[Ip-health] SUNS: Growing Movement Opposing Granting of Drug Patents

[Mike Palmedo]

Growing movement opposing granting of drug patents

SUNS #6081 Thursday 3 August 2006

Geneva, 2 Aug (Sangeeta Shashikant) -- Many more cases are being filed
in India by groups representing HIV/AIDS patients against the granting
of patents for HIV/AIDS medicines, adding to the initial two cases after
a 2005 amendment to the Indian patent law.

Four new cases of pre-grant opposition to the patenting of the HIV/AIDS
medicines have been filed by Indian groups of people living with
HIV/AIDS at three separate patent offices in India.

These new cases follow two earlier pre-grant oppositions against patent
applications pertaining Combivir and Tenofovir, also filed also by
groups of people living with HIV/AIDS.

The movement by AIDS patients to file pre-grant opposition to patent
applications is developing at a moment when there is serious public
concern whether Indian generic drug companies will be able to continue
supplying cheaper generic versions of branded products, both to India
and to other developing countries.

Recent studies (reported below) have concluded that a majority of Indian
generic firms are facing a situation of reduced incentives to produce
generics in future, due to uncertainties following recent amendments to
the Indian patent law, and the cumbersome procedures to fulfill
requirements of the recent amendments to the TRIPS Agreement of the WTO.

The movement to oppose patent applications is significant in that if
patents are not granted on the relevant drugs, then it is far more
likely for the Indian companies to produce more affordable generic
versions of the drugs.

All the four new pre-grant opposition cases were filed pursuant to
Section 25 of the Indian Patents (Amendment) Act, 2005 which allows "any
person" to oppose in writing following the publication of a patent
application. The opponents are also requesting a hearing with the patent
office.

While the details of the oppositions filed differ, the main objective is
the same i. e. to promote access to medicines for all in India and
abroad. Many developing countries rely on India as their main source of
supply of affordable generic medicines.

Thus the Indian situation is being watched closely internationally
because of the leading role of Indian companies in the global supply of
safe, effective and affordable generic medicines for AIDS and other
diseases.

Due to competition by the Indian firms, the cost of HIV/AIDS treatment has
dropped from $10,000 to $150 per person per year in recent years. The costs
of treating other ailments have similarly been reduced.

When India changed its law in 2005 to allow for product patents for
pharmaceutical products, in compliance with its obligations under the
TRIPS Agreement of the WTO, there was significant public concern whether
Indian-manufactured generic versions of patented medicines would be as
readily available as prior to 2005.

One of the new pre-grant cases is against the grant of patent
application titled "Pharmaceutical Formulations" (Application no:
727/DEL/1997A) filed on 21 March 1997 by Glaxo Group Limited. The case
was submitted by the Indian Network of Positive People (INP+) and the
Uttar Pradesh Network for People Living with HIV/AIDS at the Delhi
Patent Office.

The groups said that being a signatory of the Doha Declaration on the
TRIPS Agreement and Public Health, India must interpret the Patents Act
to give effect to the aim outlined in the Declaration i. e. that the
TRIPS Agreement should be interpreted and implemented in a manner
supportive of the WTO members' right to protect public health and in
particular to promote access to medicines for all.

The pre-grant opposition states that the patent application comprises
merely of a combination of known substances i. e. a protease inhibitor
with tocopherol, or Vitamin E, to achieve a known result. It also states
that in a further formulation, known solvents are added to make the
combination more flowable and cheaper to manufacture.

The groups thus seek that a patent not be granted on the grounds of lack
of novelty and inventive step, both critical criteria in determining
patentability. They claim that the alleged inventions are "merely a new
use of known substances" that does not result in an enhancement of
efficacy as well as a mere admixture, all of which are not patentable
under the new amended Indian patent law.

The patent application cites Amprenavir, (a drug that works by
inhibiting HIV protease, an enzyme essential for the replication of the
virus and used in combination therapies to treat HIV/AIDS) as the
preferred protease inhibitor for working the alleged invention.

Another pre-grant opposition case was filed against a patent application
titled "2-(2-Amino-1, 6-Dihydro-6-oxo-purin-9-yl)-methoxy-1,
3-propanediol Derivative" by Hoffmann-La Roche (Application No.
959/MAS/95) on 27 July 1995 at the Chennai Patent Office. The case was
filed by INP+ and the Tamil Nadu Networking People with HIV/AIDS.

According to the opponents, the patent application relates to
valganciclovir which is a pharmaceutical compound that is a pro-drug of
another known compound ganciclovir and is a critical treatment for CMV
retinitis, a common AIDS-related opportunistic infection that can cause
blindness.

The groups say that the application is about an invention that is in the
public domain and therefore not new. They add that by the applicant's
own admission, an application for patent for the same invention was
filed in the US on 28 July 1994. Referring to a press release by the
patent applicant itself that states that valganciclovir was discovered
in 1994, they said that since the compound was known before 1995 it
forms part of the state of the art.

The opponents also affirm that after studying the description of each
application, "they are virtually identical".

The groups also claim that the patent application has failed to meet the
formal disclosure requirements under Section 8 of the patent law which
requires an applicant for patent to furnish the Patent Office with
detailed particulars of any patent applications for the same or similar
inventions made in any other country and to undertake to update the
Patent Officer of detailed particular of every other application made
subsequent to filing within the prescribed time.

They further said that the patent applicant failed to reveal an
application for a substantially similar invention in the European patent
Office as well as subsequent applications, on the same invention
re-filed (as the first application filed on 28 July 1994 was abandoned)
on 30 May 1995 and again on 4 March 1997 in the US. According to the
Patents Act, a failure to comply with Section 8 is a ground for
opposition and sufficient ground to reject the patent application in its
entirety.

Another of the recent pre-grant opposition cases was filed by INP+ and
the Karnataka Network of People Living with HIV/AIDS against a patent
application titled "Anti-virally Active Heterocyclic Azahexane
Derivatives," by Novartis AG (Application No: 805/MAS/1997), filed on 21
April 1997. The application pertains to Atazanavir a vital second-line
protease inhibitor.

The opposition to the grant is on the grounds of lack of novelty and
inventiveness and the failure to provide the Patent Officer with
information as required by Section 8 of the Act.

The opponents said that well before the priority date of the patent
application, the HIV protease enzyme had been identified as a key
therapeutic target, the three-dimensional structure of the protease
enzyme, including a detailed mapping of the active site, had been
disclosed, and various assays to determine the inhibitory effect of
candidate substances had been developed. Further, there is a wealth of
pre-existing technical knowledge in developing effective inhibitors of
the HIV protease on which researchers can draw on.

As a result of these and other advancements, several protease-inhibiting
compounds had already been patented prior to the priority date of the
present application. The opponents said that one of these patents
(WO9419332) discloses compounds that overlap considerably with the
compound disclosed in the patent application. At the most, the claimed
compound is a new form of a known substance and thus not deserving a
patent under the amended patent law.

The opponents also claimed that the applicant failed to disclose two
foreign patents i. e. in Europe (EP 0900201, filed 14 April, 1997) and
in US (5849911, filed 9 April, 1997) for substantially the same alleged
invention, with a title identical as the application filed in India.

They note that in the European patent application, the patent of
WO9419332, along with other patents covering similar compounds, was
disclosed by the patent applicant, as relevant prior art, although such
a discussion is absent from the application filed in India. The
opponents submit that this is "inequitable behaviour" on the part of the
applicant.

The fourth recent opposition filed by INP+ is against a patent
application by the Glaxo Group Limited titled "A Novel Salt"(Application
No: 872/CAL/98 A) filed on 14 May 1997. The application relates to the
hemisulfate salt of a known compound Abacavir.

The grounds for opposition are that the claimed invention is not new and
stand anticipated by prior publication. The group refers to a prior
application European Patent 0434450 published on 26 June 1991.

The opponents state that the application fails to meet the test of
inventiveness, and presents two prior art publications in support of the
contention of obviousness. The opponents also add that the claimed
invention is simply a new form of a known substance with no
significantly different properties with regard to efficacy and thus not
patentable under the India patent law.

If the oppositions are successful, they will clear the way for Indian
companies to supply generic versions of these medicines.

The Indian patent law excludes from patentability drugs which have
patent priority dates prior to 1995, and thus generics production can
continue for these drugs.

For drugs which have patent priority dates between 1995 and 2005, the
Act provides that production of generic versions can continue in return
for payment of a "reasonable" royalty.

However this provision only applies to "enterprises which have made
significant investment and were producing and marketing the concerned
product prior to 1st January 2005 and which continue to manufacture the
product covered by the patent on the date of grant of the patent"
(Section 11A of the Amendment Act). It is not clear which products are
and are not covered by the provision.

When patents are granted after the coming into force of the 2005 law,
there can be no generic manufacturing unless with the permission of the
patent holder, or unless the government issues a compulsory license.

Some studies have given a pessimistic scenario for the Indian generic
drug industry and for patients relying on its medicines.

A briefing paper for the UK official aid agency DFID, "Updating on China
and India and Access to Medicines" by Cheri Grace (2005), concluded that
treatment for cancer and diabetics is most likely to be negatively
impacted by the implementation of TRIPS since these are treated with
relatively new drug classes which have little therapeutic
competition/substitution.

Classes of drugs that experience a high speed of new product development
due to emerging resistance such as antibiotics and anti-infectives (e.
g. ARVs, TB drugs and anti-malarials) will also be affected, since newer
drugs in this group may have little therapeutic competition, while the
older drugs are ineffective.

Grace highlights how the lack of access to one drug in a combination
therapy (as it is patented) can preclude appropriate treatment, and just
a few expensive patented medicines can skew entire health budgets.

Taking into account various estimates, she concludes that 10-15% of the
Indian production will initially be affected by product patent
protection, and the percentage would increase over time as new, patented
medicines become an increasing proportion of the overall market.

A decision was taken by WTO members on 30 August 2003 (which became the
basis for an amendment of the TRIPS Agreement on 6 December 2005) to
create a mechanism to deal with exporting and importing of drugs to meet
the needs of people in countries lacking drug-manufacturing capacity.

The mechanism has been criticized as being too cumbersome as it contains
many procedural requirements that the exporting and importing countries
have to follow.

A study published by the United Nations University- Institute for New
Technologies presented the results of interviews carried out with 103
Indian generic firms, which were asked whether Section 92(a) of the post
2005 Indian Patent Act (that incorporates elements of the 30 August 2003
WTO decision) constituted a favourable economic incentive for exports,
especially to least developed countries.

The study was authored by Padmashree Gehl Sampath and is titled
"Economic Aspects of Access to Medicines after 2005: Product Patent
Protection and Emerging Firm Strategies in the Indian Pharmaceutical
Industry".

It found that of the 103 generic firms, only 25 firms thought it was an
economically lucrative option, whereas 78 firms did not think so. Of the
25 firms, 15 are small, with little or no experience in exporting
pharmaceutical products, and most of them are unable to comply with the
WHO's standards for Good Manufacturing Practices and they and have no
R&D investments, given their small scale operations.

Only 6 of the large generic companies and 4 of the medium sized generic
companies responded positively. Most of the large firms did not think it
was a lucrative option due to the increase in procedural hurdles and the
low economic returns from using Section 92(A) of the Act. This requires
the issuance of a compulsory license in India and the use of several
procedural steps by both India and the importing country that would like
to make use of the 30 August 2003 Decision.

Some of the medium sized firms also mentioned the constraints posed by
the fact that their product range may be very different from the
products that the importing countries require.

Moreover they estimated it may not be profitable for them to invest in
securing supplies of active pharmaceutical ingredients that are
different from those they normally require, or to invest in reverse
engineering efforts and technological investments to produce the
medicines under a compulsory license.

In another paper, the same author projects that of the 42 Indian firms
supplying the African region in 2004-05, only 25 will do so in the
future under the requirements of Section 92(A) of the amended Indian
patent law.

In the UNU-MERIT working paper, "India's Product Protection Regime: Less
or More of Pills for the Poor?", Padmashree Sampath concludes that the
Indian generic firms, (especially the large and medium sized firms) no
longer view the production of generic versions of pharmaceuticals
patented products as a profitable activity in the post-2005 situation.

This is due to the fact that their ability to supply the drugs to
different markets and profit from increased sales in now constrained by
the introduction of product patent protection in India.

While this may be the case, "regional aggregation of demand by countries
which do not have significant manufacturing capabilities" may go a long
way to incentivise these manufacturers to produce newly patented drugs
under a compulsory license, said the paper.

Even then access to medicines would be hampered by the proviso in the
amended Indian patent law that only allows the issuance of a compulsory
license after a period of three years from the date of grant of patent.

In this rather bleak scenario, the filing of pre-grant opposition cases
against the applications for patents on drugs is a legal option which is
being used by groups of people living with HIV/AIDS and which they hope
will succeed in preventing the wrongful granting of patents.

If patents are not given to these drugs, then it would be far easier and
more profitable for the generic companies to produce their versions, and
to supply the markets of India and other developing countries.