Second medical use patents in Brazil

The protection afforded by Swiss-type patent claims is vital for incentivizing the development of inventions directed to second medical uses. These innovations involve the use of a known compound, composition or similar substance for a new therapeutic purpose, specifically, in the treatment of a disease, disorder or health condition that is different from its previously known use. 

The Brazilian Patent and Trademark Office, the Instituto Nacional da Propriedade Industrial (INPI), allows for such patent grants under circumstances specifically defined to balance the interests of all those constituting the pharmaceutical market – that is, the divergent needs of pharmaceutical companies conducting costly research, industry competitors producing generics and the patients and health systems that rely on these therapeutic products. 

According to the INPI Rule 169/2016, a "Swiss formula claim" is defined as: "Use of a compound [product, composition, etc.] of formula X, characterized by being for the preparation [production, manufacture, etc.] of a medicine to treat disease [disorder, condition, etc.] Y." 

These second medical use claims are also referred to as "package leaflet protection" since they may relate to: 

• A different group of patients / subjects
• A different etiology of the disease, disorder or health condition
• A different mechanism of action
• A new use that is not inferred from a treatment already associated with the compound 

This is to say, the Intellectual Property (IP) protection such claims afford is not derived from or a refinement of a first medical indication in the state of the art.

Determining eligibility 

The patentability requirements for second medical use claims are defined in the Examination Guidelines "Aspects Related to the Examination of Patent Applications in the Field of Chemistry," published in December 2017. As is to be expected, the criteria of novelty, inventive step and industrial applicability all apply, but particular consideration must be given to the descriptive sufficiency or enablement requirement as set forth in Article 24 of the Brazilian IP Law (Law no. 9,279/96), having its equivalents in Article 83 of the European Patent Convention (EPC) and in Section 35 U.S.C. § 112(a) in the United States.

Thereupon, to be considered novel, the subsection "New Uses of Known Products" rules that "the invention involving a new medical use must reveal the application of an already known pharmaceutical product to produce a medicine to treat or prevent a disease different from that for which this product was already used in the prior art." 

The INPI heavily scrutinizes the use of a product (compound, etc.) in itself, i.e., the route of administration or dosage regimen, as well as the patient subgroups to whom the medicine is aimed and will not acknowledge novelty if that use is already known in the state of the art. For example, consider the following claim for the "use of compound X for the manufacture of a medicine for the treatment of disease Y consisting of the administration of said medicine at a dosage regimen Z." In the case where compound X is already known for the treatment of disease Y, the claim will not be considered novel, even if dosage regimen Z is new.

As to inventiveness or non-obviousness, the Examination Guidelines state that:

• The mechanism of action of the product involved in the new use cannot be derived from the mechanism of medicinal action already revealed in the prior art.
• The new use must refer to the treatment of a disease whose etiology is different from the disease treated according to the state of the art.
• The new use cannot be derived from the structure-activity relationship of the drug in comparison to structurally related molecules, that is, from the structural analogy with other compounds that present the same activity as the invention and which are already in the state of the art.
• The new use cannot be inferred from the disclosure of adverse effects known from the prior art for the drug in question.
• The new use cannot be derived from the use of the compound of the invention for the treatment of a symptom of a disease revealed in the prior art, even if the claimed use refers to a different disease.

The stringency observed here helps diminish the likelihood of a second medical use contributing to an obstructive patent thicket.

Not unrelatedly, the "problem-solution approach" applied by the INPI appears stricter compared to EPC practice when examining the sufficiency of disclosure in the specification as filed on the filing date along with the clarity of claims submitted. (To wit, Article 83 EPC and Article 84 EPC vis-à-vis Article 24 and Article 25 of the Brazilian IP Law). 

Examination issues: specificity and proof

The Guidelines state that second medical use claims must explicitly specify the disease or condition targeted rather than employ generic terms, such as "gastrointestinal disorder," "respiratory syndrome," etc., which will be rejected for being indefinite as to the subject matter for which protection is sought. 

In addition, new medical use claims based on the mechanism of action will not be allowed if they do not clearly and precisely define the targeted disease or health condition. It should also be understood that even if the disorder or disease is described in clear and precise terms, claims will still be disallowed if the known product, whether a compound or pharmaceutical composition, is already associated with that condition. 

One example of an unacceptable claim would read: "Product X characterized by use in the treatment of disease Y." On its face, this would be indefinite according to Article 25, besides lacking novelty since product X exists in the state of the art. Another example of an inadmissible claim is: "Use of product X characterized for use in the treatment of disease Y" since, as formulated, the same is directed to a known therapeutic method.  

Accordingly, the sufficiency of the disclosure deserves special attention since the specification must contain documentary evidence of the new use on the filing date. In the absence of any corroborative material, the examiner would conclude that the claim is not supported in the specification and that the invention is not sufficiently disclosed. 

Turning to arguable aspects that the examiner may raise during examination, the results of in vitro tests evidencing a new therapeutic use are a prime example. The examiner could allege the same are not confirmed in vivo due to pharmacokinetic aspects, among others, related to the behavior of the drug within the organism. Furthermore, the examiner could put forward that it is not always possible to extrapolate the results of in vitro tests to a real therapeutic application without additional information to prove this relationship. In the case of studies carried out on animals, the models adopted must present the possibility of extrapolation to humans or the animals to be treated.

Similarly, according to the INPI Guidelines, the new medical use of a compound defined by a "Markush formula," i.e., a representation of a broad range of possible molecular arrangements, requires adequate support in the specification. Whether the burden of proof – which lies with the applicant – has been met is another arguable point that can be raised by the examiner and has to be discussed on a case-by-case basis. Although, theoretically, the compounds defined by a given Markush formula may suggest similar applications, the examiner could assert that it is not possible to extrapolate the particular use of a single compound to all others unless there is evidence proving this equivalence of effect.

Incisive tools 

Some experts criticize second medical use claims as being "without legal teeth" or comparable qualities, i.e., lacking strong enforceability. The veracity of this assessment notwithstanding, an applicant must take care to avoid being bitten during the patenting process.

Depending on the indication covered by the claims and, in addition, if allowed as an "invention by selection" (one made by narrowing for purpose a range of options disclosed in the prior art), the second medical use patent could conflict with the IP interests of the owner or originator of the pharmaceutically active compound. Generally speaking, this would demand negotiations involving cross-licensing to be able to commercialize the subject matter of the claims during the coexistence of both the first-use indication patent and the second medical use patent, both having different expiration dates.

Risks and intricacies aside, Swiss-type patent claims clearly hold both sufficient merit to be awarded exclusive rights by the INPI and other offices and sufficient commercial advantage to be sought by companies developing novel therapies. Indeed, without the incentive of (possibly) receiving patent protection, further research into active compounds known from the state of the art could conceivably be dismissed as a "financial cul-de-sac" for the pharmaceutical industry, much to the detriment of patients everywhere.