DRAFT GUIDELINES FOR PATENT APPLICATIONS EXAMINATION

Transcription

1 DRAFT GUIDELINES FOR PATENT APPLICATIONS EXAMINATION BOARD OF PATENTS, COMPUTER PROGRAMS AND INTEGRATED CIRCUIT TOPOGRAPHY

2 ABSTRACT 1 INTRODUCTION 2 2 CHEMICAL COMPOUND Novelty and inventive activity Clarity and accuracy of claims Compounds defined by Markush formulas Salts, esters and ethers Pro-drugs Reaction intermediate compounds Intermediate compounds as main invention Intermediate compounds as accessory invention Process of obtaining the intermediate compounds Chemical compounds found in nature Patent applications related to the selection of chemical compounds 7 3 STEREOISOMERS Sufficiency of Disclosure Clarity Novelty Inventive Activity 12 4 POLYMORPHS Sufficiency of disclosure Clarity and accuracy of claims Novelty Inventive activity 15 5 SOLVATES, CLATHRATES, CO-CRYSTALS 15 6 COMPOSITIONS, FORMULATIONS AND PHYSICAL FORM OF COMPOSITIONS Clarity and accuracy of claims 16 7 COMBINATIONS OF CHEMICAL COMPOUNDS Reaction intermediate compounds Intermediate compounds as main invention Intermediate compounds as accessory invention Process of obtaining the intermediate compounds Combination in that the compounds are in separate forms 22 8 ANALOGUE PROCESSES 23 9 NEW USES OF KNOWN PRODUCTS New Medical Use Novelty Inventive activity Sufficiency of disclosure Support, clarity and accuracy of claims 26 1

3 1 INTRODUCTION The clear and sufficient description of the stereoisomer in the pure form lies in the characterization of the absolute configuration of its chiral center at the time of filing of the patent application. Analytical techniques, such as circular dichroism, nuclear magnetic resonance (with addition of chiral displacement reagent), circular birefringence, optical rotational dispersion, chromatography (with chiral column), polarimetry and monocrystal X-ray diffractometry can be used for the characterization of the claimed enantiomer/atropoisomer/diastereoisomer. The parameters of the process of obtaining stereoisomer, either by asymmetric synthesis or by the purification process subsequent to the synthesis of the compound, should be specified in the specification, in order to ensure its reproducibility by a person skilled in the art. Due to the possibility of racemization of the chiral compounds during the process of obtaining, it is important that the specification discloses the reagents used (mainly in the formation step of the chiral center), the reaction conditions, the isolation and purification methods of the stereoisomer obtained by said process. The specification should also describe the possible enantiomeric excess obtained and the method of analysis used for its measurement. 2 CHEMICAL COMPOUND 2.1 Novelty and inventive activity The technical examination of the patentability requirements of patent applications claiming chemical compounds follows the same procedures applicable to products in general and are detailed in Part II of the Guidelines for Patent Applications Examination. It should only be remembered that, in compound patent applications in that the composition, formulation and/or physical form are also claimed, it is considered that the novelty and inventive activity of the compound will be based on the composition (paragraph 7.6 of the Guidelines for Patent Applications Examination - Part II), formulation and/or physical form (accessory inventions). 2.2 Clarity and accuracy of claims The most accurate format to claim a chemical compound is the one that defines it in terms of its chemical structure (general formula), nomenclature (according to IUPAC rules) or another denomination that defines it unequivocally. Only in the cases where it is not possible to defined the chemical compound as previously described, the compound may be characterized by its process of obtaining, as determined in paragraphs 3.60 and 3.61 of Part I and in paragraph 4.17 of the Guidelines for Patent Applications Examination - Part II, provided that it meets the patentability requirements. 2

4 Claims that define the compound by its process of obtaining are only possible in extreme cases in that it is not possible to define it otherwise and in that the process itself is sufficiently precise in order to avoid ambiguities as to what is being protected. This is due to the fact as the product resulting from the process includes, for example, the by-products thereof, such claims tend to be unclear as to the subject matter they protect. In this context, independent claims that define the compound solely for its physical, physicochemical or biological properties are not accepted, since such features alone do not identify the compound in question, jeopardizing the clarity and accuracy of the claimed subject matter, being in disagreement with the provisions of Article 25 of Law 9.279/96 (Brazilian Industrial Property Law, IPL). In the same way, independent claims defining a compound by its application or use, such as, for example, Compound characterized by being used for X or Compound Y characterized by being used for X are not accepted, as they represent an undefinition regarding the subject matter to be protected, being in disagreement with the provisions of Article 25 of the Brazilian IP Law (Guidelines for Patent Applications Examination, Part II, paragraph 4.16). The clarity of a chemical compound claim can also be impaired by the use of generic expressions, often employed in order to extend the scope of protection to encompass derivatives of the compound. This is the case of chemical compound claims that claim, in addition to the compounds per se, their stereoisomers, hydrates, solvates, pro-drugs, ethers and esters or other derivatives. These expressions alone do not identify clearly and precisely the derivatives of the compound, since they only define the derivatives by their chemical class or function. If the specification of the patent application sufficiently describes these objects, the set of claims may be reformulated in order to define better the claimed subject matter. On the other hand, compound claims containing generic expressions, such as pharmaceutically acceptable salts, agriculturally acceptable salts, immunologically acceptable salts can be accepted, since: 1) the compound is responsible for the activity, being the salt an active fraction releasing agent of the compound and; 2) the person skilled in the art is aware of the salts commonly used in his area of expertise. 2.3 Compounds defined by Markush formulas The claims of compounds defined by formula of the Markush type are examined according to the Guidelines for Patent Applications Examination, Part I, paragraphs 3.38 and to and Part II, paragraphs 6.1 to

5 2.4 Salts, esters and ethers Salts, esters and ethers of known chemical compounds from the state of the art are usually employed to provide to the compound properties that enable more appropriate conditions for their industrial application. The technical analysis of patent applications which claim salts, esters and ethers follows the same guidelines applied to chemical compounds in general. To be considered new, the claimed salt/ester/ether cannot have been anticipated in the state of the art. When the state of the art anticipates, in a generic way, salts/esters/ethers of known compounds, the claimed salt/ester/ether cannot have been specifically disclosed (see item 2.6 of the present Guidelines and Guidelines for Patent Applications Examination, Part II, paragraphs 4.16 to 4.25 and 5.31 to 5.34). For example, the patent application claims protection for the mesylate salt of the compound A. The document of the state of the art discloses the compound A and its salts, listing as preferred salts mesylate, fumarate and hydrochloride. In this case, the mesylate salt of the claimed compound A is considered to be specifically disclosed in the state of the art and, therefore, lacks novelty. On the other hand, if the patent application claims the succinate salt of the compound A, said salt will be considered new, since it was not specifically cited among the preferential salts in the document of the state of the art. In the possibility of a particular salt, ester or ether, changing the properties of the base compound, in a non-obvious way to a person skilled in the art, such salt, ester or ether will be considered as having inventive activity. It is worth pointing out that a person skilled in the art is aware that the physicochemical feature of a chemical compound can be altered by the modification of its counter-ion, such as, for example: solubility, dissolution, stability and organoleptic properties. Thus, the mere description of an alternative salt/ester/ether of a known compound, when disassociated with a non-obvious property or an unexpected technical effect in view of the state of the art, lacks inventive activity. Usually, the process of obtaining a salt, ether or ester involves the combination of known and classical procedures of the state of the art, since all the reactions of obtaining these classes of compounds are described in the literature and, therefore, occur in an obvious way for a person skilled in the art. However, if the salt, ether or ester is considered patentable, the processes of obtaining it can be analyzed as analogous processes (item 8 of these Guidelines) and, consequently, will also be provided with the patentability requirements. It is emphasized that the use of the generic expressions ethers thereof and/or esters thereof in claims referring to a compound per se, do not identify the derivatives ethers and esters of the compound in a clear and precise manner, since they only define the derivatives through their chemical function or class. If the specification of the patent application sufficiently describes these objects, the set of claims may be reformulated in order to better define the claimed subject matter. 4

6 On the other hand, compound claims containing generic expressions, such as pharmaceutically acceptable salts, agriculturally acceptable salts, immunologically acceptable salts can be accepted, since: 1) the compound is responsible for the activity, being the salt an active fraction releasing agent of the compound and; 2) the person skilled in the art is aware of the salts commonly used in his area of expertise. 2.5 Pro-drugs The chemical compounds can function as pro-drugs, that is, compounds that require prior biotransformation to display their pharmacological effects. They can also be regarded as inactive compounds (or substantially less active than the drug), which, after administration, undergo biotransformation giving rise to pharmacologically active compounds. The pro-drugs are generally developed from obtaining derivatives of certain functional groups of a particular compound, aiming at optimizing the physicochemical properties, biopharmaceuticals or pharmacokinetics of the pharmacologically active compounds, surpassing any barriers related to the formulation and release of the drugs, such as low water solubility, chemical instability, insufficient oral absorption, pre-systemic metabolism, inadequate penetration in the central nervous system, toxicity and local irritation. The technical analysis of this subject matter follows the same guidelines applied to chemical compounds in general. Especially regarding the analysis of the inventive activity requirement, it is important to note that, in certain cases, a known strategy to improve the pharmacological or pharmacotechnical properties of drugs can lead to an effect that would not be evident for a person skilled in the art. It is noted that the use of the generic expression such as pro-drugs thereof in claims referring to a compound per se, does not identify the pro-drugs of the compound in a clear and precise manner. If the specification of the patent application sufficiently describes these objects, the set of claims may be reformulated in order to define better the claimed subject matter. 2.6 Reaction intermediate compounds Intermediates, in the restricted sense, are chemical compounds (or groups of chemical compounds) that are used in the production route of another chemical compound (or group of chemical compounds), through chemical and/or physical alteration(s), losing its identity. As a matter of simplification, the reference to chemical compound will encompass group of chemical compounds. In the context of the present Guidelines, intermediates can be intermediate compounds per se or starting products (precursors). Evidently, there can be chemical compounds that, in addition of functioning as precursors (intermediates) of a particular chemical compound, also present final applications, such as pesticides, drugs, etc. However, in this case, that is, when they are in their function as drugs, etc., they will no longer be intermediates in the sense of these Guidelines and should be analyzed according to the previous item. Having in mind the above explanations, two situations may occur: 5

7 1. The intermediate is the main invention; 2. The intermediate is what is conventionally referred to as an accessory invention, in which the main invention may be a final chemical compound or a process of obtaining a chemical compound. In cases in that the intermediate compound is not the main invention, it should be evaluated if the intermediate and its process of obtaining belong to the same inventive concept of the main invention, which is a compound (final product) and/or its obtaining process. Here, it fits the orientation contained in the Guidelines for Patent Applications Examination, Part I Items to It is noted that in both cases, the claims related to the intermediate(s) are, necessarily, product claims and should be treated as such, applying the most appropriate orientation established in these Guidelines. Also, in both cases, it is accepted claims directed to the process of obtaining the intermediate(s) Process Claims The claims related to the intermediate(s) are, necessarily, chemical compound claims and the technical analysis of this subject matter follows the same guidelines applied to chemical compounds in general. The inventive activity of an intermediate must be judged on the basis of its application, as intermediate, and of its differences in relation to the compounds of the state of the art. Thus, if the closest state of the art discloses compounds similar to the claimed intermediate, but it does not suggest its application in obtaining other compounds, that is, its application as intermediates, it is understood that it would not be obvious or evident for a person skilled in the art to use compounds similar to those of the state of the art as synthesis intermediates. In the case in that the compounds of the closest state of the art have function of intermediate, differences must be observed between the claimed compound (intermediate) and those of the state of the art, in order to evaluate the obviousness or not of these differences, considering the function of intermediate of the claimed compound Intermediate compounds as accessory invention When the intermediate is an accessory invention in a patent application related to another compound as the main invention, it is not possible to extrapolate the novelty and inventive activity of the main invention to the intermediate, since the effects/activities/purposes of the main invention and of the intermediate are different. In cases in that the intermediate compound is not the main invention, it should be evaluated if the intermediate and its process of obtaining belong to the same inventive concept of the main invention, which is a compound (final product) and/or its process of obtaining. Here, it fits the 6

8 orientation contained in the Guidelines for Patent Applications Examination, Part I Items to Process of obtaining intermediate compounds A process of obtaining intermediate can constitute the main invention of the patent application, but the most common is that it is an accessory invention for a main invention of final compound or even of an intermediate. In the first case, in which the process of obtaining intermediate is the invention, the claims of process of obtaining intermediate should define: 1. The starting material, the product obtained and the means of transforming the first in the second and; 2. The various steps necessary to achieve the proposed objective. 2.7 Chemical compounds found in nature Chemical compounds found in nature are not considered invention, according to the provisions of Article 10 (Item IX) of the Brazilian IP Law. The synthetically obtained chemical compounds having naturally occurring counterparts, not being able to distinguish them from the compounds found in nature, are also not considered as inventions. This aspect was addressed with detail in the Guidelines for Patent Applications Examination, Part II, paragraph 1.43, and in the Guidelines for Patent Applications Examination in the area of biotechnology, item Patent applications related to the selection of chemical compounds Some patent applications can deal with a selection of compounds of a broad class of compounds described in the state of the art, such as for example, compounds described by generic formulas of the Markush type. Usually, the previous document refers to a new class of chemical compounds. The procedures for the technical examination of patent applications for the selection of chemical compounds are detailed in the Guidelines for Patent Applications Examination, Part II, paragraphs 4.19 to 4.25 and 5.31 to In general terms, to be considered new, the selected chemical compound cannot have been specifically disclosed in the state of the art in the form of examples, tests, results, lists, tables, nomenclature, individual structural formula or method of preparation. Moreover, the selection of said compound cannot occur in an obvious or evident way to a person skilled in the art from the teachings of the state of the art. Invariably, because it is a selection of compounds already generically described in an earlier document, the evaluation of the inventive activity requirement 7

9 of the patent application of selection of compounds involves the presentation of comparative data in relation to the state of the art. As defined in the Guidelines for Patent Applications Examination, Part II, paragraphs 4.19 and 5.32, the comparison must be carried out in relation to the closest state of the art, which, in this case, corresponds to the compound(s) of higher structural similarity specifically disclosed in the state of the art. The following are some examples that illustrate three situations that may occur in the technical examination of patent applications of selection of chemical compounds: 1) Selected compounds lacking novelty and inventive activity; 2) Selected compounds new, but lacking inventive activity and; 3) Selected compound new and inventive. Example 1: Compounds lacking novelty and inventive activity Invention: Tricyclic amide compounds useful in the treatment of proliferative diseases. State of the art: The document of the state of the art discloses tricyclic amide or urea compounds also used in the treatment of proliferative diseases. Invention State of the art Technical analysis: The selected chemical compounds represent a restricted group among the compounds disclosed in a generic manner in the Markush formula of the prior art document. These compounds selected in the application under analysis do not correspond to the compounds exemplified in the document of the state of the art; however, they were foreseen among the preferred compounds in the said document. Thus, the claimed compounds are regarded as specifically disclosed in the state of the art (Guidelines for Patent Applications Examination, Part II, paragraphs 4.21 to 4.23) and do not fulfill the novelty requirement. In order to demonstrate the inventive activity, the applicant presented a series of biological tests comparing the selected compounds with the compounds of higher structural similarity specifically disclosed in the state of the art. However, having in mind that the claimed compounds are not new, they also do not meet the inventive activity requirement. Example 2: New compounds, devoid of inventive activity 8

10 Invention: The patent application relates to analogous compounds of iludins with antiproliferative activity for the treatment of tumors in mammals. State of the Art: The state of the art describes in a generic way, in the Markush formula, analogues substances of iludin, useful as antiproliferative agents. Invention State of the art Technical analysis: The selected compounds represent a restricted group among the compounds disclosed in a generic way in the prior art document, but since they were not specifically disclosed among the exemplified compounds, neither among possible compounds considered as preferential, they are considered new (Guidelines for Patent Applications Examination, Part II, paragraphs 4.21 to 4.23). The Applicant submitted test results comparing the antiproliferative activity between the claimed compounds and the compounds of higher structural similarity specifically disclosed in the state of the art. The results presented did not demonstrate a non-obvious effect in relation to the state of the art, since the antiproliferative activity of the claimed compounds was very similar to the compounds disclosed in the state of the art (Guidelines for Patent Applications Examination, Part II, paragraph 5.33). In this way, although the claimed compounds are considered new, they do not meet the inventive activity requirement. Example 3: Compounds provided with novelty and inventive activity Invention: The patent application relates to phenyl substituted cyclic ketoenols, processes for their preparation and their use in pesticidal and herbicidal compositions. State of the Art: The state of the art discloses a generic description of cyclic ketoenols having pesticidal and herbicidal activity encompassing the compounds selected in the patent application under analysis. 9

11 Invention State of the art Technical analysis: The compounds claimed in the selection patent application were considered new, since, although they are chemical derivatives generically provided in the Markush formula of the prior art document, they have not been specifically disclosed (Guidelines for Patent Applications Examination, Part II, paragraphs 4.21 to 4.23). To substantiate the inventive activity of the subject matter, test data have been presented which clearly demonstrate the non-obvious technical effect of the claimed compounds as compared to the compounds of higher structural similarity specifically disclosed in the state of the art. In this way, the selected compounds were considered not obvious for a person skilled in the art (Guidelines for Patent Applications Examination, Part II, paragraph 5.34). 3 STEREOISOMERS Isomers are compounds that have identical molecular formulas, but differ in nature, in the bonding sequence or in the spatial arrangement of their atoms. Enantiomers, atropoisomers and diastereoisomers, which will be defined below, are part of the class of isomers that have the same molecular formula, but differ in the geometric and/or spatial position of their atoms. Enantiomers are molecules that have a chiral center or absence of symmetry, wherein such molecules are non-overlapping mirror images of one another. Diastereoisomer compounds are stereoisomers that are not mirror images of each other and have different physicochemical properties. Atropoisomer is a subclass of conformational isomers, which may be isolated as a pure chemical species and which arises from a restricted rotation of a single bond (usually due to very bulky substituents). Stereoisomeric mixture is a mixture of stereoisomers, in any ratio. Racemic mixture is a mixture of equimolar stereoisomers. 10

12 3.1 Sufficiency of disclosure The clear and sufficient description of the stereoisomer in the pure form lies in the characterization of the absolute configuration of its chiral center at the time of filing of the patent application. Analytical techniques, such as circular dichroism, nuclear magnetic resonance (with addition of chiral displacement reagent), circular birefringence, optical rotational dispersion, chromatography (with chiral column), polarimetry and monocrystal X-ray diffractometry can be used for the characterization of the claimed enantiomer/atropoisomer/diastereoisomer. The parameters of the process of obtaining stereoisomer, either by asymmetric synthesis or by the purification process subsequent to the synthesis of the compound, should be specified in the specification, in order to ensure its reproducibility by a person skilled in the art. Due to the possibility of racemization of the chiral compounds during the process of obtaining, it is important that the specification discloses the reagents used (mainly in the formation step of the chiral center), the reaction conditions, the isolation and purification methods of the stereoisomer obtained by said process. The specification should also describe the possible enantiomeric excess obtained and the method of analysis used for its measurement. 3.2 Clarity The stereoisomers should be defined through the official nomenclature (IUPAC) or other system that unambiguously identifies them. It is noted that the use of the generic expression such as stereoisomers thereof in claims referring to a compound per se, does not identify the stereoisomers of the compound in a clear and precise manner. If the specification of the patent application sufficiently describes these objects, the set of claims may be reformulated in order to better define the claimed subject matter. 3.3 Novelty The stereoisomers compounds will be considered new if the state of the art does not describe the claimed enantiomer/atropoisomer/diastereoisomer. The novelty should also be attributed in cases in that enantiomer/atropoisomer/diastereoisomer isolated from nature and that is now claimed the antipode thereof have been described in the state of the art. However, since in the state of the art has already been disclosed the compound in the racemic form, the pure enantiomeric or atropoisomeric compounds, itself, are not considered new, since the stereoisomeric mixture already has both the stereoisomers. It should be noted that when the state of the art does not specify the absolute configuration of the chiral centers of the described compounds, it will be considered that the distribution of the enantiomers occurs fairly, that is, it is a racemic mixture. In the case of patent applications dealing with diastereoisomer, the novelty will be proven when 11

13 the state of the art does not specifically describe the claimed diastereoisomer. In some cases, the assessment of the novelty of the claimed diastereoisomer is only possible by presenting characterization data of the known compound so that a comparison can be drawn between the claimed diastereoisomer and the state of the art. In this case, the same analytical techniques employed for the characterization of the claimed diastereoisomer should be applied to samples of the stereoisomer disclosed in the state of the art. The composition containing only one of the stereoisomers is considered new even though the state of the art describes a composition containing the compound in the form of a racemic mixture or other stereoisomeric mixture. In this case, the wording of the composition claim must, necessarily, exclude the possibility of the protection also falling on the racemic composition or other composition containing stereoisomers already described in the state of the art. Particularly, the use of the term consists, as it is considered a restrictive term, limits the constituents of a composition only to those defined in the claim (Guidelines for Patent Applications Examination, Part I, paragraph 3.48). For example, a claim of the type Composition characterized by consisting of the R enantiomer of compound X and carriers excludes the presence of any other stereoisomer other than that defined in the claimed composition. On the other hand, the use of the term comprises makes the scope of protection of composition claims broader, compromising the novelty. For example, the wording of a claim of the type Composition characterized by comprising the R enantiomer of compound X and carriers does not limit the constituents only to the elements defined in the claimed composition, which may comprise, in addition to the R stereoisomer, other constituents, including the S stereoisomer (Guidelines for Patent Applications Examination, Part I, paragraph 3.49). A composition consisting of a stereoisomeric mixture of defined constitution (determined stereomeric excess) will be considered new, provided that it has not been previously disclosed in the state of the art. The use of an isolated enantiomer/atropoisomer is not new if the state of the art already discloses the use of its racemic mixture for such purpose. The same is considered for the applications that deal with diasteroisomers of a compound, when the state of the art anticipates the claimed use for said compound. If the application concerns a new use of an isolated stereoisomer compound, the examination should be based on the Guidelines for Patent Applications Examination, Part I, paragraphs 3.73 to 3.76 and Part II, paragraph 4.18 and in the Guidelines for Patent Applications Examination - Chemical, item about New Uses of Known Products. 3.4 Inventive activity When the properties of the compound of the state of the art are known, there is an expectation that the pure stereoisomer of this compound exhibits these same properties. Thus, it is considered that there is an indication in the state of the art that would motivate a person skilled in the art to obtain this stereoisomer in order to identify the most suitable form for industrial use, such as for example, the more active or less toxic stereoisomeric form of the compound. The same positioning should be assumed for the analysis of inventive activity of stereoisomers containing compositions. 12

14 If the application refer to a new use of an isolated stereoisomer compound, the examination should be based on the Guidelines for Patent Applications Examination, Part I, paragraphs 3.73 to 3.76, and Part II, paragraphs 5.40 to 5.45, and in the Guidelines for Patent Applications Examination - Chemical, item about New Uses of Known Products. 4 POLYMORPHS Polymorphism refers to the ability of a chemical compound to exist in one or more crystalline phases that have different arrangements and/or conformation of the molecules in an ordered crystal lattice. Amorphous solids consist of solids with disordered array of molecules and do not have a defined crystal lattice. 4.1 Sufficiency of disclosure For the characterization of crystalline form, the specification must contain, on the filing date of the application, the identification data obtained by physicochemical characterization techniques of solids, such as those exemplified below or by alternative techniques validated that best identify it: a) Single-crystal X-ray diffraction (Monocrystal XRD); b) Powder X-ray diffraction (powder XRD); c) Solid state Carbon-13 nuclear magnetic resonance spectroscopy (13C NMR); d) Spectrometry in the infrared region; e) Raman spectroscopy; f) Electronic microscopy (hot stage); g) Thermal analysis: Differential Scanning Calorimetry (DSC), Thermogravimetry (TGA) and Differential Thermal Analysis (DTA). It is noteworthy that the monocrystal XRD technique is sufficient for the perfect characterization of the crystalline structure of the solid. Not being provided the XRD data of monocrystal, one should use the XRD technique by the powder method with indexing, associated with other methods of physicochemical identification of solids, provided that the set of techniques is sufficient for the unambiguous identification of the crystalline form. The parameters of the process of obtaining crystalline form must be specified in the specification, in order to guarantee its reproducibility by a person skilled in the art. The following are considered essential parameters in these processes, for example, the indication of the solvent(s) and their concentration(s), solvent(s) addition rates, heating and cooling rates, 13

15 description of the process of obtaining possible seeds used in the crystallization process and other parameters that can be considered critical. It should be noted that the claimed crystalline form is considered part of the process of preparing, that is, for the process to be considered sufficiently described to enable its reproduction by a person skilled in the art, the polymorph obtained by such a process should be duly characterized in the specification. 4.2 Clarity and accuracy of claims The identification of a crystalline form is made by physicochemical parameters that define its structure. The simple denomination by designations such as, for example, alpha or beta form, form I or II, does not clearly and precisely define the crystalline form. Examples of claims of crystalline forms having clear and precise wording will be presented, as follows. Example 1: Crystalline form of compound X characterized by having a melting point of 151 ºC, as measured by differential scanning calorimetry (DSC 2K min-1); presenting reflexions (2-theta) at 7.5, 10.1, 12.0, 12.4, 13.7, 15.0, 16.0, 17.3, 17.7, 18.0, 19.2, 19.8, 20.7, 21.0, 22.2, 22.7, 22.9, 23.6, 24.1, 25.6 and 30.5, with the respective relative intensities 11.4, 63.0, 19.0, 21.0, 7.6, 15.2, 9.5, 7.6, 5.7, 14.3, 5.7, 23.0, 11.4, 11.4, 61.0, 100.0, 13.3, 7.6, 28.6, 9.5 and 7.6, in its X-ray diffractogram; presenting maximum peaks at 3338, 1708 and 1431 cm-1 in its infrared spectrum, presenting maximum peaks at 107.9, and ppm in its 13C solid-state NMR spectrum, and presenting maximum peaks at 3080, 1580 and 122 cm-1 in its Raman spectrum. Example 2: Crystalline form of compound X characterized by presenting reflections (2-theta) at 7.5, 10.1, 12.0, 12.4, 13.7, 15.0, 16.0, 17.3, 17.7, 18.0, 19.2, 19.8, 20.7, 21.0, 22.2, 22.7, 22.9, 23.6, 24.1, 25.6 and 30.5, having the respective relative intensities 11.4, 63.0, 19.0, 21.0, 7.6, 15.2, 9.5, 7.6, 5.7, 14.3, 5.7, 23.0, 11.4, 11.4, 61.0, 100.0, 13.3, 7.6, 28.6, 9.5 and 7.6 in its X-ray monocrystal diffractogram. 4.3 Novelty The distinguishing characteristics of the crystalline forms are based on the physicochemical parameters and, in general, the closest state of the art is the one that discloses the obtaining of the compound, which mostly, is not characterized by its crystalline structure. In these cases, physicochemical characterization data of the solid compound described in the state of the art should be presented so that the comparison can be made with the claimed crystalline form. 14

16 If the state of the art already discloses the claimed crystalline form, even in a mixture with other forms, regardless of its concentration, the claimed crystalline form is not considered new. In case the state of the art describes the compound in a non-solid state (for example, liquid, pasty or oily), the physicochemical characterization data of the compound from the state of the art are unnecessary, since, in these circumstances, there is no doubts as to the novelty of the claimed polymorph. 4.4 Inventive activity Although it refers to a same chemical substance and that the possibility of formation of different crystalline lattices is a peculiar property of the solids, the polymorphic forms may have different physicochemical properties both in the processes of preparing product and in the shelf life or further, in terms of chemical effects. However, it is important to highlight that obtaining crystalline solids from a compound is a common manufacturing practice for improving the physicochemical characteristics of compounds in general. Thus, the mere description and characterization of an alternative crystalline solid of a known compound, when disassociated with an unobvious property of the solid or a relevant technical advance in view of the state of the art, it has no inventive activity. 5 SOLVATES, CLATHRATES, CO-CRYSTALS In some crystalline solids, the solvent may be incorporated into the crystalline lattice of the compound in stoichiometric or non-stoichiometric proportions. These molecular adducts are called solvates, also called pseudopolymorphs. When the water is the crystallization solvent, the resulting solid is called hydrate. When a solvate loses the molecules of the incorporated solvent into the crystalline lattice (intentionally or not) and the crystal retains the structure of the solvate, the solid obtained is called desolvate. This matter should be evaluated as discussed in the item regarding Polymorph of these Guidelines, since it refers to the crystalline form composed only of one type of molecule. 1. all are formed by at least two molecules; 2. all may assume different crystalline forms; 3. all may have different characteristics according to the structure and constituents of the crystal. In a patent application, which the invention is any one of these products, it should be considered that: 15

17 1. for the clear and sufficient description of a solvate, clathrate, crystalline or co-crystalline complex, the chemical identification of the molecule and stoichiometry is mandatory, which can be determined by thermogravimetric analysis (TGA), Karl Fischer or other validated techniques that provide such information;; 2. if the invention to be protected is a solvate, the Chemical Compound item of these Guidelines and the Guidelines for Patent Applications Examination of the Brazilian PTO must be consulted, since the solvate is considered a chemical compound different from its correspondent without solvation or anhydrous; 3. if the invention to be protected is a crystalline form (clathrate, co-crystal or solvate crystalline form), it must be characterized physic-chemically by the techniques described in the item regarding Polymorph of these Guidelines, in addition to the Guidelines for Patent Applications Examination of the Brazilian PTO, in order to define both the constituents and the structure of the crystalline form. 4. the use of the generic terms solvates thereof, hydrates thereof, clathrates thereof and/or co-crystals thereof in claims referring to a compound per se, do not identify solvates, hydrates, clathrates and co-crystals derivatives of the compound in a clear and precise manner. If the specification of the patent application sufficiently describes these objects, the set of claims may be reformulated in order to define better the claimed subject matter. 6 COMPOSITIONS, FORMULATIONS AND PHYSICAL FORMS OF COMPOSITIONS Claims of compositions, formulations and physical forms of compositions are examined according to the Guidelines for Patent Applications Examination, Part II, in its paragraphs 7.1 to Clarity and accuracy of claims As discussed in the Guidelines for Patent Applications Examination, Part II, paragraphs 7.1 to 7.15, a composition is usually defined only by its constituents. However, the compositions may further be defined by mixed features, so as to encompass physical form or application characteristics, as long as they are qualitatively and/or quantitatively defined by their constituents. Complementary examples of compositions are presented, with emphasis on the clarity and accuracy analysis of the claims (article 25 of the Brazilian IP Law), as follows. Example 1: Claim 1: A pharmaceutical composition characterized by comprising the compound A and the excipients B and C. 16

18 Claim 2: The pharmaceutical composition, according to claim 1, characterized by being for oral administration. It is in accordance with article 25 of the Brazilian IP Law, since the composition is defined by its constituents in claim 1 and the form of administration is an additional feature which restricts the claimed matter to the field of compositions for oral use (tablets, capsules, syrups, etc.). Claim 3: The pharmaceutical composition, according to claim 1, characterized by being in capsule form. It is in accordance with article 25 of the Brazilian IP Law, since the composition is defined by its constituents in claim 1 and the expression being in capsule form is an additional feature of the claimed subject matter. Claim 4: The pharmaceutical composition, according to claim 1, characterized by being for the treatment of asthma. It is in accordance with article 25 of the Brazilian IP Law, since the composition is defined by its constituents in claim 1 and its application is an additional feature, which restricts the claimed subject matter to the field of products useful for the treatment of asthma. Claim 5: The pharmaceutical composition, according to claim 1, characterized by releasing eighty percent (80%) of component A in less than thirty minutes. It is in accordance with article 25 of the Brazilian IP Law, since the composition is defined by its constituents in claim 1, and the release of component A is an additional feature, which informs about the properties of the claimed subject matter. Example 2: Claim 1: A pharmaceutical composition characterized by comprising the compound A and the excipients B and C for oral administration. It is in accordance with article 25 of the Brazilian IP Law, since the composition is defined by its constituents. The information about the form of administration is an additional feature, which restricts the claimed subject matter to the field of oral compositions (tablets, capsules, syrups, etc.). Example 3: Claim 1: A pharmaceutical composition characterized by comprising the compound A and the excipients B and C to treat asthma. 17

19 It is in accordance with article 25 of the Brazilian IP Law, since the composition is defined by its constituents. The information on the use of the composition represents only a further characterization of the composition, which restricts the claimed subject matter to the field of products useful for the treatment of asthma. Example 4: Claim 1: A pharmaceutical composition comprising the compound A and the excipients B and C characterized by being for the treatment of disease Y. Not acceptable for lacking clarity (article 25 of the Brazilian IP Law), since the composition is not characterized by its constituents but by its application. In this case, for complying with article 25 of the Brazilian IP Law, it is possible to redraft the wording of the claim by moving the constituent elements of the composition into the characterizing part (Guidelines for Patent Applications Examination, Part I, Paragraphs 3.04 to 3.09) If the composition is known from the state of the art, the claim would also not be new, since the feature related to the use of the composition does not bring novelty to the product. Example 5: Claim 1: A composition characterized by releasing eighty percent (80%) of the active ingredient in less than thirty minutes. Not acceptable for lacking clarity (article 25 of the Brazilian IP Law), since the composition is not characterized by its constituents. The percentage released of the active ingredient does not define the claimed subject matter. Example 6: Claim 1: An insecticide composition characterized by being in the form of a spray. Not acceptable for lacking clarity (article 25 of the Brazilian IP Law), since the composition is not characterized by its constituents and the application form does not define the claimed subject matter. Example 7: Claim 1: A pharmaceutical composition characterized by comprising the compound A and its excipients B and C to be used as sustained release tablets capable of releasing eighty percent (80%) of component A in less than thirty minutes. It is in accordance with article 25 of the Brazilian IP Law, since the composition is characterized by its constituents and the pharmaceutical form and the properties of the product are additional characteristics of the composition. Example 8: Claim 1: A tablet characterized by comprising the compound A and the excipients B and C. 18

20 It is in accordance with article 25 of the Brazilian IP Law, since the tablet is characterized by its constituents (in this case, the elements of the composition). Example 9: Claim 1: A pharmaceutical form characterized by being in the form of a tablet consisting of 100 mg of A, 220 mg of B and 200 mg of C. It is in accordance with article 25 of the Brazilian IP Law, since the pharmaceutical form is characterized by its constituents and by the physical form of tablet. Example 10: Claim 1: A pharmaceutical composition characterized by comprising the compound A and its excipients B and C. Claim 2: The pharmaceutical composition, according to claim 1, characterized in that the dosage of A ranges from 45 to 90 mg per kg of the patient. Not acceptable for lacking clarity (article 25 of the Brazilian IP Law), since the additional feature of the dependent claim refers to the method of administering the pharmaceutical composition, which is part of a therapeutic regimen and is unrelated to the product. The added feature does not add information about the product per se, which results in an inconsistency to the claimed subject matter. Claim 3: The pharmaceutical composition, according to claim 1, characterized in that it is administered twice a day. Not acceptable for lacking clarity (article 25 of the Brazilian IP Law), since the additional feature of the dependent claim refers to the method of administering the pharmaceutical composition, which is part of a therapeutic regimen and, not, a product. The added feature does not add information about the product per se, which results in an inconsistency to the claimed subject matter. Example 11: Claim 1: A composition characterized by comprising a compound A and a compound B. Claim 2: The composition, according to claim 1, characterized by optionally comprising other active ingredients. Not acceptable for lacking clarity (article 25 of the Brazilian IP Law), since the term optionally comprising other active ingredients does not define said active ingredients. If the specification of the application provides a sufficient description of the so-called active ingredients, the set of claims may be reformulated in order to restrict the active ingredients to those described in the specification. 19

21 Example 12: Claim 1: A gray-colored soda-lime glass composition characterized by comprising an element A and an element B at the concentrations x and y, respectively, present as coloring agents, wherein the glass has a total light transmission of < 20% for a glass having a thickness of 4 mm. Claim 2: The gray-colored soda-lime glass composition, according to claim 1, characterized in that the glass has a total light transmission of < 10% for a glass having a thickness of 4 mm. It is in accordance with article 25 of the Brazilian IP Law, since the composition is characterized by its constituents and its particular concentrations. The light transmission (physical parameter) is an additional characteristic of the claimed subject matter. Example 13: Claim 1: A fertilizer composition characterized by comprising the raw material A (for example ammonium nitrate) and the raw material B (for example calcium sulphate) at the concentrations X and Y, respectively. Claim 1: The fertilizer composition, according to claim 1, characterized by containing the nutrient Z (for example, total Nitrogen) at the concentration of 80%, by weight, and the nutrient W (for example, calcium) at a concentration of 10% by weight. It is in accordance with article 25 of the Brazilian IP Law, since the composition is characterized by its raw materials and their concentrations. The nutrients and their concentrations are additional characteristics of the composition. Example 14: Claim 1: A fertilizer composition characterized by consisting of elements X, Y, and Z (for example: carbon, hydrogen, nitrogen, phosphorus, potassium...). Not acceptable for lacking clarity (article 25 of the Brazilian IP Law), since the composition is not characterized by the raw materials containing such elements, nor does it specify their concentrations. 7 COMBINATIONS OF CHEMICAL COMPOUNDS A combination is the association of two or more compounds targeting a particular final product. The combination may be contained in a single form or in separate forms for simultaneous application. For the examination of combinations, paragraphs 5.24 to 5.30 and 7.16 to 7.23 of the Guidelines for Patent Applications Examination, Part II, should be considered. 20

22 In the particular case of inventions related to combinations, the interaction between the associated compounds must produce a non-obvious effect, as for example, a synergistic or supra-additive effect, which does not correspond to an additive effect, i.e., to the mere sum of the individual effects of each compound constituting said combination. Thus, when the result of the association of two or more known compounds is a sum of the effects that would be expected for each compound used alone, the claimed combination will be considered devoid of inventive activity, since said combination corresponds to a predictable association of known compounds to generate an expected technical effect. Evidence of the non-obvious effect of a combination, often, involves the presentation of data to allow a comparison between the effects observed with the respective compounds when used alone and those obtained from the combination of these compounds under the same experimental conditions. It should be noted that the alleged non-obvious effect cannot be suggested in the state of the art, for example in combinations of compounds having very similar chemical structures to those compounds of the combination under analysis (Guidelines for Patent Applications Examination, Part II, paragraph 7.19). 7.1 Sufficiency of disclosure, clarity and accuracy of claims The distinguishing characteristics of the crystalline forms are based on the physicochemical parameters and, in general, the closest state of the art is the one that discloses the obtaining of the compound, which mostly, is not characterized by its crystalline structure. In these cases, physicochemical characterization data of the solid compound described in the state of the art should be presented so that the comparison can be made with the claimed crystalline form Combination comprising compounds defined by Markush formula When the invention relates to a new combination of two or more compounds, in which at least one of the compounds is defined by a general formula of Markush type, such as for example, A combination characterized by comprising a compound as defined by the general formula (I) in association with compound A, special attention should be given to the clarity and accuracy of the wording of the claim and the Guidelines for Patent Applications Examination, Part II (paragraphs 6.13 and 6.14) should be consulted. 21