Hearing Update: Novartis argues that section 3(d) not applicable to its patent
application
12 September 2012, New Delhi.
Continuing arguments on behalf of Novartis, Mr Gopal Subramaniam, senior counsel,
took the Bench through the Complete Specification of Novartis’ patent application for
the beta-crystalline form of imatinib mesylate that was filed before the Patent
Controller in India. He said that it has to be ascertained whether the application has
to be tested with reference to section 2(1)(j) or with reference to section 3(d).
While explaining the background of this patent application, he said that the
application relates to a particular form of acid addition salt of methanesulphonic acid
of imatinib free base. He said that imatinib free base is disclosed in Zimmerman
patent granted in 1993. Responding to Justice Alam’s request to elaborate about the
Zimmerman patent, Mr Subramaniam said that there was, at the relevant time,
continuing research in relating to medicines including compounds which could work
against cancer. He said that medicines that could work against tumour were also
examined to see if they would work against cancer because, at that time when
research on tumour-inhibiting compounds was progressing, it was considered that
cancer was a certain kind of tumour.
Mr Subramaniam submitted that the 1993 Zimmerman patent, which had been
granted a patent in the United States, disclosed a Markush formula that covered a
wide range of compounds having anti-tumour properties. Justice Alam inquired if the
Zimmerman patent had been used as prior art against Novartis’ present application
in respect of novelty and inventive-step/obviousness. Answering in the affirmative, Mr
Subramaniam said that the Zimmerman patent, which was also Novartis’ own patent,
was being held against Novartis as prior art. He said that the Respondents
(opponents) have, in fact, argued that the disclosures in the Zimmerman patent were
adequate for a skilled person to arrive not only at imatinib mesylate but also at the
beta-crystalline form of imatinib mesylate. Pointing out that the Intellectual Property
Appellate Board (IPAB) has held in Novartis’ favour on this count, Mr Subramaniam
said that the IPAB held that the Zimmerman patent disclosed a large varieties of
compounds and wide varieties of acids and salts but did not mention particular
combinations to produce particular compounds.
In furtherance of this argument, Mr Subramaniam took the Bench through the
Zimmerman patent. Pointing to the Markush structure disclosed in the Zimmerman
patent, he explained that a large number of possible compounds could be substituted
to the formula and that the resultant compounds could be used in therapy of tumoural
diseases. He said that the Zimmerman patent itself listed several examples, of which
the compound exemplified at number 21 was imatinib free base. Mr Subramaniam
urged that though the Zimmerman patent also mentioned methanesulphonic acid, it
did not mention the combination of imatinib and methanesulphonic acid.
Replying to a question from Justice Alam, Mr Subramaniam said that a person skilled
in the art would not have been able to arrive at the claimed invention as there are
any number of acids and any number of salts. He said that the combination of
methanesulphonic acid with imatinib and the process to arrive at this combination are
most relevant. He submitted that the choice of the particular acid and the process
and conditions under which imatinib free base and methanesulphonic acid are to be
combined is not disclosed in the Zimmerman patent. Mr Subramaniam, therefore,
argued that the Zimmerman patent does not contain an enabling disclosure, which
would make it possible for a skilled person to arrive at the beta-crystalline form of
imatinib mesylate. He said that imatinib free base cannot be administered to the
human body as it is; therefore, the manner in which imatinib could be taken and
administered as a pill into the human body required research. He reiterated that it
was Novartis’ research which had led to the conclusion that imatinib and
methanesulphonic acid could be successfully combined to make imatinib mesylate,
which involved an inventive step. He said that the beta-crystalline form of imatinib
mesylate, too, was the result of Novartis’ research. Referring the judges back to
Novartis’ patent specification, Mr Subramaniam said that Novartis’ invention
comprises of two steps— (i) starting from imatinib free base and finding the particular
acid, i.e. methanesulphonic acid, to make the particular salt and (ii) finding the
manner and conditions in which imatinib free base and methanesuplhonic acid are
combined to make a crystalline form which could be administered into the body. He
urged that the beta-crystalline form of imatinib mesylate was arrived at because it
has properties such as less hygroscopicity, ability to withstand humidity and ability to
have a flow of properties. Explaining the meaning of flow properties to the court, Mr.
Subramaniam said that it is the ability of the drug to flow from the machine such that
the entire imatinib flows without being stuck in the machine.
On being questioned by Justice Alam about Zimmerman’s rights over imatinib and
whether the beta-crystalline form of imatinib mesylate would infringe the Zimmerman
patent, Mr Subramaniam said that Zimmerman was an employee of Novartis as the
patent belonged to Ciba-Geigy, a predecessor of Novartis, and clarified that the
patent was only named after the individual who came up with that particular Markush
formula.
Justice Alam inquired if the Zimmerman patent had been filed without performing the
examples described in it and also without testing the efficacy of imatinib free base.
Mr Subramaniam replied that efficacy was measured through empirical standards
and that the Zimmerman patent disclosed only the potentiality of the use of the
compounds mentioned therein. Pointing out that the Zimmerman patent stated that
the compounds disclosed by it could be used for treatment of tumours, Justice Alam
asked whether it therefore meant that the compound exemplified in example 21 was
a known substance of known efficacy. Responding to this, Mr Subramaniam said that
though the Zimmerman patent could be regarded as prior art with respect to novelty
and inventive step, it could not be regarded as prior art/known substance for the
purposes of section 3(d). He added that the efficacy of imatinib was not known and
that the use mentioned in the Zimmerman patent was a pharmacological description.
He submitted that efficacy could be determined only after human clinical trials and
not at the time of filing a patent application.
Justice Alam asked if this interpretation (efficacy established through clinical trials on
human beings) could be advanced as human clinical trials comes at a later stage as
compared to the stage of granting patents.
Mr Subramaniam replied that section 3(d) is an exception to section 2(1)(j) (definition
of invention) and that the section has a very limited application. He said that the
section was introduced only to prohibit evergreening of patents.
Explaining his interpretation of section 3(d), Mr Subramaniam stated that imatinib
was not in existence at the time the Zimmerman patent was sought. He added that
the efficacy of imatinib and imatinib mesylate had not been measured as it had not
been administered to humans and that, therefore, neither imatinib nor imatinib
mesylate could be known substances for the purpose of section 3(d). He said that
any patent seeking an addition over Gleevec/beta-crystalline form of imatinib
mesylate would attract section 3(d).
To support his proposition, Mr Subramanian relied on an English judgment involving
a patent for a derivative of a known compound. He said that, in the case, Beecham
held patents for ampicillin, which was a known antibiotic. Bristol, another company,
sold hetacillin, a derivative of ampicillin made by adding acetone. Mr Subramaniam
said that, in that case which covered what section 3(d) intended to cover, hetacillin
was described as “ampicillin with a hat on”. Justice Alam asked if the beta-crystalline
form of imatinib mesylate claimed by Novartis was imatinib with “a three piece suit”.
Justice Ranjana Desai sought a clarification on the interpretation being advanced. Mr
Subramaniam replied that, although imatinib was known in prior art, it was not the
known substance for the purposes of section 3(d), as its efficacy had not been shown
or established by clinical trials. He said that, in the present case, clinical trials were
conducted only on the beta-crystalline form of imatinib mesylate and therefore there
was no other “known substance” prior to Novartis’ invention. He submitted that,
therefore, section 3(d) would not be applicable to this case and that Novartis did not
have to demonstrate enhanced efficacy for the beta-crystalline form of imatinib
mesylate. Mr Subramaniam also advanced an alternate argument that, assuming
that section 3(d) would be applicable, the beta-crystalline form of imatinib mesylate,
in fact, has enhanced efficacy.
Responding to Justice Alam’s query whether it was his contention that section 2(1)(j),
section 2(1)(ja) and section 3(d) were mutually exclusive, Mr Andhyarujina, senior
counsel appearing for Novartis, said that the section 3(d) would not be applicable to
this case as the IPAB had upheld Novartis’ beta-crystalline form of imatinib mesylate
as an “invention”. Noting that efficacy was the controlling word of section 3(d) and its
explanation, Mr Subramaniam reiterated that, for section 3(d) to apply, the known
substance and its efficacy must be known and established. He submitted that section
3(d) could not act as an antidote to invention and that sections 2(1)(j) and 2(1)(ja)
could not be subservient to section 3(d). He further urged that the inventive step lies
in arriving at the particular beta-crystalline form of imatinib mesylate as well as in the
increased efficacy of that form.
Noting the similarity in the structure of imatinib and in the claims set out by Novartis,
Justice Alam inquired about the actual chemical structure of imatinib mesylate. Mr
Subramaniam replied that the complete specification does not disclose the exact
structure of imatinib mesylate because the methanesulphonic acid was charged and
the base is not, so it could attach itself at any of the nitrogen bonds in the imatinib
molecule and that, therefore, chemists could not predict where it would be attached
and a diagram depicting the exact position of the charged methanesulphonic acid
addition salt on imatinib could not be shown.
On being questioned by Justice Alam regarding the issue of maintainability of the
petition, Mr Subramaniam listed three primary reasons. First, there were only 4–5
years left for the term of patent were a patent to be granted and any delay would
further reduce this time. Second, another Bench of the Supreme Court had earlier
already commenced hearing arguments in the matter on merits before one of the
judges recused himself. Third, there was a question of public purpose involved in this
case which needed to be resolved as the interpretation of section 3(d) would be a
recurring question and should, therefore, be settled as soon as possible. He pointed
out that the test laid down by the Madras High Court was one of therapeutic efficacy
and that the IPAB had held that bioavailability of a drug does not enhance its
therapeutic efficacy. He, therefore, submitted that the Supreme Court had to clarify
on the meaning of efficacy, therapeutic efficacy and whether bioavailability qualified
as therapeutic efficacy.
On the issue of maintainability, Mr Grover, senior counsel appearing for CPAA, and Mr Salve,
senior counsel appearing for Cipla, informed the Court that though they had raised objections
as to the maintainability of Novartis’ petition before the Supreme Court on the ground that
Novartis had not approached the Madras High Court first, they would prefer for the Supreme
Court to decide on this matter. Rajeshwari Hariharan, counsel appearing for Natco, informed
the Court that Natco still maintained its objections on this issue.
On being asked by Justice Alam as to why the Zimmerman patent could not be taken
as showing ‘known efficacy’ of imatinib, Mr. Subramaniam replied that efficacy must
be tested in the optimum form, which is possible only through clinical trials, and that
therefore imatinib’s efficacy was not known. He further mentioned that the known
substance should be tangible and must possess efficacy. For efficacy to of a
compound to be known in the sense of section 3(d), he argued that the compound
should have been able to be administered to human beings. He said that section 3(d)
was not attracted as neither imatinib nor imatinib mesylate had been administered to
human beings.
Arguing for a strict interpretation of section 3(d), Mr Subramaniam maintained that
clinical trials in human beings would be required to prove the efficacy of imatinib and
that, at the time of the Zimmerman patent, imatinib was dormant. Mr Subramaniam
argued that if known efficacy was not interpreted as proven efficacy, then anyone
would be able to obtain a patent by showing that their subsequent form was more
efficacious. He urged that section 3(d) required demonstrability, which is empirical
efficacy.
As Mr Subramaniam relied on documents to explain how Gleevec functioned, Justice
Alam sought a clarification regarding the active molecule in Gleevec and asked if the
imatinib was the active molecule and the mesylate salt was merely the carrier of the
active molecule. Mr Subramaniam replied that though the active molecule was
indeed imatinib, the carrier was equally important because, without the carrier, the
active molecule was not capable of being administered.
Mr Subramaniam then moved on to the legislative history of section 3(d). Alluding to
the TRIPS Agreement, Mr Subramaniam said that the Patents Act, 1970 was
amended to comply with this Agreement. Referring the judges to article 27 of the
TRIPS Agreement, he submitted that the provision indicated a requirement of
granting patents to both processes and products. Adverting to the amendments in
2005, which introduced product patents for pharmaceuticals in India and section 3(d)
in its present form, Mr Subramaniam read out excerpts from the speech of the then
Minister of Commerce and Industry during the Parliamentary debates leading to the
passage of the Patent Amendment Bill, 2005, in which the public interest of
preventing evergreening was referred to as an issue that had to be addressed.
Thereafter, Mr Subramaniam cited the Report of the Mashelkar Committee and read
out its terms of reference and said that this Report suggested how section 3(d) ought
to be interpreted in the context of the TRIPS Agreement.
In response to a query from Justice Alam about the reason the Committee was
constituted, Mr Subramaniam replied that the expert committee had been constituted
to deliberate on whether it would be TRIPS-compliant to restrict patenting of microorganisms and to restrict patenting of pharmaceutical substances to only a new
chemical entity or new medical entity. He pointed out that, with reference to the
question on pharmaceuticals, the Committee had suggested that it would not be
TRIPS-compliant to restrict patenting to new chemical entities alone and that
incremental innovations should be granted patents in India.
After obtaining a clarification that the law in India had not been changed since the
submission of the Report, Justice Alam inquired about the relevance of the Report.
Mr Subramanian replied that the Mashelkar Committee Report was being cited as it
underlined the concern regarding evergreening and mentioned that invention did not
always mean a new product.
Mr Subramaniam urged that there were two ways of interpreting section 3(d). First, to
interpret it as a carving out of article 27 of the TRIPS Agreement as suggested by Mr
Salve, senior counsel appearing for Cipla. Second, to interpret section 3(d)
harmoniously with article 27 of the TRIPS Agreement such that it served a public
purpose. Mr Subramaniam also submitted that article 27(2) of the TRIPS Agreement
(which lays down a list of exclusions) made it clear that section 3(d) was not meant to
be a carve-out.
Responding to a question from Justice Alam about the relevance of interpreting
section 3(d) in light of article 27(2) of the TRIPS Agreement, Mr Subramaniam
replied that his submission was that section 3(d) should be interpreted harmoniously
with India’s international obligations under article 27(1) of the TRIPS Agreement so
that it did not destroy patent protection.
Mr Subramaniam furnished to the Court copies of Novartis’ undertaking supported by
an affidavit regarding the continuance of the patient assistance program for Gleevec.
However, Mr Grover, senior counsel for CPAA, objected to the attempt to introduce
new facts about Novartis’ Patient Assistance Programme through the form of an
undertaking. Mr Salve, senior counsel for Cipla, said that he welcomed the
undertaking as it would provide an opportunity to explain pricing strategies of
multinational pharmaceutical companies.
The Court rose for the day. Mr Subramaniam will continue his arguments on 13
September 2012.