[Ip-health] Patents Rush on Avian Fu Viruses and Vaccines

[Sangeeta]

A recent research paper (July 2007) titled "Some Intellectual Property
Issues Related to H5N1 Influenza Viruses, Research and Vaccines" by Edward
Hammond from the US-based The Sunshine Project has revealed a recent spike
in the number of patent applications covering the influenza virus (or parts
of it), as well as vaccines, treatments and diagnostics.

The paper is available at http://www.twnside.org.sg/avian.flu_papers.htm

The paper reveals recent statistics about patent applications related to
avian influenza and gives an insight into the patent claims that are made b=
y
the applicants, its impact on access and on R&D and the country of origin o=
f
the patent applicants.  According to Hammond, further claims on recent
isolates exist but are not yet available due to delays in submission of
applications and publication of patent claims.

A news report on the research paper is found below.

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Rush is on for patents on avian flu viruses and vaccines

Published in SUNS #6354 dated 30 October 2007 (reproduced here with the
permission of the SUNS)

Geneva, 29 Oct (Sangeeta Shashikant) -- Even as health authorities
increasingly worry about the possible occurrence of a deadly avian influenz=
a
pandemic, there has been a dramatic rise in international patent
applications related to the influenza virus, and vaccines and treatments
related to it.

This trend is of grave concern to public health officials and civil society
groups in developing countries who fear that patents relating to avian flu
will threaten the access of the poor and of people in developing countries
to affordable vaccines and treatment.

Many of these countries have been freely sharing avian influenza viruses
under the WHO's Global Influenza Surveillance Network, in the hope that the=
y
will be able to obtain timely, affordable and sufficient access to vaccines
and other benefits to battle a pandemic should it occur.

However, if the viruses (or parts thereof) or vaccines and technologies and
methods to make them are patented, the prices of the vaccines may become
higher and other producers may also be hindered from making the vaccines.

A recent research paper (July 2007) titled "Some Intellectual Property
Issues Related to H5N1 Influenza Viruses, Research and Vaccines" by Edward
Hammond from the US-based The Sunshine Project has revealed a recent spike
in the number of patent applications covering the influenza virus (or parts
of it), as well as vaccines, treatments and diagnostics.

Until 1993, there had been little or no such patent activity. The paper
shows that in 2006 however, more than 30 international patent applications
were filed under the Patent Cooperation Treaty (PCT) on influenza vaccines
alone, making it the year with the highest number of applications on such
vaccines.

World Intellectual Property Organization (WIPO) data indicate that during
the first half of 2007, as many influenza vaccine patent claims have been
filed as in the whole of 2006, meaning that this year is on track to at
least double the record set in 2006.

More than 80% of these applications originate from developed countries, wit=
h
at least 50% of these applications originating from the US.

The paper also identified 39 PCT patent applications between 2001 and 2007
for medicines, vaccines, microbes, peptides, nucleic acids and immunoassays
with the term "H5N1" in the claims. They include patent applications on
diagnostics, detection technologies, sequences, etc.

H5NI is a subtype of the Influenza A virus that can cause illness and death
in humans and animals, and there are fears that the virus could mutate to b=
e
spread through human-to-human transmission, and lead on to an influenza
pandemic.

The paper found that 87% of these applications had been filed in the last 1=
8
months (i. e. 14 in 2006 and 20 in the first half of 2007 alone). Patent
applicants from the US account for 46% of the applications.

The study reviewed recently published US and international patent data and
identified patent applications that cover H5N1 genes, gene sequences
(smaller pieces of genes), variations of those genes and their use.

The recent rate of growth of flu vaccine patent applications that make
claims specifically on H5N1-type influenza has surpassed that of influenza
vaccine claims in general.

Hammond stated that "because of the moving target' nature of influenza, it
may be assumed that further claims on recent isolates exist but are not yet
available due to delays in submission of applications and publication of
patent claims".

The author adds that what is most important are the worrying trends and
kinds of claims being lodged. These indicate a near-term (and long-term)
future in which H5N1 strains and all manner of technologies related to usin=
g
them in vaccines will be patented.

The WHO has declared a phase 3 pandemic alert (i. e. with no or limited
human-to-human transmission) and has cautioned that the world is now closer
to another influenza pandemic than at any time since 1968.

Thus, the recent increased enthusiasm in patenting comes as no surprise, as
the private sector and other institutions would see this situation as a
profit opportunity.

According to Hammond, "Some increase in patents is arguably to be expected
given rising concern about H5N1 and renewed interest in vaccines from major
pharmaceutical companies, not only for influenza, but for "biodefence" and
(often only from the North's view) emerging infectious diseases".

"The ultimate value of the currently claimed sequences and technologies is
uncertain, but if any prove critical to combat a pandemic, it may be
enormous", Hammond states in the paper.

This has major implications for who can manufacture the vaccines and other
related treatment products, whether there will be sufficient supplies of
vaccines in the event of a pandemic, and who can afford the medical
products.

In a number of patent applications, companies and other institutions have
made proprietary claims over viruses and their parts that originate from
developing countries. These include viruses contributed by countries such a=
s
Indonesia, Vietnam, China and Thailand, to the WHO-designated collaborating
centres and reference laboratories in the Global Influenza Surveillance
Network.

These laboratories are national institutions in the US, UK, Australia and
Japan that conduct tests to identify the virus strains that become
WHO-recommended vaccine seed strains, from which vaccines and diagnostics
can be developed. These strains have so far been made available to vaccine
developers and other institutions.

The fact that different players in the system have been seeking patents ove=
r
materials shared in good faith for public health reasons is a matter of
serious concern.

Patents grant an exclusive right that means that a patent holder can deny
others access to its patented subject matter including gene sequences,
research tools, diagnostic kits, vaccines or other products. Concerns about
patenting have frequently been raised amongst the international community a=
s
it could drastically hamper research and development as well as access to
essential medical products.

An example of such a patent application is that made by St. Jude's
Children's Hospital from the US, a laboratory designated by WHO to do
certain tests.

Its patent application on "Modified Influenza Virus for Monitoring and
Improving Vaccine Efficiency", published on 8 February 2007, claims small
changes to influenza HA genes. These changes are intended to strengthen the
immune system reaction to the genetically engineered virus. This might
improve possible pandemic influenza vaccines because people vaccinated may
exhibit a stronger immune reaction against H5N1.

This patent application claims any influenza HA gene modified in a certain
way. It specifically claims the modified HA gene from an influenza virus
isolated in Vietnam in 2004. This is the same strain whose entire HA and NA
sequences have been claimed by MedImmune (now AstraZeneca).

The study cited a number of other recent examples of patent claims over
genetic material originating from developing countries.

MedImmune (now AstraZeneca) and the US Government have filed a complicated
set of national and PCT applications over "Influenza hemagglutinin and
neuraminidase variants" that covers sequences from at least 29 influenza
strains, in many cases the entire HA and/or NA genes. The patents cover
producing influenza vaccines from them by placing the genes, or variants,
onto a "backbone" of a lab-adapted influenza strain.

Three applications are relevant to the pandemic discussion. These are: (1)
application WO2005116260 that claims the entire HA and NA sequences from
viruses originating in Hong Kong and Vietnam; (2) application WO2005116258
that claims a series of 20 H5N1 and H9N2 HA and NA sequences from viruses
originating in Vietnam and China; and (3) application WO2006098901, the
newest member of the patent family to be published that claims 48 entire HA
and NA genes from 24 different Influenza A and B viruses.

In this set of applications, the US government may have rights. If the US
government has rights, its rights would include the ability to =B3march in=
=B2 on
the patent i.e. The government may force the company to issue it a royalty
free, irrevocable licence in the event of a national emergency.  Some US an=
d
international patent applications list government inventors who are
employees of the US Department of Health and Human Services (HHS). The US
Centres for Disease Control (CDC), a WHO Collaborating Centre, is part of
HHS.

Novavax, Inc. (US) has filed a US and PCT patent application over
"Functional influenza virus-like particles" (VLPs). Novavax's technique is
to place influenza HA, NA, and M1 genes into another virus and to grow the
hybrid virus in an insect cell culture. This produces partial influenza
viruses ("virus-like particles" - or VLPs).

These may be useful for vaccines because they can, like a whole virus,
produce an immune reaction. In some cases, the influenza genes are changed
("optimized") for use in the insect cell system.

This patent application claims any influenza VLPs produced by its cell
culture methods as well as specific VLPs. VLPs claimed include those made
with HA and NA genes of virus strains from Indonesia and China, as well as
VLPs made from sequences 90% or more homologous (close in genetic structure=
)
to those particular sequences.

Another US company, Hawaii Biotech Inc., has US and PCT applications on
"Influenza recombinant subunit vaccine".

This patent application, published on 22 February 2007, claims 12 variation=
s
on production of a new type of influenza vaccine made in insect cells and
H5N1 vaccines made with the technology.

It specifically claims H5N1 genetic sequences from a virus isolated in
Indonesia in 2005 and another isolated in China in 1997. It also claims
sequences from an H3N2 virus isolated in China in 2002.

Yet another US company, Protelix Inc., filed a PCT patent application
(published on 3 May 2007) on "Influenza Combinatorial Antigen Vaccine". Thi=
s
covers nucleotide sequences from influenza HA and NA genes, a method for
selecting them, and their use in influenza vaccines.

An advantage that Protelix claims is that it can tailor vaccine composition
to the virus strains from a specific geographic area. Protelix specifically
claims HA and NA sequences derived from recent H5N1 isolates from Thailand
and Indonesia, as well as slight variations on those sequences, for use in
vaccines.

According to Hammond, such patent claims for dozens of HA and NA gene
sequences used in current vaccines are one way that a microbial resource ca=
n
be locked up. Another way is a "thicket" of smaller patent claims that
gradually leads to an overlapping and confusing mess of claims. Currently,
both types of problems are emerging for H5N1 viruses and vaccines.

In his paper, Hammond also explains the "homology fishing" strategy used by
patent applicants to extend their patent controls. He states that much of
the value of an influenza virus, from a patent perspective, lies in its
particular HA and NA gene sequences.

However, as virus sequences change faster than patent applications can be
processed, patent applications are trying to reach forward in time, and
claims are written in a way that, expressed in plain language, are the
equivalent of "we claim this gene and anything like it" (i. e. mutations
that have not occurred).

While not entirely new, homology fishing, according to Hammond, may be
reaching a new level of importance with influenza-related patents because o=
f
the potentially devastating effects of a pandemic.

The race to file patents amidst a public health disaster is not new. It is
reported that following the outbreak of Severe Acute Respiratory Syndrome (
SARS'), a form of atypical pneumonia caused by a new strain of coronavirus
in 2002, WHO coordinated a team of international scientists and researchers=
.

These scientists in Canada, Hong Kong and the US were able to sequence the
SARS virus with remarkable speed but several of the public research
institutions filed patent applications in respect of the complete genetic
sequence of the coronavirus.

According to a WHO notification of May 2003, the detailed claims in these
applications have not yet been made public but are reported to be
sufficiently broad to allow their holders to claim rights in most diagnosti=
c
tests, drugs, or vaccines that have been or would be developed to cope with
the outbreak.

Some of the university or governmental patent applicants have themselves
begun negotiations with commercial partners to develop diagnostic tests and
other products. During this time, fears were expressed that prospective
patent holders might prevent or limit access to diagnostics, vaccines and
pharmaceutical drugs which are being developed by commercial companies to
address the SARS virus.

While SARS may no longer be a problem, similar questions have now arisen fo=
r
influenza.

(Note: The paper is available at
http://www.twnside.org.sg/avian.flu_papers.htm
<http://www.twnside.org.sg/avian.flu_papers.htm> ) +