Trilateral Seminar on R

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Trilateral Seminar on RD Policies Related to
Emerging/Re-emerging Infectious
DiseasesSecurity and Intellectual Property
Constraints on Emerging Infectious Diseases
Research

• Gerald T. Keusch, M.D.
• Provost and Dean for Global Health
• Boston University

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Security and Academic FreedomBalancing
legitimate social goals
Can this be done in times of crisis?
Security needs
Academic freedom
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This is not a new debate in the U.S.

• They that can give up essential liberty to obtain
  a little safety deserve neither liberty nor
  safety.
• Benjamin Franklin, Historical Review of PA, 1759

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This is not a new debate in the U.S.

• The Association of American University
  Professors was founded shortly after the outbreak
  of the World War. The Association responded to
  our country's entry into the war by appointing a
  special Committee on Academic Freedom in Wartime.
  That committee's report was imbued with a spirit
  of jingoism extreme nationalism characterized by
  a belligerent foreign policy, as the new
  Association was eager to dispel any suspicion of
  a want of patriotic fervor on the part of the
  young academic profession.
• "Report of the Committee on Academic Freedom
  in Wartime," Bulletin of the American Association
  of University Professors (February-March 1918)
  29-47

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Report of Committee A for 1943, Bulletin of the
American Association of University Professors
(February 1944) 13

• As war in its second year becomes the accepted
  routine of American life, rather than a confused
  departure from the ways of peace, the decision of
  AAUP to hold fast to its fundamental principles
  has been justified.
• Freedoms lost are difficult to regain.
• Academic freedom is one facet of intellectual
  freedom other aspects of that larger concept -
  freedom of speech, freedom of the press, and
  freedom of religion - are among the avowed
  objects for which this war is being fought.
• It would be folly to draw a boundary line across
  the area of freedom.

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Report of an AAUP Special CommitteeAcademic
Freedom and National Security in a Time of
Crisis Academe Nov/Dec, 2003

• Historically, the government's domestic arsenal
  in times of crisis has included three weapons
  secrecy, surveillance, and suppression.
• The need to maintain secrecy of certain critical
  military information is indisputable, as is the
  imperative to gather information about an enemy's
  actions and plans.
• The law has long criminalized giving aid and
  comfort to the enemy, which entails, for
  example, trading with or providing financial
  support to the enemy.
• Confined within proper bounds, such measures need
  not pose a threat to civil liberties in general
  or to academic freedom in particular.

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On the one hand

• We have learned from experience that in the
  passion of war, and in the hands of those who may
  be properly zealous for its successful
  prosecution, the boundaries can blur.
• Information the body politic vitally needs to
  maintain oversight of public affairs has been
  made secret, and classification has sometimes
  been imposed solely to save the classifying
  entity from accountability and embarrassment.
• Surveillance has been extended to lawful
  activity. Political dissent has been suppressed
  and, at points, such suppression has threatened
  to chill the robustness of debate upon which
  democracy depends.

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On the other hand

• Although the actions of private groups may affect
  the climate of a campusthe government is
  necessarily held to a different standard.
• It has the capacity not only to preach, but also
  to act to quarantine information to place
  people, even their private telephone and
  electronic communications, under covert
  surveillance or research involving foreign
  students and to regulate scholarly exchange,
  including teaching and researchers.

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Baseline assumption security and freedom exist
in an inherent and therefore ineluctable tension.

• This report questions that assumption.
• The free exchange of scientific data- for example
  a component of a deadly toxin- may well help to
  equip a terrorist group with a means of mass
  destruction. But that same openness may better
  equip researchers to produce the means of
  preempting or neutralizing that very threat.
• Secrecy can impede the pace of scientific
  discovery for good as well as for ill.

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Deep philosophical debate how much do we (can
we) cherish academic freedom?

• There are four primary areas of academic freedom
  freedom to research, freedom to publish, freedom
  to teach, and freedom to speak.
• Since 9/11 there have been attempts to (1)
  categorize and restrict some research as
  "sensitive, and therefore subject to control
  (2) implement export control laws and select
  agent regulations, (3) limit the publication of
  research findings, (4) prohibit certain foreign
  nationals from collaborating with U.S.
  researchers and receiving education and training
  in U.S. universities, and (5) restrain faculty
  free speech.
• The debate has only begun Can even the debate
  be shut down? Will academia get involved? Can we
  afford to be complacent? Can policy be affected?

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Consensus is lacking on the best method to
balance scientific publishing and national
security.PNAS 2003, 100 1464 (Also Science,
Nature)

• Continue the current method of classification of
  research results as the most appropriate because
  imposing new restrictions will only hurt
  scientific progress, and because the usefulness
  of research results to terrorists is limited.
• Self-regulation by scientists using an
  Asilomar-like process to develop consensus (eg
  recombinant DNA). The inclusion of scientists,
  policymakers, and security personnel in the
  development phase of guidelines and regulations
  will lead to a concensus process
• Rely on publishers to scrutinize articles for
  data with potential security ramifications is
  another option.
• Mandate review by federal funding agencies,
  either before funding or publication, as a
  centralized federally based option.

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Statement of editors

• We must protect the integrity of the scientific
  process by publishing manuscripts of high
  quality, in sufficient detail to permit
  reproducibility. Without independent
  verification, a requirement for scientific
  progress, we can neither advance biomedical
  research nor provide the knowledge base for
  building strong biodefense systems.
• We recognize that the prospect of bioterrorism
  has raised legitimate concerns about the
  potential abuse of published information, but
  also recognize that research in the very same
  fields will be critical to society in meeting the
  challenges of defense.

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Statement of editors (continued)

• 3. Scientists and their journals should
  consider the appropriate level and design of
  processes to accomplish effective review of
  papers that raise such security issues.
• 4. On occasion an editor may conclude that
  the potential harm of publication outweighs
  potential societal benefits. Under such
  circumstances, the paper should be modified or
  not be published. Journals and scientific
  societies can play an important role in
  encouraging investigators to communicate results
  of research in ways that maximize public benefits
  and minimize risks of misuse.

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RD Intellectual Property Issues
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Estimated global health RD spending, US
billion - GFHR
84.4
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Sector contributions to global health research
expenditure - GFHR
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Private for profit health research spending, US
, millions - GFHR
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Present Context of IP for Products For DCs

• Increasing public attention to global disparities
  in health AIDS, Tb, malaria in particular
• Public exposure to controversies stemming from IP
  and trade issues (TRIPS), globalization, WTO,
  IMF/World Bank
• Media portrayal
• Rich vs. poor
• Big pharma vs. sick people
• Insensitive bureaucracies vs. caring relief
  organizations

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Present Context of IP for Products For DCs

• Media stories gain attention but are at best
  simplistic views that obscure underlying issues
  and at worst create barriers to solutions
• IP perceptions vary depending on perspective
• Patents are or are not the problem
• Profit based industry controls IP, guarantees
  high prices, and prevents universal access
• Failure of poor countries to implement and
  enforce laws to protect IP
• Uncertain, risky, and inherently costly nature of
  health product development

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Historical Context of US IP Laws

• 1970s Congress was concerned that IP generated
  from federally supported research and owned by
  the govt was not being applied - government patents vs 25-30 of private sector
  patents were being applied
• Major concern as well that US would fall behind
  others in technology and market dominance
• Main barrier was the unwillingness of the
  responsible agencies to grant exclusive licenses,
  in an apparent interest to protect the public
  interest.
• Companies complained that even the non-exclusive
  licensing process was excruciatingly slow
• Different policies were in effect in different
  agencies

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Congress Attempts A Solution

• Bayh-Dole Act of 1980 (officially Amendments to
  the Patent and Trademark Act, P.L. 96-517)
• Pertains to extramural research funded by
  government
• B/D extended IP right to non-government
  organizations performing federally-sponsored
  research, including universities and small
  business
• Stevenson-Wydler Act of 1980
• Provides the same rights and benefits to
  government scientists

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Congress Attempts A Solution

• Together, the 2 laws created a uniform licensing
  system for all federal agencies, reduced the
  steps needed to grant licenses, and provided
  incentives for industry to invest risk capital in
  product commercialization from federal patents.
• B/D allowed universities and small business
  government contractors to receive title to
  inventions derived from federal support
• allowed grantees and contractors to license the
  technology developed under these patents for use
  by small business and private industry
• 1983 presidential directive extended these rights
  to large businesses

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Some provisions were rejected

• Initial version included a formula for
  repayment of profits back to the taxpayers when a
  patent yielded commercial products. The
  provision was dropped only because it was
  impossible to agree on the mechanisms. This idea
  still comes up from time to time (Wyden bill),
  but is opposed by academic centers and small
  business interests.

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Some safety provisions were included

• B/D ensured that the Government retained the
  rights to meet future needs and to protect the
  public against non-use or unreasonable use of
  inventions by reserving
• right to a non-exclusive, nontransferable,
  irrevocable, paid-up license to practice for or
  on behalf of the U.S. everywhere (compulsory
  license)
• march-in rights that enable the government to
  require the patent holder or licensee holder to
  grant use rights to another user with due
  compensation under special circumstances lack of
  use within an agreed-upon time frame, or unmet
  special health or safety needs licensee

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Safety Clauses

• March-in rights have been formally tested once
• In 1997 CellPro petitioned to use a Hopkins
  stem-cell separation method because they couldnt
  negotiate a license with JHU
• CellPro used the technology anyway, was sued and
  found guilty of willful infringement on the
  Hopkins patent
• CellPros petition argued that JHU and its
  licensee failed to commercialize the technology
  in a timely fashion and that public health and
  safety needs were not being met

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Safety Clauses, continued

• NIH rejected both grounds of the petition (most
  is pre-product IP, minor part of total IP, and
  what does timely mean?)
• Universities and industry remain concerned that
  march-in will undermine licensing rights under
  B-D, and that petitions for march-in will
  prompt a full-blown legal process, with major
  time and financial burdens for all involved

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Anthrax, Cipro, and Compulsory Licenses

• The anthrax scare in the fall of 2001 led HHS to
  seek a stockpile of Cipro to treat 10 million
  people. This was far greater than the supply, or
  the capacity to produce it in a timely manner. On
  October 16, Sen. Schumer asked Sec. Thompson to
  issue a complusory licenses to generic
  manufacturers.
• (October 19, 2001) AIDS activists denounced the
  US government's decision to uphold Bayer's patent
  monopoly on ciprofloxacin, a drug approved for
  anthrax treatment. Unlike Canada, which decided
  to break Bayer's patent, the US will not make use
  of cheaper supplies of drug from competing
  generic manufacturers of ciprofloxacin by issuing
  a "compulsory license."

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January 15, 2002, Bayer 10K reportofficial
annual business and financial report filed public
companies with the SEC

• The extent of patent protection varies from
  country to country. In some of the countries in
  which we operate, patent protection may be
  significantly weaker than in the United States or
  the European Union. Piracy of patent protected
  intellectual property has often occurred,
  particularly in some Asian countries.
• In an effort to control public health crises,
  some developing countries have recently announced
  plans for substantial reductions in scope of
  patent protection for pharmaceutical products.
  These countries could facilitate competition
  within their markets from generic makers who
  would otherwise be unable to introduce competing
  products for a number of years.

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• In response to the recent bioterror attacks in
  the U.S. the U.S. and Canadian governments
  contemplated compulsory licensing of Cipro, in
  effect, permission to generic manufacturers to
  market ciprofloxacin before the expiry of our
  patent rights. Although we reached agreements
  with the two governments intended to ensure
  adequate supplies of cipro while preserving our
  existing patent rights, we cannot assure you that
  these or other governments would not impose
  compulsory licensing in future in response to
  renewed or increased bioterror attacks.
• In order to ensure that sufficient antibiotics
  will be available from U.S. governmental
  stockpiles, and in addition to donating four
  million tablets, Bayer has entered into an
  agreement with the U.S. government to supply up
  to 300 million tablets, the first 100 million
  tablets to be delivered by the end of 2001 at a
  price of 0.95 per tablet.
• In Canada, Bayer Inc. - in addition to donating
  200,000 Cipro tablets - has agreed to supply one
  million tablets of Cipro within 48 hours upon
  request from the Canadian government and has
  assured that it can meet the current and future
  demand of Cipro in Canada.

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• The 2 clauses are still debated by IP specialists
  and still provoke anxiety in academia and the
  private sector
• Because B-D expressed Congress view that the use
  of discoveries supported by public funds to
  improve health was clearly in the public
  interest, even if it must be carried out by
  government action, the question remains when and
  with what justification would the clauses be
  invoked by the government?

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A new twist

• June 2005 Supreme Court rules that local
  governments may force property owners to sell out
  to make way for private economic development when
  officials decide it would benefit the public,
  even if the property is not blighted and the new
  project's success is not guaranteed.
• Vermont and the District of Columbia have already
  proposed legislation that would allow them to
  issue compulsory drug licenses to patent holders
  under the eminent domain process. States would
  then contract with a generic manufacturer to
  produce the drug, paying the drug company a
  "reasonable royalty 4 proposed - on each
  sale. The competition would facilitate the
  "public good" by offering state residents cheaper
  drugs.

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Economic, Legal and Policy Barriers to the Fully
Effective Use of IP

• The main economic barrier is the high cost of
  developing a product from a basic discovery
• The main legal barrier is the complex ownership
  system in place to protect the interest of those
  who invest in research and development, and to
  maintain incentives to continue such investment
• The main policy barrier is the difficulty to
  balance the competing interestsscientific
  community, consumers, and industrial
  developmentthat vie for advantage in the
  potentially lucrative world of commercialized
  health products
• Even when all of these are aligned, public
  perception may preclude effective use eg Golden
  rice story

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Assessing B/D 25 Years Later

• Most assessments suggest that the laws performed
  as Congress intended
• Independent analyses conclude that the law
  increased technology transfer from researchers to
  private industry, improved government
  patenting/licensing processes, and has
  facilitated introduction of products that improve
  the health and well-being of the public
• Royalties received by universities engaged in
  technology transfer have grown by 20-30 percent
  annually proof of application of IP to product
  development and marketing
• Yet, despite these benefits, most university
  technology transfer offices have licensed few or
  no commercialized products and typically operate
  at a loss unless they have blockbuster IP and
  many products remain too expensive for those in
  need to purchase them

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Its not the patents, its the perception!
But, there is change in the wind, as universities
review their patent and licensing priorities and
give greater consideration to global public goods