Inventive step assessment of top selling monoclonal antibodies in Brazil

ABSTRACT

Introduction: The patent system is fundamental for the pharmaceutical industry development, providing a return on the large investment of time and financial resources. Among the patentability requirements, understanding how to comply with the inventive step is especially important for patent applicants. Regarding mAbs, due to the high affinity and specificity for their molecular therapeutic target, minimal structural changes can lead to unexpected properties, being a common issue among Patent Offices.

Areas covered: The present research investigated the Brazilian patents covering top-selling mAbs.

Expert Opinion: The more complete and detailed the mAb when the patent application is filed, the greater the chance of the patent being granted. It is necessary to disclose, at least, the six CDRs, the complete variable region, and/or the hybridoma. The Applicant shall specify faced obstacles during mAb generation, mainly if it is a common issue and resulted in improved properties. If it is possible, the Applicants shall compare the claimed mAbs to previous ones, focusing on the achieved unexpected or improved properties. After an objection by BRPTO, the Applicant shall submit data with quantitatively data about qualitative information disclosed at the Specification when filed. If applicable, show different epitope-binding and highlight clinical advantages of successful mAbs.

KEYWORDS:

• Monoclonal antibodies
• inventive step
• biotechnology patents

Article highlights

• All top-selling monoclonal antibodies are covered by patents or patent applications in Brazil and, among this number, 16 were granted – 2 expired – 4 are under examination and 1 was withdrawn .

• All cases with BRPTO’s decision in the first instance overcame the objection over the inventive step, reflecting that, although emicizumab was withdrawn, no patents have been denied on obvious grounds.

• The objections over inventive step turned around broad scope (four cases); humanization method (six); mAbs directed to a known target to treat a known disease (seven); the mAb has no technical advantage over prior art mAbs and/or the Applicant should demonstrate unexpected properties (nine); the mAb needs to structurally define (SEQ ID NO: or hybridoma) in order to analyze inventive step (one); and through the new BRPTO’s Preliminary Requirement established by Resolution #241/2019 (four).

• The used strategies – combined or not – by the Applicants to overcome obviousness objections were: to narrow the protection scope (four cases); to explain that the PHOSITA should be motivated to produce the claimed mAb with the disclosed SEQ ID NO: not any mAb (seven); to highlight improved properties and/or attached scientific data supporting them (nine); to define the SEQ ID NO: (one); to explain that variable region is enough for the reproducibility of mAbs (one); to prove that the mAb has a different epitope-binding (two); and to adapt the claims to international correspondent patents (four).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. The information in that article reflects only the authors’ views and analyzes and no information in that article does necessarily reflect the position or policies of the patent offices mentioned or should be considered decisive for any decision-making.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

The data that support the findings of this study are available from the Integrity (Clarivate Analytics)® database (https://integrity.clarivate.com/integrity/xmlxsl/). Restrictions apply to the availability of these data, which require registration for free under the Integrity website.

Notes

1. The previous Guidelines for Examination of Patent Applications in the Biotechnology Area were in force since 2015, through Resolution #144/2015 of BRPTO.

2. https://gru.inpi.gov.br/pePI/jsp/patentes/PatenteSearchBasico.jsp.

3. In BRPTO, in vivo results are required for second use patents, i.e., patents claiming a second medical use for a known drug [39].

Additional information

Funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) under Grant 314588/2018-3; and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) under Grant 88881.362026/2019-0.