laura traest – kirian claeyé – 25 may 2021

Regulatory Exclusivity Rights for pharmaceutical productsLaura Traest – Kirian Claeyé – 25 May 2021

Regulatoryexclusivity rights

2

→ Overview

SPC manufacturing waiver

SPCs & the CJEU

EC’s review

Polpharma ruling

A. General exclusivity rights

• Patent

• SPC

• RDP / MP

B. Exclusivity rights for specific populations

• Orphan exclusivity

• Paediatric rewards

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Overview of regulatory exclusivity rights

A. General IP / regulatory exclusivity rights• Patent

• Exclusive right granted for an invention• 20 years from filing date

• SPC – Supplementary Protection Certificate• Compensation for loss of patent protection during MA application process• Extension:

• of patent right • for product under marketing authorisation (MA)

• 5 years maximum

• SPC duration• Time lost minus 5y• SPC ≤ 5y• Patent + SPC ≤ 15y

So if MA is granted…• < 5y after patent filing date: no SPC• 5-10y after patent filing date: SPC for up to 5 years• > 10y after patent filing date: SPC for 5 years

A. General IP / regulatory exclusivity rights• Patent• SPC• RDP (Regulatory Data Protection) / MP (Market Protection)

• RDP: no reliance on data in originator’s filings for MA application• MP: market exclusivity for originator product• 8+2+1

• RDP for 8y after MA grant• MP for 2y after RDP expiry• MP for 1y if new MA for new indication during RDP period

• Separate 1y RDP for: • new indication well-established substance• classification change

1997 20122008

Patent filing

MA1 granted SPC protection

2019

MA2 granted

MA1: initial MA (non-orphan indication)MA2: new therapeutic indication representing a significant clinical benefit in comparison to existing therapies (non-orphan indication)

PE

RDP 8y MP 2y

Generic MA application

2018

MP +1y

Generic launch

RDP / MP 8+2+1

A. General exclusivity rights

• Patent

• SPC

• RDP / MP

B. Exclusivity rights for specific populations

• Orphan exclusivity

• Paediatric rewards

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Overview of regulatory exclusivity rights

B. Regulatory exclusivity rights for specific populations• Orphan medicines

• Medicines for rare conditions• 2 conditions

1. diagnosis, prevention or treatment of• life-threatening or chronically debilitating condition affecting not more than 5 in

10.000 persons in the EU, OR• life-threatening, seriously debilitating or serious and chronic condition and

without incentives it is unlikely that the marketing would generate sufficient return to justify necessary investment; AND

2. no satisfactory method authorised in the EU or, if such method exists, the medicinal product will be of significant benefit to patients

B. Regulatory exclusivity rights for specific populations

• Orphan medicines (2)• 10-year market exclusivity for the same indication in respect of a

similar medicinal product• Broader scope than ‘general’ MP

• Similar medicinal product

• = identical active substance OR an active substance with the same principal molecular structural features (but not necessarily all of the same molecular structural features) acting via the same mechanism

• Can be reduced to 6y if no longer complies with basic requirements

B. Regulatory exclusivity rights for specific populations

• Orphan medicines

• Paediatric rewards• Paediatric Investigation Plan (PIP) for MA application• New MA for paediatric indication, at least results in SmPC• 6-month SPC extension

• Not if additional year of MP obtained for new indication (8+2+1)

• 2-year market protection extension for orphan medicine

B. Regulatory exclusivity rights for specific populations

• Orphan medicines

• Paediatric rewards (2)

• PUMA (Paediatric Use Marketing Authorisation)

• MA for off-patent medicine exclusively covering therapeutic indications

relevant for paediatric population

• 8+2 RDP/MP

1997 2012

Patent filingMA1

granted

Generic MA application

Basic patent protection SPC protection

06/2022

MA2 granted

MA1: initial MA (non-orphan indication)MA2: paediatric indication for MA1

PE

RDP 8y MP 2y

2008 2016 2018

1997 20122008

Patent filingMA1

granted SPC protectionMA2

granted

MA1: initial MA (orphan indication)MA2: paediatric indication for MA1

PE

PE +2y

Orphan medicine exclusivity 10y

2018 2020

1997

Patent filingMA1

granted SPC protection

MA1: initial MA (orphan indication)MA2: paediatric indication off-patent (PUMA)

PE

2018

Orphan medicine exclusivity 10y 8+2 RDP/MP

MA2 granted

Basic patent protection SPC protection

2022 20272008

Regulatoryexclusivity rights

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Overview

→ SPC manufacturing waiver

SPCs & the CJEU

EC’s review

Polpharma ruling

A. Overview

B. Scope

C. Safeguards

D. Transitional regime

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SPC manufacturing waiver

• Article 5 SPC Regulation 469/2009 (amended by Regulation 2019/933)

• Regulation 1610/96 regulating SPCs for plant protection products remains unchanged

• Objective = remedy competitive disadvantage for generic and biosimilar manufacturers established in the EU where an SPC exists in the EU but not outside the EU

A. Overview

Exception for manufacturing of SPC-protected active ingredients and corresponding medicinal products for:

1. Export to third countries outside the EU• throughout the entire SPC lifetime

2. Storage for day-1 entry on the EU market immediately after SPC expiry• only during last six months before SPC expiry

3. Related acts strictly necessary for 1 and 2

B. Scope

NO exception for importing active ingredients, or medicinal products

containing those ingredients, into the EU merely for the purpose of

repackaging, re-exporting or storing

B. Scope (2)

• Obligations rest upon the ‘maker’ = the person, established in the Union, on whose behalf the making of a product, or a medicinal product containing that product, for the purpose of export to third countries or for the purpose of storing, is carried out

C. Safeguards

• Obligations for the maker:• Notification obligation to competent authority (DIE) and SPC holder

• Name and address, purpose (export and/or storage?), etc.

• At least three months before starting date

• Labelling obligation• In case of export: ‘EU export logo’

• Outer packaging and, where feasible immediate

packaging

• Information obligation

C. Safeguards (2)

• Obligations for the maker:• Notification obligation

• Labelling obligation

• Information obligation towards contract parties that perform acts under the waiver

• Acts fall under the waiver

• Placing on the market, (re)importing could infringe SPC where and for as long as it applies

C. Safeguards (3)

D. Transitional regime• Cut-off date: 1 July 2019Filing? Entry into force? Applicable?

Filing + entry into force before 1 July 2019 NO

Filing + entry into force on or after 1 July 2019 YES

Filing before 1 July 2019, entry into force on or after 1 July 2019 YES as of 2 July 2022

Regulatoryexclusivity rights

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Overview

SPC manufacturing waiver

→ SPCs & the CJEU

EC’s review

Polpharma ruling

A. C-650/17 – Royalty Pharma

B. C-673/18 – Santen

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SPCs : keeping the CJEU busy

Basic patent : administration of DP IV (enzyme) inhibitors- patentee = Royalty Pharma- sitagliptin = DP IV inhibitor but at the time not yet developed

Licensee of Royalty Pharma’s patent = MSD- develops sitagliptin- obtains new patent (and SPC) for sitagliptin

Royalty Pharma applies for its own SPC for sitagliptin on the basis of its first patent- German patent office refuses

C-650/17 – Royalty PharmaFACTUAL BACKGROUND

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C-650/17

Royalty PharmaLEGAL BACKGROUND (1)

Article 3(a) Regulation 469/2009 - product “protected by” a basic patent- C-493/12 – Eli Lilly

• it is not necessary for the active ingredient to be identified in the claims of the patent by a structural formula

• also if covered by a functional formula in the claims of a patento IF the claims relate, implicitly but necessarily and specifically, to that producto on the basis of those claims, interpreted inter alia in the light of the description of

the invention, as required by Article 69 EPC

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C-650/17 – Royalty PharmaLEGAL BACKGROUND (2)

should it form part of the subject matter of protection defined by the claims andshould it thus be provided to the expert as a specific embodiment?

is it insufficient if the product satisfies a functional definition in the claims, but:

- is not indicated in an individualised form as a specific embodiment? OR- was developed only after the filing date of the basic patent as a result of an

independent inventive step?

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C-650/17 – Royalty PharmaQUESTIONS

Article 3(a) Regulation 469/2009 - product “protected by” a basic patent- C-121/17 – Teva v Gilead

• from the skilled person’s viewpoint and on the basis of the prior art :1) the combination must necessarily, in light of the description and drawings of that

patent, fall under the invention covered by that patent, and2) each of those active ingredients must be specifically identifiable, in light of all

the information disclosed by that patent

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C-650/17 – Royalty PharmaLEGAL BACKGROUND (3)

Following C-121/17 – Teva v Gilead

- CJEU → BPG : Do you want to maintain your question?

- BPG → CJEU : Yes, because:

• Uniform practice is key

• Is the concept of ‘core inventive advance’ of any relevance for Article 3(a)?

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C-650/17 – Royalty PharmaBACK-AND-FORTH

Core inventive advance? NO

- C-121/17 - Teva v Gilead implicitly rejected this concept

- Any other additional criterion, such as the requirement proposed by the referring court that the active ingredient embody “the inventive advance of the patent” runs the risk, in my view, of giving rise to confusion with the criteria for determining whether an invention is patentable. The question whether a product is protected by a patent within the meaning of Article 3(a) … is not the same as the question whether that product is patentable, which is a matter exclusively for national or treaty law.

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C-650/17 – Royalty PharmaOPINION A-G

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C-650/17 – Royalty PharmaCJEU

Core inventive advance? NO - §§ 30-32:

- C-121/17 – Teva v Gilead: • did not employ the concept of core inventive advance• instead key role played by the claims - Article 69

- “In so doing, the Court clearly relied on an interpretation of Article 3(a) …, in the context of which the concept of ‘core inventive advance’ is not relevant.”

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C-650/17 – Royalty PharmaCJEU

Specific embodiment? NOT A REQUIREMENT - §§ 33-43:- Confirmation of Teva v Gilead test (C-121/17)- A product is protected by a basic patent in force, within the meaning of Article 3(a),

1) if it corresponds to a general functional definition used by one of the claims of the basic patent and necessarily comes within the scope of the invention covered by that patent, but is not otherwise indicated in individualised form as a specific embodiment of the method of that patent,

2) provided that it is specifically identifiable, in the light of all the information disclosed by that patent, by a person skilled in the art, based on that person’s general knowledge in the relevant field at the filing date or priority date of the basic patent and on the prior art at that date.

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C-650/17 – Royalty PharmaCJEU

2) Specifically identifiable?- §§ 40-42:

• is within the limits of what a person skilled in the art is objectively able, at the filing date or priority date of the basic patent, to infer directly and unequivocally from the specification of that patent as filed, based on that person’s general knowledge in the relevant field at the filing date or priority date, and in the light of the prior art at the filing date or priority date

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C-650/17 – Royalty PharmaCJEU

Developed following an independent inventive step? §§ 44-50:

- A product is not protected by a basic patent in force, within the meaning of Article 3(a), if,

• although it is covered by the functional definition given in the claims of that patent,

• it was developed after the filing date of the application for the basic patent, following an independent inventive step.

A. C-650/17 – Royalty Pharma

B. C-673/18 – Santen

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SPCs : keeping the CJEU busy

1983 : Santen obtains MA for SANDIMMUN® (cyclosporin)

2015 : Santen applies for SPC for ‘cyclosporin for use in the treatment of keratitis’:

- European patent applied for on 10 October 2005

- MA for IKERVIS® (cyclosporin to treat severe keratitis in certain patients)

French patent office rejects request

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C-673/18 – SantenFACTUAL BACKGROUND

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C-673/18

SantenLEGAL BACKGROUND (1)

C-130/11 – Neurim – 19 July 2012 : YES

the mere existence of an earlier MA does not preclude the grant of an SPC for a different application of the same product for which an MA has been granted,

provided that the application is within the limits of the protection conferred by the basic patent

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C-673/18 – SantenLEGAL BACKGROUND

‘(1) Must the concept of a “different application” within the meaning of [the judgment in Neurim] be interpreted strictly, that is to say:

[three possible interpretations]or must it on the other hand be interpreted broadly, that is to say, as including not only different therapeutic indications and diseases, but also different formulations, posologies and/or means of administration?(2) Does the expression “[application] within the limits of the protection conferred by the basic patent” within the meaning of the judgment [in Neurim], mean that the scope of the basic patent must be the same as that of the MA relied upon and, therefore, be limited to the new medical use corresponding to the therapeutic indication of that MA?’

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C-673/18 – SantenQUESTION

Reformulation of questions - §§ 32-37:- Even if the referring court has limited its questions to the interpretation of certain aspects

of EU law [= further clarification of Neurim]• That does not prevent CJEU from providing the referring court with all the elements of

interpretation of EU law which may be of assistance in adjudicating in the case- Thus … it is necessary to examine whether Article 3(d) … must be interpreted as meaning

that an MA may be considered to be the first MA, for the purpose of that provision, where it covers a new therapeutic application of an active ingredient or of a combination of active ingredients and that active ingredient or combination has already been the subject of an MA for a different therapeutic application.

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C-673/18 – SantenCJEU

NO (!)

Article 3(d) … must be interpreted as meaning that a marketing authorisationcannot be considered to be the first marketing authorisation, for the purpose of that provision,

where it covers a new therapeutic application of an active ingredient, or of a combination of active ingredients,

and that active ingredient or combination has already been the subject of a marketing authorisation for a different therapeutic application.

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C-673/18 – SantenCJEU

Motivation- Definition of ‘product’ in Article 1(b) Regulation - §§ 38-47

“‘product’ means the active ingredient or combination of active ingredients of a medicinal product”• Not limited to any particular application• No distinct product if a product is used for a new therapeutic

application- Fact that MA is first to fall within the limits of the basic patent is irrelevant:

Article 3(d) does not refer to the scope of protection - §§ 48-60

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C-673/18 – SantenANSWER

CJEU’s decision in C-130/11 – Neurim

Santen judgment explicitly acknowledges :

“the [Neurim] premise must be disregarded”

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C-673/18 – SantenANSWER

Regulatoryexclusivity rights

47

Overview

SPC manufacturing waiver

SPCs & the CJEU

→ EC’s review

Polpharma ruling

• Revision of the EU legislation on medicines for children and rare diseases (Q1 2022)

• Revision of the EU general pharmaceutical legislation (EU Pharmaceutical Strategy) (Q4 2022)

Upcoming review of IP Regulatory Rights

Joint evaluation of Regulation (EC) No 1901/2006 (medicinal products for paediatric use) and Regulation (EC) No 141/2000 (orphan medicinal products)

Executive summary

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European Commission

Joint Evaluation on paediatric & orphan medicines

Key findings- Fostered the development and availability of medicines for patients with rare

diseases and for children• More patients treated & faster availability• Off-label use decreased

- Insufficient development in areas where the need for medicines is greatest• More development in more profitable therapeutic areas

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European Commission

Joint Evaluation on paediatric & orphan medicines

Questions- Orphan medicines: is the threshold (of fewer than 5 patients in 10.000

persons) the right tool for identifying rare diseases?• Also: how to apply to personalized medicines?

- Paediatric medicines: is the paediatric extension of the term of the SPC the right main paediatric reward?

• Untargeted: an SPC extension provides for exclusivity for adults & children • Critical mass: more large sales volumes• Complex as it has to be done at the various national patent offices

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European Commission

Joint Evaluation on paediatric & orphan medicines

Further findings- Increased cost for healthcare systems is compensated by benefits for patients

with rare diseases and children- Orphan & paediatric medicines not always equally accessible in all countries- Further inefficiencies and undesirable consequences to be solved

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European Commission

Joint Evaluation on paediatric & orphan medicines

Increase current threshold (fewer than 5 out of 10.000)? Change to / add additional criterion?

- Distinguish between innovative vs repurposed drugs?- Focus on return rather than patients?- Requirement of availability in all EU Member States?

Replace with / add other incentive?- Increase public funding?- Transferable voucher for fast-track review (cf. US)?- Extension of market exclusivity?

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Options discussed for orphan medicines

Add additional criterion?- Timely completion of Paediatric Investigation Plan?- Requirement of availability in all EU Member States?

Replace with / add other incentive?- Rethink PUMA scheme?- Rethink Orphan reward?- Increase public funding?- Transferable voucher for fast-track review (cf. US)?- Extension of market exclusivity?

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Options discussed for paediatric medicines

Regulatoryexclusivity rights

55

Overview

SPC manufacturing waiver

SPCs & the CJEU

EC’s review

→ Polpharma ruling

AI = Dimethyl Fumarate (DMF)

56

T-611/18 – Polpharma v EMAFACTUAL BACKGROUND

Biogen MAs for originator products

- 1994 : BfArM (Germany) grants first MAs for Fumaderm®

• Together with monoethyl fumarate (MEF) salts

• Treatment of psoriasis

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T-611/18 – Polpharma v EMAFACTUAL BACKGROUND

Biogen MAs for originator products

- 30 January 2014 : Commission grants centralized second MA for Tecfidera®

• Single active ingredient

• Treatment of multiple sclerosis

• Following back-and-forth between Biogen and EMA, the latter eventually:

o stepped back from the fact that DMF was a ‘new active substance’

o confirmed that Tecfidera® and Fumaderm® do not belong to the same global MA 58

T-611/18 – Polpharma v EMAFactual background

Polpharma application for a MA for a generic version of Tecfidera®

- 30 July 2018: EMA rejects Polpharma’s application for the grant of MA forgeneric version of Tecfidera® (‘Contested Decision’)

• MEF and DMF are both active and not the same active substance

• Tecfidera® and Fumaderm® do not belong to the same global MA

• Data-protection period for Tecfidera® has not yet expired

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T-611/18 – Polpharma v EMAFactual background

Polpharma requested annulment of:

- Plea of illegality in respect of the Commission Implementing Decision of 30 January 2014

• Inadmissible but General Court can examine the plea of illegality in the context of the annulment of the EMA’s decision

- Annulment of the EMA’s decision of 30 July 2018

• Admissible

• General Court annuls EMA’s decision of 30 July 201860

T-611/18 – Polpharma v EMAPolpharma’s requests

Request for annulment is admissible- MA grant (Implementing Decision of 30 January 2014) = act of general application

• As it states that Tecfidera® does not belong to the same global MA as Fumaderm®- Existence of a connection between the Contested Decision and assessments disputed by

Polpharma- Polpharma was not entitled to bring an action for annulment of the Implementing Decision

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T-611/18 – Polpharma v EMAGeneral Court

Contested Decision is annulled- The fact that the MA was based on a full application (Art. 8(3) of the Community Code) has

no effect on the scope of the concept of a global MA- It instead needed to be assessed whether the lack of MEF in Tecfidera® was clinically

relevant (in other words, whether MEF in Fumaderm® had a significant therapeutic effect)- Neither the CHMP, nor the Commission assessed the role played by MEF within Fumaderm®- Implementing Decision of 30 January 2014 :

• manifest error of assessment• inapplicable regarding the finding that Tecfidera® did not belong to the same global MA

as Fumaderm®62

T-611/18 – Polpharma v EMAGeneral Court

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ALTIUS’ Life & Health Blog

Life Sciences Session #5: 28 September 2021

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THANK YOU

Kirian ClaeyéManaging Associate

kirian.claeye@altius.com

+3224215094

Laura TraestAssociate

Laura.traest@altius.com

+3224215043