FEDERAL PUBLIC SERVICE MINISTRY OF DEVELOPMENT, INDUSTRY AND FOREIGN TRADE
NATIONAL INSTITUTE OF INDUSTRIAL PROPERTY
PRESIDENCY March 12, 2015
RESOLUTION N°. 144/2015
SUBJECT MATTER: Introduce the Guidelines for Examining Patent Applications in the Field of Biotechnology.
The PRESIDENT OF THE NATIONAL INSTITUTE OF INDUSTRIAL
PROPERTY (INPI) and the DIRECTOR OF PATENTS, in the exercise of their
authority established in Articles 106, 159 and 161 of Appendix of Ordinance nº
149 of May 15, 2013, and
WHEREAS the need exists to streamline the procedures for processing
applications with a view to enhancing efficiency and ensuring quality,
WHEREAS the INPI’s Directorate of Patents seeks greater transparency
in its administrative procedures, and
WHEREAS the need exists to standardize and update criteria for
analyzing patent applications in the Field of Biotechnology,
HEREBY RESOLVE:
Art. 1 – To introduce the Guidelines for Examining Patent Applications in
the Field of Biotechnology under the terms of document “Guidelines for Examining
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Patent Applications in the Field of Biotechnology”, Appended to this Resolution.
Art. 2 – The regulatory effect conferred to items 2.3, 2.4, 2.6, 2.12 to 2.16,
and 2.25 to 2.35 of the “Guidelines for examining patent applications in the fields
of biotechnology and pharmaceuticals filed after December 31, 1994”, as stated in
the written opinion published in issue n°. 1648 of the Industrial Property Gazette
(RPI) dated August 6, 2002, is hereby revoked.
Art. 3 – This Resolution shall enter into effect on the date it is published in
the Online Industrial Property Gazette (Revista Eletrônica da Propriedade
Industrial).
Otávio Brandelli President
Júlio César Castelo Branco Reis Moreira Director of Patents
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MINISTRY OF DEVELOPMENT, INDUSTRY AND FOREIGN TRADE
NATIONAL INSTITUTE OF INDUSTRIAL PROPERTY
DIRECTORATE OF PATENTS
Guidelines for Examining Patent
Applications in the Field of
Biotechnology
March 2015
This text shall be an integral part of the Guidelines for Examining
Patent Applications and is designed to define the INPI’s current
understanding in the Field of Biotechnology. Other topics inherent to
examination shall be listed and discussed in said general guidelines.
March 12, 2015
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TABLE OF CONTENTS
1 REQUIREMENTS FOR PROTECTION IN BIOTECHNOLOGY.................5
1.1 INDUSTRIAL APPLICATION .........................................................................5
2 CONDITIONS FOR PROTECTION .................................................................... 7
2.1 UNITY OF INVENTION..................................................................................... 7
2.2 FULL DISCLOSURE (ART. 24)......................................................................... 7
2.2.1 DEPOSITING BIOLOGICAL MATERIAL .................................................. 10
2.2.1.1 Cases in which the biological material must be deposited........................... 10
2.2.1.2 Timelines for depositing biological material................................................ 12
2.2.2 FULL DISCLOSURE OF LISTING OF SEQUENCES ................................ 12
2.3 BASIS, CLARITY AND PRECISION (ART. 25) ..........................................13
2.3.1 BASIS IN THE SPECIFICATION ................................................................. 13
3 CLAIMS.................................................................................................................15
3.1 REACH-THROUGH TYPE CLAIMS IN BIOTECHNOLOGY.................15
3.1.1 TECHNICAL EXAMINATION OF CLAIMS
4 MATTER EXCLUDED FROM PROTECTION ACCORDING TO THE
INDUSTRIAL PROPERTY STATUTE ...............................................................18
4.1 DEFINITIONS ...................................................................................................18
4.2 MATTER NOT CONSIDERED INVENTIONS (ART. 10)..........................19
4.2.1 Natural biological products and processes (ART. 10 (IX)) ............................ 19
4.2.1.1 Natural biological products........................................................................... 19
4.2.1.1.1 Compositions containing natural biological product..................................20
4.2.1.1.2 Extracts .......................................................................................................20
4.2.1.1.3 Enriched extracts.........................................................................................20
4.2.1.2 Natural biological processes ..........................................................................21
4.2.1.3 Use of natural products ..................................................................................23
4.3 NON-PATENTABLE INVENTIONS (ART. 18 OF THE INDUSTRIAL
PROPERTY STATUTE) ........................................................................................23
4.3.1 NON-PATENTABLE INVENTIONS BY OF ART. 18 (I) OF THE
INDUSTRIAL PROPERTY STATUTE ...................................................................23
4.3.2 NON-PATENTABLE INVENTIONS BY VIOLATION OF ART. 18 (III) OF
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16
THE INDUSTRIAL PROPERTY STATUTE ..........................................................24
5 MICROORGANISMS..........................................................................................26
6 BIOLOGICAL SEQUENCES.............................................................................. 27
6.1 CHARACTERIZATION ................................................................................... 27
6. 1.1 MARKUSH-TYPE SEQUENCES..................................................................29
6.1.2 WHEN IT IS NECESSARY TO FILE THE LISTING OF SEQUENCES IN
CONJUNCTION WITH THE APPLICATION......................................................... 29
6.1.2 NEED TO RESTRICT THE SET OF CLAIMS TO THE SEQUENCES FILED
IN CONJUNCTION WITH THE APPLICATION ................................................... 30
6.2 HOMOLOGY VERSUS IDENTITY................................................................ 31
6.3 SEQUENCES OF NUCLEOTIDES ................................................................. 33
6.3.1 MODIFICATION OF SEQUENCE(S) OF NUCLEOTIDES.......................... 34
6.3.1.1 Modification of sequence(s) by substitutions, insertions or deletions of non-
modified nucleotides................................................................................................... 34
6.3.1.1.1 SNPs............................................................................................................. 35
6.3.1.2 MODIFICATION OF SEQUENCE(S) OF NUCLEOTIDES with modified
derivatives (inclusive with protector groups)
6.3.2 FRAGMENTS ................................................................................................... 36
6.3.3 OLIGONUCLEOTIDES (OR INITIATORS) .................................................. 36
6.3.3.1 Degenerate and modified oligonucleotides .................................................... 37
6.3.4 PROMOTORS ................................................................................................... 37
6.3.5 VECTORS ......................................................................................................... 39
6.3.6 CDNA ................................................................................................................ 42
6.3.7 ESTS – EXPRESSED SEQUENCE TAGS ........................................................ 43
6.3.8 ORFS – OPENREADING FRAMES .......................................................... ........ 43
6.3.9 RNAS ................................................................................................................. 44
6.4 SEQUENCES OF AMINOACIDS.................................................................... 44
6.4.1 CHARACTERIZATION OF AMINOACID SEQUENCES............................ 44
6.4.2 HOMOLOGOUS PROTEINS (PARALOGOUS VERSUS ORTHOLOGOUS)
..................................................................................................................................... 46
6.4.3 PROTEIN FRAGMENTS ................................................................................. 47
6.4.4 SEQUENCE MODIFICATIONS...................................................................... 49
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35
6.4.4.1 With natural aminoacids (substitutions, insertions or deletions) ................... 49
6.4.4.2 With non-natural aminoacids (inclusive with protector groups)................... 50
6.4.4.3 Groupings added to the carboxyl or amino terminus ..................................... 50
6.4.5 FUSION PROTEINS ........................................................................................51
6.4.5.1 Naturally-occurring........................................................................................ 51
6.4.5.2 Characterization ............................................................................................. 51
6.4.5.3 Integral Seq ID............................................................................................... 51
6.4.5.4 Definition of just one of the sequences present in the fusion protein ............ 52
6.4.6 ANTIBODIES.................................................................................................... 54
6.4.6.1 Process of obtaining antibodies ...................................................................... 55
6.4.6.2 Hybridomas..................................................................................................... 55
6.4.6.3 Chimeric/humanized antibodies ..................................................................... 56
6.4.6.4 Fragments of antibodies.................................................................................. 57
7 ANIMALS, PLANTS, PARTS THEREOF AND PROCESSES OF
OBTAINING THEM ................................................................................................ 58
7.1 ANIMALS, PLANTS AND PARTS THEREOF ............................................. 58
7.1.1 Products and processes involving stem cells..................................................... 58
7.2 TRANSGENIC PLANTS, PARTS THEREOF AND PROCESSES OF
OBTAINING THEM ................................................................................................ 59
7.3 PROCESS OF OBTAINING PLANTS BY CROSS-BREEDING ................ 60
8 PATENT APPLICATIONS INVOLVING COMPONENTS FROM THE
BRAZILIAN GENETIC HERITAGE.................................................................... 63
9 REFERENCES....................................................................................................... 65
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1 Requirements for protection in biotechnology
The requirements of novelty and inventive step are discussed in the Guidelines
for Examining Patent Applications. Only a few specificities of biotechnology patent
applications will be highlighted in this Appendix.
1.1 Industrial application
The concept of industrial application in the field of biotechnology must
comply with that set forth in the Guidelines for Examining Patent Applications (Block
II), and due regard shall be given to the definition of a utility for the invention
claimed.
When the invention involves biological sequences, the requirement of
industrial application is only met when a utility is disclosed for said sequence.
Accordingly, if a patent application identifies a new sequence by homology,
and the homologous sequence described in the state of the art has a known function, a
new sequence identified in the patent application is susceptible to industrial
application provided that this utility is identified in the specification.
Example 1:
The protein of SEQ ID NO: 1 was identified in different patients with prostate
cancer, and no biological function for this protein is known in the state of the art. It is
noted that this protein described in the application is an important marker for
diagnosing prostate cancer.
The inventions related to this protein (for example, use, composition,
diagnosis kit) are susceptible to industrial application since the application clearly
discloses a practical use for this sequence (marker for diagnosing in vitro prostate
cancer), even if its biological function is still unknown.
Example 2:
The application discloses a protein of SEQ ID NO: 1 which was isolated from
yeasts; however, it discloses no function/application for the same and it presents no
homology with any protein having a known function.
The specification discloses a merely speculative list of applications with no
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technical basis capable of supporting any practical application for the protein. This
protein and/or its use and/or compositions comprising same are not susceptible to
industrial application, since said subject matters present no defined practical utility.
2 Conditions for protection
2.1 Unity of invention
The patent application shall refer to a single invention or to a group of inter-
related inventions so as to comprise a single general concept (Art. 22 of the Industrial
Property Statute (Law N°. 9,279/96); see Guidelines for Examining Patent
Applications, Block I).
Example 3: Multiple nucleic acid molecules that share a common structure and encode
proteins with common properties.
Claim 1: Modified nucleic acid characterized by being selected from SEQ ID NO: 1, 2,
or 3.
The specification mentions that the three nucleic acids encode dehydrogenases
that include a sequence of conserved motive defining the catalytic site. The three
nucleic acids are isolated from three different sources (mouse, rat and human) and
modified. The specification clearly shows that these three nucleic acids are
homologous based on their global sequence identity (85-95% identity) for both
sequences of nucleotides and aminoacids.
The same technical characteristics or equivalents that are shared among the
nucleic acid molecules lies in their common properties (encoding dehydrogenases) and
their shared structural elements are essential for the common property (the conserved
motive). So, there is a special technical characteristic and SEQ ID NOs: 1, 2, and 3
have unity of invention.
2.2 Full disclosure (Art. 24)
Article 24 of the Industrial Property Statute determines that the specification
must clearly and sufficiently describe the object, to the extent of enabling a person
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skilled in the art to carry it out (see Guidelines for Examining Patent Applications,
Block I). The ‘object’ is understood to be the subject matter for which protection is
sought, that is, the subject matter contained in the set of claims. Accordingly, the
analysis of full disclosure of the matter claimed must be evaluated based on what was
disclosed in the specification, listing of sequences and drawings (as applicable).
When the application pertains to a product or process involving a biological
material, which cannot be described such that a person skilled in the art can
understand and reproduce the subject matter, then the specification must be
supplemented by depositing said material (see item 2.2.1).
Two examples of lack of full disclosure (insufficient description) in the Field
of Biotechnology warrant special attention. The first is that in which the embodiment
of the invention depends on chance. In this situation, even if the person skilled in the
art were to follow the instructions given in the application, there is no guarantee of
obtaining the contended results. These cases must be contested as a result of the
provision laid down in Art. 24 of the Industrial Property Statute (see item 2.2.1.1 and
example 4). The second is when the embodiment of the invention is inherently
impossible. For example, in a method which includes the amplification of a certain
DNA sequence by using a given pair of primers, wherein said primers are not
complementary to any part of the DNA sequence, thus rendering the execution of the
method unfeasible.
Example 4:
The application describes a mutant microorganism obtained by random
mutagenesis with UV radiation. As obtaining the microorganism depends on chance,
full disclosure of the microorganism will only be satisfied by depositing the
microorganism (see item 2.2.1.1). The document of proof of deposit of the
microorganism in question may be presented via explanations, during the technical
examination, provided that the deposit of the microorganism occurred up to the
application filing date (or priority date, as applicable). The microorganism obtained by
UV-induced mutation thus deposited will be in compliance with Art. 10 (IX) provided
that there is no concrete evidence that the microorganism having that characteristic is
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noted in nature.
Example 5:
The application describes a new and inventive method of obtaining mutant
microorganisms by random mutagenesis. Since the stages of said method are described
in detail in the specification, it is possible for a person skilled in the art to reproduce the
invention. Therefore, said method presents full disclosure, in compliance with the
provision in Art. 24 of the Industrial Property Statute. If this method is tied to obtaining
just one mutant with specific characteristics, the information on the deposit thereof must
be included in the claim, since there is no guarantee of obtaining the same result.
Example 6:
The application describes a method which uses a mutant microorganism. The
specification furnishes no details of the process of obtaining the microorganism, but
characterizes it by way of its respective filing number. In this case, it is considered
that a person skilled in the art could reproduce the method in question using the
microorganism deposited. Accordingly, the invention meets the condition of full
disclosure.
Example 7:
The specification discloses a protein by way of its access number at the NCBI
database of sequences or by reference to a scientific article, and said protein is essential
for the embodiment of the invention. To comply with the requirement of full disclosure
established in Art. 24 of the Industrial Property Statute, the filing applicant is required
to incorporate the sequence in question to the application, as disclosed in the databases
at the time of filing/priority, in the form of listing of sequences, and this shall not result
in the inclusion of subject matter, since said protein could be identified unequivocally
from its access number or by way of the aforementioned scientific article (see
additionally items 2.2.1.1 and 2.2.2).
Example 8:
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The application describes a new dopamine receptor, duly characterized by its sequence
of aminoacids. The application mentions that antagonists and agonists of the receptor
are also useful. Nevertheless, the application does not furnish a technical description
of any antagonist and agonist compounds of the receptor. A person skilled in the art
would not be able to carry out the invention related to the antagonists and agonists
owing to absence of any technical instruction on how to do so, since the mere
description of a receptor does not provide sufficient information concerning the
molecules that might stimulate or prevent its working. Therefore, it is understood that
the subject matters relating to the antagonists or agonists of the enzyme do not fulfill
the condition of full disclosure (see also item 3.1).
2.2.1 Depositing biological material
In the case of biological material that is essential for the practical realization of
the object of the application, which cannot be described in the form of Art. 24 and
which is not publicly accessible, the specification shall be supplemented by depositing
the material at an institution authorized by the INPI or recommended in an
international agreement (Treaty of Budapest; see Guidelines for Examining Patent
Applications, Block I).
Accordingly, it is considered that “biological material”, in this context of
deposit, may refer to any material containing genetic information capable of
exercising direct or indirect self-replication. Representative examples include
bacteria, archaea, protozoa, viruses, fungi, algae, seeds, lineages of animal and
vegetable cells, hybridomas, artificial chromosomes and other vectors, and the host
cell that houses these biological materials, for some of these cases, and in accordance
with the requirements of the chosen depositary center, can be deposited.
2.2.1.1 Cases in which the deposit of biological material must be carried out
It is important to emphasize, as mentioned above, that the Industrial Property
Statute refers to the deposit of biological material which cannot be described pursuant
to Art. 24, that is, it cannot be described clearly and sufficiently in the specification.
Thus, it is concluded that the deposit of the material does not necessarily apply to all
and every biological material involved in a certain invention, since, for example,
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polynucleotides and polypeptides shall be described by way of their nucleotide and
aminoacid sequences (N.B.: nevertheless, there is nothing to prevent such materials
from being deposited in addition).
In relation to the microorganisms having different nucleotide sequences from
that found in nature, the application shall present the modified nucleotide sequence by
way of the listing of sequences (see item 2.2.2), or its name known in the art, or the
deposit data of the microorganism. When essential to confer the inventive
characteristic, the description must also include specific promoters, the insertion site
of the heterologous material in the genome, the methodology of obtaining the sample,
among other essential characteristics, such that a person skilled in the art is capable of
carrying out the invention.
In cases where the microorganisms are selected from random mutagenesis and
the genetic alterations which result in a differential effect are not defined in the
application, then in order to comply with Art. 24 of the Industrial Property Statute, the
microorganism shall be deposited at an international depositary authority and the
biological material deposit data (such as declaration of deposit or name of the
institution, number and date of deposit) shall be included in the application (see item
2.2.1). Accordingly, the biological material will be available at the depositary
authority and, therefore, will be considered clear, sufficiently described and
reproducible. If the microorganism is not deposited, the subject matter will not
comply with Art. 24 of the Industrial Property Statute.
When the inventive characteristic obtained by genetic alteration is achieved
only by a specific strain used in the application under examination, it is considered
that the microorganism in itself is essential to carry out the invention and, therefore,
the biological material shall be deposited so that the subject matter complies with Art.
24 of the Industrial Property Statute. Moreover, depositing the biological material is
not necessary when the inventive characteristic can be achieved by various strains or
species of microorganisms available using the methodology described in the
application. Thus, for situations where broadly known organisms are merely
transformed to express a new and surprising characteristic, simply specify the
organism of interest, relating it expressly to the nucleic acid to be used in this
transformation, and assure that this nucleic acid is described clearly and precisely.
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In cases where the invention does not lie in a microorganism or biological
material in itself, but rather in the use, modification or cultivation thereof, and a
person skilled in the art is not capable of carrying out the invention without having
said sample in the application, the deposit of the microorganism or the biological
material is also necessary.
2.2.1.2 Timelines for depositing biological material
In connection with the original deposit of biological material for patenting
purposes, IN PR Nº 17/2013 establishes that the biological material shall be deposited
by the filing date of the patent application, and that said data shall be included in the
specification. In the event of a priority claim, the biological material shall be
deposited prior to or by the date of the priority claimed, if applicable, that is, if the
priority rights apply to the biological material.
When the data on proof of deposit of the biological material are not included in
the patent application, and the examiner finds that such data are necessary, an office
action shall be issued for the applicant to reply. If said office action is not complied
with, then the application shall be rejected, by operation of Art. 24 of the Industrial
Property Statute.
2.2.2 Full disclosure of the listing of sequences
If the object of a patent application comprises one or more sequences of
nucleotides and/or aminoacids that are supported by the description of the invention,
then the application shall contain a section of listing of sequences, with a view to
achieving full disclosure as prescribed in Art. 24 of the Industrial Property Statute (see
Guidelines for Examining Patent Applications, Block I). It is emphasized that if the
application uses and makes reference to sequences known in the art, and these are
necessary for the embodiment of the invention, the examiner may issue an office
action for the sequences to be presented. It must also be noted that the sequences shall
correspond to those included in the state of the art at the time of filing/priority (i.e. as
disclosed in the databases), bearing in mind possible refinement or alterations in the
sequences over time.
Resolution INPI Nº 228/09, incorporated into Resolution INPI PR Nº 81/2013,
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provides for procedures for presenting the listing of sequences by electronic means
and substitutes item 16.3 of AN 127/97 (see Resolution PR Nº 81/2013 and its
Appendices published in the Official Federal Gazette (DOU) - Section 1, Nº 68, April
10, 2013).
2.3 Basis, clarity and precision (Art. 25)
2.3.1 Basis in the specification
The subject matter that is the object of protection shall be duly supported in the
specification. Accordingly, the description in the specification shall furnish technical
information capable of supporting all the subject matter claimed.
Example 9:
Claim 1: immunogenic protein characterized by consisting of SEQ ID:1, and
fragments thereof.
The specification presents a mutated immunogenic protein (non-natural)
having 600 residues of aminoacids and also discloses an immunogenic fragment of
this mutated protein (non-natural), determined as consisting of residues 320 to 400 of
said protein. The set of claims, in turn, claims protection for the immunogenic protein
and for immunogenic fragments of said protein (claim 1). However, the specification
only discloses one immunogenic fragment of said protein, namely: which starts in
position 320 and ends in position 400 of the protein. In this case, considering that the
patentability requirements prescribed in Art. 8 of the Industrial Property Statute were
met, an office action shall be issued based on Arts. 24 and 25 of the Industrial
Property Statute so that the subject matter claimed is only restricted to that
sufficiently described and effectively supported in the specification, namely the
immunogenic protein and the fragment thereof that comprises residues 320 to 400 of
said protein.
In this example, even if the filing applicant files new information regarding
other immunogenic fragments of said protein which had not been described in the
subject matter initially disclosed, such information could not be considered because
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the specification did not mention immunogenic fragments of the aforementioned
protein other than that comprised between aminoacids 320 and 400 thereof.
Therefore, the fact remains that the claim for broad protection of “immunogenic
fragments of the protein” cannot be accepted owing to the absence of full disclosure
and support for the subject matter in the specification.
Example 10:
Claim 1: process for transforming plants characterized by introducing the gene X in
angiosperms and gymnosperms.
The specification presents general information on the process and a detailed
example of the transformation of the gene into an angiosperm. There is evidence for
a person skilled in the art that said process would not be applicable in the same
manner for both groups of plants, and therefore a claim which includes gymnosperms
would not be supported in the specification. This lack of support might be overcome
by evidence that the transformation of gymnosperms could be carried out under the
same conditions already mentioned for angiosperms.
However, if to achieve support for the claim for gymnosperms the data
furnished new parameters or any adaptations that are not trivial for a person skilled
in the art, such information will not be accepted. This is because it would be
necessary to include the data in the specification which would constitute the addition
of subject matter, this being in disagreement with Art. 32 of the Industrial Property
Statute.
3. Claims
There are two basic types of claims: product, related to a physical entity; and
process, related to an activity (see Guidelines for Examining Patent Applications,
Block I).
In the Field of Biotechnology, some non-exhaustive examples of subject
matters considered to be within the “products” category are: nucleic acids, peptides,
polypeptides, proteins, microorganisms, virus, cells, vectors, plants, seeds,
hybridomas, antibodies, probes, vaccines, compositions, kits, expression cassettes,
extracts, food products, and others. For “process claims”, some non-exhaustive Page 15 of 63
examples are: process for producing a compound/composition; process for selecting a
sequence of nucleic acid/polypeptides/peptides; process for producing a transgenic
microorganism/plant/animal; method of purification; processes of extraction/isolation,
among others.
3.1 ‘Reach-through’ type claims in biotechnology
‘Reach-through’ claims are a special type of claim which seek protection for
future inventions based on an invention from the present. That is, this type of claim
seeks protection for inventions that had not been identified by the inventor up to the
time of filing his patent application, but which may be identified in the future by use
of the real invention.
A frequent type of reach-through claim in biotechnology is the product claim,
said product generally corresponding to a “candidate compound”. Such claims seek to
protect compounds that are candidates for modulators of the activity of the real
invention, such as the agents that modulate the biological function of a protein or a
gene.
Reach-through products (drugs, agonists, antagonists, etc.) are usually
identified merely by reference to a material or method used in the identification of
same, without a definition of their chemical structures. Otherwise, such products are
defined in terms of the function associated to the real invention, since this is the only
information available to the inventor. Consequently, both compounds already known
in the state of the art and those yet to be identified are ultimately encompassed within
the scope of the claim, which thus become altogether broad.
The other type of reach-through claim in biotechnology is the process claim
for identifying modulator compounds. In this type of claim, the compound identified
by the process is not defined by its structure but rather by its capacity to modulate the
expression of a protein or a gene involved in a disease, for example, or else by the
screening method used to identify said compound. A common characteristic for these
types of claims is that the subject matter that is the object to be protected is not
known.
3.1.1 Technical examination of reach-through claims
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The subject matters of the reach-through claims typically do not present full
disclosure, clarity, precision and/or basis, thus being in disagreement with Arts. 24
and 25 of the Industrial Property Statute.
Example 11:
Claim 1: Process for identifying an agonist/antagonist of polypeptide X characterized
by comprising (a) contacting said polypeptide with a compound to be screened; and
(b) determining whether the compound affects the activity of said polypeptide.
Claim 2: An agonist/antagonist characterized by being for the polypeptide X as
identified by the process defined in claim 1.
The application pertains to a new and inventive process of screening for
modulators of the activity of a polypeptide already known in the state of the art
(polypeptide X), whose activity was demonstrated as involved in disease Y, though the
compounds identified by said process were not characterized.
Claim 1 defines the main invention of the application which is a method of
screening compounds of therapeutic interest and that modulates the activity of
polypeptide X, being the actual invention, and claim 2 is of the reach-through type,
which in this situation may include in its scope compounds already known and which
are not modified at all by the process used in identifying same, and compounds not yet
known.
Although the application sufficiently describes the screening process
specified in claim 1, and from this aspect could be accepted, claim 2 is not accepted
owing to lack of full disclosure (Art. 24), clarity, precision and support (Art. 25).
Claim 2 uses functional (not structural) characteristics to define the subject matter that
is the object of protection. It so happens that defining a product by functional
characteristics often causes lack of clarity of the subject matter. A person skilled in the
art could not reduce the practice to the definition of the subject matter object claimed,
because the compounds claimed per se (claim 2) have potentially unlimited structural
possibilities, and thus include compounds that are yet to be identified and/or that are
already available in the state of the art and/or are barred by the prohibitions of Art. 10
(IX).
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Claim 2 seeks protection for candidate compounds identified by the screening
method of the invention defined in claim 1. Said compounds were technically defined
only by their activity (that is, functional definition – common wording in this type of claim)
which in the present situation corresponds to a modulation (agonist/antagonist) of the
activity of polypeptide X. The structural characteristics of the candidate compounds were
not defined; said situation would oblige said technician to test innumerous compounds
already known and all the compounds as may be identified in the future using the
screening method of the invention, in order to determine which of these compounds had
the desired activity and that would thus be encompassed by the scope of the claims under
examination.
4 Matter excluded from protection according to the Industrial Property Statute
4.1 Definitions
According to the understanding adopted by this Institute, technically speaking,
the terms and expressions used in these Guidelines are interpreted as follows:
• the “whole” (of natural living beings) refers to plants, animals, microorganisms
and any living being;
• “part of natural living beings” refers to any portion of living beings, such as
organs, tissues and cells;
• “biological materials found in nature” encompass the whole or part of natural
living beings, in addition to extracts, lipids, carbohydrates, proteins, DNA,
RNA, found in nature or isolated therefrom, and parts or fragments of same, as
well as any substance produced from biological systems, for example hormones
and other secreted molecules, viruses or prions. Synthetic molecules that are
identical or indistinguishable from their natural counterparts are also
encompassed within this definition;
• “isolated from nature” is understood to be all and any subject matter extracted
and subjected to a process of isolation or purification, i.e. withdrawn from
natural context;
• “genome” is the set of genetic information of a cell, organism or virus;
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• “germoplasm” is the set of hereditary material of a sample representative of
individuals of a same species;
• “natural biological process” is any biological process that occurs spontaneously
in nature and in which human intervention does not affect the end result;
• “therapy” is a treatment method designed to cure or prevent an infirmity or
defective working of the body;
• “surgery” is defined by the nature of the treatment instead of its purpose, that is,
it does not depend on manual or instrument intervention in the body of the
patient having aesthetic or therapeutic purposes; and
• “diagnosis” refers to the identification of a particular disease.
4.2Subject matters not considered inventions (Art. 10)
4.2.1 Natural biological products and processes (Art. 10 (IX))
In terms of “product” category claims, Art. 10 (IX) of the Industrial Property
Statute establishes that the whole or part of a natural living beings and biological
materials found in nature, or isolated therefrom, including the genome or germoplasm
of any natural living being, are not considered to be inventions.
For “process” category claims, such as processes, methods, uses, applications,
among others, Art. 10 (IX) of the Industrial Property Statute refers solely to natural
biological processes, establishing that these not considered inventions.
Since Art. 10 (IX) of the Industrial Property Statute addresses the whole or
part of natural living beings and biological materials found in nature which are not
considered inventions, documents published subsequent to the priority/deposit date of
the application under analysis can be used as evidence that the subject matter claimed
does not comply with the provisions of Art. 10 (IX) of the Industrial Property Statute,
provided that the information available clearly and unequivocally proves that the
subject matter claimed exists in nature.
4.2.1.1 Natural biological products
The whole or part of natural living beings and biological materials found in
nature – even if isolated therefrom, or produced synthetically which have naturally- Page 19 of 63
occurring correspondents, there being no way of distinguishing them from the natural
ones –, are considered natural biological products, and are not considered to be
inventions because they do not comply with Art. 10 (IX) of the Industrial Property
Statute.
Accordingly, the inclusion of a disclaimer with the term “non-natural” in itself
alone does not overcome the objection in terms of Art. 10 (IX) of the Industrial
Property Statute.
4.2.1.1.1 Compositions containing a natural biological product
A composition claim whose sole characteristic is the presence of a certain
product also confers protection for this product in itself. Accordingly, a composition
claim characterized solely by containing a non-patentable product (for example, a
natural extract), cannot be granted, since it would protect the very non-patentable
product. That is, even more so here than in cases of patentable components, the claim
requires parameters or characteristics which unequivocally determine that it addresses
a de facto composition.
In these cases, special care must be taken in connection to the text of the claim
with regards the other component(s) of the composition in question, so as to prevent it
from ultimately representing a mere dilution (an aqueous solution, for example) of the
non-patentable product. Bearing in mind that the finality of a composition is to place
the active component(s) in a suitable form for the purpose for which it is destined, a
“mere dilution” would be one in which the solvent does not contribute to this end
purpose, being merely the means used for extraction. Thus, it is possible that the
aqueous or ethereal extract of a certain plant, for example, despite containing a
component (extraction solvent) besides the extract itself, does not represent a ready
composition to be used for its end purpose, and this same extract diluted in another
solvent (used for, for example, to make the active ingredient absorbable) represents a
de facto composition as opposed to a “mere dilution”.
4.2.1.1.2 Extracts
Extracts are biological materials isolated from nature and, therefore, are not
considered invention based on Art. 10 (IX).
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Thus, for compositions containing extracts, the same considerations stated
above apply for natural products.
4.2.1.1.3 Enriched extracts
Extracts differentiated from their natural correspondent by being enriched in
any of their components will only be eligible for protection when their composition
presents characteristics that cannot normally be achieved by the species and that result
from direct human intervention.
Attention must also be paid to the case of extract of transgenic bacterial cells.
Although the microorganism in itself may be patentable, its extract is not always
patentable, since there may be cases in which it is not possible to distinguish the
extract from the transgenic cell from the wild extract (for example, the transgenic
microorganism merely superexpresses the endogenous protein).
Example 12:
Claim 1: A vegetable extract characterized by being enriched with isoflavones.
The extract is enriched with isoflavones by the isolation method. In this case, it
is considered that a modification of said extract results from the simple fractioning of a
natural extract isolated from nature, and said claim, therefore, does not comply with
Art. 10 (IX).
Example 13: An extract enriched by genetic manipulation.
Claim: An enriched vegetable extract characterized by comprising human insulin.
The application describes a process of altering the composition of the plant
extract by way of expression of the human insulin gene, resulting in an enriched extract.
In this case, it is considered that the modification of said extract results from the genetic
manipulation of the organism from which it is extracted. Thus, being a material
obtained from plants which present characteristics normally unachievable by the
species, resulting from direct human intervention, said extract is eligible for protection.
4.2.1.2 Natural biological processes
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A “natural biological process” is understood to be any biological process that
occurs spontaneously in nature and in which human intervention does not affect the
end result.
If technical intervention performs an important role in determining the result,
or if its influence is decisive, the process is considered an invention. That is,
processes containing at least a technical stage that has a decisive impact on the end
result, and that cannot be achieved without human intervention, are considered
inventions.
Under this concept, the classic process of obtaining plants or animals is not an
invention. In the same way, processes only having stages which mimic events
occurring in nature, are not considered inventions. In contrast, methods based on
genetic engineering (for example, producing a transgenic plant), where technical
intervention is significant, are eligible for patenting.
Microbiological processes encompass processes that use, apply to, or result in
microorganisms. Although such processes are biological processes, the INPI
considers that they are granted by being an exception from the legal exclusions
permitted under the TRIPS Agreement (Art. 27(3b)).
In the same way, the INPI considers that biological or enzymatic processes for
obtaining chemical compounds, presenting a technical stage that is decisive for the
end result, are eligible for protection.
As in other processes, biological process claims formulated correctly define
the base material, the product obtained and the means of transforming the former into
the latter; the various stages necessary for achieving the intended purpose; or in the
case of use, the material to be used and the purpose of the use.
Examples of suitable claims (N.B.: the level of detail necessary will depend on
the specific invention under examination):
• Process for obtaining compound X characterized by cultivating
microorganism W (bacteria, fungi, yeast, etc.) on Y.
• Process for obtaining compound X characterized by using enzyme E.
• Process for obtaining compound X characterized by cultivating cells of plant
P transformed by gene T.
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4.2.1.3 Use of natural products
When the process claimed involves the whole or part of natural living beings
and biological materials found in nature, including the genome or germoplasm, but
does not consist of a natural biological process, there is no obstacle for the
patentability thereof in light of that prescribed in Art. 10 (IX) of the Industrial
Property Statute. Accordingly, the use of a natural product can be eligible for
protection, provided that is in accordance with patentability requirements.
Example 14:
Claim: Use of a natural resin obtained from Aloe vera plant leaves characterized by
being for preparing cosmetic compositions for the treatment of keratin fibers.
Claims relating to the use of a natural resin for preparing cosmetic compositions can be
accepted, with due regard for adherence to patentability requirements, since no article
in the Industrial Property Statute is contrary to the use of natural products in activities
that do not constitute natural biological processes.
Example 15:
Claim: Use of RNAse characterized by being for cleaving the RNA.
Use of a natural material for carrying out the natural function itself is not considered an
invention according to Art. 10 (IX), because it consists of a natural biological process.
4.3Non-patentable inventions (Art. 18 of the Industrial Property Statute)
4.3.1 Non-patentable inventions by violation of Art. 18 (I) of the Industrial
Property Statute
According to Art. 18 (I), “anything contrary to morality, decency and public
safety, order and health” is not patentable.
Considering that biotechnology is an invention-generating technological field
which addresses subject matter that may raise moral questions and issues of public
order, current doctrine allows the INPI to reject the patenting of these inventions
based on Art. 18 (I) of the Industrial Property Statute.
Non-exhaustive examples include: Page 23 of 63
(a) processes of cloning human beings;
(b) processes of modifying the human genome that cause modification of
the genetic identity of human germinative cells; and
(c) processes involving animals that cause suffering thereto without
resulting in any substantial medical benefit to human beings or
animals from such processes.
In claims worded “process for cloning mammal cells”, it is understood that the
term “mammal” includes human beings. Thus, said claim might adversely affect
morals, order and public health, and, therefore, would not comply with Art. 18 (I) of
the Industrial Property Statute. In this case, the exclusion of human mammals from
the scope of protection would be an acceptable disclaimer, even if human beings are
not excluded in the original specification.
4.3.2 Non-patentable inventions by violation of Art. 18 (III) of the Industrial
Property Statute
According to Art. 18 (III) of the Industrial Property Statute, the following is
not patentable: “living beings, in whole or in part, except for transgenic
microorganisms meeting the three patentability requirements – novelty, inventive step
and industrial application – listed in Art. 8 and which are not mere discoveries”.
Regarding transgenic microorganisms, the sole paragraph of Art. 18 (III) of the
Industrial Property Statute defines that “For the purposes of this law, transgenic
microorganisms are organisms, except for plants and animals, in whole or in part,
that due to direct human intervention in their genetic composition express a
characteristic that cannot normally be achieved by the species under natural
conditions”.
In accordance with this definition, the term transgenic microorganism covers
microorganisms (see item 5) which are obtained by any technique having the
consequence of altering the genetic composition, that cannot be achieved by the
species under natural conditions, by direct human interference. This definition is not
limited to microorganisms which have exogenous genes and/or other organisms
inserted therein.
In the examination of transgenic microorganism claims, it must initially be
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verified whether the term “microorganism” in the application description covers
animal and vegetable cells, which is not eligible for protection, since the whole or part
of plants and animals, even if transgenic, is not patentable. In these cases, the subject
matter claimed must be limited so as to encompass only those transgenic
microorganisms eligible for protection. Additionally, human intervention must be
clear so that it is possible to evaluable whether it is fact addresses a microorganism
that expresses a characteristic not normally achievable by the species under natural
conditions.
Denominations such as “transgenic”, “mutant” or “variant” are not sufficient to
evaluate the patentability of the microorganism, in view of the possibility that the
microorganism, even so-called “transgenic”, “mutant” or “variant”, may occur
naturally or be indistinguishable from the natural one, and therefore not constitute an
invention according to Art. 10 (IX) of the Industrial Property Statute.
5 Microorganisms
The generic term “microorganism” is employed for bacteria, archaea, fungi,
single cell algae not classified in the Plant Kingdom and protozoa. Accordingly,
among the whole or part of living beings, natural or transgenic, the Industrial Property
Statute only allows transgenic microorganisms to be patented.
Examples of suitable formulations for microorganism claims (non-exhaustive list)
• Transgenic microorganism characterized by containing SEQ ID NO: X.
• Transgenic microorganism characterized by containing SEQ ID NO: X inserted in
position Y of the genome.
• Transgenic microorganism characterized by containing sequence xxxxxxx in
position Y of the genome (see item 2.2.2).
• Transgenic microorganism characterized by containing gene X (provided that the
gene is well known).
• Transgenic microorganism characterized by containing gene X with the promoter
Z inserted in position Y of the genome (provided that the gene and the promoter
are well known).
• Transgenic microorganism characterized by containing expression vector X Page 25 of 63
(provided that this vector is well known).
• Transgenic microorganism characterized by being the ATCC-XXXX (filing
number).
Attention must be paid when SEQ ID NO: X, the gene X or the plasmid X were
isolated from a natural and non-modified microorganism. In such case, the claim
bearing the generic title of “microorganism” or “bacteria”, among others, will also
protect the original microorganism that has said gene naturally, and an objection will
be admissible based on prescribed in Art. 10 (IX) of the Industrial Property Statute.
6 Biological sequences
In general terms, in patent applications describing an invention whose
development depends on sequences of aminoacids and/or nucleotides, the following
aspects shall be noted: (i) need to include the sequence in the application for purposes
of full disclosure (Art. 24); (ii) natural occurrence (Art. 10 (IX)); (iii) clarity, precision
and basis (Art. 25) in the form in which such molecules / sequences are claimed; (iv)
novelty (Art. 11); (v) inventive step (Art. 13); and (vi) industrial application (Art. 15).
Full disclosure of biological sequences is specifically addressed in item 2.2.2.
The novelty requirement, when related to biological sequences, follows the
same general principle (see Guidelines for Examining Patent Applications, Block II),
that is, for a sequence of aminoacids or nucleotides to be new in light of the state of
the art, all the aminoacids or nucleotides shall be exactly the same and be in the same
order and, in some cases, additionally have the same structural formula as the
sequence known in the art.
The same points in which unsuitable matters are usually noted will be
addressed in the topics below.
6.1 Characterization
Having complied with the rules established in item 2.2.2 as a way of
guaranteeing clarity and precision of the subject matter claimed, the set of claims shall
refer to the biological sequences in question by way of the corresponding SEQ ID NO:
(see item 2.2.2).
In some cases, other forms characterizing biological sequences can be
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accepted:
a) when the sequences have fewer than four aminoacids or ten
nucleotides, in accordance with Resolution PR Nº 81/2013, they shall
be characterized by the sequence itself;
b) structural formulae accompanied by their corresponding SEQ ID NO: ;
c) Markush formulae accompanied by their corresponding SEQ ID NO: ;
d) deposit number (see item 2.2.1); or
e) by its name or designation, when a biological sequence is already
known in the state of the art and is not the main object of the invention.
It is emphasized that a DNA must be defined by its sequence of nucleotides,
whereas a protein, by its sequence of aminoacids, so as to define with clarity the
subject matter that is the object of protection.
Additionally, attention must be paid to claims of the following types, since
none of them bears clarity (Art. 25).
a) DNA sequence characterized by encoding a protease.
In this type of claim, the product is characterized solely by its
function, which is not sufficient to define with clarity what the product
refers to. In contrast, if this DNA is characterized by its sequence of
nucleotides, the definition of the function may be accepted, as an additional
characteristic of the product.
b) DNA sequence characterized by encoding a polypeptide presenting a
sequence of aminoacids of the protein represented by SEQ ID NO: 1.
This wording defines a DNA by the sequence of aminoacids, which is
not permitted. However, the claim may be altered so as to define the DNA
by the sequence of nucleotides, and their degenerations which generate the
same protein may be accepted. In this situation, at least one sequence of
nucleotides must be present in the application as filed, unless it is a
sequence that is already available in the state of the art and referenced in
the specification.
c) Protein characterized by presenting activity Y.
The product is characterized solely by its function, which does not
enable the scope to be clearly defined. In contrast, if said protein is
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characterized by its sequence of aminoacids, the definition of the function
may be accepted, as an additional characteristic of the product.
d) Protein with activity Y characterized by presenting the following
composition in aminoacids: (percentages of each aminoacid present).
In this type of claim, the product is characterized by its function and
by the percentage of aminoacids, which does not enable the product
claimed to be clearly defined either. The sequence of aminoacids is
necessary.
e) Plasmid characterized by being the pWn.
In this type of claim, the product is characterized by a designation
given by the inventor himself, which does not permit the product to be
defined.
6.1.1 Markush form sequences
Biological sequences can be presented in the form of a Markush formula
containing a base sequence that is substituted by one or more variable substructures,
which are accompanied by a list of definitions of these variable portions, such as, for
example:
Peptide of Formula I
Xaa1 Xaa2 His Xaa4 Pro Gly Ser Phe Ser Asp Glu Gly Asp Trp Leu;
wherein
Xaa1 is His or Thr;
Xaa2 is Ala, Gly or D-Cpa (4-chloro-Phe); and
Xaa4 is Gln, Asn or Pro.
For further details on Markush formulae, see the Guidelines for Examining
Patent Applications, Block II.
6.1.2 When it is necessary to file the listing of sequences in conjunction with the
application
Resolution PR Nº 81/2013 of the INPI establishes in Art. 2 thereof that when
the patent application contains one (or more) sequence(s) of nucleotides and/or
aminoacids, which is (are) fundamental for the description of the invention, said
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sequence(s) shall be presented in a listing of sequences.
When the invention includes the sequence per se, that is, when the set of
claims bears “protein”, “polypeptide”, “nucleic acid” claims, or any other term
designating a biological sequence, such is considered a fundamental part of the
invention, and must be included in the listing of sequences (except for sequences
having fewer than four aminoacids or ten nucleotides, cf. defined in Resolution PR Nº
81/2013).
In contrast, when a molecule in question is solely an illustrative example, said
specific sequence may not be considered a fundamental part of the invention, and
therefore, its sequence does not necessarily need to be presented as part of the
application.
Additionally, care must be taken regarding the possibility that other sequences
used in the application – and not necessarily the encoding genes / sequences – are
fundamental to carry out the invention. Thus, in these cases, it is also important to
evaluate whether the sequence in question is broadly known in the art, and whether its
use is fundamental to carry out the invention.
6.1.3 Need to restrict the set of claims to the sequences filed in conjunction with
the application
When a sequence in question solely represents a molecule that is part of a
process described, but that any other molecule having the same biological function
would present the same result (or in situations where there is no reason to believe that
such molecules would not be effective), said method does not necessarily have to refer
to a single SEQ ID NO:, since said measure would unnecessarily restrict the scope of
the method in question.
Example 16:
The application describes a method of inducing sporulation in bacteria characterized
wherein said bacteria are transformed with a vector containing a sporulation gene
under the control of any promoter. The examples presented in the application use the
spo5 gene. Nevertheless, any gene of the spo family would theoretically allow the
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same result to be achieved. Thus, in theory, there is no reason to demand that a
specific sequence of the spo5 gene be presented in said method claim.
Attention in these cases should lie on the “generic” name given to the sequence of
interest, the so-called “spo gene”, as mentioned above, because if the applicant uses
said denomination in the claims, it must be broadly known and used in the art,
unequivocally referring to a certain gene family.
Example 17: A method for inducing the expression of a given gene under certain
specific conditions.
The specification clearly states that the desired characteristic is a genic
expression in a certain condition, which is only obtained by use of promoter X, since
this promoter is only activated when the means impacts the characteristics of interest
(depletion of glucose, for example).
The application describes the use of different genes under the control of this
promoter X, demonstrating that they are all expressed solely in the conditions of
interest.
In this case, the single fundamental sequence to obtain the desired
characteristic is that of promoter X. Thus, as in the prior example, it is considered that
the presentation of the sequences of genes used is not compulsory; and even if the
applicant presented such sequences, it is not deemed necessary that the subject matter
claimed be restricted to these genes. Nevertheless, the sequence of the promoter,
which is the invention, must be described clearly and precisely by way of its
corresponding SEQ ID NO:.
6.2 Homology versus identity
When aligning and comparing nucleotide or protein sequences with each other,
the terms homology, identity and similarity may be employed. At this stage, it is
important to make the distinction between such terms.
Two sequences (of nucleotides or aminoacids) are homologous solely when
they share a same common ancestor. Therefore, the concept of being “partially
homologous” is non-existent: two sequences are either homologous or not, and it is
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incorrect to speak of percentage of homology. Homologous proteins generally share
may similarities regarding their three-dimensional structures. When two sequences are
homologous, they generally share a significant identity, though there may also be cases
to the contrary: two molecules may be homologous without sharing a statistically
significant identity between their sequences of aminoacids or nucleotides (for example,
as is the case of the family of globins).
Establishing homology between two sequences is not solely based on the
analysis of the identity between these sequences, but also on biological criteria, such
as analyzing the structure and function of the proteins, for example. Results from
comparing sequences by way of algorithms such as BLAST, FASTA and SSEARCH
do not evaluate homology between sequences: they measure the similarity and the
identity between sequences. Whereas homology refers to a qualitative inference,
identity and similarity are quantitative attributes.
The identity between two sequences refers to the occurrence of precisely the
same nucleotides or the same aminoacids in a same position in two nucleotide or
protein sequences aligned and compared to each other. Therefore, if two proteins
present 90% identity, this means that 90% of all the residues of aminoacids contained
in said proteins in corresponding positions are precisely identical.
In contrast, the percentage of similarity between two sequences of proteins
refers to the sum of the identical and similar matches (for example, the aminoacids
glutamate and aspartate are considered similar, since both are acidic). It must be
noted that the similarity can be measured based on different definitions on how related
(similar) an aminoacid residue is to the other.
Applying these terms to the examination of patent applications, the following
types of claims are not accepted:
a) claim of the type “protein (or DNA sequence) characterized by being a SEQ
ID NO: 1 or any other sequence of aminoacid with at least x% homology with
SEQ ID NO: 1” is not clear (in disagreement with Art. 25 of the Industrial
Property Statute), since, technically, the term “% homology” is not applicable,
as highlighted above; and
b) claim of the type “DNA sequence (or protein) characterized by presenting at
least 80% identity (or similarity) with SEQ ID NO: 1” cannot be accepted
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since said as worded it covers innumerous different sequences, and also does
not specify at which sites in the sequence of nucleotides (or aminoacids)
substitutions may occur; therefore, claims of this type cannot be accepted,
since the characterization of the object of protection is not clear and precise,
this being in disagreement with Art. 25 of the Industrial Property Statute.
Furthermore, the characterization of the sequence of interest based on the
identity percentage is highly broad and generally includes in its scope sequences not
supported by the specification or that do not meet patentability requirements. Lastly,
it is also important to note that in these cases, the specification does not generally
provide sufficient information to enable the reproduction of all the countless
sequences covered by said type of definition (this being in disagreement with Art. 24
of the Industrial Property Statute).
6.3 Sequences of nucleotides
Nucleotide sequences can be referred to in patent applications in different
manners: genes, vectors, plasmids, DNA sequence, RNA sequence, nucleic acid,
oligonucleotides, primers, cDNA, and other. Nevertheless, for purposes of
simplification, in these Guidelines, all these molecules will be designated, in general
terms, as “sequences of nucleotides”. This definition is valid despite the size of said
molecule. The items below will address the particular aspects of some of these
molecules.
Said sequences of nucleotides shall be characterized in accordance with the
item 6.1. Nevertheless, it must be emphasized that the molecules defined by a
sequence with fewer than ten nucleotides shall be characterized by the sequence of
nucleotides itself.
6.3.1 Modification of nucleotide sequence(s)
Modifications in nucleotide sequences with the aim of differentiating them
from natural sequences may be carried out in different ways. In theory, any
characteristic introduced into the sequence that was not described as naturally-
occurring is acceptable as a modification so as to comply with Art. 10 (IX) of the
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Industrial Property Statute, with due regard for that prescribed in item 6.3.1.1.
Nevertheless, the simple introduction of terms such as “recombinant” in natural
molecule claims cannot be accepted, since the resulting molecule would be
indistinguishable from its natural counterpart, even if produced in recombinant
manner.
6.3.1.1 Modification of sequence(s) by substitutions, insertions or deletions of
non-modified nucleotides
In general terms, modifications of natural biological sequences by inserting
non-modified nucleotides into the sequence (in the means or at the ends) are
considered sufficient so as to comply with Art. 10 (IX), provided that the resulting
sequence formed is not naturally-occurring either.
If nucleotides are deleted in the means of the sequence claimed, said
modification is, theoretically, enough to differentiate it from the natural molecule.
Nevertheless, even in cases where deleted nucleotides are contiguous and are at the
end of the sequence, this still does not comply with Art. 10 (IX), since the resulting
sequence is still identical to part of the natural sequence (see item 6.3.2).
Regarding the substitution of nucleotides by other non-modified nucleotides, it
is considered that said modification is sufficient to comply with Art. 10 (IX), provided
that there is no description of natural sequences (for instance, in related species)
containing said substitution.
Nevertheless, it should be considered that various substitutions of nucleotides
in a given sequence may not result in any modification in the protein encoded thereby,
owing to degeneration of the genetic code. Thus, in these cases, a nucleotide sequence
modified by substitutions may comply with Art. 10 (IX), whereas the sequence of
aminoacids encoded thereby remains identical to the natural one, and, therefore, does
not comply with Art. 10 (IX).
When analyzing sequences derived from the state of the art, which comply
with Art. 10 (IX), it is important to analyze the inventive step of the modification
(insertion, deletion or substitution) made, taking into account the fact that some
groups of aminoacids present common properties. Thus, the inventiveness of these
alterations in the polynucleotide sequences generally depends on the demonstration of
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an unexpected effect generated by the modification in relation to the state of the art.
6.3.1.1.1 SNPs
The SNP abbreviation refers to “single nucleotide polymorphism” and is used
to designate natural variations that occur in the genome and which involve, as the
name suggests, a single nucleotide. They may be associated to certain characteristics,
thus acting as molecule markers.
Regardless of the utility described, whenever a certain SNP – or any other
polymorphism – is described as being naturally-occurring, it cannot be considered as
an invention, according to Art. 10 (IX) of the Industrial Property Statute.
Nevertheless, the use of a set of SNPs, for example, in an in vitro diagnosis method
(such as DNA fingerprinting) or in the ambit of personalized medicine, may be
eligible for patent protection.
6.3.1.2 Modification of sequence(s) of nucleotides with modified derivatives
(including protector groups)
Inserting nucleotides that are not naturally-occurring (derivatives of natural
nucleotides) are also considered sufficient modifications for the sequences to comply
with Art. 10 (IX). Nevertheless, the presence of these nucleotides and the list of
nucleotides of interest shall be expressed in the claims, so as to prevent the natural
nucleotides from being indirectly included whereby resulting in the natural biological
sequence.
The inclusion of such nucleotides in the sequences presented in patent
applications is addressed in INPI Resolution PR Nº 81/2013, cited in item 2.2.2 of
these Guidelines; and a list with examples of modified nucleotides and the acceptable
abbreviation in their definition is available in Table 2 of the Appendix to this
Resolution (published in the Official Federal Gazette (DOU) – Section 1, Nº 68, April
10, 2013).
6.3.2 Fragments
Special attention in required in analyzing claims involving “Fragments of
sequences”, even if such sequences are inserted into the application. Said
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consideration is due to the fact that the definition of “fragments” of a said sequence
includes all and any subdivision of the sequence presented, resulting in an undefined
number of possible fragments, which do not present any function/relation with the
subject matter described in the application.
Example 18:
An application presents SEQ ID NO: 1 (hypothetican( � agctggttcgactgtctcga.
The claim refers to a “nucleic acid characterized by having a sequence of
nucleotides of SEQ ID NO: 1 and fragments thereof”. As the claim stands, said
claim includes, for example, molecules such as: agct, actg, ctgg, ggtt, ggttc, cgactgt,
and an infinity of others, including many that do not have any function
described/related with the invention.
Thus, it is clear that the reference to fragments of a given sequence cannot
be accepted in the claims, since the subject matter claimed is not supported, nor is it
clearly and precisely defined in accordance with Art. 25 of the Industrial Property
Statute. In these cases, full disclosure of the subject matter may be questioned in
accordance with Art. 24 of the Industrial Property Statute.
Moreover, if the application describes that fragments obtained from a certain
sequence are useful to the finality described in the invention, such fragments may be
claimed, provided that the desired fragments are clearly identified in the claims
(specifying the position of the initial and final nucleotides of this fragment) and are
not natural.
6.3.3 Oligonucleotides (or initiators)
Since they represent segments of sequences complementary to genes and/or
natural mRNAs, it is considered that primers are part of natural biological material,
and therefore, claims that claim such primers do not comply with Art. 10 (IX) of the
Industrial Property Statute (note the possible exceptions in item 6.3.1).
6.3.3.1 Degenerate and modified oligonucleotides
Degenerate oligonucleotides generally consist of a mixture of oligonucleotides
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which can be used for amplifying genes that have similar but not identical sequences
(such as the amplification of orthologous genes in related species), or same genes
unknown.
Attention must be paid to the possibility that one (or some) of the resulting
oligonucleotides are identical to a natural biological sequence (for example, to the
gene sequence intended for amplification), which in this case does not comply with
Art. 10 (IX). Moreover, if they present modifications, which result in a different
sequence of nucleotides to that which occurs in nature, they will comply with Art. 10
(IX) (see item 6.3.1).
Additionally, considering that a mixture of oligonucleotides (for example,
degenerate oligonucleotides, etc.) may not be clearly and precisely defined, the claims
relating to this subject matter will not comply with Art. 25 of the Industrial Property
Statute. Attention is also needed for the description of this mixture in the specification
(compliance with Art. 24 of the Industrial Property Statute).
Furthermore, so that the subject matter claimed is clearly and precisely
defined, a degenerate oligonucleotide may be characterized based on a consensus
sequence, and vary solely by one or a few pre-defined nucleotides. In such cases, the
claims relating to these degenerate oligonucleotides shall cite the consensus sequence
and the variable nucleotide positions.
6.3.4 Promoters
Promoters are the central processor of the regulation of a gene, since it
contains the binding sites for the RNA polymerases, responsible for the genic
transcription. By definition, it comprises the region 5' of the gene. The processes that
provide the transcriptional modulation are highly complex and occur by way of an
intricate network of interactions involving regulatory sequences (TATA box, CCAAT
box etc.) and other elements located further away from the transcription starting point
(enhancer and silencer sequences).
Contrary to gene sequences, which have specific “markers” for their start and
finish (for example: initiation codon, site for polyadenylation, etc.), the sequence of a
promoter does not present such delimitations. Therefore, experimental data shall be
presented to prove that the isolated DNA sequence is indeed capable of leading to the
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expression of gene sequences, that is, it shall present the promoter activity of interest.
There are intermediary cases in which the DNA sequence with promoter
potential is isolated, sequenced and analyzed by bioinformatics to predict its possible
regulatory motives (CCAAT box, TATA box, CpG islands, etc.). said analysis in
silico, though of great importance for preliminary studies, is not sufficient to
demonstrate that the sequence identified is indeed a promoter region, validation with
suitable functional assays being necessary.
In any case, as they are made up of sequences of nucleotides, promoters shall
be represented by a SEQ ID NO: X, as established in items 2.2.2 and 6.1.2.
Example 19:
Claim 1 : DNA sequence characterized by being SEQ ID NO: 1
Said sequence was isolated and presents promoter activity: said claim cannot
be accepted because it does not comply with Art. 10 (IX) of the Industrial Property
Statute.
Nevertheless, in cases where the SEQ ID NO: 1 presents mutations, deletions
and/or insertions, that is, it becomes different to the sequence as found in nature, the
examination of novelty, inventive step and industrial application of the invention is
applicable. It is important to note that deletions may result in fragments that are
considered as part of the natural material, and therefore, would not comply with Art.
10 (IX) (see items 6.3.2 and 6.3.3.1) either.
Example 20:
Claim: Expression cassette characterized by comprising the promoter sequence of SEQ
ID NO: 1 operationally bound to a gene of interest and a terminator sequence.
If SEQ ID NO: 1 was found in nature, but was subsequently modified (via
punctual mutations, deletions and/or insertions), the above claim may be accepted,
provided that the subject matter is considered new and inventive. If SEQ ID NO: 1 is as
found in nature, the claim must be restructured so as to better specify the cassette, with
the introduction of the term “heterologous”, clearly stating that it does not cover
protection for subject matter that does not comply with Art. 10 (IX) of the Industrial
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Property Statute (see item 6.3.5).
Example 21:
Claim: Expression cassette characterized by comprising a promoter sequence
selected from the group of SEQ ID NO: 1 to 3 or fragments and derivatives thereof
operationally bound to a gene of interest and a heterologous terminator sequence.
This type of claim must be analyzed taking into account the observations in the
examples above. Furthermore, the promoter sequence must be restricted solely to
the sequences for which the promoter activity of interest was demonstrated. If
promoter activity was demonstrated solely for SEQ ID NO: 1, for example, a claim
must be limited to said sequence; further, the term “or fragments and derivatives
thereof” cannot be accepted, since the subject matter claimed is not supported, nor is
it clearly and precisely defined in accordance with Art. 25 of the Industrial Property
Statute. In these cases, full disclosure of the subject matter may be questioned in
accordance with Art. 24 of the Industrial Property Statute.
6.3.5 Vectors
A vector is a DNA molecule used as a vehicle for transferring exogenous
genetic material to other cells. Normally, DNA vectors present three characteristics:
(i) they contain an origin of replication that enables the replication thereof, regardless
of the host chromosome; (ii) they contain a selection marker that enables the cells
containing the vector to be easily identified; and (iii) they present single sites for one
or more restriction enzymes. The cloning vector is designed to replicate an insertion
in a host cell. The expression vector contains an expression cassette that enables the
insertion to be expressed in the target cell in an induced or constitutive manner. The
expression cassette contains regulatory sequences, such as transcription promoter and
terminator sequences.
Regarding full disclosure pursuant to Art. 24 of the Industrial Property Statute,
the examiner shall analyze the invention in question and the level of detail necessary
for it to be reproduced, depending, for example, on whether the vector is the main
invention or an accessory invention. In this sense, certain aspects shall be noted in the
specification: Page 38 of 63
• representative drawing of the map of the vector in question, highlighting the
essential characteristics for it to work, that is, the cleavage sites for the
restriction enzymes, the appropriate restriction enzymes, the promoter used,
the repression regions, the termination regions, the marker sequences or
sequences that confer resistance to antibiotics, etc.;
• the sequence to be cloned and/or expressed in the form of SEQ ID NO: X shall
be present in the listing of sequences, pursuant to the Resolution(s) in effect;
• if the preferred codons for expressing the insertion in a given microorganism
are essential to the invention, they must appear in the listing of sequences; and
• the procedures and the conditions for manipulating the DNA/RNA, including
the enzymes used (for example, endonuclease, polymerase, ligase, etc.), the
cloning systems involved, the conditions of transfection/transformation of the
host cell, among other usual techniques.
It is important to point out that when there is no other way of defining the
vector in reproducible form (full disclosure – Art. 24 of the Industrial Property
Statute), the biological material must be deposited (see item 2.2.1).
Below are examples of claims designed to reflect commonplace situations in
which vectors are recombinants. In other words, these examples do not encompass
natural vectors found in bacteria, fungi and plants, especially in mitochondria and
chloroplasts, since these are not considered inventions in light of Art. 10, item IX, of
the Industrial Property Statute.
Example 22: Vector as main invention.
Claim: A vector characterized by consisting of filing number XXXX.
The main invention pertains to a new and inventive vector which can be
employed for cloning and/or expressing a gene of interest. In this case, the vector can
be characterized in a claim by its filing number recorded at an International
Depositary Authority. Therefore, the vector will be defined clearly and precisely,
pursuant to Art. 25 of the Industrial Property Statute.
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Example 23: Vector as main invention.
Claim: A vector that contains the sequence of origin of replication, selection marker
sequence and multiple cloning sites characterized by comprising SEQID NO:X
In this example, the structure of the vector is new and inventive owing to the
specific combination of SEQ ID NO: X with the other elements common to vectors,
such as the sequence of origin of replication, the selection marker sequence (for
antibiotics, etc.) and the sites for the restriction enzymes. Therefore, the essential
elements that distinguish this vector from others in the state of the art shall be the
only elements characterized by their respective SEQ ID NO: X, since the other
components are known by a person skilled in the art. Importantly, in this case, the
SEQ ID No: X does not correspond to the expression cassette.
Example 24: Vector as an inter-related invention.
Claim: Vector characterized by comprising the sequences defined by SEQ ID NO: X
and SEQ ID NO: Y operatively bound to the heterologous promoter and terminator
sequences.
The invention describes two genic sequences involved in the transport of
lysine which were isolated from Corynebacterium glutamicum. SEQ ID NO: X
encodes the lysine-exporter protein (LysE), whereas SEQ ID NO: Y encodes the LysE
regulator protein (LysG). Although SEQ ID NO: X and SEQ ID NO: Y are
endogenous to the host cell Corynebacterium and, therefore, natural, they are flanked
by heterologous sequences of the gene construction present in the recombinant vector.
Accordingly, the vector complies with that prescribed in Art. 10 (IX) of the Industrial
Property Statute.
Example 25: Vector as inter-related invention.
Claim: A vector characterized by comprising a DNA construction consisting of the
sequence defined by SEQ ID NO: X operationally bound to the transcription promoter
and terminator sequences.
The invention refers to a new gene sequence which bears inventive step and
is eligible for cloning/expressing in suitable host cells.
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In cases where SEQ ID NO: X is identical to that found in nature, care must
be taken such that the construction as a whole presents some heterologous sequence
as a way of differentiating it from the natural sequence. However, if SEQ ID NO: X is
altered, the term “heterologous”, as used in example 24, is not necessary.
6.3.6 cDNA
cDNA molecules represent sequences produced from RNAs. In the case of
cDNAs originating from messenger RNA (mRNA), if the originating gene has introns,
the cDNA will be different to the gene that encoded this mRNA, since the cDNA
sequence will only present the sequence of exons. Accordingly, in these cases, it
cannot be considered that a cDNA molecule is identical to a natural molecule, and its
patentability must be evaluated based on the requirements of novelty, inventive step
and industrial application.
When the cDNA addresses molecules produced from mRNAs from genes that
do not have introns, said cDNA will have an identical constitution to the DNA/gene
strand which acted as mold for synthesizing this mRNA. Thus, in these cases, the
cDNA is not considered an invention, according to Art. 10 (IX) of the Industrial
Property Statute.
In cases of cDNA obtained from other types of RNA (such as, for example,
tRNA, snRNA, rRNA), it must be verified whether they are identical to the natural
DNA, a situation in which they would not be considered an invention, according to
Art. 10 (IX).
Additionally, the simple sequencing of the cDNA without association of a
function for same, is not sufficient to guarantee industrial application (see item 1.1)
and support for the subject matter, this being in disagreement with Arts. 15 and 25 of
the Industrial Property Statute, respectively.
6.3.7 ESTs – Expressed Sequence Tags
The term “EST” refers to a partial sequence – or a fragment of the sequence –
obtained from a cDNA (hence the fact of referring solely to expressed sequences).
The simple sequencing of an EST is not sufficient to guarantee industrial
application and support for the subject matter, this being in disagreement with Arts. 15
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and 25 of the Industrial Property Statute, respectively.
Additionally, so as to comply with Art. 10 (IX), the analysis of this subject
matter follows the same criteria used for cDNA; therefore, it is necessary to know
whether said EST represents a sequence fragment of a single exon (in which case it
would be considered part of a natural biological material), or if it extends beyond the
juncture point between two different exons (in which case there would be no natural
equivalent, and therefore, could be considered as an invention).
In contrast, when addressing sequences originating from genes that do not
have introns, any EST is considered a fragment of a natural biological sequence (see
also item 6.3.2).
6.3.8 ORFs – Open Reading Frames
The term ORF refers to potentially encoding sequences, generally obtained
from DNAs sequencing. Additionally, an ORF has an initiator codon (relating to a
methionine, for the majority of organisms) and ends with a terminator codon.
Since this is a region of the genome, the ORF is deemed to be a natural
product, and is not considered an invention according to Art. 10 (IX).
An ORF represents a candidate to an encoding region of a genome that does
not necessarily result in a functional gene product. Thus, in the case of a claim of the
type “vector characterized by comprising an ORF present in SEQ ID NO: 1”, it is
important to evaluate the demonstration of the functionality of the product obtained
from the expression of this ORF, in order to meet the requirement of industrial
application (Art. 15), as well as clarity and precision of the subject matter claimed
(Art. 25).
6.3.9 RNAs
RNAs encoded by natural genes are also natural biological molecules, and
therefore, are not considered inventions according to Art. 10 (IX) of the Industrial
Property Statute.
In contrast, if they are a product of the expression of chimeric genes (such as
genes constructed to express fusion proteins and/or others in existence not found in
nature), such RNA molecules, cannot be considered a natural biological material.
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6.4 Sequences of aminoacids
For definition purposes, it is considered that in analyzing patent applications,
“proteins”, “peptides” and “polypeptides” shall be defined based on their linear
sequence of aminoacids (primary structure), regardless of their size (total number of
residues of aminoacids in accordance with Resolution PR Nº 81/2013). Therefore,
citing any one of these terms (“proteins”, “peptides” or “polypeptides”) in these
Guidelines generally refers to a “sequence of aminoacids” or “protein sequence”.
6.4.1 Characterization of sequences of aminoacids
As stated above, having followed the rules established in items 2.2.2 and 6.1,
as a form of guaranteeing clarity and precision of the subject matter claimed, the set
of claims shall refer to the proteins in question by way of corresponding SEQ ID NO:
and in some cases, additionally, by their structural formula. Sequences with up to 03
(three) residues of aminoacids shall be represented throughout the application solely
by their sequence.
Example 26: Acceptable claims for sequences of aminoacids (provided that these
sequences are not naturally-occurring).
Claim: Protein X characterized by comprising a sequence of aminoacids as defined in
SEQ ID NO: 1.
Claim: Polypeptide characterized by consisting of a sequence of aminoacids as
defined in SEQ ID NO: 1.
Claim: Protein X characterized by consisting of the sequence SEQ ID NO: 1.
Example 27: Claim not acceptable for sequences of aminoacids.
Claim: Protein characterized by consisting of a sequence of aminoacids encoded by
SEQ ID NO: 2 (sequence of nucleotides).
In this situation, an office action shall be issued for the applicant to state the
sequence of aminoacids corresponding to the sequence of nucleotides presented,
without constituting the addition of subject matter.
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Accordingly, the characterization of protein sequences solely by way of their
properties, such as three-dimensional structure, function or biological activity, name,
chemical properties (PI, molecular weight, composition of aminoacids, etc.) will not
be accepted in the claims, since the only way of clearly and precisely defining a
sequence of aminoacids in an unequivocal manner is by the sequence itself.
Additionally, attention must be paid to item 6.2 of these Guidelines, which
address biological sequence claims by way of percentage of identity and/or similarity
to a sequence of reference.
It is important to bear in mind that the use of the terms consist or comprise
results in differences of scope of the claim (see the Guidelines for Examining Patent
Applications, Block I).
Example 28:
The specification of the application describes a mutated protein (non-natural)
characterized by consisting of SEQ ID NO: W. In this case, it would not be possible
to accept a generic claim that sought protection for the mutated protein (non-natural)
characterized by comprising SEQ ID NO: W, as this would imply the possibility of
having any extension in the carboxyl and/or amino terminal regions of the protein that
might cause alterations to the three-dimensional structure of same and/or alterations
of function. Therefore, it would not be possible to assert that any protein comprising
SEQ ID NO: W would work in a similar way to the consisting of SEQ ID NO: W, and
said claim shall be questioned owing to the lack of full disclosure and support in the
specification (Arts. 24 and 25 of the Industrial Property Statute). Even if the
specification discloses certain possible extensions in the sequence of aminoacids of
the protein, such examples would not be sufficient to support that any extension would
achieve the same result.
6.4.2 Homologous proteins (paralogous versus orthologous)
Homologous proteins are proteins that derive from “common ancestral
evolution”. They may be present in a same species, being derived from gene
duplication, originating what is called paralogous (equivalent proteins – with or
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without sequence alterations produced during the course of evolution – present in a
same species). Moreover, they may be present in different species and that have
common ancestry; in this case, such proteins are called orthologous.
These definitions are important for evaluating the inventive step of
applications that describe and claim proteins similar to proteins whose function is
already known, differing solely in relation to the organisms from which the protein
originates.
Example 29:
The patent application describes protein B, isolated from a certain species. This
protein B presents sequence and activity that is highly similar to another protein,
called A, previously described in the state of the art for a different species (A and B
are, therefore, orthologous proteins). In these cases, it is considered that the simple
fact that protein B is isolated from a different organism does not necessarily make it
inventive in light of protein A. Thus, the evaluation of inventive step may consider
whether protein B presents any unexpected characteristic in light of its orthologous A.
Even so, in this case, protein B in itself would not be considered an invention
according to Art. 10 (IX).
Additionally, when the applications involve “variants” or “modifications” of
proteins natural, attention must be paid for compliance with Art. 10 (IX), since such
“modifications” may result in another provably natural biological molecule,
originating solely from a different species to the one described in the application.
Example 30:
An application describes modifications in a bovine protein so as to render it suitable for
a certain use, and claims the modified protein itself. Nevertheless, the protein resulting
from the alterations introduced, for example, substitutions, results in a sequence
identical to that of the canine version of said protein, which is already known. In this
case, even though it is not identical to the natural equivalent of the organism in which it
was obtained, the protein claimed is identical to an orthologous protein – natural from
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another species –, and, consequently, does not comply with Art. 10 (IX) either.
6.4.3 Protein fragments
A protein fragment, in the same way as a protein, must be characterized at
least by its sequence of aminoacids (see item 6.4.1). Accordingly, when a protein
fragment is claimed, and characterized solely by its sequence linear, the examiner
must perform a search by the characterizing sequence of aminoacids. If a sequence is
found in the state of the art as part of a protein or peptide of natural origin, the subject
matter claimed will not comply with Art. 10 (IX) of the Industrial Property Statute,
because it constitutes a part of natural living beings and/or biological materials found
in nature.
When a peptide containing few aminoacids is claimed, it is likely found in a
protein in nature, even without a known function in the protein or in a different
context to the subject matter presented in the application under examination. Even so,
the subject matter claimed does not comply with that prescribed in Art. 10 (IX) of the
Industrial Property Statute, since no delimitation is established in the Industrial
Property Statute regarding a minimum size for a fragment to constitute a part of a
natural biological material. Therefore, not any part of natural living beings and
biological materials (i.e. fragments) found in nature shall not be considered to be an
invention.
It is possible for a fragment claimed to be identical to a part of the whole
molecule found in nature. In these cases, even when the fragment claimed presents
innovative activity, function, or chemical properties in light of the state of the art,
since it constitutes a part of a natural living being or a biological material found in
nature, it is not an invention according to Art. 10 (IX) of the Industrial Property
Statute, so it is inappropriate to perform any type of analysis regarding its novelty and
inventive step.
It is important to note that the presence or inclusion of the term “recombinant”
in a natural molecule claim cannot be accepted, since the resulting molecule would be
indistinguishable from its natural counterpart, even if produced in a recombinant
manner.
Therefore, it is clear that any portion of a protein found in nature, regardless of
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the number of aminoacids, must be considered a part of natural living beings and
biological materials found in nature and, therefore, is not considered an invention
according to Art. 10 (IX) of the Industrial Property Statute.
Example 31:
Claim: Peptide characterized by the sequence Ile-Leu-Arg.
Protection is claimed for a biologically active peptide, obtained synthetically,
with immune-regulatory properties, comprised of three aminoacids. The search
revealed that the sequence is contained in various natural proteins. The application
contends that the peptide may be different to the natural polypeptide from various
aspects such as folding, spatial conformation, aggregation and physical-chemical
properties. Although there are differences in the physical-chemical properties of the
molecule claimed with relation to natural polypeptides that comprise the same
sequence, the peptide claimed presents a sequence of aminoacids found in nature,
and this is why the subject matter is not considered an invention according to Art. 10
(IX) of the Industrial Property Statute.
Example 32:
Claim: Protein characterized by presenting SEQ ID NO: 1 wherein positions 1 to 6 have
been deleted.
A cytokine having 76 aminoacids when truncated in the sixth aminoacid amino-
terminal begins to display antagonist activity of the whole cytokine and thus can be used
to manufacture medicines to treat diseases wherein a cytokine antagonist is needed.
Although human interference resulted in an innovative activity, said fact was solely due
to the deletion of part of the molecule, maintaining the sequence obtained identical to
the sequence of aminoacids 6-76 found in the whole natural molecule 1-76. According to
Art. 10 (IX) of the Industrial Property Statute, said analog is not considered an
invention because it is part of the natural molecule, and accordingly is not patentable.
6.4.4 Sequence modifications
Modifications in protein sequences in order to differentiate them from natural
sequences can be carried out in different way. Theoretically, any characteristic Page 47 of 63
introduced into the sequence that was not described as naturally-occurring is
acceptable as modification, for purposes of compliance with Art. 10 (IX) of the
Industrial Property Statute.
6.4.4.1 With natural aminoacids (substitutions, insertions or deletions)
As highlighted above for modifications, in general terms, modifications of
biological sequences by inserting L-natural aminoacids in the sequence (in the means
or at the ends) are considered sufficient for purposes of compliance with Art. 10 (IX),
provided that the resulting sequence formed is not naturally-occurring either.
For deleting aminoacids, the position of the deleted aminoacid results in
different situations to be considered. If it is located in the central part of the sequence
of the protein, said modification is, theoretically, sufficient to differentiate it from the
natural molecule. Nevertheless, even in the case of deleted aminoacids being
contiguous and being at the end of the sequence, same still fails to comply with Art.
10 (IX), since the resulting sequence continues to be identical to a part of the natural
sequence (see example 32).
Regarding the substitution of aminoacids by other natural aminoacids, it is
considered that said modification is sufficient for the sequence to comply with Art. 10
(IX), provided that there is no description of natural proteins in related species
containing said substitution (see item 6.4.2 of orthologous proteins).
When analyzing proteins already described in the state of the art, care must be
taken to evaluate the inventive step of the modification (insertion, deletion or
substitution) made, taking into account the fact that some groups of aminoacids
present common properties. Thus, the inventiveness of these alterations in the protein
sequence generally depends on the demonstration of an unexpected effect generated
by the modification in relation to the state of the art.
6.4.4.2 With non-natural aminoacids (including protector groups)
Insertions of aminoacids which are not naturally-occurring (deriving from
natural aminoacids) are also considered sufficient modifications for the protein
sequences to comply with Art. 10 (IX). Nevertheless, for purposes of clarity and
precision, said aminoacids shall be appropriately identified in the claims, so as to
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avoid the indirect inclusion of natural aminoacids, and thereby result in the natural
biological sequence.
The inclusion of such aminoacids in the sequences presented in patent
applications is also addressed in INPI Resolution PR Nº 81/2013, cited in item 2.2.2 of
these Guidelines; and a list with examples of non-natural aminoacids and the
acceptable abbreviations in the definition thereof is available in Table 4 of Appendix
of this Resolution (published in the Official Federal Gazette (DOU) - Section 1, Nº 68,
April 10, 2013).
6.4.4.3 Grouping added to carboxyl or amino terminus
A protein sequence can also be altered by binding chemical groupings at their
ends, these having the purpose of allowing anchorage to a certain surface or structure,
increase of protein activity, modulation of bioavailability and/or circulating half-life,
etc.
Once again, attention must be paid to the form in which said molecule is
claimed, in order to guarantee the presence of the chemical grouping in said molecule,
since it is this grouping that will differentiate it from its natural equivalent. Fmoc, t-
boc, other chemical groupings, prosthetic groups, lipids, carbohydrates, iron, calcium,
heme, are examples of groupings which when added to proteins may potentially
differentiate them from natural ones.
6.4.5 Fusion proteins
By definition, these proteins are created by union (fusion) of parts of two or
more different protein sequences. Accordingly, a fusion protein involved in a patent
application is formed by at least a “functional” portion, responsible for the property
related to the invention.
Thus, for purposes of definition in accordance with Art. 25, it is important to
underline that in a fusion protein, all the functional portions constituting the end
protein must be described in the application.
6.4.5.1 Naturally-occurring
Rare cases of naturally expressed fusion proteins are noted in some types of
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cancer, owing to chromosome translocation, which may lead to the fusion of different
genes, for example: fusion proteins gag-onc, Bcr-abl, and Tpr-met.
Once the occurrence of a natural identical structure is proven, with due regard
for that prescribed in item 4.2.1 (for example, Bcr-abl, with a portion 1-50 of Bcr
fusioned to the portion 13-78 of abl), such proteins cannot be considered inventions
according to Art. 10 (IX) of the Industrial Property Statute.
6.4.5.2 Characterization
In general terms, in defining fusion proteins, the rules defined for any other
protein sequences apply (see item 6.4.1). Thus, no references are accepted for
percentages of homology/similarity/identity, and the proteins shall be referred to by
way of at least one of their sequences of aminoacids or SEQ ID NO: corresponding to
the functional portion.
6.4.5.3 Integral Seq ID
When the polypeptide sequence described in the patent application is claimed
in the form of a fusion protein, it must always be at least by way of its sequence of
aminoacids or corresponding SEQ ID NO:, for a clear and precise definition of the
subject matter claimed relating to the invention.
When various peptides are related to the property described in the invention,
and all are present in the fusion protein claimed, all these peptides shall be referred to
at least by way of their sequence of aminoacids or corresponding SEQ ID NO:.
Special attention must be paid to cases where the “fusion” protein is in fact
formed by fragments of a same naturally-occurring protein: in accordance with the
form as claimed, the end protein produced (fusion protein) may be an identical result
to the natural molecule.
Example 33:
Claim: Fusion protein characterized by comprising:
a) a first polypeptide that consists of the sequence of aminoacids 41-56 of SEQ
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ID NO: 2;
b) a first spacer of 6-27 aminoacids;
c) a second polypeptide that consists of the sequence of aminoacids 69-84 of
SEQ ID NO: 2;
d) a second spacer of 5-11 aminoacids; and
e) a third polypeptide that consists of the sequence of aminoacids 92-105 of SEQ
ID NO: 2.
In this claim, since the spacers of interest are not defined, said ranges being compatible
with the interval between the sequences defined, the resulting “fusion” protein
encompasses in its scope the very protein whose sequence is described in SEQ ID NO:
2, which is naturally-occurring, and so the claim does not comply with Art. 10 (IX).
6.4.5.4 Definition of just one of the sequences present in the fusion protein
When the protein of interest is fusioned to another other polypeptide that will
solely act as “label/reporter”, said reporter can be defined by way of its sequence of
aminoacids or corresponding SEQ ID NO:, as established previously, to any
polypeptides. Nevertheless, since said polypeptide “reporter” is broadly known in the
art, optionally the reference thereto can be made solely by way of its abbreviation, for
example, to molecules such as GFP (green fluorescent protein), GST (glutathione S-
transferase), CAT, c-Myc, FLAG, among others.
Potentially, an application may present the type of situation in which the
inventive characteristic of the fusion protein is solely in the presence of the protein
described in the application – which can also be the reporter portion – and it can be
fusioned to various others.
Example 34:
The application describes a polypeptide X which, in isolation, has no
surprising activity, but which is capable of enhancing the immunological response of
antigens fusioned thereto. In the set of claims, there is claimed a “fusion protein
characterized by consisting of protein X (defined by SEQ ID NO:) bound to an
antigen”.
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In this case, attention must be paid to clarity and precision of the way in
which the fusion protein is claimed, since the antigen fusioned thereto is not defined
in the claim, and the decision to be taken shall consider the information available in
the specification.
Situation 1: The specification presents examples of X fusion protein with various
different antigens, not related, and demonstrates the indisputable efficiency of all the
resulting proteins for the proposed purpose, so there is no indication that another
antigen would not work in the same manner. In this case, it is not necessary to
require that the application list all the possible antigens for use in the fusion protein,
and it is considered that the claim as worded above is acceptable.
Situation 2: the application presents examples of X fusion protein with various
different antigens, not related, but the results demonstrated do not present
consistency, demonstrating that the fusion protein is effective for some antigens and
not for others. In this case, the very application does not provide full disclosure and
basis in accordance with Arts. 24 and 25 to support that the fusion protein works
with any antigen (it may include antigens for which there is no evidence that they
work as described). Therefore, the set of claims shall be limited to the subject matter
described and supported in the application in accordance with Arts. 24 and 25 of the
Industrial Property Statute, that is, the claims must specify which antigens of interest
are present in the fusion protein claimed.
6.4.6 Antibodies
Antibodies are plasma proteins which bind specifically to substances known as
antigens, and include polyclonals and monoclonals; therefore, they shall be analyzed
as proteins, and also in terms of that prescribed in Art. 10 (IX) (see item 6.4 and
subitems thereof).
Polyclonal antibodies are derived from different lineages of B cells. They are
a mixture of immunoglobulin molecules secreted against a specific antigen, each
recognizing a different epitope. These antibodies are biological products isolated
from nature and, therefore, are not considered inventions according to that prescribed
in Art. 10 (IX) of the Industrial Property Statute. It must be underscored that the
isolation of a specific antibody from this pool of antibodies does not exclude this Page 52 of 63
molecule from compliance with Art. 10 (IX).
Monoclonal antibodies are antibodies from a single specificity, i.e. specific to
a single epitope of an antigen. Through human intervention, a monoclonal antibody
can be obtained by means of different techniques, such as hybridoma (see item
6.4.6.2) or genetic engineering.
Provided that it is obtained by hybridoma and characterized thereby, the
monoclonal antibody cannot be considered natural and, therefore, complies with that
prescribed in Art. 10 (IX). In this situation, this monoclonal antibody can be
additionally defined by its specific sequence (SEQ ID NO:). Since monoclonal
antibodies obtained by genetic engineering, they are defined by their sequence, and
can be accepted provided that they comply with that prescribed in Art. 10 (IX) (see
item 4.2.1).
Example 35: Wording of antibody claim antibody eligible for protection.
Claim: Monoclonal antibody against protein X characterized by the fact that it is
produced by hybridoma HHH, deposited under number YYYY.
Example 36: Unacceptable claims for antibodies.
Claim 1: Antibodies characterized by the fact that they are specific for protein X.
As the antibodies claimed are not clearly and precisely defined, these claims
cannot be accepted since they do not comply with Art. 25 of the Industrial Property
Statute, and may encompass natural molecules, which is contrary to Art. 10 (IX).
Claim 2: Human monoclonal antibody characterized by the fact that it recognizes
protein X and has an affinity of 2x10-9 M.
Claim 3: Monoclonal antibody and fragments thereof characterized by the fact that it is
capable of binding to protein X.
As the antibodies claimed are not clearly and precisely defined, nor which
fragments are being claimed, these claims cannot be accepted, since they do not
comply with Art. 25 of the Industrial Property Statute.
6.4.6.1 Process of obtaining antibodies
The process of producing a polyclonal antibody which consists solely of Page 53 of 63
exposing an animal to an antigen, followed by purification, is considered a natural
biological process, and is not considered invention, thus not complying with Art. 10
(IX). In some cases, however, when there is a non-trivial technical stage involving the
determination of the epitope or modification of the antigen to elicit the immunological
response, it is considered that there is significant human intervention, since it has a
direct action on the molecule, which has a decisive impact on the end result obtained.
In these cases, such processes are eligible for protection.
In contrast, owing to human intervention, the process of producing monoclonal
antibodies is not considered a natural biological process, be it involving the
obtainment of a hybridoma or by genetic engineering techniques.
Regarding the characterization of the process of obtaining antibodies, care
must be taken for the need to define the stages of the process (see item 4.2.1.2).
6.4.6.2 Hybridomas
Hybridomas are the result of a fusion of two cell types, a myeloma with a
lymphocyte B, and produce antibodies. They bear characteristics not achievable by
such cell types under natural conditions, being the product of direct human
intervention. According to the understanding adopted by this Institute, technically
speaking, a hybridoma is considered a transgenic microorganism, and accordingly,
said subject matter is patentable because it complies with Arts. 10 and 18 of the
Industrial Property Statute.
At the same time, since this concerns biological material essential for the
practical realization of the object of the patent application, and cannot be characterized
clearly and precisely in the specification, in order to comply with the sole paragraph of
Art. 24 of the Industrial Property Statute, it is essential to deposit the hybridoma by
the filing date of the patent application or its priority date, and the submission of the
deposit number in the patent application (see item 2.2.1).
6.4.6.3 Chimeric/humanized antibodies
When the monoclonal antibodies of mice, rabbits, etc., are used as therapeutic
agents in humans, the strange proteins are recognized by the immune system of the
human host. The advent of chimeric/humanized antibodies is a mechanism used to
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solve this therapeutic obstacle.
The technology for producing a humanized antibody differs from the
production of a monoclonal antibody because it does not depend on cultivating the
hybrid cell, but implies obtaining the sequence of the immunoglobulin (human Fc
portion and variable portion of the non-human Fab fragment). These sequences are
merged and placed in an expression vector for subsequent cultivation of the
transfected host cell and subsequent stages of purification. Owing to this difference in
the production route, the characterization of humanized antibody requires the
presentation of a SEQ ID NO: X containing a sequence of aminoacids of the variable
portion of the antibody and the definition of the other elements (Fc portion).
Example 37: Wording of antibody claims eligible for protection.
Claim: Humanized antibody against a-actin characterized by comprising the murine
variable region which consists of SEQ ID NO: X and human y chain regions.
Claim: Humanized antibody against a-actin characterized by comprising the murine
complementarity determining regions (CDR1; CDR2; CDR3) which consist of SEQ
ID NO: X, SEQ ID NO: Y and SEQ ID NO: Z in the light chain and SEQ ID NO: A,
SEQ ID NO: B and SEQ ID NO: C in the heavy chain and human y chain regions.
6.4.6.4 Fragments of antibodies
An antibody molecule can be cleaved generating different fragments with
distinct functions. If originating from antibodies found in nature, or are part of other
natural proteins, the fragments in themselves are not patentable owing to Art. 10 (IX)
of the Industrial Property Statute (see item 6.4.3).
Modifications of antibody fragments may also constitute subject matter
eligible for protection, as in the case of single-chain variable fragments (ScFv). The
Fv fragments are not covalently connected, so the heterodimers of the VH and VL
domains can easily dissociate. However, Fv fragments can be constructed so as not to
dissociate, that is, the VH and VL domains can be joined by a connector, creating a
single-chain FV fragment. Despite being an antibody fragment, this construction
complies with Art. 10 (IX) of the Industrial Property Statute, since these fragments are
not found in nature joined by the connector.
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7 Animals, plants, parts thereof and processes of obtaining them
7.1 Animals, plants and parts thereof
If natural/isolated, these are not considered an invention, according to Art. 10
(IX). When resulting from genetic manipulation by the human being, they are not
patentable, according to Art. 18 (III).
7.1.1 Products and processes involving stem cells
Stem cells are undifferentiated cells (totipotent, pluripotent or progenitor)
which can be stimulated to specialize in the tissues that make up the human body.
According to these Guidelines, products and processes involving stem cells
refer exclusively to pluripotent or progenitor stem cells. These cells can be obtained
directly from various tissues of the adult organism (such as, for example, from bone
marrow, from adipose tissue), or even from the umbilical cord, or can be obtained by
de-specializing a specialized adult cell (as in the case of the induced pluripotent stem
cell – IPS).
Alternatively, they can be obtained from the internal mass of the blastocysts
originating from human embryos produced by in vitro fertilization, according to the
provisions of Art. 5 of the Biosafety Act – N°. 11,105/2005.
In accordance with the Industrial Property Statute, the cells themselves
obtained directly from an animal or with some gene modification, are not patentable in
light of that prescribed in Art. 10 (IX) or 18 (III), respectively. Nevertheless,
compositions containing these cells, the processes of obtaining stem cells and
applications (uses) thereof can be considered patentable provided that they do not
imply or include a therapeutic and/or surgical method (Art. 10 (VIII), and provided
that they comply with the provisions of Art. 18 (I) of the Industrial Property Statute.
For example, the following products and processes involving stem cells can be
considered eligible for patenting:
• Compositions containing cells and other ingredients (various implants
containing cells, cell and matrix formulation, cells and growth factors ... ).
• Composition containing mixtures of different types of stem cells. Page 56 of 63
• Processes of purification, preparation, conditioning, specialization, de-
specialization, or any processing of stem cells provided that it is
performed in vitro.
• Uses of cells for preparing medicines to treat disease X.
• Uses of cells for preparing implants to treat disease X.
• Uses of cells for preparing compositions for diagnosing disease X.
• Processes of diagnosis which include stages that employ cells or synthetic
tissues, provided that they are performed in vitro.
• Drug tests which include stages that employ stem cells or synthetic tissues,
provided that they are performed in vitro.
• Processes of cultivating stem cells.
• Conditioned culture means obtained during the cultivation of stem cells.
7.2 Transgenic plants, parts thereof and processes of obtaining them
These are plants that had their genome modified by the introduction of a DNA
manipulated by recombinant DNA techniques, and whose modification would not
occur under natural conditions of cross-breeding or recombination.
Transgenic plants and parts thereof (for example, transgenic cell, tissue
transgenic and transgenic organs) are not considered to be patentable subject matters
according to Art. 18 (III and sole paragraph) of the Industrial Property Statute.
Even if the process of obtaining transgenic plants is patentable, it is important
to emphasize that the intermediary and/or end products of this process, that is, the
transgenic plant and/or parts of this plant constitute subject matters expressly
prohibited from patentability according to Art. 18 (III and sole paragraph) of the
Industrial Property Statute. Nevertheless, there is no restriction on the patenting of the
processes of obtaining these plants.
Examples of claims eligible for protection
• Method of producing a transgenic plant characterized by the fact that it
comprises the stages of:
(a) obtaining an explant from the plant;
(b) exposing the explant to the Agrobacterium tumefaciens culture
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that contains the vector defined by claim X (duly described with
a selection gene, a heterologous gene and the sequence
promoter(s);
(c) cultivation of the explant in a means with the specific conditions
for cultivating a vegetable tissue; and
(d) selecting and cultivating transformed calluses that express the
heterologous gene, to induce the formation of the embryonic
callus.
• Method for producing a transgenic dicotyledonous plant, characterized by
comprising:
(a) transforming plant cells using an Agrobacterium transformation
vector that comprises a chimeric genic construction Y;
(b) obtaining a transformed plant cell; and
(c) regenerating a genetically-transformed plant from a transformed
plant cell.
7.3 Process of obtaining plants by cross-breeding
Article 10 (IX) of the Industrial Property Statute establishes that natural
biological processes are not considered inventions, and therefore excludes patenting of
natural biological processes, including those for producing plants.
A “natural biological process” is understood to be any process that does not use
technical means to obtain biological products or that, even using a technical means, it
would be eligible for occurring in nature without human intervention, consisting
wholly of natural phenomena. In this sense, biological processes are considered non-
natural when human intervention is direct in the genetic composition and are
permanent in character.
Thus, processes involving the cross-breeding of plants genetically-modified by
direct human intervention are eligible for protection.
Example 38: Non-transgenic parentals.
Claim 1: Method for producing a plant of X characterized by comprising the stages
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of:
a) selecting a plant of X homozygote for the gene A;
b) selecting a plant of X homozygote for the gene B; and
c) cross-breeding the plants selected in stages (a) and (b) for producing a
hybrid plant.
Conventional methods of producing plants based on stages of selection, cross-
breeding and propagation are considered natural biological processes, and
do not comply with Art. 10 (IX). In these cases, human interference by way of
selection and induction of specific cross-breeding is not essential for the
process to occur, solely accelerating or limiting that which would occur in
nature.
Example 39: Non-transgenic parentals.
Claim 1: Method for producing a plant of X with high levels of compounds W
characterized by comprising the stages of:
a) identifying the gene markers connected to high levels of W;
b) selecting the individuals comprising the markers identified in stage (a); and
c) cross-breeding the individuals selected in stage (b).
Conventional methods of producing plants based on stages of selection, cross-
breeding and propagation in which human intervention consists solely of providing
additional technical means to facilitate or direct the process – in this case, the
identification of gene markers – are considered natural biological processes, not
complying with Art. 10 (IX). In these cases, human interference is not decisive in order
to obtain the end result, merely accelerating or limiting that which would occur
naturally.
Example 40: Transgenic parentals.
Claim 1: Method of producing hybrid seeds characterized by comprising the cross-
breeding of a herbicide-resistant plant with a plant endowed with an enhanced
nutritional value comprising in its genome a heterologous gene encoding a modified
albumin.
Claim 2: Method of introducing the characteristic of resistance to a herbicide in a plant
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endowed with enhanced nutritional value characterized by comprising the stages of:
a) cross-breeding a plant resistant to at least one herbicide with a plant
comprising in its genome a heterologous gene encoding a modified albumin;
b) developing base populations;
c) evaluating the plants obtained individually; and
d) selecting plants endowed with enhanced nutritional value comprising the
characteristic of herbicide resistance.
This process involves the technical stage that is essential for obtaining plants that do not
occur in nature and, therefore, complies with Art. 10 (IX).
8 Patent applications involving components from the Brazilian genetic heritage
Patent of invention applications for a process or product obtained from a sample of
components of the Brazilian genetic heritage, deposited as of June 30, 2000, shall adhere
to the rules in effect, as established in MP 2186-16/01 dated August 23, 2001, as well as
CGEN Resolution Nº 34 dated February 12, 2009 and INPI PR Nº 69/2013, dated March
18, 2013.
MP 2186-16/01 provides, among other things, on property, rights and obligations
relating to access to components from the Brazilian genetic heritage existing in national
territory, on the continental shelf and in the exclusive economic zone for purposes of
scientific research, technological development or bioprospecting, as well as access to
traditional knowledge associated to the genetic heritage, relevant to the conservation of
biological diversity, to the integrity of the country’s genetic heritage and to the use of
components thereof (Art. 1, items I and II).
In Art. 31, the provisional presidential decree determines that the grant of the
industrial property right over a process or product obtained from a sample of a component
of the genetic heritage requires compliance with the Provisional Presidential Decree (MP),
and the applicant shall inform the origin of the genetic material and the associated
traditional knowledge, as applicable.
The rules established in Provisional Presidential Decree (MP) 2186-16/01 shall be
adhered to for patent applications involving genetic heritage. Non-exhaustive examples
include organisms (plants, animals, fungi, bacteria, archaea, etc.), parts of organisms
(leaves, nails, skin, mucus, blood, roots, extracts, organs, oils, venoms, fangs, etc.),
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molecules isolated from organisms (DNA, RNA, proteins, sugars, lipids, etc.), and their
synthetic correspondents, as well as compositions and processes containing any of the
items mentioned above. In accordance with Art. 3, the MP does not apply to human
genetic heritage.
The applicant shall always furnish information relating to the origin of the material
through petitions established in INPI Resolution PR Nº 69/2013: a petition for access
information or a petition of declaration that the application filed does not involve access
under the terms of MP 2186-16/01. Pursuant to CGEN Resolution Nº 35/2011, for
purpose of regularization, the request protocol for authorization to access a genetic
resource may be accepted, and the allowance of the patent application shall require
presentation of the definitive authorization to access the genetic resource.
Page 61 of 63
9 References
Correa, C. M. (2000). “Intellectual Property Rights. The WTO and Developing Countries.
The TRIPS Agreement and Policy Options”. Third World Network, Malaysia.
Das, M.K. & Dai H.K. (2007). “A survey of DNA motif finding algorithms”. BMC
Bioinformatics 8(Suppl 7):S21.
Eden, E., Lipson, D., Yogev, S. & Yakhini, Z. (2007). “Discovering motifs in ranked lists
of DNA sequences”. PLoS Comput Biol. 3(3):39.
EPO – European Patent Office (2006). “Case Law of the Boards of Appeal of the
European Patent Office”, Fifth Edition, Germany. Disponível em:
http://www.europeanpatent-office.org.
EPO – European Patent Office (2010). “Guidelines for Examination in the European
Patent Office”, Germany. Disponível em: http://www.epo.org/law-practice/legal-
texts/guidelines.html.
Fickett, J. W. & Hatzigeorgiou, A. G. (1997). “Eukaryotic promoter recognition”.
Genome Res. 7(9):861-78.
Griffiths, A.J.F., Gelbart, W.M., Miller, J.H. & Lewontin, R.C. (1999). “Modern Genetic
Analysis”. New York: W. H. Freeman & Co.
India – (2008). “Manual of patent practice and procedure”. Disponível em:
http://ipindia.nic.in/ipr/patent/DraftPatentManual2008.pdf.
INPI – “Guidelines para the exame de patent applications nas áreas de biotechnology and
farmacêutica depositeds após 31/12/1994”.
INPI (Argentina) – (2003). “Directrices sobre Patentamiento”. Disponível em:
http://www.inpi.gov.ar.
JPO – Japan Patent Office (2011). “Examination Guideline for Patent and Utility Model
in Japan”, Disponível em: http://www.jpo.go.jp/quicke/indextokkyo.htm.
Lewin, B. (2001). “Genes VII”. Trad. Ferreira, H. & Pasquali, G. Porto Alegre, Astmed
Editora Ltda.
Oficina Internacional de la OMPI (2004). “Manual para el examinen de solicitudes de
Patentes de invención en las oficinas de propriedad Industrial de los países de la
comunidad Andina”. Disponível em: http://www.comunidadandina.org.
Pertsemlidis, A. & Fondon, J. W. (2001). “Having a BLAST with bioinformatics (and
avoiding BLASTphemy)”. Genome Biol. 2(10):1-10.
Page 62 of 63
Petsko, G. A. (2001). “Homologuephobia”. Genome Biol. 2(2):COMMENT1002.
Pevsner, J. (2009). “Bioinformatics and Functional Genomics”. John Wiley, New York, 2ª
ed., 2009, p.48, 49, 53 and 123.
Simmons, S. E. (2003). “Markush structure searching over the years”. World Patent
Information, 25:195-202.
Simmons, S. E. (1991). “The Grammar of Markush Structure Searching: Vocabulary vs
Syntax”. J. Chem. Inf. Comput. Sci. 31:45-53.
Stryer, L. (1996). “Bioquímica”. 4ª ed. Trad. de A. J. M. da S. Moreira; J. P. de Campos.
L. F. Macedo; P. A. Motta; P. R. P. Elias. Rio de Janeiro: Guanabara Koogan.
USPTO – United States Patent and Trademark Office (2010). “Manual of Patent
Examining Procedure (MPEP)”. Original 8th Edition, August 2001, Latest Revision
July 2010. Disponível em: http://www.uspto.gov/web/offices/pac/mpep/index.htm.
Webber, C. & Ponting, C.P. (2004). “Genes and homology”. Curr. Biol. 14(9):R332-3.
WIPO – (2004). “PCT International Search and Preliminary Examination Guidelines”.
Disponível em: https://www.wipo.int.
Whyte, B., Persson, B. & Jörnvall, H. (1996). “Primary structure and homology”. FEBS
Letters. 380(3):301.
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