection by
the Examining Division of the EPO (“the ED”) of an application which disclosed
BDP-1, a new polypeptide, said to be a member of the so-called PTP-PEST family.
The application suggested that PTP-PESTs played an important role in certain
specified cellular functions, and were possible “candidate anti-cancer proteins”. It
also disclosed that BDP-1 was expressed in most tissues and cell lines, particularly
in epithelium origin cell lines and in cancer cell lines.
45. The Board began its reasoning by giving some general guidance. At
T0870/04, para 3, it said that the concept of “industry” in Article 57 was very
broad, extending to all activities carried out for “for financial (commercial) gains”.
In the following paragraph, it explained that “a ‘practical’ application of the
invention has to be disclosed” so that there is “some profitable use for which the
[claimed] substance can be employed.”
46. Turning to the disclosure in the particular application, the Board pointed out
at T 0870/04, paras 11-12 (and in the light of the subsequent jurisprudence, I draw
particular attention to para 12):
“11. … [T]he application does not explicitly disclose the specific
nature and the possible significance of [the] suggested roles for
BDP1. … [T]he application stops short of suggesting, let alone
identifying, an anti-cancer activity for BDP1 or a therapeutic use of
BDP1 as a tumour-suppressor agent. There is no evidence as to
whether BDP1 plays a passive role … or an active role in cancer. …
12. Nor can the identification of BDP1 as a PTP-PEST be taken as
any clear indication of its function or use, as the prior art does not
attribute clear functions to PTP-PESTS as a class. …”
47. At T 0870/04, paras 21-22, the Board concluded:
“21. … [A]lthough the present application describes a product (a
polypeptide), means and methods for making it, and its prospective
use thereof for basic science activities, it identifies no practical way
of exploiting it in at least one field of industrial activity. In this
respect, it is considered that a vague and speculative indication of
Page 14
possible objectives that might or might not be achievable by carrying
out further research with the tool as described is not sufficient for
fulfilment of the requirement of industrial applicability. The purpose
of granting a patent is not to reserve an unexplored field of research
for an applicant. …
22. The present case is already on the [wrong] side of the borderline.
… [T]he only practicable use suggested is to use what is claimed to
find out more about the natural functions of what is claimed itself.
This is not in itself an industrial application, but rather research
undertaken either for its own sake or with the mere hope that some
useful application will be identified.”
48. Shortly after this, on 28 June 2005, the Board decided T 1329/04 Factor9/John Hopkins, in which it again upheld the ED’s refusal of a patent application.
At T 1329/04, para 4, the Board embarked on its familiar problem/solution
approach, and described “the problem to be solved … as isolating a further
member of the TGF-β superfamily”, whose established members it described as
“[having] influence on a wide variety of differentiation processes such as
adipogenesis, myogenesis etc”. The Board went on to say that the patent’s claimed
solution was the nucleotide sequence encoding for the claimed polypeptide, and
described the issue as being “[w]hether or not the problem … has been plausibly
solved”.
49. The Board concluded on this issue at T 1329/04, para 11, in a passage
which illuminatingly indicates what was lacking in the application:
“[A]s a significant structural feature fails to be identical in TGF-9
and the members of the TGF-β superfamily, and no functional
characterisation of TGF-9 is forthcoming in the application, it is
concluded that the application does not sufficiently identify this
factor as a member of this family i.e. that there is not enough
evidence in the application to make at least plausible that a solution
was found to the problem which was purportedly solved.”
50. The Board added at T 1329/04, para 12, that “even if supplementary postpublished evidence may in the proper circumstances also be taken into
consideration, it may not serve as the sole basis to establish that the application
solves indeed the problem it purports to solve.”
Page 15
51. In T 0604/04 PF4A receptors/Genentech, decided on 16 March 2006, the
Board allowed an appeal from the OD where the claim was to certain polypeptides
on the ground that they were members of the PF4AR family of chemokine
receptors. At T 0604/04, para 6, dealing with the issue of inventive step, and
having accepted that “there is no absolute certainty that the [claimed] polypeptides
… are receptors for members of the PF4A family of cytokines to which IL-8
belongs”, the Board said that “[certain] structural features make it plausible that
this is indeed the case.” In the following paragraph, the Board expressly
distinguished T 1329/04, “where it was not accepted that the polypeptide … then
claimed was a member of the TGF-β superfamily”.
52. Dealing with Article 57, the Board said this at T 0604/04, para 13:
“In summary, the patent in suit identifies applications for the claimed
polypeptides which may ultimately lead to some profitable use. It
provides a structural characterisation which enables their assignment
to the category of receptors which bind members of the PF4A family
of chemokines and, insofar, indicates what their function might be.
Yet, in the absence of any characterisation of their ligands, this
function remains at best incompletely understood”.
53. After referring to T 0870/04, the Board said at T 0604/04, para 15:
“[T]he technical data provided in respect of the [claimed]
polypeptides … fall somewhat short of fulfilling them insofar as, as
already above mentioned, there is no evidence available as to which
ligands these polypeptides bind to. Yet, of course, each case has to
be considered on its own merit …and it is important here to take into
account the common general knowledge at the priority date as well
as the then prevalent attitude of the person skilled in the art as it may
be inferred from the documents illustrating this common general
knowledge.”
54. At T 0604/04, para 16, the Board said that, as at the priority date:
“chemokines were already known as mediators of the inflammatory
response, a role which most of them were thought to play, in
particular, through … a biological interaction of the chemokines with
the cells which they attract which involves binding to the receptors
present on the cell surface. Thus, the skilled person would
Page 16
understand that any role of a given chemokine was reflected in its
receptor.”
55. At T 0604/04, para 18, the Board concluded that:
“It is clear … that chemokines as a family were considered not only
to be interesting in fundamental research but also as important for
the pharmaceutical industry irrespective of whether or not their role
had been clearly defined. It follows that their receptors must have
been considered equally important since the mode of action of
chemokines is through their receptors. It is, thus, reasonable to
conclude that the [claimed polypeptides] which exhibit the
characteristics of receptors of members of the PF4A family of
cytokines would have been regarded as important to the
pharmaceutical industry, i.e. that industrial applicability may be
acknowledged.”
56. The Board also said at T 0604/04, para 22 that in its “judgment, and in the
absence of any evidence to the contrary, the patent specification provides adequate
experimental instructions for the skilled person to be able to reproduce without
undue burden the [claimed] polypeptides …”.
57. I turn now to the Board’s decision on 7 July 2006 in T 0898/05. This was an
appeal against the ED’s refusal of a patent application, which disclosed the
nucleotide sequence and the encoded amino acid sequence of a polypeptide and
receptor, Zcytor1, and claimed inter alia the encoding nucleotide and the
polypeptide.
58. As in T 0870/04, the Board made some general observations at the outset.
Thus, at T 0898/05, para 4, after referring to the reasoning in T 0870/04, the Board
said that “a patent application [must describe] its subject invention in sufficiently
meaningful technical terms that it can be expected that the exclusive rights
resulting from the grant of a patent will lead to some financial or other commercial
benefit.” And in the next paragraph, the Board said that “the invention claimed
must have such a sound and concrete technical basis that the skilled person can
recognise that its contribution to the art could lead to practical exploitation in
industry.”
59. The Board then elaborated its approach in these terms:
Page 17
“6. .. [T]he expression ‘profitable use’ should be understood more in
the sense of ‘immediate concrete benefit’. This conveys, in the words
‘concrete benefit’, the need to disclose in definite technical terms the
purpose of the invention and how it can be used in industrial practice
to solve a given technical problem, this being the actual benefit or
advantage of exploiting the invention. The essence of the
requirement is that there must be at least a prospect of a real as
opposed to a purely theoretical possibility of exploitation. Further,
the use of the word ‘immediate’ conveys the need for this to be
derivable directly from the description, if it is not already obvious
from the nature of the invention or from the background art. It
should not be left to the skilled reader to find out how to exploit the
invention by carrying out a research programme. ….
7. Accordingly, a product whose structure is given (e.g. a nucleic
acid sequence) but whose function is undetermined or obscure or
only vaguely indicated might not fulfil the above criteria, in spite of
the fact that the structure of the product per se can be reproduced. If
a patent is granted therefor, it might prevent further research in that
area, and/or give the patentee unjustified control over others who are
actively investigating in that area and who might eventually find
actual ways to exploit it.
8. On the other hand, a product which is definitely described and
plausibly shown to be usable, e.g. to cure a rare or orphan disease,
might be considered to have a profitable use or concrete benefit,
irrespective of whether it is actually intended for the pursuit of any
trade at all. Thus, although no particular economic profit might be
expected in the development of such products, nevertheless there is
no doubt that it might be considered to display immediate concrete
benefits.”
60. The claimed disclosure is described at T 0898/05, paras 13-16. In summary
terms, it disclosed the nucleotide sequence and the encoded amino acid sequence
of the cytokine, Zcytor1, its tissue distribution, including in “both B- and T-cells”,
and claims that Zcytor1 accordingly had various roles such as “in proliferation,
differentiation, and/or activation of immune cells” and that it could therefore be
“useful in different therapeutic conditions”, of which a fair number of different
possibilities were given. No experimental evidence was provided to support these
claimed roles or uses.
61. At T 0898/05, para 19, the Board identified the two reasons the ED had
refused the patent application. They were “(i) the use of a computer-assisted
Page 18
alignment … did not allow any concrete conclusions to be made as to the actual
specific function of the protein, because such studies provided only speculation of
a vague nature and no specific therapeutic or diagnostic use could be ascertained
therefrom”; and (ii) Zcytor1 “was only a research tool … whose disclosure was
only the first step in the quest for industrially applicable matter”.
62. The Board then started its consideration of the ED’s two reasons for
refusing ZymoGenetics’ application in these terms:
“21. In the present case, based on computer-assisted sequence
homology studies and on tissue distribution studies, the Zcytor1
receptor was identified in the application as a putative member of the
hematopoietin receptor family and it was assigned a role in
proliferation, differentiation and/or activation of immune cells and
thus a possible role for its ligands in therapeutic conditions
associated with the functioning of the immune system. Admittedly,
no experimental evidence for the suggested role of the receptor
and/or its ligands is made available in the application. Later
evidence, however, confirmed this sort of ‘educated guess’, which
the examining division considered to be – in its own words –
‘reasonably credible’.
22. The fact that the putative function of the Zcytor1 receptor was
assigned in the examples based on computer-assisted methods, rather
than on the basis of traditional wet-lab techniques, does not mean
that it has to be automatically disregarded or excluded from a careful
and critical examination. … [The] probative value [of such
examples] has to be examined on a case-by-case basis regarding the
nature of the invention and the prior art relating thereto. Such
methods of analysis are increasingly becoming an integral part of
scientific investigations and can often allow plausible conclusions to
be made regarding the function of a product before it is actually
tested.”
63. The Board then explained at T 0898/05, para 24, that the identification of
“the Zcytor1 receptor … as a putative member of [the] hematopoietin receptor
family” of cytokines was “based on [its] general structure”, and was not called into
question by anything in the Patent or by any other evidence. The Board also said
that “post-published evidence, which confirms the preliminary finding and actually
supports the conclusion, cannot be ignored.”
Page 19
64. After quoting the ED’s view that the “suggested role” of the Zcytor1
receptor was too “vaguely defined”, not least because “the members of the family
all obviously have different functions”, the Board said this at T 0898/05, para 27:
“It might well be possible that members of a structurally related
family have, notwithstanding their related structure, a different
activity and function. However, there is no reference to the prior art
in the decision under appeal which supports such a case in the
hematopoietin receptor family. In fact, from the prior art cited in the
application and concerned with this family of receptors …, it may be
derived that, although none of these members are precisely
interchangeable in terms of their biological action, there is
considerable redundancy of action as well as an ability to elicit,
under certain conditions, similar biological responses. Even more
important is the fact that this prior art does not cast significant or
serious doubts on the suggested role of the Zcytor1 receptor. Thus,
the assumption (or ‘educated guess’) made in the patent application
is plausible.”
65. At T 0898/05, paras 29-31, the Board concluded as follows:
“29. … The function of a protein (and thus of the nucleic acid
encoding it) can be seen at different levels. These include: (i) the
biochemical activity of the protein …, i.e. its molecular function; (ii)
the function of the protein in cellular processes …, i.e. its cellular
function; and (iii) the influence of those cellular processes within a
multicellular organism, …. this being its biological function in a
broad sense. …
30. The elucidation of one of these particular levels of function
might result, under certain conditions, in a straightforward industrial
application, even though the other levels of activity remain
completely unknown or only partially characterized. … For the
purpose of Article 57 …, none of these levels is more fundamental
… than the other ones … .
31. In the present case, the suggested role of [Zcytor1] corresponds
to the level of the biological function and the practical applications
or the concrete technical benefits derived therefrom are clearly
disclosed in the present application, namely the stimulation of cellmediated immunity and of lymphocyte proliferation by agonist
ligands of Zcytor1 and the suppression of the immune system by
Page 20
antagonists of the Zcytor1 receptor … . Although the details of the
biochemical activity and the cellular function of the Zcytor1 receptor
have not been elucidated in the application, the (therapeutic)
treatments directly derivable from the biological function identified
by the computer-assisted method cannot be considered to be so
‘vaguely defined’ that they do not suggest any therapeutic or
diagnostic use. On the contrary, the treatments referred to in the
application are specifically in relation to the function plausibly
attributed to the molecule, and are in the areas of rheumatoid
arthritis, multiple sclerosis, diabetes mellitus, etc.”
66. In T 1452/06 Serine protease/Bayer (10 May 2007) the Board considered
and applied its reasoning in T 0870/04 and T 0898/05, when upholding a decision
of the ED refusing an application claiming a patent for a polypeptide and its
encoding gene. Having said that there was “no experimental evidence whatsoever
… in support of [the claimed] serine protease activity” of the claimed polypeptide,
the Board then said at T 1452/06, para 4, that such support “might be provided by
a (computer-assisted) comparison of [the disclosed] sequence with sequences of
known serine proteases and, more particularly, with the allegedly closely related
sequence of [the already known] epithin”. The Board accepted, at para 6, that such
support “might be obtained by a straight (computer-assisted) comparison of the
[disclosed] sequence with the sequence of [epithin]”. However, the Board pointed
out that “epithin is defined as a putative serine protease” (original emphasis) and
there was no “experimental evidence in support of [its] serine protease activity nor
of any other activity at all.” (para 7)
67. In T 1165/06 IL-17 related polypeptide/Schering, decided 19 July 2007, the
main issue was obviousness, but the Board also addressed the question whether the
requirements of Article 57 had been satisfied, and concluded that they had. At T
1165/06, para 14, the Board, adopting its problem/solution approach, said “the
technical problem to be solved can be defined as the isolation of a further
polypeptide of the IL-17 cytokine family, and a nucleotide sequence encoding the
polypeptide”. The appellant’s case was that the claimed polypeptide exhibited
“significant sequence similarity to the [IL-17 cytokine family which had four
established members, all of] which functioned in controlling physiology,
development and differentiation of mammalian cells”
68. At T 1165/06, para 25, the Board concluded:
“The sequence information provided in the application with respect
to the presence in IL-174 of the characteristic cysteine spacing of the
IL-17 cytokine family makes it plausible that [the claimed]
polypeptide may belong to this family and have biological activities
Page 21
similar to those of the other family members known at the filing
date, in particular CTLA-8. This is confirmed by post-published
evidence filed by the appellant.”
The reasoning and conclusions of Kitchin J and of the Board
69. As I have mentioned, in their respective decisions, both Kitchin J and the
Board referred to and relied on the Board’s jurisprudence, but they came to
different conclusions. It is therefore appropriate to turn to the reasoning in the two
decisions in a little more detail, and in particular the identification of what the
notional addressee would get from the Patent, and why the Patent did or did not
satisfy Article 57.
70. As to the overall effect of the teaching of the Patent, it is convenient to refer
to what Kitchin J said at [2008] RPC 29, paras 231-233, as the view which he
expressed was very similar to that of the Board, and was not challenged in this
court by HGS. In those paragraphs, he summarised his view as to what the Patent
disclosed thus:
“231. In this case I am quite satisfied that the skilled person would
consider the Patent does not of itself identify any industrial
application other than by way of speculation. … [I]t contains an
astonishing range of diseases and conditions which Neutrokine-α and
antibodies to Neutrokine-α may be used to diagnose and treat and
there is no data of any kind to support the claims made. The skilled
person would consider it totally far-fetched that Neutrokine-α could
be used in relation to them all and … would be driven to the
conclusion that the authors had no clear idea what the activities of
the protein were and so included every possibility. To have included
such a range of applications was no better than to have included none
at all.
232. But that is not the end of the matter because the disclosure must
be considered in the light of the common general knowledge …. The
skilled person would have known that TNF was involved as a
primary mediator in immune regulation and the inflammatory
response and had an involvement in a wide range of diseases as
septic shock, rheumatoid arthritis, inflammatory bowel disease,
tissue rejection, HIV infection, and some adverse drug reactions. He
would have known that all the members of the TNF ligand
superfamily identified hitherto were expressed by T-cells and played
a role in the regulation of T-cell proliferation and T-cell mediated
Page 22
responses. Further, … the skilled person would anticipate that the
activities of Neutrokine-α might relate to T-cells and, in particular,
be expressed on T-cells and be a co-stimulant of B-cell production;
that it might play a role in the immune response and in the control of
tumours and malignant disease; that it might have an effect on B-cell
proliferation … .
233. On the other hand, the skilled person would have also known
that the members of the family had pleiotropic actions; that some of
those activities were unique to particular TNF ligands and others
were shared by some or all the other TNF ligands and that no disease
had been identified in which they were all involved. Moreover, …
the therapeutic application of TNF-α monoclonal antibody for the
treatment of rheumatoid arthritis was believed to operate by
interrupting the cytokine cascade and by controlling the recruitment
and trafficking of blood cells to the joint – a rather specific activity.”
71. Eli Lilly’s case to the effect that the teaching of the Patent fell short of the
requirements of Article 57 was accepted by Kitchin J at [2008] RPC 29, paras 230
and 234-5 (which were effectively approved by the Court of Appeal). But before
quoting them, it is appropriate to refer to three earlier passages in his judgment.
72. At [2008] RPC 29, para 118, the Judge accepted that the claims of the
Patent in relation to Neutrokine-α were “significant” because:
“[T]hey reveal the importance of the identification of the tissues
where [it] is expressed, the tissues where it acts, the nature of its
biological activity and how that profile varies in any particular
disease state. However, no data is provided to support these claims.
Further, … the variety of conditions for which the described method
is said to be useful [is] puzzlingly wide and … the method itself
impossible to operate in the absence of any information as to the
standard level of Neutrokine-α expressed in each of these tissues in
normal conditions.”
73. Having considered the description of the Patent, the Judge concluded at
[2008] RPC 29, para 134, that there was “nothing by way of experimental
evidence to support the claims made and … the idea that Neutrokine-α and [its
antagonists] could be used to treat the extraordinary range of diseases identified
was fanciful.” He then said that, in his view, “the skilled person would come to the
conclusion that the inventors had no idea as to the activity of Neutrokine-α when
drafting the Patent” and that it taught “the skilled person nothing useful about its
Page 23
activity other than that Neutrokine-α is another member of the TNF ligand
superfamily”.
74. The Judge also considered in some detail the work carried out since October
1996, and concluded at [2008] RPC 29, para 176, that this work established
Neutrokine-α’s functions more clearly, and in particular that it “plays a significant
and particular role in the proliferation and differentiation of B-cells … [and] in the
regulation of T-cell proliferation and activation”. He went on:
“Neutrokine-α has now been shown to have an important role in the
development of autoimmune disease and B-cell cancers; but, at the
same time, much of its biology remains unclear and is the subject of
continuing study by many different research centres. In my judgment
the nature and extent of all this research work, the limited
conclusions ultimately drawn and the amount of work that remains to
be done point strongly to the conclusion that the therapeutic and
diagnostic applications suggested in the Patent were indeed
speculative.”
75. Turning then to the passage in which he expressed his conclusions, [2008]
RPC 29, paras 230 and 234-5, Kitchin J said this:
“230. I accept that the contribution made by HGS was to find
Neutrokine-α and to identify it as a member of the TNF ligand
superfamily. However it is clear from the cases to which I have
referred that simply identifying a protein is not necessarily sufficient
to confer industrial utility upon it. … It may be sufficient if the
identification of the protein will immediately suggest a practical
application, such as was the case with insulin, human growth
hormone and erythropoietin. But if the function of the protein is not
known or is incompletely understood and if no disease has been
attributed to a deficiency or excess of it, then the position may well
be different. In these cases the industrial utility must be identified in
some other way. …
234. Does [the] common general knowledge, taken as a whole,
disclose a practical way of exploiting Neutrokine-α? Or does it
provide a sound and concrete basis for recognising that Neutrokine-α
could lead to practical application in industry? In my judgment it
does not. The fact that Neutrokine-α might be expected to play a role
in regulating the activities of B-cells and T-cells and play an
unspecified role in regulating the immune and inflammatory
Page 24
response did not reveal how it could be used to solve any particular
problem. Neither the Patent nor the common general knowledge
identified any disease or condition which Neutrokine-α could be
used to diagnose or treat. Its functions were, at best, a matter of
expectation and then at far too high a level of generality to constitute
a sound or concrete basis for anything except a research project.
235. I believe this conclusion is confirmed by the activities of those
in the pharmaceutical industry in the years following the filing of the
application. HGS, Lilly and Biogen (and possibly others too) carried
out research programmes to try and find out where Neutrokine-α was
expressed, where its receptors were expressed and what its activities
appeared to be. They carried out in vitro assays and animal studies
and determined that it appeared to have an activity in relation to B
lymphocytes with a particular biological profile. On the basis of this
work they recognised that it was an important therapeutic target –
some two to three years after the application for the Patent had been
filed. It is significant that in so doing they considered that its utility
might lie in the treatment of B-cell disorders of particular kinds.”
76. The passage I have just quoted from Kitchin J’s judgment encapsulates Eli
Lilly’s case, and HGS’s case is well summarised in the Board’s reasoning at
T0018/09, paras 22-26. The first of those paragraphs sets the scene in terms of the
general approach:
“22. As pointed out in T 870/04, [paras 5 and 6], in many cases the
allocation of a newly found protein to a known protein family with
known activities suffices to assign a specific function to the protein
because normally the members of the family share a specific
function. This may be a well-characterized and perfectly understood
function which provides in a straightforward manner enough support
for industrial applicability. In such cases, the ‘immediate concrete
benefit’ is manifest. In other cases, where the members of a protein
family have different, pleiotropic effects which may even be
opposite and neither completely characterized nor understood, no
effect can be assigned to a new member without relying on some
experimental data. Between these two extreme situations, a variety
of other situations may arise for which a detailed examination of all
the facts may be required. Indeed, this is the case for the TNF ligand
superfamily.”
77. In the next two paragraphs, the Board sought to follow that approach in
relation to the instant Patent:
Page 25
“23. As known in the art and acknowledged in the [Patent], all
members of the TNF ligand superfamily are known to participate in
the regulation of (immune) cell proliferation, activation, and
differentiation, and are involved in various medical conditions. They
are pleiotropic cytokines which display a wide range of activities and
have distinctive, but also overlapping biological functions…. As
acknowledged in the art, a feature common to all members (without
exception) of the TNF ligand superfamily is the expression on
activated T-cells and the ability to co-stimulate T-cell proliferation
… In view of the assignment of Neutrokine-α to the family, the
skilled person expects it to display this common feature, the relevant
question here being whether anything in the Patent specification
contradicts this expectation.
24. The Patent specification, besides providing the undisputed
structural identification of Neutrokine-α as a member of the TNF
ligand superfamily, also provides some further relevant technical
data which are fully in line with the expected properties of a member
of that superfamily. In particular, it discloses the tissue distribution
of Neutrokine-α mRNA expression using the nucleic acid sequence
encoding the Neutrokine-α protein, as a cDNA probe and, as
expected, reports – although without concrete experimental data – the
expression of Neutrokine-α in activated T-cells… . It further states
that ‘(l)ike other members of TNF family, Neutrokine-α exhibits
activity on leukocytes including for example monocytes, lymphocytes
and neutrophils. For this reason Neutrokine-α is active in directing
the proliferation, differentiation and migration of these cell types’
…. This broad statement, far from contradicting the ability of
Neutrokine-α to co-stimulate T-cell proliferation, actually supports
it. In the light of the common general knowledge of the TNF ligand
superfamily and its properties, no serious doubts can be cast on this
explicit additional information. Nor can this information be taken as
a mere theoretical or purely hypothetical assumption. First of all, it is
plausible and, secondly, there is ample post-published evidence on
file confirming both the presence of Neutrokine-α on activated Tcells and its ability to co-stimulate T-cell proliferation.”
78. The Board then turned to Eli Lilly’s contention that “in view of the
numerous contradictory statements and of the broad range of conditions and
diseases referred to in the patent-in-suit, the skilled person would have disregarded
such information as constituting only hypothetical assumptions or speculations”,
and said this at T 0018/09, para 26:
Page 26
“When reading the patent specification, a skilled person would
distinguish the positive technical information such as that mentioned
above from other allegedly contradictory and broad statements found
in the patent-in-suit, such as … the wide range of activities and
conditions for which Neutrokine-α could be useful. This is because
the skilled person realises that the description of the structure of
Neutrokine-α, its structural assignment to the family of TNF ligands,
and the reports about its tissue distribution and activity on
leucocytes, are the first essential steps at the onset of research work
on the newly found TNF ligand superfamily member. In view of the
known broad range of possible activities of such a molecule, the
skilled person is aware of the fact that the full elucidation of all
properties requires further investigations which will gradually reveal
them. In this context, the skilled person regards the long listing of
possible actions of Neutrokine-α and of medical conditions in which
it might take part as the enumeration or generalisation of the
properties of the TNF ligand superfamily. This is seen as the frame
in which the newly found molecule has to be placed as one could
prima facie have a reasonable expectation that most of them could in
fact be present.”
79. The Board accordingly concluded at T 0018/09, para 27 that “the
description of the patent delivers sufficient technical information, namely the
effect of Neutrokine-α on T-cells and the tissue distribution of Neutrokine-α
mRNA, to satisfy the requirement of disclosing the nature and purpose of the
invention and how it can be used in industrial practice.”
80. At T 0018/09, paras 28-30, the Board then considered the arguments that
“in view of the technical difficulties involved in measuring the co-stimulation of
T-cells by Neutrokine-α”, the implementation of the teaching of the Patent would
involve an “undue burden”, and that, in any event, “no industrial application can
be directly derived from a mere co-stimulation of T-cells”. Those arguments were
also rejected. Although the Board acknowledged that such assays had produced “a
few contradictory results”, there was “post-published evidence” which showed that
Neutrokine-α activity could be reasonably easily measured in relation to both Tcells and B-cells. Further, the Board said that the activities of Neutrokine-α, as
taught by the Patent (“in particular, the inhibition of co-stimulation and/or
proliferation of lymphocytes”) “may represent a valid basis for a possible
industrial application”.
81. The Board went on to say at T 0018/09, para 30, that the Patent’s teaching
as to “the expression of Neutrokine-α mRNA in B-cell and T-cell lymphomas
provides in itself in the context of the disclosure a valid basis for an industrial
application”, adding that the “presence of Neutrokine-α in these lymphomas,
Page 27
which is also confirmed by post-published evidence … may be used to develop
appropriate means and methods for their diagnosis and treatment based on the
disclosure of the [Patent]”.
82. In the next four paragraphs, the Board also rejected the contention that
“alleged technical problems” meant that “no industrial application could be
derived from [the] information [in the Patent]”; this was because Eli Lilly was
unable to establish “serious doubts, substantiated by verifiable facts”, so that it was
relying on mere “unsupported assumptions”.
Following the Board’s jurisprudence
83. Where the EPO decides that a patent, or a claim in a patent, is invalid, then
that is the end of the issue (subject, of course, to the patentee or applicant
appealing to the Board) in relation to all countries which are signatories to the
EPC. Where, however, the EPO decides that a patent, or a particular claim, is
valid, then, as this case shows, it is still open to a national court to decide that the
patent, or claim, is invalid within its territorial jurisdiction. In all cases, however,
the EPO and each national court are, of course, applying the principles contained
in the EPC. It is plainly appropriate in principle, and highly desirable in practice,
that all these tribunals interpret the provisions of the EPC in the same way.
84. In a number of recent decisions of the House of Lords, attention has been
drawn to “the importance of UK patent law aligning itself, so far as possible, with
the jurisprudence of the EPO (and especially decisions of its Enlarged Boards of
Appeal)”, to quote Lord Walker in Generics (UK) Ltd v H Lundbeck A/S [2009]
UKHL 12; [2009] RPC 13, para 35. It is encouraging that the same approach is
being adopted in Germany by the Bundesgerictshof – see Case Xa ZR 130/07 (10
September 2009), para 33.
85. However, as Lord Walker went on to explain in Generics [2009] RPC 13,
para 35, “National courts may reach different conclusions as to the evaluation of
the evidence in the light of the relevant principles” even though “the principles
themselves should be the same, stemming as they do from the EPC”. Thus, the
EPO (or another national court) and a national court may come to different
conclusions because they have different evidence or arguments, or because they
assess the same competing arguments and factual or expert evidence differently,
or, particularly in a borderline case, because they form different judgments on the
same view of the expert and factual evidence.
Page 28
86. As Lord Hoffmann said in Conor Medsystems Inc v Angiotech
Pharmaceuticals Inc [2008] UKHL 49, [2008] RPC 28, para 3:
“A European patent takes effect as a bundle of national patents over
which the national courts have jurisdiction. It is therefore inevitable
that they will occasionally give inconsistent decisions about the same
patent. Sometimes this is because the evidence is different. In most
continental jurisdictions, including the [EPO], cross-examination is
limited or unknown. Sometimes one is dealing with questions of
degree over which judges may legitimately differ. Obviousness is
often in this category. But when the question is one of principle, it is
desirable that so far as possible there should be uniformity in the way
the national courts and the EPO interpret the [EPC].”
87. Further, while national courts should normally follow the established
jurisprudence of the EPO, that does not mean that we should regard the reasoning
in each decision of the Board as effectively binding on us. There will no doubt
sometimes be a Board decision which a national court considers may take the law
in an inappropriate direction, misapplies previous EPO jurisprudence, or fails to
take a relevant argument into account. In such cases, the national court may well
think it right not to apply the reasoning in the particular decision. While
consistency of approach is important, there has to be room for dialogue between a
national court and the EPO (as well as between national courts themselves).
Nonetheless, where the Board has adopted a consistent approach to an issue in a
number of decisions, it would require very unusual facts to justify a national court
not following that approach.
88. In the present instance, as discussed above, there has been little helpful
domestic guidance as to the application of Article 57 to patents for biological
material, but there have been a number of decisions of the Board which have
addressed the topic and which at least purport to adopt a consistent approach to the
issue. It is true that there is no decision of the Enlarged Board on the instant point,
but there was no such decision on the point at issue in Generics [2009] RPC 13.
But, again as in that case, there is what may be described, at its lowest, as an
intended consistent approach to the issue in a number of carefully considered
decisions of the Board. Further, it is not irrelevant to mention that there is unlikely
to be a decision of the Enlarged Board on the instant point in the near future, as the
Board refused to make a reference in T 0898/05, para 33.
89. Further, while there has been some attack on the reasoning of the Board in
its decision on the instant Patent, T 0018/09, both in the judgment of Jacob LJ in
the Court of Appeal ([2010] RPC 14, paras 146, 155 and 156) and in the
submissions on behalf of Eli Lilly in this court, there has been no attempt either
Page 29
here or below to suggest that the reasoning in the earlier decisions of the Board
was wrong, save that Mr Waugh QC, on behalf of Eli Lilly, did make the point that
decisions on appeal from the ED, perhaps particularly T 0898/05, should carry less
weight as they were unopposed, or ex parte.
90. In relation to the Board’s assessment of the factual and expert evidence in a
particular ex parte appeal, I can see the force of the point. But I am unimpressed
with the point in so far as it is invoked in relation to the applicable principles. In
particular, I would reject the implicit suggestion that the Board has been too
favourable to patentees in some of the decisions discussed above, as a result of the
hearing being ex parte. First, all the decisions discussed above appear to me to
demonstrate a consistent approach to the issue raised on this appeal. Secondly,
those decisions include an appeal from the OD, namely T 0604/04. Thirdly, the
decision of the Board in relation to the instant Patent was from the OD, after strong
opposition from Eli Lilly, and, far from resulting in the Board modifying its
position, it is Eli Lilly’s case in this court that the Board went further in this case in
favour of the patentee than in any appeal from the ED.
91. In these circumstances, it seems to me to be right to take the law as being
that laid down in the Board’s jurisprudence I have discussed. But, of course, as
explained by Lord Hoffmann and Lord Walker in the passages quoted above, this
does not necessarily mandate the same outcome as the Board arrived at in T
0018/09.
92. It is unlikely that the Board and Kitchin J received very different arguments
in the present case, in the light of the reasoning in the two decisions, and the fact
that the parties in the two sets of proceedings were the same. It is less clear how
similar the evidence before each tribunal was: the witnesses were different, and
there was at least one further expert witness statement (on behalf of HGS) before
the Board which post-dated Kitchin J’s judgment. Further, unlike before Kitchin J,
there was no cross-examination of witnesses before the Board.
93. As Jacob LJ said at [2010] RPC 14, paras 25-26, citing the well-known
observations of Lord Hoffmann in Biogen Inc v Medeva plc [1997] RPC 1, 45,
“appeals are conducted on the evidence and materials before the court of first
instance” and “the Court of Appeal gives very considerable deference to the
findings of fact of the first instance court. So also to its value-judgments”. That is
all the more true of appeals to this court from the Court of Appeal, especially
where, as here, there are concomitant findings (i.e. where the Court of Appeal has
upheld the trial judge’s findings of fact and value judgments).
Page 30
94. In these circumstances, the question which needs to be decided is whether,
as the Court of Appeal held, Kitchin J followed the principles laid down by the
Board’s jurisprudence. If he did, then it seems to me that it would be inappropriate
to interfere with his conclusion that the Patent did not satisfy the requirements of
Article 57, unless the conclusion was one which he could not reasonably have
reached. If he did not, then things would stand on a very different footing.
95. Before turning to that question, however, it is appropriate to mention
another, and rather wider, reason for consistency of approach to patents in the
biological field.
Consistency and policy: the wider picture
96. The BioIndustry Association (“the BIA”), which has intervened in these
proceedings, describes itself as “a trade association for innovative enterprises in
the UK’s bioscience sector” and its membership extends to hundreds of companies
with an aggregate turnover in 2010 of about £5.5bn, and around 36,000 employees.
97. The requirements of clarity and certainty in this area of law are emphasised
by the BIA. As its submissions also explain, after the discovery of a naturally
occurring molecule, particularly a protein and its encoding gene, a large amount of
research and development is required before there can be any therapeutic benefit.
It is therefore important for bioscience companies to be able to decide at what
stage to file for patent protection. Thus,
“If the application is filed early, … [t]he company will be left with
no patent protection, but would have disclosed its invention in the
published patent application to competitors. If the application is filed
late, there is a risk in such a competitive environment where several
companies may be working on the same type of research projects,
that a third party will already have filed a patent application covering
the same or a similar invention, in which case the company may not
be able to gain any patent protection for its work and by continuing
their programme they may risk infringing that third party’s patents.
In both cases, the company will have lost much of the benefit of its
costly research and development.”
98. Similarly, funding for research and development on the potential
therapeutic value of a newly discovered and characterised protein or its antibodies
is dependent on the funders being reasonably confident that the patent (or patent
application) concerned will be reasonably safe from attack (or likely to be
Page 31
granted). It is also relevant that bioscience companies attract investment by
reference to their patent portfolios, which gives rise to the same need for certainty.
99. As the BIA suggests, it is worth remembering the purpose of the patent
system, namely to provide a temporary monopoly as an incentive to innovation,
while at the same time facilitating the early dissemination of any such innovation
through an early application for a patent, and its subsequent publication. Although
this is true in any sector, it has particular force in the pharmaceutical field, where
even many of those who are sceptical about the value of intellectual property rights
accept that there is a public interest in, and a commercial need for, patent
protection.
100. For obvious reasons, the BIA has not set out to support either of the two
parties to this appeal in its trenchant written submissions in these proceedings.
However, it does suggest that if we agree with the reasoning of the Court of
Appeal there is at least a risk that it will “make it appreciably harder for patentees
to satisfy the requirement of industrial applicability in future cases.” If that were
so, it is suggested that this “would cause UK bioscience companies great difficulty
in attracting investment at an early stage in the research and development process”.
101. This consequence is said to arise from the reasoning of the Court of Appeal
(and hence of Kitchin J), on the basis that there will normally be a need to conduct
tests to provide experimental data to establish to the standard they require that a
protein (or its antagonists) have therapeutic use. This in turn is said to lead to two
problems. First, such tests will or may involve clinical work, which, as I
understand it, would be hard to keep confidential, especially in the age of the
internet. Secondly, such tests would often be expensive to run, and, as already
mentioned, funding would be hard to obtain for a project of this sort which had no
protection in the form of a patent application.
102. Having said this, the BIA accepts that it would be wrong in principle to
enable applications for patents to be made when the applicant can reveal no more
than “a vague indication of possible objectives that might or might not be
achievable by carrying out further research”. After all, as the BIA also states, the
purpose of the patents system is not “to reserve an unexplored field of research for
the applicant nor to give the patentee unjustified control over others who are
actively investigating in that area and who might eventually find ways actually to
exploit it.”
Page 32
Did the courts below follow the Board’s jurisprudence?
103. As already mentioned, despite its very wide-ranging and generalised
suggestions as to the uses to which Neutrokine-α and its antibodies might be put,
over and above revealing the existence and structure of the new protein and its
encoding gene, the only relevant teaching of the Patent ultimately arises from its
teaching as to the tissue distribution of Neutrokine-α, its expression in T-cell and
B-cell lymphomas, and the fact that it is a member of the TNF ligand superfamily.
Accordingly, the question is whether the Judge was right, or at least entitled, to
conclude that the inferences which would have been drawn from this in 1996
would not have been enough to satisfy Article 57.
104. The determination of that issue, as I see it, ultimately involves focussing on
the Judge’s conclusion at [2008] RPC 29, para 234, quoted at para 75 above. In
that passage, he concluded that the fact that the description in the Patent, even
taken together with knowledge which should be attributed to its addressee, neither
“reveal[ed] how [Neutrokine-α] could be used to solve any particular problem” nor
“identified any disease or condition which [it] could be used to diagnose or treat”
was fatal to the patent’s validity. He considered that the functions of Neutrokine-α
“were, at best, a matter of expectation and then at far too high a level of generality
to constitute a sound or concrete basis for anything except a research project”.
105. My initial reaction, like that of the Court of Appeal, was that this was a
conclusion to which Kitchin J, as the trial judge, who had heard a great deal of
evidence, which he had impressively and cogently analysed, was entitled to come,
and with which it would be inappropriate to interfere. Standing back, it also
seemed to be a conclusion which could be said to accord with good sense. As he
held in the next paragraph of his judgment (also quoted in para 75 above), it
required what may fairly be characterised as a research project to enable the
therapeutic qualities of Neutrokine-α to be identified, or, as HGS would put it, to
be confirmed.
106. However, on further reflection, like Lord Hope, I have come to the
conclusion that the basis upon which the Judge decided the issue was not
consistent with the approach adopted by the Board in the decisions which are
discussed above.
107. The essence of the Board’s approach in relation to the requirements of
Article 57 in relation to biological material may, I think, be summarised in the
following points:
Page 33
The general principles are:
(i) The patent must disclose “a practical application” and “some
profitable use” for the claimed substance, so that the ensuing
monopoly “can be expected [to lead to] some … commercial
benefit” (T 0870/04, para 4, T 0898/05, paras 2 and 4);
(ii) A “concrete benefit”, namely the invention’s “use … in industrial
practice” must be “derivable directly from the description”,
coupled with common general knowledge (T 0898/05, para 6, T
0604/04, para 15);
(iii) A merely “speculative” use will not suffice, so “a vague and
speculative indication of possible objectives that might or might
not be achievable” will not do (T 0870/04, para 21 and T
0898/05, paras 6 and 21);
(iv) The patent and common general knowledge must enable the
skilled person “to reproduce” or “exploit” the claimed invention
without “undue burden”, or having to carry out “a research
programme” (T 0604/04, para 22, T 0898/05, para 6);
Where a patent discloses a new protein and its encoding gene:
(v) The patent, when taken with common general knowledge, must
demonstrate “a real as opposed to a purely theoretical possibility
of exploitation” (T 0604/04, para 15, T 0898/05, paras 6, 22 and
31) ;
(vi) Merely identifying the structure of a protein, without attributing
to it a “clear role”, or “suggest[ing]” any “practical use” for it, or
suggesting “a vague and speculative indication of possible
objectives that might be achieved”, is not enough (T 0870/04,
paras 6-7, 11, and 21; T 0898/05, paras 7, 10 and 31);
(vii) The absence of any experimental or wet lab evidence of activity
of the claimed protein is not fatal (T 0898/05, paras 21 and 31, T
1452/06, para 5);
(viii) A “plausible” or “reasonably credible” claimed use, or an
“educated guess”, can suffice (T 1329/04, paras 6 and 11, T
0640/04, para 6, T 0898/05, paras 8, 21, 27 and 31, T 1452/06,
para 6, T 1165/06 para 25);
(ix) Such plausibility can be assisted by being confirmed by “later
evidence”, although later evidence on its own will not do (T
1329/04, para 12, T 0898/05, para 24, T 1452/06, para 6, T
1165/06, para 25);
(x) The requirements of a plausible and specific possibility of
exploitation can be at the biochemical, the cellular or the
biological level (T 0898/05, paras 29-30);
Where the protein is said to be a family or superfamily member:
(xi) If all known members have a “role in the proliferation,
differentiation and/or activation of immune cells” or “function in
controlling physiology, development and differentiation of
mammalian cells”, assigning a similar role to the protein may
Page 34
suffice (T 1329/04, para 13, T 0898/05, para 21, T 1165/06,
paras 14 and 16, and T 0870/04, para 12);
(xii) So “the problem to be solved” in such a case can be “isolating a
further member of the [family]” (T 1329/04, para 4, T 0604/04,
para 22, T 1165/06, paras 14 and 16);
(xiii) If the disclosure is “important to the pharmaceutical industry”,
the disclosure of the sequences of the protein and its gene may
suffice, even though its role has not “been clearly defined” (T
0604/04, para 18);
(xiv) The position may be different if there is evidence, either in the
patent or elsewhere, which calls the claimed role or membership
of the family into question (T 0898/05 para 24, T 1452/06, para
5);
(xv) The position may also be different if the known members have
different activities, although they need not always be “precisely
interchangeable in terms of their biological action”, and it may be
acceptable if “most” of them have a common role (T 0870/04,
para 12, T 0604/04, para 16, T 0898/05, para 27).
108. As already explained, Kitchin J concluded that (a) the Patent discloses
Neutrokine-α as a new member of the TNF ligand superfamily; (b) all known
members of the superfamily had pleiotropic effects, (c) there were some features
which all those known members shared, such as expression by T-cells and a role in
the regulation of T-cell proliferation and T-cell mediated responses; (d) however,
there were other features which some family members had, but others did not; (e)
it would be anticipated that the activities of Neutrokine-α “might relate to T-cells
and, in particular, be expressed on T-cells and be a co-stimulant of B-cell
production; that it might play a role in the immune response and in the control of
tumours and malignant disease; that it might have an effect on B-cell
proliferation”; (f) subsequent research has confirmed that was indeed the case; (g)
there was a search for new members of the family as they were of interest to the
pharmaceutical industry.
109. In those circumstances, it seems to me that, subject to dealing with a
number of specific arguments to the contrary, the disclosure of the existence and
structure of Neutrokine-α and its gene sequence, and its membership of the TNF
ligand superfamily should have been sufficient, taking into account the common
general knowledge, to satisfy the requirements of Article 57, in the light of the
principles which I have attempted to summarise in para 107 above. Points (viii),
(ix) and (x) appear to apply so far as the plausibility of at least some of the claims
are concerned, and points (xi), (xii) and (xiii) all appear to be satisfied, given the
evidence in relation to the TNF ligand superfamily (and point (xiv) cannot be
invoked by Eli Lilly).
Page 35
110. Like Lord Hope, I derive considerable assistance from the approach set out
at T 0018/09, para 22, which appears to me to be entirely consistent with the
Board’s earlier jurisprudence (as summarised in para 107 above), and the
application in the ensuing four paragraphs, of that approach to the Board’s view of
what constituted the centrally relevant facts, which (subject to the arguments
considered in the next section of this judgment) do not appear to me to be
inconsistent with the findings made by Kitchin J.
111. As Lord Hope says at para 152 below, the Board’s conclusion was
effectively this, that the disclosure of what was accepted to be a new member of
the TNF ligand superfamily (coupled with details of its tissue distribution)
satisfied Article 57, because all known members were expressed on T-cells and
were able to co-stimulate T-cell proliferation, and therefore Neutrokine-α would be
expected to have a similar function. This conclusion was supported, or reinforced,
by the statement that Neutrokine-α was expressed in B-cell and T-cell lymphomas
(referred to in T 0018/09, para 30), and indeed by the interest and effort in the
pharmaceutical industry in finding a new member of the superfamily (as explained
by Kitchin J at [2008] RPC 29, paras 72-74).
The arguments in support of the conclusion reached below
112. The first argument to the contrary is based on the fact that the members of
the TNF ligand superfamily were known to have pleiotropic effects. On behalf of
Eli Lilly, Mr Waugh QC therefore relies on point (xv) i.e. that the claim to a new
member of a superfamily is not good enough because the known members of the
family have different activities. In my opinion, that point does not apply in a case
where all known members of the superfamily also manifest to a significant degree
common activities which are, of themselves, enough to bring the patent within the
ambit of points (xi), (xii) and (xiii).
113. Given that the fact that all known family members have sufficient common
features to satisfy those points can justify a patent for a new member, it would
seem somewhat bizarre if the fact that they had additional, but differing, qualities,
should preclude the grant of such a patent. The disclosure of a new member would
not only be of greater potential value than if the additional qualities did not exist,
but the reason for the grant of the patent is the perceived value of a new member
because of the common features of all known members, a feature which is
unaffected by the additional qualities.
114. I believe that this conclusion is supported not only by the Board’s decision
in this case, but also by the Board’s conclusion in T 0898/05 that the disclosure of
Zcytor1 satisfied Article 57, in circumstances where its predicted activity was
Page 36
based on its membership of a family. As already explained, the Board stated that
“although none of these members are precisely interchangeable in terms of their
biological action, there is considerable redundancy of action as well as an ability to
elicit, under certain conditions, similar biological responses” – T 0898/05, para 27.
115. I also derive support from the fact that the Board in T 0604/04 was prepared
to uphold a patent granted in respect of a novel molecule on the basis that it was a
member of a family, only “most of” whose known members “were thought to play
[a role as] mediators of the inflammatory response”; nonetheless, it was held that
the evidence established that it was “reasonable to conclude that the [claimed]
polypeptides which exhibit the characteristics of receptors of members of the
PF4A family of cytokines would have been regarded as important to the
pharmaceutical industry, ie that industrial applicability may be acknowledged”
(see T 0604/04, paras 16-18).
116. A second argument raised against validity is the unsatisfactory drafting of
the Patent (mentioned by the Court of Appeal at [2010] RPC 14, para 148). If the
Judge had found that the drafting of the specification of the Patent was so
confusing and potentially misleading that the skilled reader would have been put
off the scent in relation to what would otherwise have been appreciated from
common general knowledge and reading the literature as to the potential and
plausible uses to which the disclosure could be put, that may well have been a
problem for HGS’s case. However, although the Judge was (in my view, rightly)
critical about the drafting of the specification, he did not anywhere in his full and
careful judgment say, or even suggest, that its wide-ranging prolix contents would
have actually diverted the notional addressees, the appropriately skilled persons,
from what they would otherwise have understood the Patent to be revealing, in the
light of what was appreciated about the properties of the known members of the
TNF ligand superfamily. Indeed, Mr Thorley QC, for HGS, identified passages in
the evidence of Professor Saklatvala, which would have made such a finding
difficult to justify.
117. Mr Waugh’s submission that the extravagant and wordy claims of the
specification should count against HGS as a matter of policy has some attraction.
However, I refer again to the Board’s comments at T 0018/09, para 27, cited in
para 6 above. The drafting of a patent is a ticklish business, no doubt particularly
in some types of case, of which biological patents may well be an example, not
least because it is a fast developing field, with substantial commercial and
scientific pressures.
118. In the end, the question is whether the drafting of the Patent would actually
have diverted the notional addressees from what their search of the literature,
coupled with common general knowledge, would otherwise have led them to
Page 37
understand represented the teaching of the Patent. The Board held that it would not
have done so – see at T 0018/09, para 26. Given (a) the fact that the Judge made no
express finding that there would have been such a diversion, (b) the evidence of
Professor Saklatvala suggested that there would have been no such diversion, and
(c) the way in which the Judge expressed himself at [2008] RPC 29, paras 232 and
234 (quoted respectively at paras 70 and 75 above), I would infer that Kitchin J did
not think differently. That is unsurprising, given the fact that there was fairly
intense interest in the TNF ligand superfamily as the Judge held at [2008] RPC 29,
paras 72 and 74 (quoted at para 26 above), and the fact that there is nothing in the
description which positively points away from what was known about the family.
119. A third argument is based on the Judge’s remarks at [2008] RPC 29, paras
176 and 234, that the disclosure in the Patent as to the uses of Neutrokine-α, even
when taken together with common general knowledge, was no more than
“speculative” and did not give rise to an “immediate concrete benefit”– i.e.
invoking on points (ii) and (iii). This argument (which was also relied on by the
Court of Appeal – see at [2010] RPC 14, para 132) proceeds on the implicit
assumption that the disclosure of the Patent as summarised in para 108 above is
not sufficient in itself to satisfy the requirements of Article 57.
120. However, if, as I consider, the effect of the Board’s jurisprudence is that the
sort of disclosure summarised in para 108 above does justify patentability, then the
fact that the “plausible” predictions for the use of the invention could also be said
to involve speculation takes matters no further. If the known activities of the TNF
ligand superfamily were enough to justify patentability for the disclosure of a
novel molecule (and its encoding gene) which was plausibly identified as a
member of that family, the fact that further work was required to see whether the
disclosure actually had therapeutic benefits does not, at least without more,
undermine the validity of a patent. In other words, in agreement with Lord Hope, I
think that the approach of the Board in this case, in particular at T 0018/09, paras
22-30, appears more in line with the previous EPO jurisprudence than the
approach of Kitchin J and the Court of Appeal.
121. The Court of Appeal made much of the Board’s statement that a patent
should yield an “immediate concrete benefit” (see at [2010] RPC 14, paras 146,
149, 155 and 156). I certainly accept that, in some cases, different tribunals can
and will legitimately come to different views as to whether a particular claimed
invention can satisfy the requirement of providing an “immediate concrete
benefit”. However, I am not persuaded that such an argument is open to Eli Lilly
in this case. In my view, the Court of Appeal’s approach, like that of the Judge,
was implicitly predicated on the mistaken basis that it was not enough for the
Patent to satisfy the requirements of points (xi) to (xiii).
Page 38
122. Further, at least in the context of the present case, I do not consider that the
Courts below gave proper weight to points (viii), (ix) and (x). In particular, in my
judgment, the Court of Appeal did not approach the concept of plausibility
consistently with the jurisprudence of the Board. That is well demonstrated by
Jacob LJ’s observation at [2010] RPC 14, para 112, that “[i]t is not good enough to
say this protein or any antibody to it probably has a pharmaceutical use. Such a
statement is indeed plausible, but is of no real practical use. You are left to find out
what that use is.” If the statement “is indeed plausible”, then, in the absence of any
reason to the contrary, it at least prima facie satisfies the requirements of Article
57 according to the Board.
123. I appreciate that the dividing line between “plausibility” and “educated
guess”, as against “speculation”, just like the contrast between “a real as opposed
to a purely theoretical possibility of exploitation”, can be difficult to discern in
terms of language and application, and is a point on which tribunals could often
differ. (I might add that the notion that the dividing line is not very satisfactory is
illustrated by the fact that, at one point in his evidence, Professor Saklatvala
effectively equiparated speculation with an educated guess.) However, as a result
of the decisions discussed above, the Board’s approach to patents such as that in
this case is, I believe, tolerably clear.
124. I also consider that the Judge did not give sufficient weight to point (x), in
that he concentrated on the absence of firm evidence of specific therapeutic roles,
as opposed to the other roles of Neutrokine-α. This is well demonstrated by his
reliance in what is perhaps the crucial paragraph of his judgment, [2008] RPC 29,
para 234, on the fact that “[n]either the Patent nor the common general knowledge
identified any disease or condition which Neutrokine-α could be used to diagnose
or treat”. He did not, in this context, take into account the roles at other levels
which could be attributed to Neutrokine-α as a result of its membership of the TNF
ligand superfamily and their known activities. (The same point may be made about
Jacob LJ’s judgment at [2010] RPC 14, paras 112 and 119, quoted by Lord Hope
at para 150 below).
125. Eli Lilly also relied on the Judge’s finding at [2008] RPC 29, para 234 that
the precise uses to which Neutrokine-α could be put would, on the basis of the
disclosure in the Patent, involve “a research project”, effectively raising point (iv).
Although the Court of Appeal also relied on this point (see at [2010] RPC 14, para
149), it does not appear to me to be maintainable, essentially for the reason given
in the immediately preceding paragraphs of this judgment.
126. I draw support for this conclusion from the Board’s third reason for
rejecting a similar argument raised by Eli Lilly in the EPO, namely that “the
skilled person would not have been able to reproduce [the activities of Neutrokine-
Page 39
α as described in the Patent] without the undue burden of undertaking a research
programme”. The Board said that the disclosure of the Patent “may represent a
valid basis for a possible industrial application. In particular, the inhibition of costimulation and/or proliferation of lymphocytes might be prima facie of relevance
for certain immune diseases” – in T 0018/09, para 29. If a patent advances an
appropriately plausible function for the claimed protein, then the question of undue
burden has to be considered in relation to the making of the protein, as the Board’s
observation at T 0604/04, para 22 that “the patent specification provides adequate
experimental instructions for the skilled person to be able to reproduce without
undue burden the [claimed] polypeptides” shows.
127. A further argument, which is really another formulation of the same point,
is that, as was emphasised by the Court of Appeal at [2010] RPC 14, para 152, one
important reason why Kitchin J reached a different conclusion from the Board was
because he concluded that the necessary assays to determine the precise role and
potential of the patent’s disclosure would be a “complex task”, whereas the Board
thought it would simply involve “standard assays” – compare [2008] RPC 29, para
77, and T 0018/09, para 29 respectively.
128. As the Court of Appeal rightly observed, such a conflict is entirely
legitimate and understandable, in view of the different evidence, the benefit of
cross-examination, and/or the room for difference of opinion between two
tribunals. In another case, such a difference in assessment of the evidence could
well justify a difference in outcome. But not in this case. Once one concludes that
the effect of the Board’s jurisprudence is that, in the light of the common general
knowledge, the disclosure of Neutrokine-α as a member of the TNF ligand
superfamily (coupled with its amino acid and encoding gene sequences and the
tissues in which it is expressed), the claims in relation to the invention’s potential
satisfy Article 57. As a result, the relevance of the degree of effort needed in
relation to any subsequent work falls away. (The same point undermines Eli
Lilly’s reliance on a number of other small differences between the findings of the
Judge and the Board on the expert evidence).
Conclusion on the main issue, Article 57
129. Accordingly, I would allow HGS’s appeal on the issue as to whether the
Patent satisfied the requirements of Article 57, and hold that it does. As explained,
I have reached this conclusion by applying my understanding of the jurisprudence
of the Board to the facts found by Kitchin J. However, particularly as I have stated
in para 105 above that there is good sense in the contrary conclusion reached by
the Judge and the Court of Appeal, it is right to emphasise that there is also good
sense in the result which, at least in my view, is mandated by the Board’s approach
to the law in this field.
Page 40
130. Just as it would be undesirable to let someone have a monopoly over a
particular biological molecule too early, because it risks closing down competition,
so it would be wrong to set the hurdle for patentability too high, essentially for the
reasons advanced by the BIA and discussed in paras 97-100 above. Quite where
the line should be drawn in the light of commercial reality and the public interest
can no doubt be a matter of different opinions and debate. However, in this case,
apart from the fairly general submissions of the parties and of the BIA, we have
not had any submissions on such wider policy considerations.
131. That is not the end of this appeal, for two reasons. First, there is an
argument based on insufficiency: Eli Lilly contends that, even if the Patent
satisfies Article 57, it is invalid on the ground of insufficiency, an argument which
largely turns on an issue of interpretation, on which the Judge found against Eli
Lilly. Secondly, if Eli Lilly’s insufficiency argument fails, there remain some
points decided by Kitchin J and not determined by the Court of Appeal, which it is
agreed should be remitted to the Court of Appeal.
The contention that claim 1 of the Patent is insufficient
132. The Judge held that, in addition to failing to comply with Article 57, the
Patent was invalid on the ground of insufficiency, namely that “the specification
does not disclose the invention clearly enough and completely enough for it to be
performed by a person skilled in the art” – [2008] RPC 29, para 238. The basis for
this conclusion was explained in these terms by the Judge at [2008] RPC 29, para
259: “it would have required a research programme and been far from routine for
the skilled person to produce a candidate pharmaceutical or diagnostic composition
comprising an antibody to Neutrokine-a, that is to say the pharmaceutical or
diagnostic equivalent of a workable prototype”.
133. Although the Court of Appeal did not consider this point, Jacob LJ did say
at the end of his judgment, that he “rather suspect[ed]” that the insufficiency
argument “would go hand-in-hand with Article 57” – [2010] RPC 29, para 159.
Subject to one point, which turns on the meaning of Claim 1 (as well as some of
the other claims), it seems to me that that must be correct. If Claim 1 is simply to
the encoding gene of Neutrokine-α, then, subject to any other points which have
yet to be decided by the Court of Appeal, the reason why I consider the Judge and
the Court of Appeal were wrong to hold that Article 57 is not satisfied is the same
reason for holding the claim to be sufficient.
134. In T 0898/05, para 6, the Board explained the close connection, indeed
overlap, between Article 57 and sufficiency in a passage, of which the first
sentence has already been quoted:
Page 41
“It should not be left to the skilled reader to find out how to exploit
the invention by carrying out a research programme. [This]
corresponds to the requirements of Articles … 57 (the need to
indicate how to exploit the invention), and 83 EPC (the need to
provide a sufficient disclosure of the claimed invention). All those
provisions reflect the basic principle of the patent system that
exclusive rights can only be granted in exchange for a full disclosure
of the invention.”
135. However, Eli Lilly contend that the Judge was wrong to hold, as he did at
[2008] RPC 29, para 137, that claim 1 “is now limited to an isolated nucleic acid
molecule comprising one of two sequences which are specifically disclosed and
are not defined by reference to their activity”. They contend that, on its true
construction, the claim requires the claimed protein, or polypeptide to demonstrate
what is referred to in the specification as “Neutrokine-α activity”, and that such
activity is too imprecisely defined and too difficult to establish, following the
teaching of the Patent and any prior art, to be sufficient.
136. Claim 1, which I have not so far set out, is in the following terms:
“An isolated nucleic acid molecule comprising a polynucleotide
sequence encoding a Neutrokine-α polypeptide wherein said
polynucleotide sequence is selected from the group consisting of:
(a) a polynucleotide sequence encoding the full length
Neutrokine-α polypeptide having the amino acid
sequence of residues [as defined]; and
(b) a polynucleotide sequence encoding the
extracellular domain of the Neutrokine-α polypeptide
having the amino acid sequence of residues [as
defined]”.
137. In my view, the Judge was right to conclude that the reference to a
“Neutrokine-α polypeptide” was simply a reference to the polypeptide, and did not
incorporate a provision that the polypeptide had certain activities. There is no
express reference in the claim to the polypeptide having any specific activities, and
I see no grounds for implying into claim 1 such a provision. There is no
commercial or technical reason for implying such a provision, and, of course, it is
well established that a term is only to be implied into a written document if there
are strong reasons in support.
Page 42
138. It is true that the phrase “Neutrokine-α” before the word “polypeptide” is
strictly redundant on this basis, but that is no reason for giving the phrase an
unnatural meaning. The fact that the phrase is strictly redundant does not alter the
fact that its natural meaning is to describe the polypeptide by the name which the
specification has given to it. It is also true that the specification refers to the
claimed invention involving “Neutrokine-α activity” in more than one place.
However, the very fact that this expression is not included in claim 1, when it is (to
some extent) defined and, in more than one place used, in the specification
suggests that it is not intended to apply to the claim.
139. Accordingly, I would dismiss Eli Lilly’s cross-appeal on the insufficiency
issue.
Conclusion
140. It follows from this that, at least in my opinion, HGS’s appeal on the Article
57 issue should be allowed, Eli Lilly’s cross-appeal on the insufficiency issue
should be dismissed, and the case should be remitted to the Court of Appeal to deal
with the outstanding issues.
LORD HOPE
141. This is a difficult and troublesome case. It is well known that modern
techniques in the field of biomedical science offer immense benefits in the
promotion of human health, particularly in the combating of a wide range of
degenerative diseases previously thought to be incurable and in the provision of
techniques for the effective treatment of cancers. As the BioIndustry Association
has pointed out in its written intervention, patent portfolios are often the most
valuable asset of companies in the bioscience industry. So assessments of the value
of a bioscience company’s patent portfolio are likely to be a key consideration in
deciding whether to acquire or invest in such a company. This in turn affects the
funding that is made available for research and development, without which
effective progress in putting a patented invention to practical use is likely to be
very limited. The evaluation of a patent specification for this purpose will depend
on whether it discloses an invention that is reasonably capable of industrial
application.
142. There is thus much common ground between the aims of those whose
funding is essential for the sustained programme of research and development that
will almost always have to be carried out before a product can be placed on the
Page 43
market and the tests that the law lays down for patentability. Article 52(1) of the
European Patent Convention provides:
“European patents shall be granted for any inventions, in all fields of
technology, provided that they are new, involve an inventive step
and are susceptible of industrial application.”
Article 57 provides:
“An invention shall be considered as susceptible of industrial
application if it can be made or used in any kind of industry,
including agriculture.”
These articles were implemented in domestic law in sections 1(1)(c) and 4 of the
Patents Act 1977. As the tests in both articles are the same, it is convenient to refer
to the issue which they raise as the article 57 issue. It is plain that the standard to
be applied for determining whether this test has been satisfied must in principle be
the same for patents in the bioscience industry as for those in other fields.
143. The bioscience industry is particularly dependent, however, on funding for
long term research and development. It is commonplace for those who need money
for these activities to have to look to other organisations to provide it. The tests
that must be applied are necessarily very rigorous, and it may require many years
of investment before a product can be declared safe for use in the promotion of
health in humans. The gap between the point of initial research and the point
where the discovery is ready to be developed by the pharmaceutical industry can
be very wide. Various steps along this uncertain road can be identified in the
present case. First, there is the inventive step itself. In this case it revealed the
existence of Neutrokine-α, a previously unknown member of the TNF ligand
superfamily. The characteristics of the newly discovered protein had then to be
examined and analysed. In this case the task was to determine whether the
Neutrokine-α molecule had characteristics that offered the prospect of influencing
biological mechanisms in the same way as other members of the superfamily. If
that could be achieved, there would then have to follow a large amount of research
and development before the molecule could be deployed therapeutically. The
question that this case raises is how far along that road the process must go before
the invention can be held to be susceptible of industrial application and patented.
144. The core of HGS’s argument for the industrial application of Neutrokine-α
was identified by their expert witness Professor Noelle in his first witness
statement. In para 72 he said:
Page 44
“In my opinion, the inventive concept of the Patent is the
identification of a new member of the TNF ligand superfamily,
which the inventors named Neutrokine-α, and elucidation of its
nucleic acid and amino acid sequences. Once the nucleic acid
sequence of a novel member of the TNF ligand superfamily became
available, it opened up the field such that it was possible to use well
known techniques to express the protein, analyze the protein,
develop antibodies and make therapeutics and diagnostics for
diseases associated with under or over expression of the protein.”
In para 75 he said that disclosure of this novel gene and its encoded protein, and
the provision of information about its structure and activities enabled the making
of products which could be used in studying its role in disease and for the
development of potential diagnostic and therapeutic applications. In para 79 he
said that, since the activities ascribed to Neutrokine-α in the Patent were consistent
with those activities possessed by other TNF superfamily members, the skilled
addressee would consider the activities of Neutrokine-α described in the Patent as
specific and also credible. His point, in short, was the description of the protein,
when taken with common knowledge as to the techniques that could be applied to
it, was sufficient to show that it was possible to use it in the respects that he
identified. For him the fact that it opened up the field indicated that it was
susceptible of industrial application.
145. The significance of his observations can be seen by comparing what Jacob
LJ said in the Court of Appeal with the judgment of the Technical Board of Appeal
(“TBA”) of the European Patent Office (“the EPO”) in the present case, which was
published on 1 December 2009: Neutrokine-α/Human Gennome Sciences Inc T
0018/09. The Board reached a different conclusion from that which the trial judge,
Kitchin J, had reached on 31 July 2008 when he held that the claimed invention
was not susceptible of industrial application at the date of the Patent: [2008] RPC
29, para 237. In the Court of Appeal Jacob LJ attributed this to the fact that the
Board was working on different evidence and was using a different procedure:
[2010] RPC 14, para 157; see also para 154, where he noted that the judge’s
findings were arrived at following an extensive examination of the evidence. I
think that, while both of these things are true, the conclusion ought to have been
that tests that the Board applied were materially different from those applied by the
judge and by the Court of Appeal.
146. In para 22 of the reasons for its decision that the Patent provided a concrete
technical basis for the skilled person to recognise a practical exploitation of the
claimed invention in industry, the TBA said:
Page 45
“22. As pointed out in T 870/04 of 11 May 2005 [Max-Planck] (cf in
particular points 5 and 6 of the Reasons), in many cases the
allocation of a newly found protein to a known protein family with
known activities suffices to assign a specific function to the protein
because normally the members of the family share a specific
function. This may be a well-characterized and perfectly understood
function which provides in a straightforward manner enough support
for industrial applicability. In such cases, the ‘immediate concrete
benefit’ is manifest. In other cases, where the members of a protein
family have different, pleiotropic effects which may even be
opposite and neither completely characterized nor understood, no
effect can be assigned to a new member without relying on some
experimental data. Between these two extreme situations, a variety
of other situations may arise for which a detailed examination of all
the facts may be required. Indeed, this is the case for the TNF ligand
superfamily.”
147. The expression “superfamily” does not appear to have a precise meaning, as
Jacob LJ observed in the Court of Appeal: [2010] RPC, para 73. As he explained,
the general idea is that it includes not only very closely homologous compounds
but also those with rather less homology. The contrast is between a closely knit
family with known activities, and a wider family with a variety of different,
pleiotropic effects: cousins, second cousins, distant uncles and so on. The same
contrast between two extremes is to be found in para 22 of the TBA’s judgment.
But the important point that emerges from its comment that it was dealing with a
superfamily is to be found in the last two sentences. This case is not one where the
different, pleiotropic effects are so poorly understood that it is plain that no effect
can be assigned to a new member without relying on some experimental data. That
is not true of the TNF ligand superfamily as it lies between the two extremes.
148. So a detailed examination of all the facts is needed before it can be
determined whether or not an effect can be assigned to this particular new member.
As the TBA said in T 0898/05 (7 July 2006) Hematopoietic cytokine
receptor/ZymoGenetics, para 22, the probative value of the claimed invention must
be examined on a case-by-case basis regarding the nature of the invention and the
prior art relating thereto:
“Such methods of analysis are increasingly becoming an integral part
of scientific investigations and can often allow plausible conclusions
to be made regarding the function of a product before it is actually
tested.”
Page 46
In other words, that examination may be enough in itself to show, without further
experiments, that what the TBA refers to as “a specific function” can be assigned
to the new member of the family. This is because that “well-characterized and
perfectly understood function” is shared by other members of the family which it
has been shown to belong to.
149. In paras 6-8 of its judgment in ZymoGenetics the TBA contrasted a product
whose structure was given but whose function was undetermined or obscure or
only vaguely indicated with one which was “definitely described and plausibly
shown to be usable”. In the former case, the granting of a patent might give the
patentee unjustified control over others who were actively investigating in that
area and who might eventually find ways to exploit it. In the latter, because it was
plausibly shown to be “usable”, it might be considered to display concrete benefits.
As these benefits are assumed not yet to have been confirmed by research, the
exercise that these passages indicate is necessarily one of prediction. That is why
the Board used the word “plausibly”. I would not quarrel with Jacob LJ’s
comment, after consulting the Shorter Oxford English Dictionary, that the sense
that word conveys is that there must be some real reason for supposing that the
statement is true: para 111. The important point, however, is that the standard is
not any higher than that. Further experiments are not needed if sufficient
information is provided in the description, when common general knowledge is
taken into account, to show that a positive answer can be given to the question
whether a profitable use can readily be identified: ZymoGenetics, para 20.
150. In para 102 of his judgment in the Court of Appeal, however, having
reviewed the EPO case law, Jacob LJ said:
“It is clear from these authorities that discovering a nucleotide
sequence encoding for a human protein and being able to show that
the protein concerned has some common homology with known
proteins (ie is a member of a family) may satisfy article 57. But
whether it does or not is case dependent and in particular depends
upon how well established the functions of the other members of the
family are. To say, ‘my new protein is similar to a known family of
proteins’ is not all that helpful in indicating a possible use if the
function of that family is itself poorly understood at best.”
In para 112, having said that to be “plausible” a statement must be sufficiently
precise, he added:
“It is not good enough to say this protein or any antibody to it
probably has a pharmaceutical use. Such a statement is indeed
Page 47
plausible, but is of no real practical use. You are left to find out what
that use is.”
In para 119, having summarised the findings and conclusions of Kitchin J, he said:
“So the Judge addressed the crucial question: is it enough to make
the invention ‘susceptible of industrial application’ to tell the skilled
reader that Neutrokine-α is ‘structurally similar to TNF and related
cytokines and is believed to have similar biological effects and
activities’? That depends on what was known about the biological
effects and activities of the known members of the superfamily. Each
of the postulated uses of Neutrokine-α or its antagonists was possible
in the sense that one could not rule that out as a matter of science
based on what was known about other superfamily members. So in
one sense each was ‘plausible’, even though all of them collectively
were not and indeed some contradicted others so both could not be
true. But that is miles away from being able to say that any particular
use was plausible in the sense of being taken, by the reader, to be
reasonably so. In reality one was faced with a research programme to
see which, if any, of the possible uses of the Neutrokine-α or its
antagonists was real.”
151. I think that there are indications in these passages that the standard which
Jacob LJ was setting for susceptibility to industrial application was a more
exacting one than that used by the TBA. He appears to have been looking for a
description that showed that a particular use for the product had actually been
demonstrated rather than that the product had plausibly been shown to be “usable”.
152. In para 23 of the reasons for its decision in the present case the TBA noted
that, as known in the art and acknowledged in the Patent, a feature common to all
members of this particular superfamily without exception was the expression on
activated T cells and the ability to co-stimulate T cell proliferation. It followed, in
view of the assignment of Neutrokine-α to the family, that the skilled person
would expect it to display that common feature. Asking itself whether there was
anything in the patent specification which contradicted that expectation, the Board
found that the technical data in the patent specification, far from contradicting the
ability of Neutrokine-α to co-stimulate T-cell proliferation, actually supported it.
That information could not be taken as a mere theoretical or purely hypothetical
assumption.
Page 48
153. In para 26 the TBA said that a skilled person, when reading the patent
specification, would distinguish the positive technical information from the
contradictory and broad statements to which Eli Lilly had drawn its attention:
“This is because the skilled person realises that the description of the
structure of Neutrokine-α, its structural assignment of the family of
TNF ligands, and the reports about its tissue distribution and activity
on leucocytes, are the first essential steps at the onset of research
work on the newly found TNF ligand superfamily member. In view
of the known broad range of possible activities of such a molecule,
the skilled person is aware of the fact that the full elucidation of all
properties requires further investigations which will gradually reveal
them. In this context, the skilled person regards the long listing of
possible actions of Neutrokine-α and of medical conditions in which
it might take part as the enumeration or generalisation of the
properties of the members of the TNF ligand superfamily. This is
seen as the frame in which the newly found molecule has to be
placed as one could prima facie have a reasonable expectation that
most of them could in fact be present.”
154. This is in sharp contrast to Jacob LJ’s comment in [2010] RPC 14, para 145
that the Patent, even in relation to T-cell activity, was just too speculative to
provide anything of practical value other than information upon which a research
programme could be based. Referring to the first sentence of the passage which I
have just quoted, he then said that “a first step at the onset of research work” was
hardly enough to provide “an immediate and concrete benefit”: para 149. The
phrase “immediate concrete benefit” – the “and” which Jacob LJ inserted into this
phrase is his own word – comes from para 6 of the TBA’s reasons for its decision
in ZymoGenetics; see also para 21 of its reasons in the present case. Here again
there is an indication that Jacob LJ was applying a different test from that applied
by the TBA. The immediate concrete benefit that he was looking for was
something more than that there was a reasonable expectation that the molecule
would be usable for the purposes of research work.
155. In para 27 the TBA said that, despite its long list of conditions and
activities, the description of the Patent delivered sufficient technical information
(namely the effect of Neutrokine-α on T-cells and the tissue distribution of
Neutrokine-α mRNA) to satisfy the requirement of disclosing the nature and
purpose of the invention and how it could be used in industrial practice. In para 29
it rejected Eli Lilly’s arguments that, in view of the technical difficulties involved
in measuring the co-stimulation of T cells by Neutrokine-α and the absence of any
detailed experimental information on the activities of Neutrokine-α listed in the
Patent, the skilled person would not have been able to reproduce them without the
undue burden of undertaking a research programme and that no industrial
Page 49
application could be directly derived from a mere co-stimulation of T-cells. It
pointed out that there was a convincing body of post-published evidence showing
that, using standard assays, Neutrokine-α activity was indeed present on T-cells,
that the reference in the Patent to the presence of Neutrokine-α activity in
lymphocytes would prompt the skilled person to look for that activity in all types
of lymphocytes, including B lymphocytes as well as T lymphocytes. Contrary to
Eli Lilly’s view, it held that these activities might represent a valid basis for a
possible industrial application. The industrial application that it had in mind was
the use of the molecule for research, which it must be taken to have regarded in
itself as an industrial activity.
156. Developing this point further, the TBA said in para 30:
“In the board’s judgment, the tissue distribution of Neutrokine-α
mRNA disclosed in the patent-in suit, in particular the expression of
Neutrokine-α mRNA in B-cell and T-cell lymphomas (cf paragraph
[0032]), provides in itself in the context of the disclosure a valid
basis for an industrial application. The presence of Neutrokine-α in
these lymphomas, which is also confirmed by post-published
evidence on file (cf inter alia document D126), may be used to
develop appropriate means and methods for their diagnosis and
treatment based on the disclosure of the patent-in-suit.”
157. These passages are important not so much for the assessment of the
evidence that was before the TBA, with which the national court may properly
disagree if presented with evidence which it accepts to the contrary, as for the clear
indication that they give as to the point in the development of an invention in the
biosciences field where it may be said that the requirement that the invention shall
be considered as susceptible of industrial application can be taken to have been
satisfied. The concluding words of the last sentence of para 30 indicate that the
test which the Board was applying, as in ZymoGenetics, para 8, was whether
Neutrokine-α was plausibly shown to be “usable”. I read this as indicating that it
was satisfied that the protein was a research tool which could be used to develop
appropriate means and methods for the diagnosis and treatment of B-cell and Tcell lymphomas. In the Board’s judgment that was enough for it to be susceptible
of industrial application within the meaning of article 57 of the Convention.
158. Kitchin J did not have the benefit of seeing the judgment of the TBA in this
case, as it was published more than a year after he handed down his judgment on
31 July 2008. He identified the principles that had emerged from the decisions of
the EPO in his judgment at [2008] RPC 29, para 226. Among them were the
following (case references omitted):
Page 50
“(vi)…the purpose of granting a patent is not to reserve an
unexplored field of research for the applicant nor to give the patentee
unjustified control over others who are actively investigating in that
area and who might eventually find ways actually to exploit it.
(vii) If a substance is disclosed and its function is essential for
human health then the identification of the substance having that
function will immediately suggest a practical application. If, on the
other hand, the function of that substance is not known or is
incompletely understood, and no disease has been identified which is
attributable to an excess or a deficiency of it, and no other practical
use is suggested for it, then the requirement of industrial
applicability is not satisfied. This will be so even though the
disclosure may be a scientific achievement of considerable merit.
(viii) Using the claimed invention to find out more about its
activities is not in itself an industrial application.”
He derived these principles from the reasons that the TBA gave for its decisions in
BDP1 Phosphatase/Max-Planck T 0870/04 (11 May 2005) and, in the case of the
second part of the principle in para (vi), from para 8 of ZymoGenetics. But he did
not pick up the point made in para 8 of ZymoGenetics that a product which is
definitely described and plausibly shown to be usable might be considered to have
a profitable use or concrete benefit, or the point made in para 22 that computerised
methods of analysis are increasingly becoming an integral part of scientific
investigations and that they can often allow plausible conclusions to be made
regarding the function of a product before it is actually tested. Careful though his
analysis was, I think that it tended to divert attention away from points that were
likely to produce an appropriately balanced decision in this case.
159. In para 230 the judge said:
“I accept that the contribution made by HGS was to find Neutrokineα and to identify it as a member of the TNF ligand superfamily.
However it is clear from the cases to which I have referred that
simply identifying a protein is not necessarily sufficient to confer
industrial utility upon it. Multimeric Receptors/Salk Institute is just
one example. It may be sufficient if the identification of the protein
will immediately suggest a practical application, such as was the
case with insulin, human growth hormone and erythropoietin. But if
the function of the protein is not known or is incompletely
understood and if no disease has been attributed to a deficiency or
Page 51
excess of it, then the position may well be different. In these cases
the industrial utility must be identified in some other way.
In paras 231-232 he said that he was quite satisfied that the skilled person would
consider that the Patent did not by itself identify any industrial application other
than by way of speculation. The range of diseases and conditions which
Neutrokine-α and antibodies to Neutrokine-α might be used to diagnose and treat
were astonishing and there was no data of any kind to support the claims made.
But he recognised that the disclosure had to be considered in the light of the
common general knowledge. Thus the skilled person would have known that TNF
was involved as a primary mediator in immune regulation and the inflammatory
response and had an involvement in a wide range of diseases, that all the members
of the TNF ligand superfamily identified hitherto were expressed by T cells and
played a role in the regulation of T cell proliferation and T cell mediated
responses. Further, as Eli Lilly’s expert witness Professor Saklatvala accepted, the
skilled person would anticipate that the activities of Neutrokine-α might relate to T
cells, be expressed in T cells and be a co-stimulant of B cell production and that it
might play a role in the immune response and in the control of tumours and
malignant disease and have an effect of B cell proliferation.
160. Thus far, his analysis of the evidence matches that in paras 27-30 of the
reasons which the TBA gave for its decision in this case: see paras 155-156, above.
But he then went on to say in para 233 that the skilled person would also have
known that the members of the family had pleiotropic actions, that some of those
activities were unique to particular TNF ligands and others were shared by some or
all the other TNF ligands, that no disease had been identified in which they were
all involved and that the known therapeutic application of the TNF-α monoclonal
antibody was a rather specific activity. In para 234, drawing these conclusions
together, he said:
“Does that common general knowledge, taken as a whole, disclose a
practical way of exploiting Neutrokine-α? Or does it provide a sound
and concrete basis for recognising that Neutrokine-α could lead to
practical application in industry? In my judgment it does not. The
fact that Neutrokine-α might be expected to play a role in regulating
the activities of B cells and T cells and play an unspecified role in
regulating the immune and inflammatory response did not reveal
how it could be used to solve any particular problem. Neither the
Patent nor the common general knowledge identified any disease or
condition which Neutrokine-α could be used to diagnose or treat. Its
functions were, at best, a matter of expectation and then at far too
high a level of generality to constitute a sound or concrete basis for
anything except a research project.”
Page 52
In para 237 he said that he was satisfied that this was a case where the claimed
inventions were not susceptible of industrial application at the date of the Patent. It
was no answer to say that subsequent research had shown that they might be useful
to treat diseases associated with particular B cell disorders.
161. I think that there is here a significant drift away from the approach indicated
by the TBA’s reasons in ZymoGenetics as subsequently confirmed by the reasons
for its decision in the present case. This is not just because the Board was working
on different evidence and was using a different procedure, as Jacob LJ seems to
have thought. There is a very obvious difference of view as to the test that the
invention had to satisfy to be susceptible of industrial application. For the TBA,
the question was whether, taking the common general knowledge into account, it
had been plausibly shown that the molecule was usable. It was not necessary for a
skilled person to undertake a research programme to conclude that the presence of
Neutrokine-α in B cell and T cell lymphomas might be used to develop appropriate
means and methods for their diagnosis and treatment: para 30. For the judge, this
did not go far enough. For him the critical point was that neither the Patent nor the
common general knowledge identified any disease or condition which Neutrokineα could be used to diagnose or treat: [2008] RPC 29, para 234.
162. In para 29 of its reasons in ZymoGenetics the TBA said that the function of
a protein, and thus of the nucleic acid encoding it, could be seen at different levels:
(i) its molecular function, revealed by the biochemical activity of the protein; (ii)
its cellular function, in regard to cellular processes; and (iii) the influence of those
cellular processes in a general and more complex network within a multicellular
organism, this being its biological function in a broad sense. In para 30 it said that
the elucidation of one of those particular levels of function might result in a
straightforward industrial application, even though the other levels of activity
remained completely unknown or only partially characterised. In ZymoGenetics
the suggested role for the receptor corresponded to the biological function, and the
therapeutical treatments directly derivable from it were not considered to be so
vaguely defined that they did not suggest any therapeutic or diagnostic use: para
31. In the present case the role that the TBA saw for Neutrokine-α was in
connection with activities at the level of the cellular function, and this in itself was
seen to provide a valid basis for an industrial application: paras 29-30.
163. Jacob LJ observed, I think correctly, that the Board thought that standard
assays, of the kind revealed by common general knowledge, would do the job of
providing an immediate concrete benefit: [2010] RPC 14, para 152. He then said
that the judge’s finding on the facts was to the opposite effect. He quoted the
following passage from para 77 of Kitchin J’s judgment:
Page 53
“…In my judgment the skilled person would indeed have been able
to identify or develop from his common general knowledge some
assays with which to begin the study of the new ligand and start to
asses at least some of its possible activities. But I am not satisfied
that such studies would have produced informative results and I have
no doubt that to carry out a comprehensive screening programme so
as to identify the role of the ligand in the biology of any particular
cell type would be an altogether more complex task, and one
properly characterised as a research programme.”
In other words, it was necessary for the skilled person to be able to identify the
role of the ligand in the biology of a particular cell type before the newly
discovered molecule could be said to be susceptible of industrial application. The
test which both he and the judge were applying was not that indicated by the TBA.
164. The same approach is to be found in early parts of his judgment. In para 119
he said that the reader was faced with a research programme to see which, if any,
of the possible uses of Neutrokine-α or its antagonists “was real”. In para 130, in
his discussion of Gruss and Dower’s assessment of the practical usefulness of the
TNF ligand superfamily as a whole he said that their observations were far from
saying that any member of the superfamily or its agonists had “real or indeed any
potential as a therapeutic or diagnostic agent”. In para 142 he referred to the fact
that the judge had preferred Professor Saklatvala’s evidence that by 1996 only
TNF-α “had been shown to be biomedically useful” to Professor Noelle’s
comment that he would expect Neutrokine-α to be useful in the same way as other
members of the TNF ligand superfamily. In para 145 he said that the Patent was
just too speculative to provide anything of practical value “other than information
upon which a research programme can be based.” It is clear from these passages
that for him the fact that the skilled addressee would see that the molecule was
usable for a programme of research work, which the TBA thought he would, was
not sufficient.
165. For these reasons I cannot agree with Jacob LJ that the differences between
the conclusions reached by the judge and the TBA are attributable to the fact the
Board was working on different evidence and was using a different procedure. It
seems to me that they are attributable to differences of principle about the amount
of information that was needed to show that the invention was susceptible of
industrial application. The test to be applied to determine this issue is a question of
law, not one of fact. As Jacob LJ observed, our practice is to follow any principle
of law clearly laid down by the TBA: [2010] RPC 14, para 39.
166. It is a strong thing to disagree with the concurrent findings of judges with
such experience in this field. But our decision in this appeal does not depend on a
Page 54
re-evaluation of the evidence. It turns on the principle of law which I find clearly
set out by the TBA in the passages to which I have referred. In my opinion that
principle leads inevitably to the conclusion that HGS’s appeal on the article 57
issue must be allowed and the decision of Kitchin J that the claimed inventions
were not susceptible of industrial application at the date of the Patent set aside. I
would dismiss Eli Lilly’s cross-appeal on the issue of insufficiency for the reasons
given by Lord Neuberger. I too would remit the case to the Court of Appeal to deal
with the outstanding issues.
LORD WALKER
167. As Lord Hope observes, this is a difficult and troublesome case. It is also an
important case: not only for the parties, but also for the bioscience industry
generally (as the intervention of the BioIndustry Association makes clear) and, in
some measure, for the future course of patent law in the United Kingdom.
168. I have to say that all my instincts, as an appellate judge, are for dismissing
this appeal. The issue is one of multi-factorial evaluation of evidence, a task which
has already been carried out twice, with the same result, by a very experienced
patent judge, and a division of the Court of Appeal presided over by a Lord Justice
with even more experience in the field of patents. Their task was to evaluate the
evidence against a statutory test expressed in simple terms, whose meaning is not
necessarily made much clearer by elaborate judicial exposition (see the quotation
in para 170 below).
169. This Court has recently, in Lucasfilm Limited v Ainsworth [2001] UKSC 39,
[2011] 3 WLR 487, para 45, reinforced Lord Hoffmann’s much cited statement of
the importance, in cases of this sort, of deference to the conclusions of the trial
judge. What Lord Hoffmann said in Biogen Inc v Medeva Plc [1997] RPC 1, 45 is
too well-known to need repetition. It applies even more strongly in the case of
concurrent findings. The same thought was expressed (in a dissenting judgment)
by Justice Kirby in the High Court of Australia in Aktiebolaget Hassle v
Alphapharm Pty Ltd [2002] 212 CLR 411, para 95 (references omitted):
“The conclusions on obviousness in the proceedings below
represented the outcome of a judicial evaluation of a mass of
evidence. In the assessment of that evidence, and in the conclusion
to be derived from it, the primary judge and the Full Court were
better placed to perform the function of fact-finding than this Court
is. Unless some error is shown in the application of the relevant law,
it would be a rare step for this Court to condescend to re-evaluate
Page 55
such a factual conclusion, reached by concurrent decisions at two
levels of the judicial hierarchy.”
170. Kirby J also quoted from Biogen, observing (para 97):
“Any exposition of judicial reasons explaining such factual findings
is ‘inherently an incomplete statement of the impression which was
made upon [the judge] by the primary evidence.’ Judges having
replaced juries in such matters in Australia, and having entangled
themselves in a web of horrible verbal formulae, must do their best
to explain their conclusions where, in the past, juries simply
announced their verdicts.”
171. Nevertheless the powerful and sustained analysis and reasoning in the
judgments of Lord Hope and Lord Neuberger has persuaded me, against my
inclination, that this appeal must be allowed. There is nothing that I can usefully
add to their reasoning, except to repeat that there are two strong policy arguments
for allowing the appeal. The first is to reduce the risk of a chilling effect on
investment in bioscience (though here the arguments are certainly not all one way).
The other is to align this country’s interpretation of the European Patent
Convention more closely with that of other contracting states. To my mind these
considerations justify this Court in taking what would otherwise be a questionable
course.
LORD CLARKE
172. Like Lord Neuberger, I was initially attracted by the submission that, as the
Court of Appeal held, Kitchin J was entitled to reach the conclusion he did.
Moreover, Lord Walker has expressed with clarity the correct approach of an
appellate court in a case such as this. In short, where the judge, especially a judge
of great experience in his field has carried out what Lord Walker calls a multifactorial evaluation of the evidence and the Court of Appeal has refused to
interfere with that evaluation, it will be the rare case indeed in which this Court
will be entitled to interfere.
173. However, like Lord Walker, I have been persuaded by the detailed analysis
by Lord Neuberger of the decisions in this and other cases of the Technical Board
of Appeal of the European Patent Office that the appeal should be allowed. In all
the circumstances I would allow the appeal for the reasons given by Lord
Neuberger and Lord Hope.
Page 56
LORD COLLINS
174. For the reasons given by Lord Neuberger and Lord Hope, I would allow the
appeal.
