Public health, innovation and intellectual property 1 |

Patents & health:

focus on access

– TBS

October 2017

Dr Peter Beyer, Senior Advisor

Public health, innovation and intellectual property 2 |

Patent

Gives the right to the inventor to exclude others from

commercially using the invention against disclosure

Claims define the scope and can differ from one country

to the other depending on examination

Only what is claimed is protected: a patent on use of

an antibiotic to treat ophthalmological infections does not

prevent marketing a generic tablet; patent on polymorph

B does not prevent a tablet using polymorph A

Public health, innovation and intellectual property 3 |

Patents

There is nothing such as a worldwide patent!

WIPO Patent Cooperation Treaty allows for worldwide

filing, but applicant receives individual national/regional

patents

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, The art of using secondary patents to improve protection,

International Journal of Medical Marketing,

Volume 3, Number 3, June 2003, pp. 226-238(13)

First patent: covers class of compounds (Markush claim)

Second patent: individual compound

Third patent: Crystalline form(s)

Combination with other drugs

Composition&dosage

Life cycle patents

Typical patent flow

for pharmaceuticals

(chemicals)

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/

Public health, innovation and intellectual property 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

Public health, innovation and intellectual property 8 |

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 9 |

Patentability criteria: incremental

innovation vs. "evergreening"

India: patent applications rejected as known substances

are not considered novel under Section 3d Patent Act

(e.g. paediatric formulations, combination patents,

polymorphs) unless patent applicant can prove

enhanced efficacy

Examples: patents refused on: polymorph of imatinib

mesylate; suspension of nevirapine hemihydrate;

tenofovir disoproxil

PATENT LANDSCAPE

IMATINIB

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

Patent 1 Patent 2 Patent 3

Pyrimidine Derivatives & their Preparation Covers base compound imatinib, pharmaceutically acceptable salt, method of use for chemotherapy, […]

Crystal Modification of a N-Phenyl-2-Pyrimidineamine […] Covers the beta crystalline form of imatinib (imatinib mesylate)

Treatment of Gastrointestinal Stromal Tumors Covers use of imatinib mesylate for treatment of gastrointestinal stromal tumors – GIST

Patent No. US 5,521,184 EP 0998473 B1 WO2002/34727

Expected Expiry 25 March 2013 16 July 2018 26 October 2021

Brazil Granted Patent No. PP1100739 (expired)

App No. PI9810920 Refused – Under Appeal

App No. PI0114870 Refused – Under Appeal

China Granted Patent No. 1043531 (expired)

Granted Patent No. 1134430

Granted Patent No. 1276754

European Patent Office (EPO)

Granted Patent No. 0564409 (expired)

Granted Patent No. 0998473

Granted Patent No. 1332137

India Not filed App 1602/MAS/1998 Refused by Supreme Court following pre-grant oppositions

No patent

Kenya (ARIPO) Not filed Not filed Not filed

OAPI Not filed Not filed Not filed

South Africa Granted Patent No. 9302397 (expired)

Granted Patent No. 9806362

Granted Patent No. 200302155

Public health, innovation and intellectual property 11 |

More examples of relevance to GF

Patent on tenofovir fumarate salt (WO9905150) rejected

in Brazil and India; granted in China and Mexico

Abacavir:

– base patent on abacavir expired in 2010

– patent on hemisulfate salt will expire in 2018

– patent on composition for paediatric use will expire in 2019

Patents on rilpivirine in combination with TDF and FTC

Patent on lopinavir soft gel capsules

Public health, innovation and intellectual property 12 |

What is a voluntary license?

The owner of a patent can allow others to use the

invention, in particular to manufacture, sell, export or

import the patented product

Such a mutual agreement is called voluntary license

Public health, innovation and intellectual property 13 |

What is a voluntary license?

The owner of a patent can allow others to use the

invention, in particular to manufacture, sell, export or

import the patented product

Such a mutual agreement is called voluntary license

It lays down the conditions, namely

– the territory (list of countries in which the licensee may sell the

invention)

– Royalties

– Exclusive or non-exclusive

Voluntary licenses HIV treatments (adults) June 2016 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 15 |

What is a compulsory license?

National patent laws mandate national authorities to allow

third parties to use a patented invention without the

authorization of the patent owner under certain conditions

to address certain unwanted consequences

– unfair competition,

– not working the invention,

– abusively high prices,

– health emergencies and others

WTO TRIPS contains certain conditions, but does not

limit the grounds

Public health, innovation and intellectual property 16 |

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

HIS/EMP | Communications Planning WHO/HIS/EMP | October 10, 2017

Patent protection vs Data Exclusivity P

ate

nt A

pplic

ation F

iled

Pate

nt

Issued

FD

A A

ppro

ved

Data Exclusivity, NCE (5 yrs)

Data Exclusivity, Non-NCE (3 yrs)

Orphan Drug Market Exclusivity (7 yrs)

Patent Term

Restoration

Original Patent Term - 20 Years from filing

Biologicals (12 yrs)

Public health, innovation and intellectual property 18 |

WHO Patent Landscapes

sofosbuvir (updated)

Harvoni

Gilead

Sciences

ledipasvir (updated) Gilead

Sciences

Daclatasvir (updated) BMS

dasabuvir Viekira Pak

with ritonavir

AbbVie

ombitasvir AbbVie

paritaprevir AbbVie

simeprevir Janssen

www.who.int/phi/implementation/ip_trade/ip_patent_landscapes/en/

Public health, innovation and intellectual property 19 |

The of intellectual property in local

production in developing countries

http://www.who.int/phi/publications/int_pro

p_local_prod_opportunities_chanllenge

s/en/

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

Public health, innovation and intellectual property 20 |

http://www.who.int/phi/publicat

ions/category/en/

WHO Global Report on Access to Hepatitis C

Treatment

Public health, innovation and intellectual property 21 |

Promoting Access to Medical Technologies

and Innovation

www.who.int/phi/promoting_access_me

dical_innovation/en/

www.who.int/phi/publications/category/e

n/

Dr Peter Beyer

Senior Advisor

World Health Organization

beyerp@who.int

Tel. +41-22-791 25 07