INTELLECTUAL PROPERTY ISSUES IN VACCINE DEVELOPMENT. Cecilia Oh Global Health and Technology Access Program Duke University

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1 INTELLECTUAL PROPERTY ISSUES IN VACCINE DEVELOPMENT Cecilia Oh Global Health and Technology Access Program Duke University

2 Outline Changes in global vaccines market IPRs and vaccine development Lessons from Influenza vaccine project

3 Vaccines: Weapons of mass protection? Globalization and public health Threats of old and new infectious diseases Anthrax (bioterrorism), SARS, H5N1, H1N1 Beyond domestic health concerns Global vaccine development priorities Previously, low-margin, limited-use products New drivers for vaccine development Emergence of manufacturers in developing countries But, what is impact of IPR on innovation and access?

4 Vaccine market growth Growth in global vaccine market (US$ bil.) over selected years between

5 Complexity of vaccine IPR Components of a modern vaccine may be protected by different IPRs Platform/ process DNA seq Expression Vehicle Antigen Adjuvant vaccine Delivery device Immunostim Excipient

6 ALL PCT PATENT APPLICATIONS FOR INFLUENZA VACCINES (1983 March 2011) PCT Classification A61K 39/145 (Orthomyxoviridae). Source: WIPO/PatentScope The 482 international applications in this category claim influenza A, B, and C vaccines for animals or humans. Claims may relate to adjuvants or other formulation technology, sequences, production, or a combination thereof. Source: Hammond (2011), An Update on Intellectual Property Claims Related to Global Pandemic Influenza Preparedness

7 PCT PATENT APPLICATIONS FOR INFLUENZA VACCINES WITH THE TERM H5N1 AND/OR H1N1 APPEARING IN THE PATENT CLAIMS PCT Classification A61K 39/145 Source: WIPO/PatentScope The 58 international applications matching this search claim influenza A vaccines for animals or humans. Claims may relate to adjuvants or other formulation technology, sequences, production, or a combination thereof. The were no matching applications before Source: Hammond (2011)

8 PCT PATENT APPLICATIONS FOR INFLUENZA VACCINES WITH THE TERM H5N1 AND/OR H1N1 APPEARING IN THE PATENT CLAIMS Surge since 2007 in influenza vaccine applications making specific H5N1and/or H1N1claims continues unabated Applications by Year (YTD) 3 Applications by country of origin Source: Hammond, E (2007) Some IP issues related to H5N1 influenza viruses, research and vaccines Source: Hammond (2011)

9 Vaccine patents: What do they cover? Vaccine Methods of prophylaxis and treatment Modified de-activated organism DNA, amino acid sequence of antigens, modifications, fusion proteins Expression systems Adjuvants Formulations, dosage, carriers, excipients, diluents etc. Delivery device and dosing regimen Research tools and platform technologies Processes conjugation technology, expression systems, manufacturing and purification processes

10 What are the implications? What is being patented? Where are they patented? What obstacles does patent protection present for the development and production of vaccines? How can one legally manufacture and import/ export vaccines? What is the timeline for IPR protection on the technologies? What obstacles does patent protection present for rapid dissemination of vaccines in time of public health need/crisis?

11 IPR and access to medicines Global debate on patents and access to medicines WTO TRIPS Agreement Minimum standards of IPR protection; e.g., 20 year patent term Lessons from the global response to AIDS: scale up of HIV treatment facilitated by access to affordable generic medicines Role of generic competition in reducing prices Doha Declaration and use of TRIPS flexibilities to enable access to generic medicines

12 IPR and access to medicines Use of TRIPS flexibilities Flexibilities in TRIPS, implemented within national law E.g., compulsory licences to enable import and/or local production of generic versions of patented medicines CL granted in Malaysia, Indonesia, Brazil, Ecuador Thailand s experience with TRIPS flexibilities Universal access to healthcare and access to medicines on NLEM Compulsory licences for import and/or local production of 2 ARVs and 5 other medicines Relevance to vaccine development and production?

13 Small molecules vs. vaccines Differences between small molecules and vaccines Vaccine processes to ensure quality and potency are often more complex and costly than for small molecules Regulatory pathways are similar, but for small molecule drugs the regulatory approval process for a 'generic' can be done entirely on chemical composition Can vaccines be copied in the same way as generic drugs? Each vaccine typically must undergo full preclinical and clinical development for approval.

14 IPR relevant to vaccines Patents Upstream patents (e.g., on derived sequences and research tools) and downstream patents (e.g., on production technologies, adjuvants, delivery mechanisms) Undisclosed information Know how and trade secrets are forms of undisclosed information that can be protected under TRIPS Agreement. Importance of know how in vaccine production. Undisclosed test data Information arising from clinical trials submitted for marketing approval. Reliance on test data for proving bioequivalence is a key factor in speedy and cheaper approvals of generic drugs. But, may be less relevant in case of vaccines

15 IPR barriers to vaccine development Since many EPI vaccines were produced over 20 years ago, patents may not present significant barrier to manufacture Some of the basic methods involved in earlier technology (e.g., egg-based technology) may no longer be patented But there may be new technologies and variations of the basic methods that could be patented: Improved formulations (e.g., combinations, adjuvants, doses, delivery routes, etc) Improved processes for manufacture (costeffectiveness, improved immune response, etc.)

16 IPR barriers to vaccine development Technical know-how: Conventional egg-based vaccines requires technical know-how and skills that may not be readily found outside of existing companies Access to regulatory dossiers: Generation of a regulatory dossier from the beginning, including extensive preclinical and clinical safety data, genetic stability etc may take years. Licensing such products from manufacturers who have already generated the data would avoid the need to repeat this process IPRs and licensing can have an impact on vaccine developer s own innovation and on their ability to produce an existing vaccine

17 Claims : U.S. Patent (SKB) 1. A combined vaccine composition comprising Hepatitis B surface antigen (HBsAg) and a number (n) of other antigens against one or more of the following pathogens: diphtheria, tetanus, pertussis, polio, Haemophilus influenzae b, Hepatitis A, meningitis A, meningitis B, meningitis C, and otitis media, in combination with an adjuvant comprising one or more aluminum salts and in which the adjuvant used to adsorb the HBsAg is aluminum phosphate, with the proviso that when n is 1 the other antigen is not an antigen against hepatitis A. 2. The combined vaccine composition according to claim 1 in which the HBsAg is adsorbed to aluminium phosphate and in which at least one of the other antigens is adsorbed to aluminium phosphate.

18 Identifying relevant patents What is the relevant technology? Has the patent been granted? Where is patent in force? When does the patent expire? What is the scope of the patent claims? Does my vaccine product infringe the patent? Where do I wish to make, use and sell my vaccine? Are there non-infringing alternatives?

19 Lessons from Influenza vaccine project UNCTAD-WHO case study WHO GAP and GPO s influenza vaccine project Technical support and technology transfer to GPO Some observations: Vaccine development capacity in Thailand Policy framework and direction R&D Investment and infrastructure Regulatory approval process IPRs and technology transfer