Pitfalls loom when applying for patent term extensions covering
fixed combination medicinal products. Attention has to be paid
during prosecution to the impact of the wording of claims on
availability of patent term extensions for combination products. At
the same time, those involved in product development should take
into account the wording of the claims with a view toward securing
patent term extension.
This Commentary addresses the validity of European patent
term extensions, namely supplementary protection certificates
("SPCs"), covering fixed-combination medicinal
products.
An SPC provides an extension of the patent term by a maximum of
five years in order to compensate patent proprietors for the time
consumed by development and the market authorization procedure
required for medicinal and plant protection products.
SPCs for medicinal products are granted on the basis of the
European Community Regulation 469/2009 concerning the supplementary
protection certificate for medicinal products ("SPC
Regulation").
Article 3 of the SPC Regulation stipulates four basic requirements
for obtaining a certificate, the first two being of particular
relevance for the validity of SPCs covering fixed-combination
medicinal products. Art. 3 (a) requires that the
product—the active pharmaceutical ingredient
("API") or a combination of APIs—be protected
by a basic patent in force, and Art. 3 (b) requires that a valid
authorization to place the product on the market as a medicinal
product ("marketing authorization") must have been
granted.
The question arises whether the requirements of Art. 3 (a) and (b)
are fulfilled when the patent claims the API A, but the SPC
application is relying on the authorization for a medicinal product
containing API A in combination with a further API B. The same
question arises when the basic patent claims a combination of two
APIs, A and B, whereas the SPC application refers only to API A.
Similarly, the SPC application may refer to API(s) that are not
identical to those used in the authorized medicinal product.
Although the SPC Regulation is based on European Community law, and
the Court of Justice of the European Union (Court of Justice, CJ)
is the final authority to decide about legal issues relating to
SPCs, national authorities such as patent offices are appointed to
grant SPCs. Also, appeals from the rejection of SPCs are dealt with
by national courts. Thus, there has been a number of important
decisions of national courts, in particular the High Court in
London, relating to SPCs for fixed-combination medicinal
products.
Art. 3 (a) of the SPC Regulation
Regarding the requirement of Art. 3 (a) of the SPC Regulation,
it appears that there are two different concepts of how to handle
the question of whether the product, i.e., the API, is
protected by the basic patent. Some of the national jurisdictions
seem to follow the so-called "infringement test," and
other jurisdictions appear to apply a test that can be described as
the "identification test."
The rationale behind the "infringement test" appears
familiar: whether a fixed-combination medicinal product containing
the APIs A and B, which is the object of an SPC application, would
infringe a patent claiming the API A. Applying the basic principles
of infringement, it would seem that the product of the SPC
infringes the patent because the combination of A and B fulfills
all features of a claim directed to A. Thus, in such a situation,
the product of the SPC is regarded as being protected by the basic
patent pursuant to Art. 3 (a) of the SPC Regulation. In contrast,
an SPC referring to an API A only would not infringe a patent
claiming the combination of A and B and would thus not be in
accordance with Art. 3 (a). This position appears to be taken for
instance by the German Federal Court of Justice (see below for
details).
In contrast, in other jurisdictions, it is held that the
application of the principles of infringement confers the patent
proprietor a legal position far beyond what was intended by the SPC
Regulation. Instead, the product that is the object of the
certificate must be identifiable with the invention of the
designated basic patent.
This kind of "identification test" was applied in various
decisions of the High Court of London (cf. Takeda, 2003
EWHC 649 (Pat), Gilead, 2008, EWHC 1902 (Pat);
Astellas, 2009, EWHC, 1916 (Pat); Medeva, 2010,
EWHC, 68 (Pat)) and the U.K. Patent Office (Imclone –
Aventis, 2010, O/066/10). Also, the Dutch and Swedish
authorities appear to follow this concept (Ranbaxy v.
Warner-Lambert, 2008, The Hague Court of Appeal, IEPT20080221;
Aventis, 2009, District Court of the Hague/Council of
State, JGR 2008/32; A/B Hässle, Supreme
Administrative Court of Sweden, Case number 3248-1996). However,
the question of how clearly identifiable in the basic patent the
object of the certificate must be remains uncertain.
In the Gilead case, the basic patent covered a class of
new antiretroviral compounds useful in the treatment of HIV,
including tenofovir. Gilead Sciences, Inc. sought SPC protection
for a combination of tenofovir and another antiretroviral called
emtricitabine. The hearing officer did not consider the combination
of tenofovir and emtricitabine to be protected by a claim directed
to tenofovir and argued that he could not find a "clear
pointer" to the specific combination of antiretroviral
compounds. In his opinion, the particular ingredient must be
specifically disclosed.
On appeal, the High Court agreed with the hearing officer's
opinion that a claim directed to compound A does not protect the
combination of A and B in the sense of Art. 3 (a) of the SPC
Regulation. However, the SPC was granted on the basis of a
dependent claim directed to a combination of tenofovir and
"other therapeutic ingredients." The High Court did not
agree that a "clear pointer" was required and considered
this test—which is not set out in the SPC
Regulation—to be too vague. According to the High Court,
the test as set out in Takeda was to identify the active
ingredients of the product that are relevant to a consideration of
whether the product falls within the scope of a claim of the basic
patent. It is those ingredients, and only those ingredients, that
can be said to be protected within the meaning of the SPC
Regulation. The High Court considered that the combination of
tenofovir and emtricitabine fell within the scope of the claim of
the basic patent.
Thus, the "identification test" applied in the
Gilead case did not require the specific disclosure in the
basic patent's claims of the combination of API referred to in
the SPC application. At the same time, it was admitted that
compared to the "infringement test," the application of
the "identification test" could produce harsh
results.
How harsh these results can be becomes apparent from another case
decided by the High Court (Medeva, 2010, EWHC, 68 (Pat)).
In the Medeva case, five different applications for SPCs
for a variety of combination vaccines were at issue. The underlying
basic patent claimed vaccines against whooping cough containing the
antigens pertactin and filamentous haemagglutinin
("FHA"). In fact, all five SPC applications referred to
API combinations of pertactin and FHA, but four of them
additionally contained numerous other antigens for vaccination
against various diseases. Only one of the SPC applications was for
pertactin and FHA only.
The High Court denied the SPCs covering pertactin and FHA together
with other antigens because the other antigens were considered as
not being identifiable in the basic patent. Thus, although national
health policies in some instances force companies to market
combination vaccines directed to multiple diseases and to apply for
marketing authorizations covering these combination vaccines, the
SPCs were denied. The High Court acknowledged that this harsh
result is produced by the application of the "identification
test," but these results are not limited to the field of
vaccines, and there is no basis in the SPC Regulation for applying
different criteria to different classes of products.
The Court of Appeal recently referred this case to the Court of
Justice for a preliminary ruling on several questions regarding
Art. 3 (a) and (b) of the SPC Regulation. In particular, the Court
of Appeal queries the test to be applied in order to determine
whether "the product is protected by a basic patent in
force." Moreover, with reference to the particular situation
in the Medeva case, the Court asked whether a different
test should be applied in cases where the product is a
multi-disease vaccine and whether it is sufficient for the purpose
of Art. 3 (a), in the context of a multi-disease vaccine, that the
basic patent in force protects one aspect of the product.
Similarly, with regard to Art. 3 (b), the Court asked if the
product may be limited to the part of a multi-disease vaccine that
is protected by the basic patent in force.
Pending a decision of the Court of Justice, the application of the
"identification test" results in a reduced freedom of the
patent proprietor to choose the form in which a new pharmaceutical
is to be placed on the market. Accordingly, the holder of a patent
claiming API A is restricted to a medicinal product containing A
and cannot market a fixed-combination medicinal product containing
A and B in case supplementary protection by an SPC is
desired.
As discussed above, the introduction of an "identifier"
toward the combination of APIs into the claims of the patent,
e.g., a claim directed to an API in combination with at
least "other therapeutic ingredients," could overcome
these limitations. However, careful attention should be paid to
make this a dependent claim only and not to limit the claims to
fixed-combinations only (to the extent possible with regard to
novelty and inventive step). Inadvertently limiting the claims to
fixed-combinations only would result in significantly raising the
regulatory bar for successful application for a marketing
authorization. Applications for fixed-combination products may not
only refer to the respective ingredients and dossiers thereto, but
have to provide a dossier on the fixed-combination as such,
justifying the use of the fixed-combination over the use of the
respective single compound products.
Art. 3 (b) of the SPC Regulation
Whether an "identifier" in the right direction could
also overcome rejections based on the requirement of Art. 3 (b) of
the SPC Regulation is questionable because of the difference
between the underlying legal provisions, i.e., the
difference between Art. 3 (a) and Art. 3 (b).
In the above-mentioned U.K. cases Imclone –
Aventis and Medeva, an SPC was denied because the API
of the SPC application did not correspond to the respective
marketing authorization. In the Takeda case, refusal was
based on Art. 3 (a), but Art. 3 (b) was also discussed in the
reasons.
As mentioned above, in the Medeva case, one of the five
SPC applications was for pertactin and FHA only. However, all five
marketing authorizations were for vaccines containing pertactin and
FHA in combination with numerous other antigens for vaccination
against various diseases. In the Imclone –
Aventis and Takeda cases, in summary, the SPC
application was for the combination of A and B, but the relevant
marketing authorization only covered A. In all three cases, it was
considered that the requirement of Art. 3 (b) of the SPC Regulation
had not been fulfilled.
Interestingly, in the Takeda case, the High Court argued
that even if a marketing authorization contains information
implying that the product may (or should) be used as a combination
therapy, the marketing authorization is for the single product and
not for a combination therapy. Hence, such "identifier"
contained in the marketing authorization was not considered to
establish compliance with Art. 3 (b) of the SPC Regulation.
Also, in a similar situation, the German Federal Court of Justice
("BGH") was presented with a case where the SPC
application related to a combination of pantoprazol and certain
anti-helicobacter compounds (Anti-Helicobacter
Präparat, BGH - X ZB 1/08). The marketing authorization
was obtained for a medicinal product containing only pantoprazol.
The basic patent claimed the combination of pantoprazol and the
anti-helicobacter compounds. Although the marketing authorization
contained an "identifier" in the right direction (in that
it referred to the possible use of pantoprazol for certain types of
cancer in combination with the respective anti-helicobacter
compounds), the BGH denied the grant of an SPC. Interestingly, in
its reasoning, the BGH did not focus on the question of whether the
product of the SPC is covered by the marketing authorization, but
discussed the scope of protection of the basic patent. The BGH
considered that a basic patent claiming a combination of A and B
does not confer protection for A or B alone. Thus, although dealing
with Art. 3 (b) of the SPC Regulation, the BGH considered the scope
of protection of the basic patent in order to reject the SPC
application. However, also in this case, the "identifier"
in the marketing authorization did not remedy the discrepancy
between the products of the SPC and the marketing
authorization.
Regarding the above decision, it is further interesting to note
that the BGH also stated that the protection conferred by the SPC
must fall within the scope of the basic patent. As already
discussed above, this indicates that with regard to Art. 3 (a) of
the SPC Regulation, the BGH appears to apply the "infringement
test" rather than the "identification test."
The Take-Away
Several decisions from national courts, in particular the High
Court of London, confirm that applicants for SPCs for combination
products can be caught between the requirements of Article 3 (a)
and Article 3 (b) of the SPC Regulation. Although this
Commentary focuses on SPCs for medicinal products,
consequences outlined herein will be equally applicable to SPCs for
plant protection products.
With regard to Art. 3 (b), the ruling of national authorities
appears to be consistently restrictive and in line with several
decisions of the Court of Justice instructing to interpret the term
"product" in Art. 3 (b) narrowly (Massachusetts
Institute of Technology, 2006, CJ, C-431/04; Yissum,
2007, CJ, C392/97).
Concerning Art. 3 (a), there appears to be no uniform way to
interpret this provision in the different EC member states.
Although the Court of Justice ruled that the criteria for the
application of Art. 3 (a) are determined by the national law
relevant for the basic patent (Farmitalia, 1999, CJ,
C-392/97), i.e., Art. 69 of the European patent convention
and its protocol in conjunction with the national case law
regarding the scope of protection, it is not clear whether the
Court of Justice either endorses or rejects the "infringement
test."
While waiting for the Court of Justice to decide on the
Medeva case, the Gilead case teaches that even
when applying the stricter "identification test," one can
be saved by including in the basic patent a claim for the active
ingredient in combination with at least "other therapeutic
ingredients," preferably in combination with specific
candidates for future combination therapy. This should be kept in
mind when drafting patent specifications and claims.
But even without an "identifier" that could prevent
refusal of an SPC application in a country applying an
"identification test," filing an SPC application covering
a combination product in countries applying the "infringement
test" might be worthwhile to consider. Protection in a few
major European countries might be sufficient to prevent competitors
from starting production, because entering the market with a
pharmaceutical product only in some European countries might not be
viable from a business perspective.
For pending proceedings, where the circumstances are as described
above, a request for suspension of the proceedings until the Court
of Justice has decided in the Medeva case should be
considered. This might be advantageous not only in cases where SPC
applications are refused by granting authorities but also in
national invalidation proceedings where a granted SPC is attacked
as not fulfilling the requirements of Art. 3 (a) and 3 (b) of the
SPC Regulation.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.