CELEX: 62015CJ0138
Appeal
Orphan medicinal products
Regulation (EC) No 141/2000
Regulation (EC) No 847/2000
Refusal to grant marketing authorisation for the generic version of the orphan medicinal product ‘imatinib mesylate’

By their appeal, Teva Pharma Europe BV and Teva Pharmaceuticals Europe BV, companies governed by Netherlands law (together,
‘the Teva companies’), seek to have set aside the judgment of the General Court of the European Union of 22 January 2015 in
Case T‑140/12
Teva Pharma and Teva Pharmaceuticals Europe
v
EMA
(EU:T:2015:41) (‘the judgment under appeal’), by which that court dismissed their action for annulment of the decision of
the European Medicines Agency (EMA) of 24 January 2012 rejecting their application to place on the market the generic version
of the orphan medicinal product imatinib mesylate, in so far as concerns the therapeutic indications for the treatment of
chronic myeloid leukaemia (‘the contested decision’).

Legal context

Regulation (EC) No 141/2000
Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products
(OJ 2000 L 18, p. 1), as amended by Regulation (EC) No 596/2009 of the European Parliament and of the Council of 18 June 2009
(OJ 2009 L 188, p. 14), lays down procedures for the designation of medicinal products as orphan medicinal products and for
the marketing authorisation of such products.
Recital 8 of Regulation No 141/2000 reads as follows:
‘[E]xperience in the United States of America and Japan shows that the strongest incentive for industry to invest in the development
and marketing of orphan medicinal products is where there is a prospect of obtaining market exclusivity for a certain number
of years during which part of the investment might be recovered; data protection under Article 4(8)(a)(iii) of Council Directive
65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or administrative action relating
to medicinal products [OJ, English Special Edition, 1965, p. 20] is not a sufficient incentive for that purpose; Member States
acting independently cannot introduce such a measure without a Community dimension as such a provision would be contradictory
to Directive 65/65/EEC; if such measures were adopted in an uncoordinated manner by the Member States, this would create obstacles
to intra-Community trade, leading to distortions of competition and running counter to the single market; market exclusivity
should however be limited to the therapeutic indication for which orphan medicinal product designation has been obtained,
without prejudice to existing intellectual property rights; in the interest of patients, the market exclusivity granted to
an orphan medicinal product should not prevent the marketing of a similar medicinal product which could be of significant
benefit to those affected by the condition.’
Article 3(1) of Regulation No 141/2000 is worded as follows:
‘A medicinal product shall be designated as an orphan medicinal product if its sponsor can establish:
(a)      that it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition
affecting not more than five in 10 thousand persons in the [European Union] when the application is made, or
that it is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and
chronic condition in the [European Union] and that without incentives it is unlikely that the marketing of the medicinal product
in the [European Union] would generate sufficient return to justify the necessary investment,
and
(b)      that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been
authorised in the [European Union] or, if such method exists, that the medicinal product will be of significant benefit to
those affected by that condition.’
Under the procedure set out in Article 5 of Regulation No 141/2000, a medicinal product designated as an orphan medicinal
product by the European Commission is entered in the Community Register of Orphan Medicinal Products.
Article 8 of Regulation No 141/2000 states as follows:
‘1.      Where a marketing authorisation in respect of an orphan medicinal product is granted pursuant to [Council] Regulation (EEC)
No 2309/93 [of 22 July 1993 laying down Community procedures for the authorisation and supervision of medicinal products for
human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products (OJ 1993 L 241, p. 1)]
or where all the Member States have granted marketing authorisations in accordance with the procedures for mutual recognition
laid down in Articles 7 and 7a of Directive 65/65/EEC or Article 9(4) of Council Directive 75/319/EEC of 20 May 1975 on the
approximation of provisions laid down by law, regulation or administrative action relating to medicinal products [OJ 1975
L 147, p. 13], and without prejudice to intellectual property law or any other provision of [EU] law, the [European Union]
and the Member States shall not, for a period of 10 years, accept another application for a marketing authorisation, or grant
a marketing authorisation or accept an application to extend an existing marketing authorisation, for the same therapeutic
indication, in respect of a similar medicinal product.
…
3.      By way of derogation from paragraph 1, and without prejudice to intellectual property law or any other provision of [EU] law,
a marketing authorisation may be granted, for the same therapeutic indication, to a similar medicinal product if:
(a)      the holder of the marketing authorisation for the original orphan medicinal product has given his consent to the second applicant,
or
(b)      the holder of the marketing authorisation for the original orphan medicinal product is unable to supply sufficient quantities
of the medicinal product, or
(c)      the second applicant can establish in the application that the second medicinal product, although similar to the orphan medicinal
product already authorised, is safer, more effective or otherwise clinically superior.
4.      The Commission shall adopt definitions of “similar medicinal product” and “clinical superiority” in the form of an implementing
Regulation.
…’

Regulation (EC) No 847/2000
Article 3(2) of Commission Regulation (EC) No 847/2000 of 27 April 2000 laying down the provisions for implementation of the
criteria for designation of a medicinal product as an orphan medicinal product and definitions of the concepts ‘similar medicinal
product’ and ‘clinical superiority’ (OJ 2000 L 103, p. 5) provides as follows:
‘For the purposes of the implementation of Article 3 of Regulation … No 141/2000 on orphan medicinal products, the following
definitions shall apply:
–        “significant benefit” means a clinically relevant advantage or a major contribution to patient care.’

Background to the dispute
It is apparent from paragraphs 10 to 20 of the judgment under appeal that by decision of 14 February 2001 the Commission designated
imatinib mesylate (‘imatinib’) an orphan medicinal product for the treatment of chronic myeloid leukaemia (‘CML’) and entered
that product in the Community Register of Orphan Medicinal Products in accordance with Article 5(9) of Regulation No 141/2000.
On 7 November 2001, the Commission granted Novartis a marketing authorisation for imatinib under the commercial name Glivec
for the treatment of adult patients with CML in chronic phase after failure of interferon-alpha therapy, or in accelerated
phase or blast crisis. Subsequently, the Commission extended the terms of that marketing authorisation to cover other orphan
conditions. Pursuant to Article 8 of Regulation No 141/2000, the period of exclusivity enjoyed by Glivec expired on 12 November
2011.
On 22 May 2006, the Commission designated and registered as an orphan medicinal product nilotimib, a medicinal product for
the treatment of CML, which was sold under the commercial name Tasigna and developed by the holder of the marketing authorisation
for Glivec. In the course of the marketing authorisation procedure for Tasigna, that holder indicated to the EMA that it consented
to authorisation being granted for the marketing of that similar medicinal product for the same therapeutic indications as
those covered by the marketing authorisation granted for Glivec, in accordance with Article 8(3)(a) of Regulation No 141/2000.
On 19 November 20007, the Commission adopted a decision authorising the marketing of Tasigna for the treatment of adult patients
with CML in chronic phase and accelerated phase, with resistance or intolerance to prior treatment involving Glivec. That
decision was mentioned in the
Official Journal of the European Union
of 28 December 2007 (OJ 2007 C 316, p. 48).
On 20 December 2010, the Commission extended the terms of that marketing authorisation to cover the treatment of adult patients
with newly diagnosed CML in chronic phase. The relevant decision was mentioned in the
Official Journal of the European Union
of 25 February 2011 (OJ 2011 C 61, p. 1).
On 5 January 2012, Teva Pharmaceuticals Europe BV applied on behalf of Teva Pharma BV for authorisation to place on the market
a generic version of Glivec. That application referred, inter alia, to certain CML therapeutic indications covered by the
marketing authorisation granted for Tasigna.
By the contested decision, the EMA refused to grant that application, in so far as it covered the CML therapeutic indications
for which Tasigna enjoyed marketing authorisation, on the ground that those therapeutic indications still enjoyed market exclusivity
protection under Article 8(1) of Regulation No 141/2000.

The procedure before the General Court and the judgment under appeal
On 28 March 2012, the Teva companies brought an action for the annulment of the contested decision.
By order of the President of the First Chamber of the General Court of 6 September 2012, the Commission was granted leave
to intervene in support of the EMA.
By the judgment under appeal, the General Court dismissed the Teva companies’ action and ordered them to pay the costs.

Forms of order sought by the parties
The Teva companies claim that the Court should set aside the judgment under appeal, annul the contested decision and order
the EMA to pay the costs.
The EMA and the Commission contend that the Court should dismiss the appeal and order the Teva companies to pay the costs.

The appeal

The first part of the single ground of appeal, alleging that the General Court erred in law in its interpretation of the conditions
for the application of the ten-year market exclusivity period
Arguments of the parties
Teva takes issue with the General Court’s interpretation of Regulation No 141/2000 in paragraph 78 of the judgment under appeal
and does not accept that a marketing authorisation granted pursuant to Article 8(3) of that regulation can enjoy a period
of market exclusivity under Article 8(1) of the regulation. That interpretation fails to take account of the aim of Article 8(3)
of the regulation, which is to protect a similar medicinal product notwithstanding the market exclusivity provided for in
Article 8(1). As it constitutes a derogation, Article 8(3) should be construed narrowly; it cannot be interpreted as conferring
the right to market exclusivity provided for in Article 8(1).
Moreover, the General Court’s interpretation is contrary to the scheme of Article 8 of Regulation No 141/2000. Article 8(1)
is intended to provide a reward for the first orphan medicinal product authorised for a particular indication, that reward
taking the form of market exclusivity. The notion of exclusivity implies a status that may be enjoyed by only one product.
If the legislature had intended to confer market exclusivity on several medicinal products at the same time, it would have
so stated in an express provision, as is apparent from the Explanatory Memorandum to the Proposal for a European Parliament
and Council Regulation (EC) on orphan medicinal products submitted by the Commission on 28 July 1998 (OJ 1998 C 276, p. 7).
The Teva companies maintain that the General Court’s interpretation is, in certain respects, conflicting. In particular, Article 8(3)(a)
of Regulation No 141/2000 expressly provides that a medicinal product may be authorised with the consent of the holder of
the marketing authorisation for the original orphan medicinal product. They observe, however, that if the Commission has already
granted to a third party a marketing authorisation for a second similar orphan medicinal product which independently enjoys
a period of market exclusivity, the provisions of Article 8(1) and 8(3) will be in direct conflict.
The holder of the marketing authorisation for the original orphan medicinal product would be denied the possibility of consenting
to the placing on the market of the product in question, whereas the consent of the holder of the authorisation for the second
medicinal product would be required. Where the marketing authorisation holders are independent entities, it is unlikely in
practice that such consent would be forthcoming. The Teva companies submit that the holder of the marketing authorisation
for the second medicinal product would also be denied the possibility of consenting to a subsequent marketing authorisation
application for a similar medicinal product, as that application would then be in conflict with the market exclusivity enjoyed
by the original product.
The fact that Article 8 gives no indication as to how those conflicts could be resolved shows that the legislature did not
envisage such situations.
The EMA and the Commission contend that Article 8(1) of Regulation No 141/2000 is applicable to any medicinal product designated
an orphan product in accordance with the criteria laid down in Article 3 of the regulation.
Findings of the Court
It should be noted that in paragraph 78 of the judgment under appeal the General Court found that ‘the marketing authorisation
granted for an orphan medicinal product in respect of the same therapeutic indications as those for which the original orphan
product was authorised, including on one of the grounds laid down in Article 8(3) of Regulation No 141/2000, automatically
confers on that product the ten-year period of market exclusivity provided for in Article 8(1) of that regulation’.
It should be recalled in that connection that, in order to provide the pharmaceutical industry with an incentive to sponsor
the research, development and marketing of orphan medicinal products, Regulation No 141/2000 offers the sponsors of such products
the prospect of obtaining market exclusivity for a certain number of years. In line with that objective, referred to in recital
8 of the regulation, Article 8(1) thereof provides that ‘where a marketing authorisation in respect of an orphan medicinal
product is granted … the [European Union] and the Member States shall not, for a period of 10 years, accept another application
for a marketing authorisation, or grant a marketing authorisation or accept an application to extend an existing marketing
authorisation, for the same therapeutic indication, in respect of a similar medicinal product’.
As is apparent from recital 8 of Regulation No 141/2000, that regulation nevertheless seeks to circumscribe that period of
exclusivity in order not to prejudice existing intellectual property rights and, in the interests of patients, not to prevent
the marketing of a medicinal product similar to the orphan product which could be of significant benefit to those affected
by the condition in question.
Accordingly, Article 8(3) of Regulation No 141/2000 provides that it is possible to derogate from the ten-year exclusivity
period and grant marketing authorisation for a similar medicinal product in respect of the same therapeutic indication and
to do so in three cases, namely (i) where the holder of the marketing authorisation for the original orphan product consents
or (ii) is unable to supply sufficient quantities of the medicinal product and (iii) where the second applicant can establish
that his product, ‘although similar to the orphan medicinal product already authorised, is safer, more effective or otherwise
clinically superior’.
None of the provisions referred to above expressly provides that a marketing authorisation granted on the basis of Article 8(3)
of Regulation No 141/2000 is to be denied the benefit of the ten-year period of exclusivity provided for in Article 8(1) of
the regulation. The General Court was therefore entitled to state, in paragraph 73 of the judgment under appeal, that there
is nothing in that provision concerning whether the authorisation referred to in Article 8(3) of the regulation confers market
exclusivity on a similar medicinal product and, in paragraph 78 of the judgment, that there is nothing in the regulation to
suggest that application of Article 8(3) precludes the application of Article 8(1).
It is also apparent from the factors referred to above that although the market exclusivity provided in Article 8(1) of Regulation
No 141/2000 is reserved for orphan medicinal products alone, the derogations exhaustively set out in Article 8(3) of the regulation
relate to any similar medicinal product within the meaning of Regulation No 847/2000, irrespective of whether or not the product
is an orphan product. As the General Court was correct to observe in paragraph 80 of the judgment under appeal, Regulation
No 141/2000 does not contain any provision under which it is possible not to apply the ten-year period of market exclusivity
to orphan medicinal products that have been granted marketing authorisation for certain therapeutic indications, with the
exception of the situations set out in Article 8(2) of the regulation. As a consequence, where a similar medicinal product
that has been granted marketing authorisation under Article 8(3) of Regulation No 141/2000 is an orphan product, it enjoys
the market exclusivity provided in Article 8(1) of the regulation.
Contrary to the contentions of the Teva companies, that interpretation is neither illogical nor at odds with the purpose or
scheme of Article 8 of Regulation No 141/2000. Paragraphs 1 and 3 of Article 8 of the regulation, although complementary,
are different in scope and purpose. The fact that an orphan medicinal product enjoys the period of market exclusivity provided
in Article 8(1) of Regulation No 141/2000 does not preclude a second, similar product which has been authorised in accordance
with Article 8(3) of the regulation being granted, in turn, market exclusivity, as long as it also fulfils the requirements
set out in Article 3(1) of the regulation for designation as an orphan medicinal product.
The General Court was therefore correct to state, in paragraph 80 of the judgment under appeal, that it is precisely in order
to ensure attainment of the objective pursued by Regulation No 141/2000 — namely to encourage investment in the research,
development and marketing of orphan medicinal products — that market exclusivity must be granted in all cases in which an
orphan product has been given marketing authorisation.
It follows from all the above considerations that the first part of the single ground of appeal is unfounded and must be rejected.

The second part of the single ground of appeal, alleging that the General Court erred in law in its interpretation of the
term of the market exclusivity period
Arguments of the parties
The Teva companies dispute the General Court’s finding in paragraph 74 of the judgment under appeal that ‘if [the similar
product] is an orphan medicinal product, the ten-year period of market exclusivity with which it is endowed by virtue of Article 8(1)
of the regulation cannot be curtailed as a result of the fact that there exists an orphan medicinal product which has received
marketing authorisation for the same therapeutic indications and which benefits from market exclusivity for those indications’
and that ‘similarly, the market exclusivity attaching to that product will not be extended as a result of the fact that marketing
authorisation has been granted for the second medicinal product’.
The Teva companies consider that interpretation to be clearly at odds with the objective of Article 8 of Regulation No 141/2000
as it would lead, in practice, to the prolongation of the market exclusivity period beyond its ten-year term. Accordingly,
they claim that if the marketing authorisation had been granted for Tasigna on 11 November 2011, that interpretation would
have the effect of conferring market exclusivity until 11 November 2021, that is, for a period of 20 years, during which no
generic version could be placed on the market. Such an extension of the market exclusivity period is particularly unjustified,
given that it would not have been possible if Tasigna had represented a development that was sufficiently novel not be regarded
as a similar product within the meaning of Regulation No 847/2000. Paradoxically, the effect of the contested decision would
therefore be that a generic version of Glivec could not enjoy market exclusivity after the grant to Novartis of a marketing
authorisation for a different product, whereas that company would have the benefit of market exclusivity for a similar medicinal
product. That analysis would create ‘perverse’ incentives for undertakings to develop a series of slightly different, but
nevertheless similar, orphan products, thereby benefiting from a prolongation of the period of market exclusivity, which is
normally limited to 10 years.
The EMA and the Commission submit that there is no formal extension of the market exclusivity period of the first orphan medicinal
product. The authorisation of any subsequent similar orphan product would have no impact on the decision to remove the first
product from the Register of Orphan Medicinal Products at the end of the ten-year exclusivity period.
Findings of the Court
As observed in paragraph 31 above, where a similar medicinal product that has been granted marketing authorisation under Article 8(3)
of Regulation No 141/2000 is an orphan medicinal product, it enjoys the market exclusivity provided in Article 8(1) of the
regulation. In line with the objective pursued by Regulation No 141/2000, which is to provide the pharmaceutical industry
with an incentive to sponsor the research, development and marketing of orphan medicinal products by granting them a period
of market exclusivity, Article 8(1) of the regulation does not provide for any exception to the duration of that period or
for any modification of the period. The General Court was therefore entitled to find, in paragraph 70 of the judgment under
appeal, that ‘no provision [is] made for any extension of that period, which may be reduced, under Article 8(2) of Regulation
No 141/2000, only in situations in which it is established that the medicinal product in question no longer meets the requirements
laid down in Article 3(1) of the regulation’.
The General Court did not therefore err in law in finding, in paragraph 74 of the judgment under appeal, that the ten-year
period of market exclusivity with which an orphan medicinal product is endowed by virtue of Article 8(1) of Regulation No 141/2000
‘cannot be curtailed as a result of the fact that there exists an orphan medicinal product which has received marketing authorisation
for the same therapeutic indications and which benefits from market exclusivity for those indications’ and that ‘similarly,
the market exclusivity attaching to that product will not be extended as a result of the fact that marketing authorisation
has been granted for the [similar] medicinal product’.
It follows from all the foregoing considerations that the second part of the single ground of appeal is unfounded and must
be rejected.

The third part of the single ground of appeal, alleging that the General Court failed to examine the alternative case put
forward by the Teva companies
Arguments of the parties
The Teva companies take issue with the General Court on the ground that it distorted the meaning of its alternative case and
failed to address that case. According to paragraph 79 of the judgment under appeal, those companies had argued that ‘if a
second, similar orphan medicinal product which has been granted marketing authorisation for the same therapeutic indications
as those for which the marketing of the original orphan product was authorised may benefit from a ten-year period of market
exclusivity that is independent of that enjoyed by the original orphan product, that period of exclusivity could operate only
to prevent marketing authorisation being granted for products that are similar to the second medicinal product’.
The Teva companies contend that that description is not an accurate reflection of paragraphs 42 to 44 of the application which
they submitted to the General Court or of paragraph 38 of their reply, in which they submitted that the market exclusivity
granted to a second medicinal product should prevent only the authorisation of products that are similar to the second product,
while not being similar to the first orphan product. Even if Article 8 of Regulation No 141/2000 may be construed as providing,
in principle, an independent period of market exclusivity for the second product, there should be an exception to that market
exclusivity so as to permit the authorisation of a generic version of the first product, once the period of exclusivity for
that first product has expired.
The EMA questions whether the third part of the single ground of appeal is admissible, in that it relates to an appraisal
of the facts. The EMA maintains, like the Commission, that this part of the ground of appeal is in any event unfounded as
the General Court did not distort the Teva companies’ written pleadings.
Findings of the Court
It is apparent from paragraph 42 of the judgment under appeal that the Teva companies maintain that the market exclusivity
enjoyed by a second orphan medicinal product does not preclude marketing authorisation being granted for a product that is
similar to the first orphan product. In paragraph 58 of the judgment under appeal, the General Court stated that the applicants
submitted, in the alternative, that even if a similar orphan medicinal product authorised under the derogation in Article 8(3)
of Regulation No 141/2000 may benefit from an independent ten-year period of market exclusivity, that second period of exclusivity
would preclude only authorisation for the marketing of products that are similar to the second orphan product and that such
a period of exclusivity cannot operate to prevent marketing authorisation being granted for medicinal products that are similar
to the first authorised orphan product, in particular generic versions of that product, after the expiry of the period of
market exclusivity attaching to the first orphan product. In thus setting out the Teva companies’ arguments referred to in
paragraph 42 above, the General Court did not distort those arguments.
As those arguments were rejected on the grounds set out in paragraph 79 of the judgment under appeal, the General Court cannot
be criticised for failing to rule on the arguments.
It follows that the third part of the single ground of appeal is clearly unfounded. The appeal must therefore be dismissed.

Costs
Under Article 138(1) of the Rules of Procedure, applicable to the procedure on appeal pursuant to Article 184(1) of those
rules, the unsuccessful party is to be ordered to pay the costs if they have been applied for in the successful party’s pleadings.
Since the EMA has applied for costs against the Teva companies and the Teva companies have been unsuccessful, they must be
ordered to bear their own costs and pay the costs incurred by the EMA.
In accordance with Article 140(1) of the Rules of Procedure, applicable to the procedure on appeal pursuant to Article 184(1)
of those rules, the Commission, which intervened in the proceedings, is to be ordered to bear its own costs.
On those grounds, the Court (Sixth Chamber) hereby:
1.
Dismisses the appeal.
2.
Orders Teva Pharma BV and Teva Pharmaceuticals Europe BV to bear their own costs and to pay the costs incurred by the European
Medicines Agency (EMA).
3.
Orders the European Commission to bear its own costs.
[Signatures]
*
Language of the case: English.