[Ip-health] New guidelines for the examination of pharmaceutical patents adopted in Argentina

Carlos Correa quiess at gmail.com
Tue May 29 06:40:29 PDT 2012


*Argentina adopts guidelines to examine patent applications for
pharmaceuticals*

The Ministry of Industry, the Ministry of Health and the National
Industrial Property Institute of Argentina jointly adopted guidelines for the
examination of patent applications for
pharmaceutical inventions (an unofficial translation is reproduced below).

The guidelines provide specific instructions regarding the application of
the patentability standards in the pharmaceutical field. They are largely
based on the working document,
published by WHO, ICTSD, UNCTAD and UNDP, '*Guidelines* for the Examination
of Pharmaceutical Patents: Developing a Public Health Perspective'
(available at
http://www.iprsonline.org/resources/docs/Correa_Patentability%20Guidelines.pdf
).

Carlos Correa

Joint Resolution 118/2012, 546/2012 and 107/2012 (Ministry of Industry,
Ministry of Health and National Industrial Property Institute)

Adoption of Guidelines for Patentability Examination of Patent Applications
for Chemical and Pharmaceutical Inventions

*Buenos Aires, 5/2/2012*

*Date of publication in the Argentine Official Gazette: May 8, 2012*



HAVING REVIEWED File No. 253-78027/11 of the NATIONAL INDUSTRIAL PROPERTY
INSTITUTE Registry, a self-governing body within the former Ministry of
Industry and Commerce of the Ministry of Industry, and :

WHEREAS Law No. 24425 endorses the final negotiations of the Uruguay Round
and the Marrakesh Agreement - and its Annexes - establishing the WORLD
TRADE ORGANIZATION.

WHEREAS the Agreement on Trade-Related Aspects of Intellectual Property
Rights (TRIPS) - Annex 1C - establishes the requirements for patentability
while granting member countries the power to determine the novelty and
inventive step standards to be met by inventions to be patentable under
their respective national laws.

WHEREAS in the case of pharmaceutical inventions, this power was ratified
by the Declaration on the Agreement on Trade-Related Aspects of
Intellectual Property Rights (TRIPS) and Public Health, adopted by the
Ministerial Conference of the WORLD TRADE ORGANIZATION in the City of Doha,
QATAR, in November 2001.

WHEREAS on December 4, 2009, during the XXVII Meeting of Ministers held in
the City of Montevideo, Uruguay, the Ministers of Health of the Southern
Common Market (MERCOSUR) remarked the importance of establishing common
objectives for public policies and the intellectual property system,
particularly in the development and application of patentability criteria
in the region, particularly in view of the proliferation of patents whose
subject matter is not properly an invention or which is only a marginal
development; and whereas the Ministers agreed on that occasion to promote
within the Southern Common Market (MERCOSUR) the adoption of criteria to
protect public health through patentability guidelines or guides.

WHEREAS, at multilateral level, the Global Strategy and Plan of Action on
Public Health, Innovation and Intellectual Property endorsed as part of the
WORLD HEALTH ORGANIZATION (WHO), a member body of the UNITED NATIONS (UN),
proposes and establishes actions ratifying these aspects and which were
approved by all its members.

WHEREAS the ARGENTINE REPUBLIC is actively involved as a member of the
WORLD HEALTH ORGANIZATION (WHO).

WHEREAS the right to health is a corollary of the right to life protected
implicitly in the unnamed guarantees (Section 33 of the ARGENTINE
CONSTITUTION).

WHEREAS Section 75, paragraph 22 of the Argentine Constitution grants
constitutional status to several treaties relating to Human Rights which
include, among others, the health protection concept

WHEREAS, Section 4 of Law No. 24481 (as restated by Decree No. 260/96), on
Patents and Utility Models, as amended, provides that any inventions,
whether products or processes, are patentable provided they are new,
involve an inventive step and are susceptible of industrial application,
and establishes as Application Authority the NATIONAL INDUSTRIAL PROPERTY
INSTITUTE, a self-governing body within the MINISTRY OF INDUSTRY.

WHEREAS the National Patent Authority of the NATIONAL INDUSTRIAL PROPERTY
INSTITUTE has expressed its opinion regarding the technical aspects of this
measure.

WHEREAS the SECRETARY OF HEALTH DETERMINANTS AND HEALTH RELATIONSHIPS of
the MINISTRY OF HEALTH has expressed its opinion regarding the adequacy of
this measure to the objectives of public health and access to medicines.

WHEREAS the competent Legal Services have reviewed these presents under the
provisions of Section 7, paragraph 7(d) of the National Administrative
Procedures Act No. 19549.

WHEREAS these Guidelines are issued pursuant to the powers granted by the
Law of Ministries (consolidated by Decree 438/92) as amended and Law No.
24481 (as restated by Decree No. 260/96).

NOW, Therefore, THE MINISTER OF INDUSTRY, THE MINISTER OF HEALTH AND THE
PRESIDENT OF THE NATIONAL INDUSTRIAL PROPERTY INSTITUTE

HAVE DECIDED:

Section 1 - To issue the "GUIDELINES FOR PATENTABILITY EXAMINATION OF
PATENT APPLICATIONS RELATING TO CHEMICAL AND PHARMACEUTICAL INVENTIONS",
which are set forth in an Annex containing TEN (10) pages which is an
integral part hereof .

Section 2 - This resolution shall take effect as from the day following its
publication in the Argentine Official Gazette and shall also apply to
pending applications.

Section 3 - Let it be known, published, and sent to the National Official
Registry Office archives.

Signed by:* - Debora A. Giorgi. - Juan L. Manzur. - Mario R. Aramburu.*





*ANNEX*



GUIDELINES FOR THE EXAMINATION OF PATENT APPLICATIONS RELATING TO CHEMICAL
AND PHARMACEUTICAL INVENTIONS



These Guidelines provide instructions for the patentability examination of
patent applications relating to chemical and pharmaceutical inventions.

The application of these Guidelines to patent applications is the
responsibility of the National Patent Authority (in Spanish, Administración
Nacional de Patentes, ANP). They are addressed primarily to the staff of
the ANP, but they are also expected to be of assistance to the parties
involved in the prosecution and practices related to patent applications.

These Guidelines are intended to cover usual cases. Therefore, they must be
considered as general instructions; any exception should be duly justified.



*1) Considerations about molecular structures*



(i) *Polymorphs.*

Polymorphism is an inherent property of the solid-state of drugs used in
the pharmaceutical industry (active ingredients and excipients). That is,
it is not a man-made invention but a property of each substance. When
referring to the phenomenon of polymorphism in a solid compound we are
talking about the existence of different crystalline forms of the same
substance.

A substance may be present in more than one crystalline form, depending on
environmental conditions (pressure, temperature, concentration, etc), which
determine each crystal form.

Solid compounds have a crystalline external appearance and an internal
crystalline lattice, which is the one we are interested in, but which is
not visible to us, and can only be appreciated using specific physical
tests.

In other words, a substance in the solid-state may exist as an amorphous
solid and/or in different crystal forms corresponding to different
arrangements of molecules in their internal structure, according to the
physical conditions existing during their formation. These arrangements are
specific of each polymorphic form and independent of any human
intervention. An example of this independence is the occurrence of a new
crystalline form in the capsules of a drug during storage without any human
intervention.

Such differences in the arrangement of atoms and/or molecules of the same
substance in the crystal unit cell, may result in modifications of some
physicochemical properties of pharmaceutical significance (such as melting
point, solubility, dissolution profile, bioavailability), not to mention
that the substance will naturally tend to its most stable form even without
any human intervention.

This evolution over time may occur or not, depending on the substance in
question.

1. As polymorph claims are based on the mere identification and/or
characterization of a new crystalline form of a substance already known in
the art, they are not patentable, even if they have pharmacokinetic or
stability differences with known solid forms (amorphous and/or crystalline
forms) of the same substance.

2. Processes for obtaining polymorphs are a routine experimentation in the
preparation of drugs. They are not patentable because it is obvious to try
to obtain the most suitable pharmaceutically polymorph using conventional
methods.





(ii) *Pseudopolymorphs (hydrates and solvates).*

Pseudopolymorphs are considered by the International Conference on
Harmonization (ICH) within the "polymorphs" category. This type of compound
is formed by the incorporation of solvent molecules into the crystal
structure of chemicals.

Pseudopolymorphs are also referred to as "solvates", and in the specific
case in which the solvent is water, they are referred to as "hydrates".
Solvated crystals exhibit a wide range of behaviors and in many cases
solvent molecules are an integral part of the crystal structure.

The ability to incorporate solvent molecules into the crystal structure of
a chemical substance is an intrinsic property of that substance. For this
reason it is not possible to "design" in advance the solvate to be obtained
when a substance is exposed to solvation conditions (such as temperature,
pressure, concentration) and different types of solvents.

Although hydrates and solvates have a different chemical composition from
the known active ingredients, hydrates are formed by exposing a chemical
compound to certain hydration conditions, and solvates result from
application of specific conditions. Consequently, they cannot be patented
independently from their active ingredient.

Consequently, processes to obtain pseudopolymorphs are a routine
experimentation in the preparation of drugs and they are not patentable.



(iii) *Enantiomers.*

Chiral molecules can have one or more chiral centers. When they have a
single chiral or asymmetry center there may be two different forms related
to each other as non-superimposable mirror images, referred to as
enantiomers.

Enantiomeric compounds (or optical isomers) are stereoisomers whose mirror
image is not superimposable and that due to the spatial arrangement of
their atoms on the chiral center rotate the plane of the polarized light in
opposite directions.

When the molecules have more than one chiral center, the spatial
arrangement obtained will show enantiomers as well as diastereomers, which
are collectively called stereoisomers.

When disclosing the molecular structure of a racemic compound (having both
enantiomers in a 1:1 ratio) the novelty of the enantiomeric compounds
forming it is also lost, since, being the molecular formula previously
known (whether or not it is written in a three-dimensional form) the
existence of enantiomers and diastereomers is necessarily revealed to a
person skilled in the art. Therefore, they are not patentable even if the
application describes different properties.

However, the processes for the preparation of individual enantiomers may be
patentable, provided they are new, involve an inventive step, and are
clearly described and the result obtained therefrom are well characterized
by means of spectroscopic data.



*2) Considerations about generic structures*



(iv) *Markush-type formula.*

These are generic chemical structures, which can have multiple chemical
substituents attached to a central core, covering a variety of compounds
with properties that, despite not having been tested for all claimed
compounds, can be inferred for the whole group.

The Markush formula is often used for claiming a large number of compounds
without the need of describing them individually.

In the case of compounds described by Markush formulas, the disclosure of
the basic structure, including all the possibilities of radical
substitution, is equivalent to disclosing each of the compounds resulting
from these substitutions.

1. The disclosure of a group of chemical compounds, even generically, is
considered as a disclosure of all the components of that group, which in
this way become part of the state of the art.

2. Compounds represented by a Markush formula shall be admissible only if
unity of invention is demonstrated, if they comply with the requirements
for patentability (novelty, inventive step and industrial application) and
if the specification sufficiently describes how to obtain each of the
compounds claimed under the Markush formula. Where an invention involves
multiple compounds claimed under a Markush-type formula, a reasonably
logical and proportional relationship between the scope of the claims and
the related matter disclosed in the description shall be required. The
description should include experimental procedures which, taking into
account combinations of different substituents or reasonably acceptable
equivalents thereof, are representative of the entire scope of the claimed
matter. If the working examples are not sufficiently representative of the
claimed scope of the invention, and therefore the claims lack sufficient
support in the description, the applicant should be required to limit it.

3. For an adequate description of the compounds included in the claimed
Markush formula, the embodiments of the invention described in the working
examples should be representative of all the compounds to be protected. In
all cases, these embodiments shall be perfectly exemplified by providing
all the data characterizing the compound obtained by physicochemical
characterization techniques (such as melting point, boiling point, -IR-
infrared spectrum, proton nuclear magnetic resonance -1HNMR- and carbon
13-13CRMN-), indicating whether polymorphic compounds have been detected.

4. Thus, the protection of Markush formulas should be limited to the matter
supported by the description, that can be effectively reproduced by a
person skilled in the art and whose industrial application comes up
unambiguously from the description.





(v) *Selection Patent Applications.*

Selection patent applications are those where a single element or small
group of elements is selected from a larger group, and they are claimed
independently, based on a characteristic or characteristics not previously
attributed to the larger group.

Selections can be made from products (chemical compounds, their salts,
isomers, esters, compositions, etc) and/or processes (obtention of
compounds or pharmaceutical compositions and others).

1. The disclosure of a group of chemical compounds (Markush formula) or
groups of pharmaceutical compostions, even generically, discloses all the
components of that group, which in this way become part of the state of the
art.

2. There is no novelty in the selection of one or more elements already
disclosed by the prior art, even though they may have different or improved
properties, not previously demonstrated.

3. The discovery of a different or improved characteristic or property for
a particular element or group of elements already known in the prior art
does not mean that the product or process is novel.

4. Pharmaceutical compositions, their methods of preparation and
medicaments containing them are not patentable if they are specifically
related to an element or elements selected from a larger group of elements,
since the product or process are not considered new.





*3) Consideration of chemically related elements*



(vi) *Salts, esters and other derivatives of known substances.*

New salts of known active ingredients, esters of known alcohols, and other
derivatives of known substances (such as amides and complexes) are deemed
to be the same known substance and are not patentable.



(vii) *Active metabolites.*

In some cases, pharmaceutical compounds generate, when administered to a
patient, an active metabolite, which is the product of the metabolism of
the compound in the organism.

Metabolites are products derived from the active ingredients used. They
cannot be considered to have been "created" or "invented".

Metabolites are not patentable independently from the active ingredient
from which they derived, even though they may have safety and efficacy
profiles differing from those of the parent molecule.



(viii) *Prodrugs.*

There are inactive compounds referred to as prodrugs, which when hydrolyzed
or metabolized in an organism, can give rise to a therapeutically active
ingredient.

In some cases, patent claims protect a drug and the prodrug(s) thereof.

A prodrug may produce benefits if it can be administered more easily than
an active compound. Patents on prodrugs, if granted, should exclude from
the claim the active ingredient as such, if the latter has already been
disclosed or if it is not patentable.

As any subject matter claimed in a patent, a prodrug must be sufficiently
supported by the information provided in the specification. It must comply
with the requirements of novelty, inventive step and industrial application
and include a description of the best method of obtaining it with an
adequate characterization of the product obtained.

In addition, the application should contain evidence that the prodrug is
inactive or less active than the claimed compound, that the generation of
the active compound (in the organism) ensures an effective level thereof,
while minimizing the direct metabolism of the prodrug.



*4) Consideration of pharmacotechnical characteristics*



(ix) *Formulations and Compositions.*

Composition or formulation claims refer to the use of active ingredients
and excipients or carriers pharmaceutically suitable such as diluents,
binders, disintegrants, lubricants, coloring and flavoring agents.

In some cases, a claimed formulation is associated with certain effects,
such as controlled release of a drug at a given site in the body. To
achieve this is part of the usual skill of a person specialized in the
formulation of pharmaceutical products, who can select from existing
manuals the suitable excipient to achieve the desired effect.

Formulation techniques and the components which can be used to develop
pharmaceutical products in their various forms are well known elements to a
person skilled in the art.

For example, the use of stabilizing agents in particular is not an
inventive step (as pH buffers) nor the use of certain components to modify
the bioavailability of a drug (a term which indicates the measurement of
the actual speed and the total quantity of drug reaching the general
circulation from an administered pharmaceutical form), as is widely known
that the pharmaceutical form used can affect bioavailability.

New forms and compositions as well as the processes for their preparation
as a general rule should be considered obvious in view of the prior art.

The same rule applies in relation to compositions or forms related to
polymorphs.

Likewise, claims related to pharmacokinetic parameters (such as Tmax, Cmax,
plasma concentration), micronization of a known product or distribution by
particle sizes should not be considered patentable.

As an exception, formulation claims may be acceptable when they solve in a
non obvious way a longstanding problem. In this case the description should
include a description of the tests conducted and the results obtained.



(x) *Combinations.*

Combination Claims of previously known active ingredients, in some cases
specify the specific compounds they include and the amounts they cover,
while others only refer to a class of therapeutic compounds, such as
antacids and anti-viral agents, without specifying which compounds are
included.

Most combinations have already been tested in medical practice by
administering the components independently. Claims on combinations of
previously known active ingredients in practical terms are equivalent to
claims on medical treatments whose patentability is excluded.



(xi) *Dosage/Dose.*

Some patent applications are directed to inventions consisting of dosages
of an existing product, such as once a day pediatric dosages or dosage
forms. While at times they are filed as product claims, they are equivalent
to claims on medical treatment methods, since dosage is not a product or
process, but a dose of the product with which the therapeutic action is
obtained for that use. Therefore, they are not patentable.



(xii) *Second Medical Indication (New medical uses).*

Use Claims, including a second medical indication (or other medical uses)
of known compounds are not admissible. Often, applications are limited to
describing pharmacological activity trials in order to confirm the
discovery of further use possibilities. Patent applications for second
medical indications (or other medical uses) are equivalent to therapeutic
treatment methods and have no industrial application.

This rule applies even if the claim is drafted under a "Swiss formula",
that is, "use of x for the manufacture of a medicament for the treatment of
"y" “, or its variants .



(xiii) *Analogous Processes.*

Patentability of products and processes should be evaluated according to
the properties and characteristics of such products or processes,
considered separately.

Synthetic or manufacturing processes which are not new and inventive by
themselves, should be considered non-patentable as such, even if their
starting or intermediate materials or their final product are new and
inventive. An example of this is the new salification of a known product.



*5) Other considerations*



(xiv) *Sufficiency and scope of the description.*

For the purposes of any type of evaluation, any exemplary embodiments added
to aid a better understanding of the claimed invention, as well as any data
and/or information filed by request of the examiner, will be taken into
account, as long as such information does not extend the scope originally
disclosed in accordance with the provisions of Section 19 of Annex II of
Decree No. 260 issued on March 20, 1996.

In order to be patentable, manufacturing methods must allow to obtain an
industrial result, therefore, manufacturing processes of active ingredients
and other pharmaceutical components described in the specification must be
reproducible and applicable on an industrial-scale without additional
experimentation and/or substantial changes in the described physical and
chemical parameters and their characterization.

Extrapolation of these Guidelines to pharmaceutical and biotechnological
inventions should be analyzed in each particular case.



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