Patents in the pharmaceutical Patents in the pharmaceutical industryindustry

Lars Sparre Conrad

Senior Patent Counsel

Corporate Patents and Trademarks

Slide 2

The patent departmentThe patent department

• Chemical engineer, DTU (chemistry), 1990• PhD, DTU (bio-inorganic chemistry), 1992• European Patent Attorney, 2005

• Research chemist, Novo Nordisk, enzyme business, 1992-2000

• Patent departments• 2000-2003 Leo Pharma• 2003-2005 Novo Nordisk• 2005- H Lundbeck

Slide 3

The Patent DepartmentThe Patent DepartmentLundbeckLundbeck

• 11 patent counsels• 5 Chemical engineers• 2 Human biolog• 2 Cand Pharm• 1 Chemists• 1 Lawyer

• 5 Counsels in the US

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Role of the Patent DepartmentRole of the Patent Department

DrugDiscovery

Drug Development

On the Market

Target Assay Compound Indication Salts Polymorphs

Formulation Process Device More indications Biomarkers

Life Cycle Management Prosecution

Freedom-To-Operate

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Examples from real lifeExamples from real life

• Duloxetine (SNRI) from Lilly approved 2004 in the US and 2005 in EP

• First compound application 1986• In the period 1986-2003 (at least)

• 2 compound applications• 11 indication applications• 13 combo application• 2 formulation applications• 1 process application

• Janssen lists 16 patents for Risperidone in Orange Book

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Why PatentsWhy Patents

• Value of company not associated with tangible assets

• Value associated with an “idea” and exclusive execution of the “idea”

• IPR is they way to protect ideas• Protection of investments

• The average cost of developing a prescription drug is about 800 mill $

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Patent Department involvementPatent Department involvement

• Extreme cost and duration of pharmaceutical development

=> Focus on exclusivity– “The right to prevent others form doing

something”

=> Focus on Freedom-to-Operate– “The right to do what you plan to do”

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WhyWhy

USA Development in Share of Total Rx

0%

5%

10%

15%

20%

25%

02-0

7-0

4

30-0

7-0

4

27-0

8-0

4

24-0

9-0

4

22-1

0-0

4

19-1

1-0

4

17-1

2-0

4

14-0

1-0

5

11-0

2-0

5

11-0

3-0

5

08-0

4-0

5

06-0

5-0

5

03-0

6-0

5

01-0

7-0

5

29-0

7-0

5

26-0

8-0

5

23-0

9-0

5

21-1

0-0

5

18-1

1-0

5

16-1

2-0

5

13-0

1-0

6

10-0

2-0

6

10-0

3-0

6

07-0

4-0

6

05-0

5-0

6

02-0

6-0

6

30-0

6-0

6

28-0

7-0

6

25-0

8-0

6

22-0

9-0

6

Sh

are

of

To

tal R

x

Celexa Generic Citalopram Zoloft Generic Sertraline

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WhyWhy

The number of application is ever increasing

Slide 10

Slide 11Børsen, 30 Juli 2003

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What is a patentWhat is a patent

• A patent is an exclusive right which is granted in return for the technical contribution to the society

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Limitations of RightsLimitations of Rights

Time – 20 years

Geography – Country by country

Scope – The claims

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What rightsWhat rights

• Gives the right to stop others frommakingofferingputting on the market or using the product or process using/importing a product

obtained by a process which is patented

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What rightsWhat rights

A patent does not give you the right to:

Exercise your own inventionSomebody may have a dominating patentFreedom-to-operate

Circumvent legislation in particular fields (pharmaceuticals, agrochemicals, chemicals in general, biotechnology, weapons, broadcasting etc.)

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What can not be patented What can not be patented

• Discoveries, scientific theories and mathematical methods

• Artistic creations• Plans, rules or methods for intellectual

activity, for games or for business activity or computer programs (outside US)

• Presentation of information

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What can not be patentedWhat can not be patented

• Methods for surgery / therapy / diagnosis (Patentable in the US!!!!!)

• Cloning human beings• Germ line modification• Uses of human embryos • Modifying the genetic identity of

humans

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Claims in the Pharma IndustryClaims in the Pharma Industry

• Compounds• Salts• Enantiomers• Polymorphs

• Use of compound in therapy• Known compound; first use in therapy

• Pharmaceutical composition comprising compound• E.g. in combination with specific excipients

R2R1

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Claims in the Pharma IndustryClaims in the Pharma Industry

• A method of treating X by the administration of compound

• Compound for use in the treatment of X• Use of compound in the manufacture of a

medicament for the treatment of X• Process of manufacture• Dosing regimes• Combination treatments

US OnlyUS Only

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Claims in the Pharma IndustryClaims in the Pharma Industry

• Biomarkers/patient selection/personalized medicine

• Assays• Devices

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Claims in the Pharma IndustryClaims in the Pharma Industry

• Method of treatment claims• Allowed in the US• Not allowed in EP

– Not considered industrially applicable – pre-2007

– Not considered patentable for moral reasons – post-2007

• Second medical use claims the equivalent outside US

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Requirements for patentabilityRequirements for patentability

• Three separate criteria:

• Novelty

• Inventive step

• Industrial applicability - seldom a problem

• The criteria are examined individually and all must be fulfilled!

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NoveltyNovelty

• Absolute novelty approach

• Everything which is made public available prior to the filing date belongs to prior art

• Photographic identity

• Written, orally or in any other way

• Not a question of whether somebody has actually read the document but whether it was available to anyone who wanted to see it

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NoveltyNovelty

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NoveltyNovelty

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Inventive stepInventive step

• The invention must not be obvious to the skilled person in view of the state of art

• A leap in cognitionKnown to use alkali metal salts Probably

obvious to use the sodium salt

• Allowed to combine documents or information when evaluating inventive step

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Inventive stepInventive step

• Insulin solution characterised in that it comprises Zn2+ ions in an amount of above 4 Zn2+ per hexamer insulin but below the limit for precipitation of zinc-insulin complexes

• Prior art disclosed insulin solutions with 4 Zn2+ per hexamer insulin

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Inventive stepInventive stepS

tab

ility

fact

or

Zn++ / insulin hexamer

Inventive step

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Novelty Inventive step

Prior art

Not novel

Invention

Prior art

Invention

Inventive?

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From cradle to graveFrom cradle to grave

Year 0

Prio

rity fi

ling

12 m

onth

sPC

T fi

ling

18 m

onth

sPublica

tion

2-7

years

Gra

nt

7-1

0 y

ears

Oppositio

n

20 y

ears

Enfo

rcem

ent

30 m

onth

sN

atio

nal/re

gio

nal

filin

gs

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How to obtain a patentHow to obtain a patent

• File application, pay fees and prosecute

• Priority application (T=0) One application in one country Filing date determines what is prior art Provides 12 months period to evaluate the invention

• PCT – Patent Corporation Treaty (T=12 months) One application for “the whole world” Does not issue patents Issues a preliminary opinion on patentability Delays need for expensive translations

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How to obtain a patentHow to obtain a patent

• National/regional filings (T=30 months)EPO – European Patent OfficeOne application for ~35 European countriesIssues patents – bundle of national patents

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StakeholdersStakeholders

Innovative PharmaLong exclusivity for ensure revenue on investments

Society/PayersStimulate innovation - Make innovation worthwhile - No resting on the laurelsAffordable medicine

Generic IndustryShort exclusivity for earlyMarket entry

Slide 35

Patent peculiarities in PharmaPatent peculiarities in Pharma

• 1st medical use claim• Patent term extension• Limitation of exclusivity• Rewards for challenging pharma

patents in courts (Hatch-Waxman act)

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Supplementary Protection Supplementary Protection CertificateCertificate

Counsel regulation 1768/92• Pharmaceutical research plays a decisive

role in public health• Pharmaceutical research long and costly• Effective exclusivity period ineffective to

cover investment

• Extension of the patent term

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SPC – conditions for grantSPC – conditions for grant

• Product must be protected by the patent in force

• MA has been issued• An SPC has not already been issued for

the active compound• The MA is the first MA in EU

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SPC - TermSPC - Term

• (Market authorisation – Patent Filing)-5 years• Max 5 years extension• Max 15 years market exclusivity

•A balance of interests

0Marketentry

20 +5

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SPC – Scope of protectionSPC – Scope of protection

• Only the product covered by the patent within the limits of the patent

• The patent as such is not extended• Esters and salts covered – ECJ392/97

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Patent Term ExtensionPatent Term Extension

• Investigational New Drug• New Drug Application• Marketing Authorisation

• PTE=

• Maximum 5 years extension• Maximum 14 years market exclusivity

)(2

NDAMAINDNDA

IND NDA MA

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Limitation of scopeLimitation of scopeBolar ProvisionBolar Provision

• 2004/27/ECConducting the necessary studies and trials with a view to the

application of paragraphs 1, 2, 3 and 4 and the consequential practical requirements shall not be regarded as contrary to patent rights or to supplementary protection certificates for medicinal products

• 35 U.S.C §271(e)(1)It shall not be an act of infringement to make, use, offer to sell, or

sell within the United States or import into the United States a patented invention (..)solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

Slide 42

Patents

Tech.Difficulties

Reg.Environ

mentData

Exclusivity

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Data Exclusivity EUData Exclusivity EU

• Counsel regulation 2001/83 and 2004/27

• A generic may refer to the originators registration data 8 years after originators MA

• A generic drug cannot be marketed before 10 years after originators MA

• Global Marketing Authorisation

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Data Exclusivity EUData Exclusivity EU

• Data exclusivity extended to 11 years if originator obtains MA for new indication• Within 8 years• Requiring clinical trials• Superior to existing treatment

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Data Exclusivity EUData Exclusivity EU

• Generic drugSame active substance

Salt, ester, ether, derivative etc unless they differ significantly

Same pharmaceutical form All oral IR formulation are ”same”

Bio-equivalence

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Orphan drug EU Orphan drug EU

• EU regulation 141/2000• Life-threatening or debilitating disease

affecting less than 5 out of 10000, or• Where the development of drug is

unlikely to generate sufficient return, and• With no existing treatment• 10 years exclusivity for similar drug and

same indication

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Orphan drug EUOrphan drug EU

• Exclusivity period reduced or annuled if• There is a profitable return• A superior product is brought to the

market

Slide 48

Paediatric exclisivity EUPaediatric exclisivity EU1901/20061901/2006

• Paediatric Investigation Plan (PIP) after Phase I• Deferral• Waiver

• Data must be included in MA application and leaflet

• Incentives• 6 months extension of SPC• Paediatric Use Marketing Authorisation (PUMA)

– 10 years data exclusivity

• Orphan drug period extended to 12 years

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Data exclusivity USData exclusivity US

• NDA – New Drug Application• ANDA – Abbreviated New Drug Application• 505(b)(2)

• FDA cannot accept an ANDA for same active moiety before 5 years after originators MA

• 4 years if §IV certification• Certification

I. No patentII. Patent expiredIII. Patent will expire before marketingIV. Patent not infringed or invalid

Slide 52

Data Exclusivity USData Exclusivity US

• Orange Book• List all patents allegedly covering a

product• If patent owner challenges ANDA => 30

months stay at FDA• §IV certification is patent infringement in

and of itself• 180 days exclusivity for first §IV applicant

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Data Exclusivity US Data Exclusivity US

• 3 additional years• New indication for already marketed drug• Requiring clinical investigations

• Exclusivity only for same drug and new indication

Slide 54

Generic DrugGeneric Drug

• Same active ingredient• Same strength, dosage form and route

of administration• Bio-equivalent