“…A statute is best interpreted when we know
why it was enacted. … If a statute is looked at, in the context of its
enactment, with the glasses of the statute-maker, provided by such context, its
scheme, the sections, clauses, phrases and words may take color and appear
different than when the statute is looked at without the glasses provided by
the context…” - Justice Chinnappa Reddy in Reserve Bank of India v.
Peerless General Finance and Investment Co. Ltd. and others
Introduction
The recent compulsory licensing
judgments have done their bit in bringing concepts such as “Public Interest”
and “Public Morality” in to the limelight in the Intellectual Property
arena. An increasing number of people are now talking about “Role of Patents
in Facilitating Affordable Drugs” and mechanisms through which one can
maintain the balance between “Patent Rights” and “Public Rights”.
Thus, it was, but expected that the recent decision
by Supreme Court of India in the Glivec patent case would trigger
another round of heated discussions on India’s stance on drug patents. The
Glivec decision has left the multinationals apprehensive and unsure about their
strategies in India. Industry pundits are speculating that the Glivec decision
will drive the pharmaceutical multinationals away from India to regions which
they believe would provide more fertile grounds for their R&D as well as
generate better returns on their IP.
There are also sections in the Industry who believe
that India has stuck the right chord and the Glivec decision will ensure that
essential drugs can now be made available more easily to those in need as well
as the judgment can act as precedent to similar patent cases all over the
world, especially in the developing countries.
Background
Following is a snapshot of some of the key points as
well as summarization of circumstances surrounding the Glivec decision.
CGP
571481 in free base form (International Nonproprietary
Name ‘Imatinib’), was one of the derivatives of N-phenyl-2- pyrimidineamine (formula
I) invented by Jürg Zimmermann. The free base form and other
derivatives displayed valuable anti-tumoral properties. These properties allow
them to be used in anti-tumoral drugs and in drugs for treating atherosclerosis.
A patent application was filed on April 28, 1994 by Novartis in the
United States for the N-phenyl-2-pyrimidine-amine derivatives, including Imatinib
and the application was granted as US Patent No. 5,521,184
on May 28, 1996.
In their submission, Novartis stated that starting
from Imatinib free base one could reach to the beta crystal form of Imatinib
Mesylate in two ways. The two ways are specified below:
1.
By digesting another crystal form (Alpha
crystal form) or an amorphous starting material of the methane sulfonic acid addition
salt of compound of formula I. In this
process, one would first arrive at Imatinib Mesylate in amorphous form, as the
intermediate stage, and thereafter, following further processes, reach the beta
crystal form of Imatinib Mesylate.
2.
By dissolving another crystal form (Alpha
crystal form) or an amorphous starting material of the methane sulfonic acid
addition salt of compound of formula I. In
this process one would reach the beta crystal form of Imatinib Mesylate
directly thereby skipping the intermediate stage of the amorphous form.
In their submission, Novartis also stated that the
best way to produce the beta form is by directly proceeding from the free base
form to the beta form by introducing a specified amount of the beta crystals at
a specified step during the processing.
The beta crystal form of Imatinib Mesylate,
according to Novartis, had the following benefits over the alpha crystal form
of Imatinib Mesylate:
·
Better flow properties
·
Better thermodynamic stability
·
Lower hygroscopicity
Based on the above benefits, a patent
application was filed in India claiming the beta crystal form as a “new” and
“superior” invention. However, an important point to be
noted is that no claim of superiority of the beta crystal form of Imatinib
Mesylate in regard to the beneficial properties over the starting material Imatinib,
or even over Imatinib Mesylate in amorphous form or any form other than the alpha
crystal form was made.
The patent application was filed on July 17, 1998 at the Chennai Patent Office bearing
application number 1602/MAS/1998.
The priority date for the application was July
18, 1997, the date on which the patent application was filed in
Switzerland. An important thing to point here is that Switzerland was not a
convention country as defined under section 2 (1)(d) read with section 133 of
the Act and it was notified as a convention country only on November 30, 1998.
Stage 1: Patent Office
As India’s patent laws on product (Drugs) patent were
still evolving in 1990s, the Indian patent application was kept in the
“mailbox” and was taken out of the “mailbox” only after January 1, 2005 when
India started recognizing product patents (facilitated by deletion of Section 5
of the Act).
However, before the application was taken out of the
mailbox, some interesting events had already happened. Novartis had received a grant
of exclusive marketing rights (EMR) on the subject matter of the patent
application on March 27, 2002. Also, the patent application had received five pre-grant oppositions.
The Assistant Controller at the Indian Patent Office
heard all the parties of pre-grant opposition on December 15, 2005 and rejected the Indian patent application (1602/MAS/1998).
The main reasons for the rejection were:
1.
The Indian patent application was anticipated
by US Patent 5,521,184 (Novartis
own patent on N-phenyl-2-pyrimidine-amine derivatives, including Imatinib).
2.
The patent was not allowed under section
3(d) of the Indian Patent Act; and
3.
The priority date (July 18, 1997) was
wrongly claimed as the priority date for the Indian patent application and was
thus also anticipated by the patent application filed in Switzerland.
In response, Novartis filed five writ petitions
challenging the orders of the Assistant Controller as well as two writ
petitions challenging the constitutionality of Section 3(d) in the Madras High
Court. While the five writ petitions were transferred to the IPAB as
appeals, the Madras High Court dismissed the two writ petitions on Section
3(d).
Stage 2: IPAB
The IPAB heard the five appeals challenging the
decision of the Assistant Controller and pronounced its judgment on June 26,
2009. In the decision, the IPAB reversed
the findings of the Assistant Controller on the issues of anticipation and
obviousness and said that the Indian patent application fulfilled the tests of
novelty and non-obviousness. The IPAB also accorded the priority date of July
18, 1997 to the Indian patent application based on the amended Section 133.
However, the IPAB rejected the application based on
Section 3(d) stating that India’s laws on drug patents demanded higher level of
inventiveness so that the act was successful in preventing evergreening of
patents. The IPAB also weighed in the pricing of Glivec (Rs 1, 20,000 per
month) under Section 3(b) and concluded that while a process patent could be
given for preparation of Imatinib Mesylate in beta crystal form, a product patent
on Glivec would be disastrous to public order and morality and thus Novartis
could not be granted a product patent.
Stage 3: Supreme Court
“…Patent systems are not created in the
interest of the inventor but in the interest of national economy. The rules and
regulations of the patent systems are not governed by civil or common law but
by political economy…” - Michel on Principal National Patent Systems
Before dwelling into the merits of the case, the
Supreme Court took a look into the history of patent laws in India,
specifically; they cited the Justice Ayyangar’s work and recommendations on
revamping the patent system of India. The Supreme Court observed that historically,
barring USA, the rest of the world did not allow product patents in the field
of food, medicines and chemistry.
In addition to Justice Ayyangar’s report, the
Supreme Court also cited works of Sudip Chaudhuri in his book “The
WTO and India’s Pharmaceuticals Industry” to understand the performance
of Indian Pharmaceutical Industry and how it has been impacted time and again
with changes in Patent Laws. The Supreme Court also cited letters from various
organizations such as HIV/AIDS Director of the WHO, and Director
of Advocacy, Communication and Leadership for UNAIDS to the Indian
Government expressing their concern on availability of affordable drugs to poor
nation and role of Indian pharmaceutical industry in ensuring the continued
availability of such drugs.
Coming to Section 3(d), the Supreme Court observed
that the section was specifically amended to deal with chemical substances and
more particularly to pharmaceutical products. Thus, the Supreme Court viewed Section 3(d) as a second tier of
qualifying standards to identify genuine inventions in chemical and
pharmaceutical domains and thereby put a check on evergreening of patents.
In an interesting turn of events, the Supreme Court took
time to discuss the differences between the concepts of “inventions” and
“patentability” during the proceedings. The Supreme Court acknowledged the fact
that Section 3(d) represents the concept of “patentability”. However, the
Supreme Court also stressed on the fact that when Section 3(d) is isolated from
rest of Section 3 and when the legislative history behind the incorporation of
Chapter II in the Patents act, 1970 is disregarded, one can observe that it is
possible to see Section 3(d) as an extension of the definition of “invention”. Thus, the Supreme Court concluded that
the Act sets different standards for qualifying as “inventions” things
belonging to different classes.
During the hearing, the following arguments were
made by Novartis:
1.
The Genesis of beta crystalline
form of Imatinib Mesylate (derivative of N-phenyl-2- pyrimidine-amine) was
disclosed in example 21 of the US patent number 5,521,184.
2.
The beta crystalline form was
brought to being by not one but two inventions.
The first invention was to select example 21 and the second invention was to
choose methane sulfonic acid to produce the methane sulfonic acid addition salt
of the free base Imatinib, called Imatinib Mesylate. Novartis claimed that 5,521,184 patent did not teach or
suggest to a person skilled in the art to select example 21 in preference to
other compounds. Moreover, US patent 5,521,184 did
not teach a person to select one particular salt even when example 21 was
selected. Thus, Novartis argued that creating Imatinib Mesylate from Imatinib
in free base was the result of an invention that involved technical advance as
compared to the existing knowledge. Further, Novartis argued that once the salt
form of Imatinib was arrived at, further research was required to ensure that
that particular salt form of Imatinib is suitable for administration in a solid
oral dosage form. As the relevant crystalline form of the salt that was
synthesized needed to be invented, Novartis said that arriving at the beta-crystalline
comprised two inventions.
The Supreme Court observed the following in response
to arguments made by Novartis:
1.
The US patent 5,521,184,
granted on May 28, 1996 expressly stated that the compounds of N-phenyl-2-pyrimidine-amine
derivatives included their respective salts.
“Salt-forming
groups in a compound of formula I are groups or radicals having
basic
or acidic properties. Compounds having at least one basic group or at
least
one basic radical, for example a free amino group, a pyrazinyl radical or a
pyridyl
radical, may form acid addition salts,
for example with inorganic
acids, such as hydrochloric acid,
sulfuric acid or a phosphoric acid, or with
suitable organic carboxylic or
sulfonic acids…”
“….any reference to the free compounds should
be understood as including the corresponding salts, where appropriate and
expedient.”
2.
The application also stated that “Acid
addition salts can be convened into the free compounds in customary manner, for
example by treatment with a suitable basic agent.”
3.
The application for beta crystalline
form of Imatinib Mesylate was filed in the US on January 18, 2000 and was
granted on May 17, 2005 following the order of US Appellate Court dated
November 23, 2003.
4.
The Drug, Glivec, was however launched
much earlier in the market based on US patent 5,521,184 itself.
5.
The patent information filed along with
the New Drug Application (NDA) filed on February 27, 2001 showed that the
active ingredient as Imatinib Mesylate.
6.
The description on package of GLEEVEC
(Imatinib Mesylate capsules), launched on July 3, 2001stated that the capsules
contained Imatinib Mesylate equivalent to 100 mg of Imatinib free base.
Based on the above facts, the Supreme Court
concluded that Imatinib Mesylate, marketed under the name Gleevec, was covered by
US patent 5,521,184. Moreover, the
court also stressed on the fact that how Novartis had used the European
counterpart of the US patent 5,521,184 for preventing Natco
Pharma to market its drug, VEENAT 100 in UK in order to support its conclusion.
The Court also cited the findings of US Board of Patent Appeals in its judgment
granting patent for beta crystalline form of Imatinib Mesylate. The court
brought to notice that even the US Board of Patent Appeals mentioned in their
judgment that though the beta crystal form might not have been covered by US
patent 5,521,184,
it did have the teaching for the making of Imatinib Mesylate from Imatinib, and
for its use in a pharmacological compositions for treating tumours or in a
method of treating warm blooded animals suffering from a tumoral disease.
Thus, the Supreme Court held that Imatinib Mesylate
as a substance and its pharmacological properties were well known in the art.
Having concluded on Imatinib Mesylate, the Supreme Court then focused on beta
crystalline form of Imatinib Mesylate. As the beta crystalline form of Imatinib
Mesylate is a pharmaceutical substance and moreover a polymorph of Imatinib
Mesylate, it is governed by Section 3(d) of the Act.
The counsel for Novartis argued that in order to
attract section 3(d), the subject product must be a new form of a known
substance having known efficacy. The counsel also stated that a “conceivable”
substance is not a “known substance” within the meaning of the provision. He
contended that the word “known” connotes proven and well-established and thus “known
efficacy” would imply efficacy established empirically and proven beyond doubt.
As neither Imatinib nor Imatinib Mesylate had any known efficacy, he contended
that there was no question of showing that the beta crystalline form of Imatinib
Mesylate had any enhanced efficacy over Imatinib or Imatinib Mesylate.
However, the Supreme Court rejected the counsel’s
arguments as unacceptable both in law and on facts. Consequently, the court
concluded that beta crystalline form of Imatinib Mesylate would correspond to a
new form of a known substance, i.e., Imatinib Mesylate, of which the efficacy
was well known as described in the NDA filed with the US FDA. The court also
went on to defined efficacy as “the ability to produce a desired or intended result”.
An interesting point over here is that Supreme Court also brought to attention
how the patent application for beta form was based on US patent 5,521,184,
and how most of sections were directly lifted from the US patent 5,521,184.
In another interesting aspect, the court observed
that while the application for grant of patent lay in the “mailbox”, Novartis
was granted Exclusive Marketing Rights on November 10, 2003, following which
Gleevec was marketed in India as well. The package described the drug as
“Imatinib Mesylate Tablets 100 mg” and it was further stated that “each film
coated tablet contains: 100 mg Imatinib (as Mesylate)”. However, nowhere on the
package is a reference to Imatinib Mesylate in beta crystalline form. This indicates that what were sold as Gleevec were
Imatinib Mesylate and not the subject product, the beta crystalline form of
Imatinib Mesylate. This leads one to believe that the claim for patent for beta
crystalline form of Imatinib Mesylate is nothing but an attempt to obtain
patent for Imatinib Mesylate, which would otherwise not be permissible.
Thus, the Supreme Court held that the beta crystalline
form of Imatinib Mesylate, does not qualify the test of Section 3(d) of the Act.
Conclusion
This decision has forced the pharmaceutical
multinationals to come up with new strategies as well as create a checklist for
launching new patented drugs in India. Companies are going to be more
apprehensive than ever before to do business in India. Partnerships with local
companies may emerge as one of the short term solution but questions are being
already raised on its implications in the long run. Till then, it will be
interesting to see whether India continues to be the “pharmacy of the world”.
