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EXCO MEETING
KYOTO
6-10 APRIL 2014
CET WORKING DOCUMENT
TITLE:
DRAWN UP BY:
TABLED TO:
PURPOSE:
Briefing Paper for Workshop on Utility Problems and Pharmaceutical
Patents
Michael Caine, Chair CET Group 3 and Roberto Pistolesi, Chair CET
Group 5
All ExCo attendees
For Discussion
QR CODE :
The TRIPS Agreement establishes minimum standards of patent protection that member
countries must afford to patent applicants from other WTO member countries. However, the
TRIPS Agreement was intended to incorporate certain "flexibilities" to allow members to
implement the Agreement in a manner appropriate to their particular needs and circumstances.
This flexibility comes from Article 1.1 of the TRIPS Agreement, which indicates that members
"shall be free to determine the appropriate method of implementing the provisions of this
Agreement within their own legal system and practice".
According to Article 27.1 of TRIPS, member countries are required to make patents available for
"any inventions, whether products or processes, in all fields of technology, provided that they
are new, involve an inventive step and are capable of industrial application." The Agreement
clarifies that the terms "inventive step" and "capable of industrial application" can be deemed by
member countries to be synonymous with the terms "non-obvious" and "useful" respectively.
Subject to some transitional provision, Article 27.1 requires members to ensure that patents are
available and patent rights enjoyable "without discrimination as to place of invention, the field of
technology and whether products are imported to locally produced.
Article 27.2 allows members to exclude from patentability inventions, the commercial
exportation of which would be considered contrary to morality or ordre public. Under Article
27.3 members are permitted to exclude from patentability diagnostic, therapeutic and surgical
methods for the treatment of humans or animals, plants and animals other than microorganisms
and essentially biological processes for the production of plants or animals, other than nonbiological and micro-biological processes.
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Guidance as to the subject matter encompassed by the TRIPS Agreement can also be found in
Article 70.8 which provides special arrangements for member countries who, prior to the entry
into force of the WTO Agreement, did not make patent protection available for pharmaceutical
or agricultural chemical products. This makes it particularly clear that the TRIP Agreement was
intended to require all member countries to provide patent protection for pharmaceutical
products.
Article 29 of the TRIPS Agreement sets out the minimum requirements for a patent specification.
According to this article, members "shall require that an applicant for a patent shall disclose the
invention in a manner sufficiently clear and complete for the invention to be carried out by a
person skilled and may require the applicant to indicate the best mode for carrying out the
invention known to the inventor at the filing date or, where priority is claimed, at the priority
date of the application."
The PCT includes requirements which are similar to those set out in the TRIPS Agreement.
Article 5 of the PCT indicates that the description "shall disclose the invention in a manner
sufficiently clear and complete for the invention to be carried out by a person skilled in the art".
According to Article 6 the claims should be clear and concise and fully supported by the
description. Importantly, for the purpose of this workshop, Article 27(1) stipulates that "no
national law shall require compliance with requirements relating to the form or contents of the
International application different from or additional to those which are provided for in this
treaty and the regulations". However, sub-sections 5 and 6 of Article 27 appear as follows:
"(5)
Nothing in this Treaty and the Regulations is intended to be construed as
prescribing anything that would limit the freedom of each Contracting State to prescribe
such substantive conditions of patentability as it desires. In particular, any provision in this
Treaty and the Regulations concerning the definition of prior art is exclusively for the
purposes of the international procedure and, consequently, any Contracting State is free to
apply, when determining the patentability of an invention claimed in an international
application, the criteria of its national law in respect of prior art and other conditions of
patentability not constituting requirements as to the form and contents of applications.
[Underlining added].
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(6)
The national law may require that the applicant furnish evidence in respect of any
substantive condition of patentability prescribed by such law."
Accordingly, it would appear from sub-sections (5) and (6) of Article 27 that Contracting States
are not free to impose additional requirements "as to the form and contents of applications", but
that they may require the applicant to furnish evidence in respect of any substantive condition
of patentability. Accordingly, as to form and contents of a specification, it would seem that a PCT
applicant should not be required to go beyond the requirements of Articles (5) and (6).
Despite the TRIPS Agreement, some countries have adopted practices which make it difficult,
and in some cases impossible, to obtain valid or enforceable protection in relation to
pharmaceutical inventions. Of particular concern are the practices which have developed in
Canada, China and India. Accordingly, the workshop will focus on the "promise" or "sound
prediction" doctrine for the assessment of utility in Canada, the assessment of sufficiency under
Article 26.3 of Chinese patent law, and the requirement in Section 3(d) of the Indian Patents Act
for claims to new forms of known substances to possess an enhancement of the known efficacy.
These practices will be compared to the practices of other countries, such as the United States,
Europe and Australia, where the requirement for utility, industrial applicability or "technical
effect" are interpreted in a manner favourable to pharmaceutical inventions.
CANADA
In Canada utility is assessed by considering whether or not the claims extend beyond the limits
of sound prediction based on exemplification and information provided by the inventor in the
patent application. The purpose of the "sound prediction doctrine" is to allow inventors to
expand the breadth of their claims to cover subject matter not tested or explored, in
circumstances where the inventor could soundly predict that the additional subject matter
would have the same utility as the subject matter tested. The doctrine of sound prediction is
derived from a decision of Graham J in Olin Mathieson v Biorex [1970] RPC 157.
However, the way the doctrine of sound prediction is applied, was altered substantially by the
Supreme Court in Apotex Inc v Wellcome Foundation Ltd., [2002] 4 S.C.R. 153, otherwise known as
the AZT decision. According to this decision the level of predictability required to satisfy the
utility requirement has been substantially increased. Following this decision of the Supreme
Court, applicants are now required to demonstrate the utility of the invention in the patent
specification, or to provide in the patent specification a factual basis and line of reasoning to
provide a sound prediction that the invention as claimed will have the promised utility.
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According to the new test, the Judge is also required to subjectively construe the "promise" of
the patent from the disclosure of the patent specification, and then evaluate whether that
promise has been fulfilled. According to the current approach applied by the courts, seemingly
innocuous statements describing the nature of the invention can be construed as promises,
which are then subjected to the sound prediction test.
The "sound prediction" or "promised" doctrine has led to the invalidation of a large number of
pharmaceutical patents, including the patents covering Eli Lilly's Strattera and Zyprexa
products, and Sanofi's Plavix product. These patents have been found to be valid and
enforceable in other countries around the world, but have been rejected by Canadian courts.
While Eli Lilly's patents have been finally rejected by the Canadian courts, the Plavix patent is
currently the subject of its second appeal to the Supreme Court. The increase in the number of
pharmaceutical patents being challenged in Canadian courts for want of utility has increased
substantially since the AZT decision, as can be seen in the bar chart below.
2013 Total Annualized
Annual Number of Utility
Challenges in Canadian Courts
AZT ruling by Supreme Court of Canada
Canadian Patent Utility Coalition 2013
According to Eli Lilly, 18 Canadian pharmaceutical patents have been invalidated for lack of
utility in Canada since the AZT decision whereas only 2 pharmaceutical patents were invalidated
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for lack of utility in the preceding 25 years, and those were invalidated on the basis that the
claimed inventions were devoid of utility in fact. Since Eli Lilly failed to obtain leave to appeal to
the Supreme Court in relation to their Strattera and Zyprexa patents, they have commenced an
action against the Canadian Government under the North American Free Trade Agreement. In
this regard, Eli Lilly contends that Canada has violated the investment protections provided to
foreign investors under Chapter 11 of NAFTA.
In documents filed in support of its NAFTA action, Eli Lilly points out that Strattera and Zyprexa
have both been approved by Health Canada as safe and effective, and are currently being used by
thousands of patients in Canada. This demonstrates that Strattera and Zyprexa do have utility in
fact. Eli Lilly also makes reference to the importance of patent protection in allowing the
innovative pharmaceutical sector to bring new medicines to the market, explaining that, on
average, it costs more than a billion dollars to bring a new medicine to market.
Strattera is a pharmaceutical product useful in treating patients with ADHD. The claimed
invention was supported by a small scale, 7-week clinical trial involving 22 adult patients with
ADHD. Unfortunately for Eli Lilly, the Court read into the Strattera patent and implied promise,
based on the nature of ADHD as a chronic condition, that it would effectively treat humans with
ADHD. This implied that Strattera would work in the longer term. However, in view of the short
period of the clinical trial, the Court considered that the specification did not contain enough
evidence to enable a sound prediction that Strattera would be useful in treating ADHD. Eli Lilly's
appeal to the Federal Court of Appeal was dismissed and Eli Lilly was denied leave to appeal to
the Supreme Court of Canada.
Zyprexa is a pharmaceutical indicated for the short- and long- term of Schizophrenia and related
psychotic disorders and for the short term treatment of manic or mixed episodes in Bipolar I
disorder. The patent application included some clinical trial data showing positive results in
relation to the drug's anti-psychotic effects. The patent was invalidated by the Court because
they believed it failed to meet a construed promise of marked superiority over other antipsychotic agents over the long term. However, no such promise was made in the patent
application. The Court took the view that at the filing date Eli Lilly did not demonstrate that they
had sufficient information to be able to soundly predict that it would provide markedly superior
clinical treatment of Schizophrenia with a better side effect profile than other known antipsychotics. The same patent has been challenged and upheld throughout the world in many
countries, and Canada is the only jurisdiction in the world that has invalidated the Zyprexa
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patent on the basis of utility. Eli Lilly failed to obtain leave to appeal to the Supreme Court of
Canada in relation to the Zyprexa patent.
Although Eli Lilly failed to obtain leave to appeal to the Supreme Court of Canada in relation to
their Strattera and Zyprexa patents, Apotex was granted leave to appeal to the Supreme Court of
Canada on 30 January 2014 in respect of a decision of the Federal Court of Appeal which
overturned a Federal Court decision which invalidated Sanofi's Plavix patent. This will be the
second time the Supreme Court of Canada will consider the validity of the Plavix patent. It is
hoped that in this decision the Supreme Court of Canada will provide some clear guidance in
relation to the assessment of utility, and the application of any "sound prediction" or "promise"
doctrine.
CHINA
Article 26.3 of Chinese patent law states the following:
"The description shall set forth the invention or utility model in a manner sufficiently clear
and complete so as to enable a person skilled in the relevant field of technology to carry it
out……".
Accordingly, the language of Article 26.3 corresponds closely with the wording of Article 29 of
the TRIPS Agreement and Article 5 of the PCT. The language also corresponds with the
sufficiency requirement set out in Article 83 of the European Patent Convention. According to
the examination Guidelines the description should enable a person skilled in the art to
reproduce a technical solution, resolve the technical problem, or achieve the expected technical
effect without any inventor activity. Unfortunately, the manner in which the provision has been
interpreted in China has caused major difficulties for applicants claiming pharmaceutical
products or their uses. In this regard, a section on page 39 of the Examiner's Manual suggests
that animal or clinical data may be required to convince an Examiner in relation to the activity of
pharmaceutical compounds:
"For a new pharmaceutical compound or pharmaceutical composition, not only its specific
medical use or pharmacological action, but also its effective amount and the method of
application shall be described. If a person skilled in the art is unable, on the basis of the
prior art, to predict that the said use or action stated in an invention can be carried out, the
qualitative or quantitative data of the laboratory test (including animal test) or clinical
test shall be sufficiently provided for the person skilled in the art to be convinced that the
technical solution of he invention can solve the technical problem or achieve the technical
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effect as expected. The description shall describe effective amount, method application or
method of formulation to such an extent that a person skilled in the art can carry it out."
Chinese Examiners have been using the provisions of Article 26.3 to reject patents relating to
pharmaceuticals. A number of organisations representing patent applicants, and
representatives from the pharmaceutical industry, have made extensive submissions to SIPO
requesting reconsideration of this practice. These submissions have been supported by
numerous examples of patents which have been granted in the US, Europe and Japan, but
rejected in China. One of the main issues with the current practice in relation to Article 26.3 is
that SIPO has not allowed the submission of post-filing data to support or provide evidence of
the utilities disclosed in the patent specification.
In late November 2013, a FICPI delegation composed of Bastiaan Koster, Coleen Morrison, Julian
Crump, Eric Le Forestier, Brett Slaney and Michael Caine visited both the Beijing Patent
Examination Cooperation Centre (PECC) and SIPO. The delegation was given the opportunity to
give a presentation to a group of 30+ examiners from the PECC. Julian Crump, Brett Slaney and
Michael Caine gave presentations on the way sufficiency, claim support and utility are assessed
in Europe, North America, Australia and New Zealand. Brett Slaney was able to explain to the
examiners the problems caused by the Canadian "promise" approach the assessment of utility,
and how this has led to International criticism. Two case studies were then presented (see
Attachments 1 and 2) and discussed with the group of Examiners. The second case study was
closely based on the facts of the German Federal Court of Justice decision dated 11 September
2013 concerning German Patent No. 19616486, relating to Dipeptidyl peptidase inhibitors. By
discussing the two scenarios, they were able to explain to the examiners why the claims
presented would be considered allowable in Europe, the United States, Australia and New
Zealand. It also provided an opportunity for them to discuss with the examiners how claims
would be assessed under Chinese law, particularly under Article 26.3, and whether any postfiling data could be submitted to assist.
While it was clear that the examiners had been told that they were now able to receive and
consider post-filing data, it was also clear that most examiners would have been quite
uncomfortable allowing any of the claims presented in the case studies. It seemed from the
discussions with the examiners that they were somewhat reluctant to believe submissions made
by or on behalf of applicants.
The FICPI delegation also had the opportunity to discuss Article 26.3 with a group of SIPO
officials, including Ms Zhou Hubin, the Director of the Examination Guidelines Division of the
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Patent Examination Affairs and Administration Department. Ms Hubin explained that there had
been multi-level discussions in relation to Article 26.3 with the USPTO and various industry
groups. She went to some length to explain that the sufficiency of disclosure requirement set out
in Article 26.3 must be satisfied as of the filing date. If a specification as of its filing date contains
insufficient disclosure, post-filing data or details of further experiments cannot remedy this
deficiency. She emphasised that the invention described in a patent application must be a
completed invention, and must be workable by virtue of what is in the patent application, not
through data submitted after the filing date.
In relation to recent changes in practice, and in particular the recent change to allow examiners
to accept post-filing data, she indicated that examiners have been asked to consider Article 26.3
requirement through the eyes of a person skilled in the art in the specific technical field. She
said that supplementary data proving that the invention has the effects described in the
specification, constituting evidence that the invention works as described, will be considered.
However, the ability to rely on supplementary data would be assessed on a case by case basis.
Such supplementary data may help the examiner carry out the assessment of Article 26.3
compliance from the perspective of a skilled person, it may assist in understanding the scope of
the claims, and may help the Examiner appreciate the foreseeability of the invention based on
the prior art, or appreciate the nature of the invention. It was emphasised that it would be up to
the Examiner to make the judgment.
Ms Hubin was asked whether the Examiner's Manual would be amended to clarify the
circumstances according to which an Examiner may place reliance on supplementary post-filing
data. She was also asked to provide an example of a situation where reliance on post-filing data
would be acceptable. A straight-forward example was explained to Ms Hubin, where an
application is filed indicating that a set of identified and characterised compounds have binding
activities within a particular useful range. Ms Hubin was asked whether it would be possible in
these circumstances to submit to the examiner the actual data showing the binding affinity
measured for each compound. In reply, Ms Hubin indicated that the examination guidelines
would not be amended, but that the examiners would be instructed to judge the requirements of
Article 26.3 from the perspective of the person skilled in the art. She declined to give any
examples of circumstances where reliance on post-filing data would be permitted, and did not
comment on the specific example given to her.
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It was explained to Ms Hubin that the generation of data confirming the activity of
pharmaceutically active compounds is extremely expensive to generate, particularly for human
clinical trial data. It was explained that it is the patent protection, or at least the potential to
obtain patent protection, that provides the incentive to spend the money to generate this data
and that it is usually not possible to include such data in a patent application. In response to this
comment Ms Hubin confirmed that it was not necessary to provide human data or animal data to
support claims to pharmaceutically active compounds. Unfortunately, the section from page 39
of the Examiner's Manual discussed above suggests that such animal or clinical data is required.
While some of the comments made by SIPO relating to Article 26.3 and post-filing data are
encouraging, it remains to be seen whether there will be any change of practice within SIPO.
Unfortunately in the Workshop Chair's recent experience little has changed and post filing data
confirming the biological activity of compounds claimed in a patent application, supplementing
data provided in the specification, was not taken into account in assessing the patentability of
claim directed to a narrow class of compounds.
It is also interesting that a number of CIPO decisions have been successfully appealed to Chinese
courts, which might also eventually lead to a change in practice in SIPO.
INDIA
The Indian Patents Act, 1970 contains Section 3(d), which includes particular requirements
which must be satisfied for a new form of a pharmaceutical substance to be patentable. Section
3(d) appears as follows:
"(d)
the mere discovery of a new form of a known substance which does not result in the
enhancement of the known efficacy of that substance or the mere discovery of any new
property or new use for a known substance or of the mere use of a known process, machine
or apparatus unless such known process results in a new product or employs at least one
new reactant.
Explanation: — For the purposes of this clause, salts, esters, ethers, polymorphs,
metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations
and other derivatives of known substance shall be considered to be the same substance,
unless they differ significantly in properties with regard to efficacy;"
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Accordingly, new or subsequent uses of known pharmaceutical substances are not patentable in
India, and any new form of a known substance must have enhanced efficacy over the known
form of that substance.
Accordingly, in India it is not possible to obtain any form of patent directed towards second or
subsequent uses of pharmaceutical substances, and there are significant limits on the
patentability of pharmaceutical substances which represent new forms of known substances.
Section 3(d) of the Indian Patents Act was first interpreted by the Supreme Court of India when
it delivered its judgement rejecting Novartis' Indian patent directed to the β-crystalline form of
imatinib mesylate, which is a pharmaceutical used to treat chronic myeloid leukemia. Novartis'
drug is marketed worldwide under the names "Glivec" or "Gleevec". This case raised a number of
issues in relation to interpretation and application of Section 3(d).
First, there was a dispute as to the nature of the known form of imatinib against which the βcrystalline form of imatinib mesylate should be compared. Novartis took the view that the
known form was the free-base form, called imatinib, which appeared as Example 21 of a
previous patent application filed by Novartis in 1993, known as the Zimmermann patent.
Novartis argued that the selection of the β-crystalline form of imatinib mesylate involved at least
two steps, one being the selection of methane sulfonic acid to produce the mesylate salt, and
then the steps taken to make imatinib mesylate suitable for oral administration, which resulted
in the β-crystalline form of imatinib mesylate.
However, the opponents argued that in addition to disclosing imatinib, the Zimmermann patent
also disclosed imatinib mesylate. In this regard, the Zimmermann patent described a broad
range of compounds of Formula I and indicated that they "may form acid addition salts, for
example with inorganic acids, such as hydrochloric acid, sulphuric acid or a phosphoric acid, or
with suitable organic carboxylic or sulfonic acid, for example…….. aliphatic sulfonic acids, such as
methane-, ethane- or 2-hydroxy-ethane-sulfonic acid, …..". The specification also indicated that
any reference to the three compounds "should be understood as including the corresponding
salts, where appropriate and expedient".
In light of this disclosure, the Supreme Court held that the Zimmermann patent did in fact
disclose imatinib mesylate as well as its pharmacological properties, even though at no point in
the specification of the Zimmermann patent was their a disclosure of the combination of
imatinib and methane sulfonic acid. The Supreme Court therefore believed that the appropriate
comparison was between the β-crystalline form of imatinib mesylate and imatinib mesylate.
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Secondly, the Supreme Court had to look at what was meant by the term "efficacy", which is not
defined in the Patents Act. According to the Oxford dictionary the term means "the ability to
produce a desired or an intended result". They therefore went on to decide that the test of
efficacy in relation to a medicine can only be a "therapeutic efficacy". Accordingly, when
interpreting Section 3(d) the Supreme Court held that the new form of a known substance must
have significant advantageous and beneficial properties over the known substance, which in this
case was considered to be imatinib mesylate, a substance that before the invention under
consideration had not been prepared or tested. Unfortunately for Novartis, the evidence they
presented related to a demonstration of enhanced efficacy over imatinib itself, not the methane
sulfonate salt. The advantageous properties included more beneficial flow properties, better
thermo dynamic stability, lower hygroscopicity, and a 30% increase in bioavailability relative to
imatinib. The first three properties were disregarded by the Supreme Court since they related
to improved processability and not therapeutic efficacy. With regard to the improved
bioavailability, the Supreme Court accepted that this could lead to enhancement of efficacy, but
took the view that such data demonstrating this had not been presented to them. The data
provided simply indicated that "the β-crystalline form of imatinib mesylate will produce an
enhanced or superior efficacy (therapeutic) on molecular basis than could be achieved with
imatinib free-base in vivo animal."
While the decision of the Supreme Court indicates that post-filing data may be considered to
support arguments of improved therapeutic efficacy, it introduces problems in relation to the
appropriate "known substance" for comparison purposes.
There is another case currently before the Indian courts which will also consider Section 3(d) of
the Indian Patents Act. This is an appeal to the divisional bench of the Delhi High Court from the
decision of a single judge in relation to Merck Sharp & Dohme's patents relating to sitagliptin
phosphate. In April last year Glenmark introduced generic versions of two MSD products,
Januvia (sitagliptin phosphate) and Janumet (sitagliptin phosphate and Metformin), and MSD
sought an injunction to stop the sales of these generic products. It is understood that MSD failed
to get an injunction to stop Glenmark's product launch, but was later successful in obtaining an
injunction to prevent the launch of similar generic products by another Indian pharmaceutical
company, Aprica Pharmaceuticals. At the core of this matter is the question of whether the
phosphate salt form of sitagliptin should have been eligible for patent protection under Section
3(d). MSD has two patents in India, one directed towards sitagliptin and another directed to
sitagliptin phosphate, and the generic companies will need to establish that they do not infringe
either patent.
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ATTACHMENT 1
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ATTACHMENT 2
[End of document]
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