PROBLEMS OF PHARMACEUTICAL INVENTIONS
UNDER THE EPC AND THE GERMAN PATENT ACT
I.
Medical Indications - Categories of Claims
In principle, pharmaceutical inventions are subject to the same basic requirements of
patentability as any other inventions, i.e. they have to meet the requirements of
novelty, inventive step and industrial application in accordance with Articles 52(1),
54, 56 and 57 of the European Patent Convention (EPC) and §§ 1(1), 3, 4 and 5 of the
German Patent Act (PA). Both sets of provisions are identical in substance.
Patentability requirements in the member states of the EPC are in general harmonized
with the EPC provisions.
There are, however, specific provisions for pharmaceutical inventions which have
consequences for the categories in which a pharmaceutical invention may be claimed:
Article 52(4) EPC and § 5(2) PA
Methods for treatment of the human or animal body by surgery or therapy and
diagnostic methods practised on the human or animal body shall not be
regarded as inventions which are susceptible of industrial application within
the meaning of paragraph 1. This provision shall not apply to products, in
particular substances or compositions, for use in any of these methods.
Article 54(5) EPC and § 3(3) PA1
The provisions of paragraphs 1 to 4 shall not exclude the patentability of any
substance or composition, comprised in the state of the art, for use in a method
referred to in Article 52, paragraph 4, provided that its use for any method
referred to in that paragraph is not comprised in the state of the art.
1
In § 3(3) PA,the references are to paragraphs 1 and 2 and to § 5(2), respectively.
1
According to European and German practice, there are two basic categories of claims,
i.e. claims to a physical entity (product, apparatus) and claims to an activity (process,
use). Applicants prefer product claims since they confer the broadest protection e.g.
against any form of production or use of the product.
1. Absolute Product Protection
The following types of product claims are common for pharmaceutical inventions
-
substance
-
composition
-
physical form e.g.
o Fluid
o Powder
o granules
-
galenic preparation e.g.
o tablet
o capsule
o retard preparation
o carrier material
o dosage unit
-
kit of parts, e.g. different pharmaceuticals arranged in the order to be taken
-
mode of administration, e.g.
o peroral2
o subcutaneous3
o new combination of administration of known medicaments
As regards novelty, product protection requires that the claimed subject-matter is
different from the state of the art in respect of at least one physical feature which has
to be defined. In case of a medicament, it is not necessarily the pharmaceutically
active substance which provides novelty, it can be any auxiliary or carrier substance.
Whereas a functional feature like the pharmaceutical indication may imply in a
2
T 143/94, OJ EPO 1996, 430.
3
T 51/93 of 08.06.1994, not published in OJ EPO.
2
specific case a physical difference of the claimed pharmaceutical, the mere indication
that there is an unspecified auxiliary substance does not establish a distinction from
the available prior art 4.
Neither is a product rendered novel by the mere fact that it is produced by means of a
new process5. Therefore, a claim to product X obtained by process Y is only novel if X
is physically different from known products. It does not make any difference whether
obtained or obtainable is used in the claim. The reason is that in any case the claim is
directed to the product per se and confers absolute protection.
2. Special Categories for Medical Uses
The problems with the protection of new therapeutic applications stem from the fact
that Article 52(4) EPC excludes therapeutic methods from patent protection Therefore,
EPO practice does not allow claims like use of substance in the treatment of illness Z.
1.1
First Medical Indication
Article 54(5) EPC exempts by fiction a known substance or composition so far not
known for a pharmaceutical use from the state of the art when the same substance or
composition is claimed for its first pharmaceutical use. This fiction makes a limited
product protection available for the introduction of a known product into pharmacy.
In this case a broad indication of the use in the claim is allowed, e.g. substance X for
use as a medicament. The indication of the specific illness is not required in the claim.
Hence, the protection covers any medical use and is not restricted to the specific
indication disclosed in the application.
4
T 80/96, OJ EPO 2000, 050.
5
T 150/82, OJ EPO 1984, 309.
3
2.2
Second Medical Indication
2.2.1
EPO
Whereas in the case of the first medical indication the novelty creating effect of the
use was provided for by the legislator of the EPC, this had to be done for the second
and any further medical use by the case law. The Enlarged Board of Appeal held that
it was the purpose of the exclusion of therapeutic treatment to free from restraint noncommercial and non-industrial medical activities but not to exclude further medical
indications. Therefore, it was considered legitimate to allow claims directed to the use
of a substance for the production of a medicament for a specified new and inventive
therapeutic application, even if the manufacturing process did not differ from a known
process using the same active ingredient6. As a result, the intended use of the product
is the feature establishing novelty. This approach differs from the practice in other
technical fields, since the intended use of a product is not a feature of the process for
its preparation. In other technical fields only a process or use claim can contain a
feature establishing novelty by a feature related to the use of a product, unless such a
feature clearly implies a physical property of the product distinguishing it from the
prior art.
The correct claim format for a further medical indication is Use of substance X for the
manufacture of a medicament for curing disease Z or an equivalent drafting. This
claim format is known as Swiss-type claim, since it had been recommended by the
Swiss Patent Office before the above decision of the Enlarged Board of Appeal. It
does not give protection for the use in curing other diseases.
Novelty is not excluded by the fact that a previously unrecognised substance has been
found in nature. For example biological material isolated from its natural environment
is considered novel.
It is sometimes difficult to decide whether a modified use implies a new medical
indication. Even if the same illness is treated, a new indication is accepted when
6
G 5/83, OJ EPO 1985, 64.
4
different groups of patients are treated7. On the contrary, there is no new indication
when the specified use of a pharmaceutical is only the explanation for the mechanism
in the human body which is the reason for the known fact that a certain disease is
cured by the known pharmaceutical8. At present, there is a divergence in the case law
of the Boards of Appeal whether the regimen of administration (e.g. a dosage of 10mg
once a day) amounts to a new medical use9. So far the unsolved legal problem has not
yet been referred to the Enlarged Board of Appeal.
Since the intended use can establish novelty only for a medical indication, achieving a
mere cosmetic effect on the human body by applying a substance is not a basis for
establishing novelty of a Swiss-type claim. Since such treatment is not excluded from
patentability under Art. 52(4) EPC, it can be claimed as a process according to the
normal requirements.
So far EPO case law has abstained from giving a universally valid definition for the
term medicament. However, an essential characteristic of a medicament is that it be
administered to a patient's body in order to treat a disease. This means that the
medicament is brought into contact with the body in order to deliver and apply a
substance or composition in an effective form and dose for it to develop its therapeutic
effects within the patient's body. Therefore, an adsorbent which may be used in an
extra-corporal treatment of blood in order to remove certain proteins was not
considered as a medicament10.
2.2.2
Germany
The German Federal Supreme Court has chosen a different approach in solving the
problem how to give appropriate protection to further medical indications. It held that
the treatment of the human body by applying chemical substances did not only
comprise the treatment of the patient but also the preparation in the industrial sector of
7
T 19/86, OJ EPO 1989, 24.
8
T 254/93, OJ EPO 1998, 285.
9
T 1020/03 of 29 October 2004, to be published in OJ EPO.
10
T 138/02 of 27 June 2006, not foreseen for publication in OJ EPO
5
the chemical substances used. § 5(2) PA should be interpreted as excluding only those
methods which take place wholly outside the industrial sector11. Therefore, German
practice allows claims in the format use of substance X for curing disease Z. This
approach does not solve the problem how to exempt the physician from the effects of a
patent in his medical activities which is the essential purpose of the exclusion of
therapeutic treatment from patentability.
2.2.3
EPC 2000
At the end of the year 2007, the revised version of the EPC will enter into force which
contains a special provision adapting the legal situation for the protection of further
medical indications to the present provision for the first medical indication. Article
54(5) EPC 2000 extends the fiction that a substance or composition is not comprised
in the state of the art to the situation that a specific use in a therapeutic method is
claimed. This will make possible claims in the following format: substance X for use
in the treatment of illness Z.
In Germany, a bill for the ratification of the EPC 2000 is in preparation which also
contains provisions adapting the German substantive patent law to the EPC 2000.
Therefore, it may be expected that the different approaches in European and German
law for the protection of further medical indications will disappear since both systems
will provide limited product protection for this type of inventions.
3. Plurality of Claims
In the case of a new substance, the applicant may choose to include all the above
forms of claims. Whereas the claim to the substance gives the broadest scope as
absolute product protection, claims in the format for a first indication and for further
indications are allowable as fall back positions from the outset.
11
BGH, OJ EPO 1984, 26 - Hydropyridine
6
4. The Pharmaceutical Effect
As far as inventive step and sufficiency of disclosure are concerned, normally in
vitro12 or animal tests are submitted, in order to establish an alleged pharmaceutical
effect. Clinical tests are normally not required. The decisive question is whether it is
plausible that the pharmaceutical effect is present under all the circumstances of the
case.
In respect of the necessary number of examples, no special rules apply for
pharmaceutical inventions. The question of the breadth of the claims may arise under
the requirement of sufficiency of disclosure if the effect is part of the claim (first and
further medical indication) or under the requirement of inventive step if it is not
(product per se), in grant proceedings also under the requirement of support of the
claims by the description.
The general principle is that the protection conferred by a patent should correspond to
and be justified by the technical contribution to the art. The information provided in
the application must enable the skilled person to achieve the envisaged result within
the whole ambit of the claim on the basis of his common general knowledge without
undue burden. In other words, a broad claim requires the disclosure of a concept which
is fit for generalisation13.
The presence of a certain number of examples is not a formal requirement of an
application. Objections to lack of sufficiency of disclosure or inventive step must not
be based on speculation. If there are no concrete grounds for believing that the effect
cannot be achieved within the whole range claimed, there is no reason not to allow
broad claims. In other words, the examiner has to give reasons why he is of the
opinion that the skilled person cannot achieve the pharmaceutical effect over the
whole breadth of the claims. Such objections may be based on common general
knowledge in the relevant technical field or on the available prior art. Quite often they
boil down to a statement that certain alternatives are known to have certain properties
relevant to the alleged effect whereas others are not. In particular if the alternatives are
12
T 241/95, OJ EPO 2001, 103.
7
structurally different, this allows the conclusion that it is not plausible that the effect
can be achieved by embodiments using the second group of alternatives. For different
areas of technology, the expectation whether a structural variation implies a change of
properties varies considerably. Therefore, general rules are not possible and each case
has to be assessed on its own merits14.
13
T 435/91, OJ EPO 1995, 188.
14
See for example the very detailed discussion in T 694/92, OJ EPO 1997, 408 concerning a plant patent.
8
II.
Virtual Objects
1.
Non-existing Biologically Active Substances
It is not a requirement of European or German patent law that a claimed product has
actually been produced. For an enabling disclosure, it is sufficient if the patent
application teaches how the product can be produced. This is of particular relevance if
a claim covers many possible alternatives.
This principle also applies if a computer is used to design certain claimed products, in
particular chemical substances.
Problems may arise inter alia in assessing the following criteria:
-
identity of the substance
Does the application give enough detailed information in order to assess which
substances fall under the claims. If not, an objection to lack of clarity under Art. 84
EPC may be raised.
-
novelty
Does the program for designing the claimed substances contain features ensuring that
only novel substances are designed. Otherwise also a lack of clarity or even a lack of
novelty objection may be raised. Such a situation arises if the only distinguishing
feature is a functional feature defining the activity and if substances are known
exhibiting this activity.
-
presence of the alleged activity
It is up to the applicant to establish that all substances comprised by the claims exhibit
the alleged activity. If this is not at least made plausible, an objection to lack of
sufficient disclosure or to lack of inventive step may be raised, as the case may be.
9
Obtaining substances exhibiting the desired activities must be possible without undue
burden. Hence, necessary screening or test methods in order to obtain appropriate
candidates must not involve undue effort. Otherwise an objection to lack of
sufficiency of disclosure may be raised.
2.
Combinatorial Libraries
Possible forms of libraries used in combinatorial chemistry are:
a mixture of potentially active compounds,
an array of spatially separate chemical entities.
It depends on the claim format whether protection is sought (only) for the library as a
whole or whether the protection also extends to individual members of the library. In
cases of doubt, it is to be assumed that the broader interpretation extending to
individual members applies. Otherwise an objection to lack of clarity may be raised.
As to individual requirements the following general remarks may be made:
-
Novelty
If the claims are also directed to individual members of the library, quite often lack of
novelty may be present. If the claims are only directed to the library as a whole,
known individual members do not destroy the novelty of the library, unless all
members are known.
-
Inventive Step
In the EPO, the presence of an inventive step is assessed on the basis of the problemsolution approach. This also applies to inventions related to combinatorial libraries.
Normally, the closest prior art would be a library of the same or a similar type.
Considering the development of combinatorial chemistry, the preparation of a library
for the purpose of screening in order to identify chemical substances with desired
10
activities may, depending on the filing date and the technology, be seen as a routine
task for the skilled person. In other words the mere use of combinatorial chemistry for
a certain purpose may today not amount to a contribution to inventive step.
A different assessment of inventive step may be justified if an unexpected effect of the
claimed library in relation to the available state of the art is shown. Such an effect
could be any advantage in identifying or isolating chemical substances with the
desired properties.
So far the Boards of Appeal have had little opportunity to deal with the technology of
combinatorial libraries.
In each of two parallel cases15 a collection of compounds represented by Markushformulae was claimed. The applications had been refused on the grounds of lack of
inventive step by the Examining Division.
The Board raised an objection to the definition of some of the substituents which were
defined as combinatorial unit. The applicant argued that this term was generally
accepted in the art. The Board held that even on the basis of the description defining a
combinatorial unit as
"any monomer unit which can be used to build a chain attached to the solid support,
usually by a linking group. Examples of molecules suitable for such chain building are
found in Schreiber et al. (JACS, 120, 1998, pp.23-29), which is incorporated herein by
reference"
the skilled person could not find out which compounds did fulfil its purpose
“to allow the identification of compounds having highly specific biological activities”
and were embraced within the definition of the claim. Hence the claim did not meet
the requirement of clarity.
The applicant overcame the objection by replacing the term combinatorial unit by the
term amino acid residue cited in the description as an important example of a
combinatorial unit.
15
T 1057/03 and T 1173/03, both of 29 June 2006, not foreseen for publication in OJ EPO.
11
As to inventive step, the Board did not agree with the Examining Division’s reasoning
that an inventive step could not be attributed to the mere provision of a collection of
new compounds which themselves did not have any unexpected effects. The Board
emphasized that the problem underlying the application was not the provision of
compounds having unexpected properties but the reduction of the time it takes to
identify a compound having the desired biological activity. Hence, the relevant
question was whether it was obvious to provide the claimed collections in order to
solve the problem in comparison with the classical method of synthesizing and testing
compounds one by one and separately. The Board found that the Examining Division
had not properly dealt with the detailed arguments of the Appellant why it was not
obvious to apply library technology for the first time to pyrrolobenzodiazepine (PBD)
compounds.
On this basis the cases were remitted to the first instance in accordance with Article
111(1) EPC for further examination.
In a further case concerning libraries of backbone-cyclized peptodomimetics the
Examining Division also held that inventive step was lacking. Claim 1 was directed to
A method of screening for active peptide analogs comprising:
(a)
generating a library of chemical compounds;
(b)
testing members of the library for biological activity; and
(c)
identifying the active members of the library,
wherein the library of chemical compounds comprises a mixture of conformationally
constrained backbone-cyclized peptide analogs, each analog comprising a peptide
sequence … (follows the definition of the sequence).
The Board of Appeal confirmed the refusal of the application 16. Stating that peptides
falling under the definition of Claim 1 and the concept of backbone cyclization for the
16
T 1293/04 of 7 September 2006, not foreseen for publication in OJ EPO.
12
manufacture of conformationally constrained peptides were known, the Board saw the
problem in providing an alternative method for screening for active peptide analogs.
Based on the available state of the art, the Board concluded that the use of libraries of
conformationally constrained compounds for this purpose was obvious. Although the
concept of backbone-cyclisation had not been mentioned in a detailed review article
dealing with the application of combinatorial technologies to drug development, it had
been disclosed in three other documents. Thus, the claimed subject-matter did not
involve an inventive step.
In summary, it may be said that the few available decisions confirm that an
appropriate assessment of patentability of applications in the specific technology of
combinatorial libraries appears to be possible on the basis of the normal criteria.
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