[Ip-health] Update on the Novartis case before IPAB – 18 November 2008

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Update on the Novartis case before IPAB – 18 November 2008



Chennai, 18 November 2008



The Intellectual Property Appellate Board (IPAB) today resumed hearing the
appeals filed by Novartis AG (Novartis) challenging the Indian Patent Office’s
decision to reject its patent application for the beta-crystalline form of
imatinib mesylate (Gleevec).





Mr. Bhushan read out portions from the prosecution history of the
corresponding patent application in other countries.  He said that in the
United States Patent and Trademark Office (USPTO) as well, the patent
examiner had initially rejected the subject application on the grounds of
anticipation and obviousness.  He pointed out that the USPTO Appeals Board
reversed the patent examiner's rejection, holding that the patent examiner
had not relied on any data to show that the 1993 patent "inherently
disclosed" the beta-crystalline mesylate salt.  Mr. Bhushan added that the
very advantageous properties of the beta crystalline form such as better
flow properties and non-hygroscopicity amounted to efficacy and that the
terms “advantageous properties” and “efficacy” were interchangeable terms.
Referring to the utility of the beta-crystalline form of imatinib mesylate
for treating cancer, he said that an enhanced utility amounted to enhanced
efficacy.





Mr. Bhushan said that 5521184, the 1993 US patent, disclosed only imatinib
and merely suggested the various possible salts that could be formed.  He
added that since imatinib was never patented in India, it was always
possible for the Indian companies to market it.  He argued the fact that no
company marketed the drug before Novartis’ discovery of the beta-crystalline
form showed that it was the beta-crystalline form only which had the
advantageous properties required to treat cancer.  Referring to the
arguments of the Indian generic companies that the beta-crystalline form was
no more efficacious than any other form of imatinib, he said that it was
still open to them to manufacture the other forms of imatinib.  He argued
that the fact that the Indian companies were opposing Novartis’ patent
application itself showed that it is only the beta-crystalline form which is
efficacious.  He challenged the Indian pharmaceutical companies to go ahead
and market any other form of imatinib.





Mr. Bhushan then addressed the issue of evergreening, which, according to
him, had been contended by all the parties against Novartis.  Explaining
evergreening, he said that it refers to the concept of extending the life of
a patent.  He argued that because the free base of imatinib was never
patented in India, there was no question of extending the life of the patent
and thereby engaging in evergreening.





Mr. Negi asked Mr. Bhushan to explain the Exclusive Marketing Rights (EMRs)
granted to Novartis.  Mr. Bhushan read out the relevant provisions of the
law under which an EMR was granted to Novartis for Gleevec in November 2003.
He explained that until 2005, when the mailbox applications were to be
examined, India was required to grant an EMR to a patent applicant on the
satisfaction of certain conditions.  He said that an EMR were granted to
Novartis until such time as its patent application was disposed off.  He
added that based on the EMR, the Madras High Court had restrained some
companies from manufacturing generic versions of Gleevec, while the Bombay
High Court had refused to restrain some other companies from manufacturing
generic versions.  The EMR, therefore, came to an end with the Indian Patent
Office’s decision to reject Novartis’ patent application.  Mr. Grover,
counsel for Cancer Patients Aid Association (CPAA), informed the IPAB that
CPAA had challenged the grant of exclusive marketing rights before the
Supreme Court of India.  Ms. Rajeswari, counsel for Natco Pharma Ltd.
(Natco), too informed the IPAB that Natco’s challenge to the exclusive
marketing rights was still pending before the Supreme Court.  Mr.
Chakraborti inquired if the challenge to the exclusive marketing rights were
part of the record before the IPAB.  Mr. Grover replied that he would point
out the relevant records during argument.





Mr. Bhushan then addressed the arguments relating to section 3(d) and argued
that neither the main section nor the explanation to section 3(d) were
attracted to the case at hand.  He said that section 3(d) referred to new
forms of a known substance.  He argued that the known substance as disclosed
by the 1993 US patent was the free base of imatinib.  Mr. Chakraborti
queried if the customary salts disclosed by the 1993 US patent were also to
be considered as known substances.  Mr. Bhushan replied that the 1993 US
patent only suggested the possibility of preparation of different salts; and
while it could be argued that the 1993 US patent anticipated imatinib
mesylate, it was not relevant to the analysis under section 3(d).  He said
that a known substance was one which had already been brought into
existence.  In the present case, the free base of imatinib was the only
molecule that had been brought into existence and no document disclosed the
existence of imatinib mesylate.  He argued that the beta-crystalline form of
imatinib mesylate is a new form of imatinib mesylate, but is not a new form
of the known substance­­—imatinib.  Taking aid to an example to explain this
further, he said that while iron was a known substances, all compounds
containing iron could not be said to be new forms of iron.  Therefore, the
main clause of section 3(d) which disallows patenting of new forms of a
known substance was not applicable.  Using the same argument, he said that
since imatinib was the only known substance, the explanation would come into
play only if Novartis had claimed a patent for a salt form of imatinib such
as imatinib mesylate.  However, as Novartis had claimed a polymorph of
imatinib mesylate, the explanation could not be applied as imatinib mesylate
was not a known substance.  He added that where a change from one form to
another required human intervention, the explanation to section 3(d) could
not be applied.



Mr. Bhushan then disputed the evidence submitted by Natco relating to
studies conducted by two reputed institutes: the Indian Institute of
Technology (Delhi) and the Indian Institute of Chemical Technology
(Hyderabad). These studies had confirmed that while making the mesylate salt
of imatinib in a variety of conditions, the beta-crystalline form was
invariably produced.  Mr. Bhushan claimed that this data was entirely
irrelevant, as Natco had allegedly supplied the institutes with the
beta-crystalline form.  He argued that because the beta-crystalline form had
not been excluded from the laboratory, it was impossible to arrive at any
other lesser stable form, such as the alpha form.  Mr. Bhushan pointed out
that both the studies followed the same procedure and used the same solvents
indicating that they were provided the study model by Natco.





Mr. Bhushan referred the IPAB to the application filed by Natco before the
Drug Controller General of India to market the alpha-form of imatinib
mesylate.  If the IIT and IICT study results were to be believed and the
beta-crystalline form was invariably formed on preparation of imatinib
mesylate, he questioned how Natco had obtained the alpha-form for which it
had sought marketing approval.





Mr. Bhushan then relied on some orders passed in infringement proceedings
against Natco in the UK, in which Natco had agreed not to market or sell the
beta-crystalline form because it would infringe Novartis' 1993 patent.  At
this, Ms. Rajeswari, counsel for Natco, clarified that Novartis had filed an
infringement suit against Natco alleging that Natco’s generic version
(Veenat) containing the beta-crystalline form infringed the 1993 patent.
Mr. Bhushan countered that Novartis had alleged infringement of both the
1993 patent and the patent on the beta-crystalline form.





Returning to his argument on section 3(d), Mr. Bhushan read out portions of
the decision of the Madras High Court [Novartis AG v. Union of India and
Others] dismissing Novartis’ constitutional challenge to section 3(d).  He
argued that the beta crystalline form has three major improvements over the
free base of imatinib, i.e. 30% increased bioavailability, less
hygroscopicity and improved stability. He said that due to this, cancer
could be treated by using a smaller quantity of the drug.  He read out the
expert evidence filed before the Patent Controller and other data to show an
increase in bioavailability.



Mr. Negi observed that all the experts were employees of Novartis.  Mr.
Bhushan conceded that it was up to the IPAB to believe the expert evidence.



Mr. Bhushan then referred to the reply affidavit of the government, which
said that a 30% increase in bioavailability did not amount to an enhanced
efficacy.  Stating that a 30% increase in any field is significant, he
alleged that Mr. Chandrasekaran did not have any idea of oncology.



The hearing was adjourned to 19 November 2008.  Mr. Bhushan is expected to
close his arguments tomorrow.





In solidarity,

Lawyers Collective HIV/AIDS Unit