Public health, innovation and intellectual property 1 |

Public Health and Intellectual Property

management: the challenges on access

to medicines

Dr. Inthira Yamabhai

2 |

Overview

Intellectual property (IP) and implications on access to

medicine

– Trade Related Aspect of Intellectual Property Rights (TRIPS)

– TRIPS+ through trade agreements

Sources of information

3 |

Different forms of IP

Trademark: name under which product is marketed

Patent: compound, crystalline forms, process, method of

use, etc

Protection of undisclosed data: clinical test data

Copyright: package insert

Design protection: packaging

4 |

Patents

There is nothing such as a worldwide patent!

WIPO Patent Cooperation Treaty allows for worldwide

filing, but applicant receives a bundle of national patents;

same principle under European Patent Convention

WTO TRIPS sets certain minimum standards:

– Term: 20 years from filing data

– Mandatory for all fields of technology

– Criteria: novelty, inventive step, industrial applicability

– Flexibilities: e.g. parallel importation and compulsory licensing

One drug = one patent???

"…a key element of life cycle

management strategies is to extent

patent protection for as long as

possible by filing secondary patents to

keep generics off the market"

(Burdon and Sloper 2003)

2024

• Broad compound patent (Markush)

• WO2005003147A2

2028

• Compound patent on prodrug

• WO2008121634A2

2031

• Crystalline forms

• WO2011123645A2

2032

• Combination with ledipasvir

• WO2013040492A

2032

• Composition & dosage

• WO2013082003A1

Sofosbuvir: Expiry without patent term extension(s)

Market

Authorization

US: 2013/14

www.who.int/phi/impl

ementation/ip_trade/ip

_patent_landscapes/e

n/

7 |

Incremental innovation vs life cycle management

Incremental advances for public health can include:

ƒƒ Combinations & new dosage forms with improved efficacy:

co-formulation of antiretroviral drugs

ƒ Formulations with better product characteristics: vaccines

stored in fridge rather than freezer

New routes of delivery: tablets or nasal spray vs injections

Paediatric formulations: dispersible flavored tablet of

artemether-lumefantrine

8 |

Granting patent in India:

Imatinib case

Novartis claims the drug is more easily absorbed into the blood that

is enough of an improvement to warrant patent protection. India

Patent Office disagreed that Novartis had shown significantly

increased efficacy and refused to grant a patent on Glivec (imatinib

mesylate)

Novartis file a case and India’s Supreme Court refused to grant a

patent for Glivec, as it’s known in some countries

India’s trade and industry minister, Anand Sharma, has defended the

decision, and was quoted by Agence France-Presse as saying it was

“absolutely justified under the law” and that India’s patent law

“does not accept evergreening.”

9 |

Estimated impact of evergreening

84% of patent applications during 2000-2010 are evergreening

patents

For 59 patented medicines, Thailand could have saved around 1,177

million THB (35 million USD) from 2000-2010

Source: Sutapak U et al (2011), Evergreening patent applications of

pharmaceuticals and access to medicines

10 |

Differential pricing

Sofosbuvir 12 weeks treatment course:

US: US$84,000 (reductions since Abbvie came to market)

UK: US$57,000

Egypt: US$900 (same price offered to public programme in Lao PDR; Mongolia)

Pakistan: US$1,620 (private sector)

11 |

Where to draw the line?

Opposing trends:

Argentina, India and Philippines follow new approaches in the pharmaceutical area to limit secondary patents Brazil and South Africa consider similar rules (only new chemical compounds are patentable unless new form is more efficacious)

US through trade agreements endeavours to expand patentability, e.g. secondary uses, methods of use and to prevent limitation of secondary patents

Public health, innovation and intellectual property 12 |

Policy options

Price controls: ‘Value-based pricing’; price/volume

agreements; pay for performance; risk-sharing

agreement / patient access schemes; reference pricing

schemes…

Differential pricing/price negotiations

Voluntary licensing agreements

Local production/import

TRIPS flexibilities, including compulsory licenses

Public health, innovation and intellectual property 13 |

Voluntary licenses HIV treatments (adults) INN Licensor Year Scope No countries Licsees

EFV MSD 2007 South Africa 1 (allows export to

SSA)

Several

d4T BMS 2001 SSA, India. country list 50 Several

DDL BMS 2006 SSA; India; country list 50 Several

RAL MSD 2011 LIC; SSA 56 2

SQV Roche 2006 LDC; SSA 65 Several

DRV Tibotec (Janssen/J&J) 2012 Non-assert: LDC; SSA

License: India

65

1+non-

assert.

ZDV; ZDV/3TC ViiV Healthcare 2010 LDC; LIC; SSA 69 Several

TPV Boehringer-Ingelheim 2004/07 LIC; LDC; Africa, India 78 Several

NVP Boehringer-Ingelheim 2004/07 LIC; LDC; Africa; India 78 Several

DTG; DTG/ABC MPP: ViiV Healthcare 2014 Country list 73 (+ no patent

count.)

MPP

EVG; QUAD

TDF+FTC+EVG

MPP: Gilead Sciences 2011 Country list 100 Several

EVG; QUAD

TDF+FTC+EVG

Gilead Sciences 2011 Country list 100 + 9 semi-

exclusive licenses for

MICs

4

ATV MPP: BMS 2013 Country list 110 (+ 34 no patent

count.)

MPP

RPV/TDF/3TC or

FTC; RPV

Tibotec (Janssen/J&J) 2011 Country list 112 5

TDF Gilead Sciences 2006/11 Country list 112 Several

TDF; TAF; FTC MPP: Gilead Sciences 2011/14 Country list 112 Several

Public health, innovation and intellectual property 14 |

Recent compulsory licenses & government use

Country Medicine Indication Measure Period Royalties Remarks

Ecuador Abacavir+la

mivudine

HIV/AIDS Gov use 2012 5% of US

price

adjusted by

diff. in GDP

Local prod.

Indonesia Seven

products

HIV/AIDS;

hepatitis

Gov use 2012 0.5% Local prod.

India Sorafenib Cancer CL 2012 6% Local prod.

Ecuador Ritonavir HIV/AIDS Gov use 2010 0.42% of US

price

Import; local

prod.

Thailand erlotinib;

letrozole;

docetaxel;

clopidogrel;

lopinavir/rito

navir

Cancer;

heart

disease;

HIV/AIDS

Gov use 2006-2008 3-5% Import

Brazil Efavirenz HIV/AIDS Gov use 2007 1.5% Import &

local prod.

Thailand Efavirenz HIV/AIDS Gov use 2006 0.5% Import

15 |

Impact of CLs: Examples

Brazil: – price reduction (from US$1.59 to US$0.43)

– first import from India, followed by local production after two years (argument:

lack of sufficient disclosure)

Ecuador: – price reduction (from US$1000 to US$800 initially; 50% reduction anticipated)

– import from India (2010 CL); local production (2012 CL)

Thailand: – price reduction (3.4 to 6.4 fold for efavirenz and ritonavir)

– GPO could initially not ensure local production of high quality products –

import from India

India: – price reduction from Rs.280000 to 8880, plus free supply to 600 patients

annually

Source: Kamp R, Doha Declaration on TRIPS & Public Health:

Creating Legal Avenues for Access to Medicines, Trade and Public Health Workshop,

2016

16 |

New mega-RTAs

Trans-Pacific Partnership (TPP)

Transatlantic Trade and Investment Partnership (TTIP)

(EU-US)

Regional Comprehensive Economic Partnership (RCEP)

(East Asia, 16 countries)

Free Trade Area of the Asia-Pacific (FTAAP) (APEC, 21

countries)

17 |

Source: http://www.bilaterals.org/?businesses-believe-apec-s-free

Size of new coming RTAs

18 |

IP protection requirements: TRIP-Plus

Expand scope of patentability – new forms of existing entities – new uses – new formulations and combinations, etc.

Data exclusivity (exclude use of registration data) 5+ years

New indication, formulation, method of administration 3+ years

Biological products8+ years

Extend patent term for regulatory delays

Patent linkage: Link drug registration and patent status

Criminal enforcement mechanisms for patent infringement

19 |

TRIP-Plus impedes the use of TRIP

flexibilities

IP Chapter Article 18.76:

Special Requirements related

to Border Measures

– German customs authorities

wrongfully seized a drug

shipment of “Amoxicillin” on the

suspicion that it infringed the

brand name “Amoxil” 4 weeks

delay

– Dutch customs authorities seized

a shipment of abacavir sulfate

while it was en route from India to

Nigeria.

Sources: WTO, European Union and a Member State – Seizure Of Generic Drugs in Transit, May 19, 2010. Zarocostas, J., Brazil and India file complaint against EU over seizure of generic drugs, BMJ 2010;340:c2672

• Investment Chapter Annex 9

(3B): expropriation

– Philip Morris filed a case

against Australian government

due to warnings on cigarette

packaging and removing

branding from cigarette

packaging its trademark and

investment rights

Source: https://au.news.yahoo.com/thewest/a/29064155/tobacco-giant-sues-australia/

Public health, innovation and intellectual property 20 |

Sources of Information

WHO-WIPO-WTO Study on “Promoting Access to Medical

Technologies and Innovation (2013): www.wto.org/english/res_e/booksp_e/pamtiwhowipowtoweb13_e.pdf

All you need to know about IP and health:

http://www.who.int/phi/publications/category/en/

Everything that is not happening in the WTO: www.bilaterals.org

WTO RTA database: http://rtais.wto.org

20

21 |

World Trade Report 2011: The WTO and Preferential Trade

Agreements:

http://www.wto.org/english/res_e/publications_e/wtr11_e.

htm

Texts of RTAs:

www.ustr.gov

www.efta.int

http://ec.europa.eu/enterprise/policies/international/facili

tating-trade/free-trade/index_en.htm

Sources of Information

22 |

Thank you

Dr Peter Beyer

Senior Advisor

World Health Organization

beyerp@who.int

Tel. +41-22-791 25 07

Dr Inthira Yamabhai

Technical officer

yamabhaii@who.int