Best practices for patenting antibodies

There are several rules to watch out for when seeking patent protection for antibodies in Brazil.

Despite the continuing efforts to harmonise patent practice in all countries, some differences persist. When it comes to technological domains such as biotechnology, minor differences can have a significant impact. This is the case with antibody patentability. Although Brazilian practice is inspired by European practice, most practitioners agree that it comes with several restrictions.

In Europe, while antibodies are most commonly defined according to their amino acid sequences, it is also acceptable to claim antibodies in terms of their functions, provided that a skilled person can isolate or make such antibodies without experimental uncertainties. This flexibility is also reflected in granted claims on functional features relating to aspects of antigen binding, such as binding to a defined epitope and competing for binding with another antibody. Such functional definition is regularly rejected in Brazil.

It is common to observe Brazilian applications with foreign priority claims defining antibodies by percentage identity or similarity and by functional languages. These will most likely face objections at the examination stage. So the question is: what is acceptable?

Non-naturally occurring antibodies

Article 10(IX) of the Industrial Property Law stipulates that biological materials found in or isolated from nature are not considered to be inventions. Polyclonal antibodies are interpreted as biological products isolated from nature and are therefore excluded from patent protection.

On the other hand, once monoclonal antibodies have been produced by different techniques (eg, hybridoma or genetic engineering), they are not considered as naturally occurring by the Brazilian Patent and Trademark Office (INPI) and therefore are subject to protection. The same is applicable for chimeric and humanised antibodies. The question now is thus: how to claim them?

The INPI analyses antibodies as proteins. In this sense, monoclonal antibodies should be defined according to the deposit number of the hybridoma producer cell or by their own amino acid sequence (sequence identification numbers). Examples of accepted claims include:

• “monoclonal antibody, characterised by being produced by the cell line deposited under American Type Culture Collection access number PTA-4837”;
• “an artificial antibody with specific affinity for a characteristic epitope of the ED-B domain of fibronectin, characterised in that… the antibody has the following amino acid sequence: VH… (SEQ ID NO: 19), linker, VL… (SEQ ID NO: 21)”; and
• “humanised antibody that specifically binds to an epitope… characterised by comprising: a humanised light chain variable region comprising the following sequence: Asp Xaa Val Met Thr… (SEQ ID NO: 7) wherein Xaa in position 2 is Val or Ile… a heavy chain variable region comprising the following sequence: Xaa Val Gln Leu Val… (SEQ ID NO: 8) wherein Xaa in position 1 is Glu or Gln”.

The INPI considers hybridomas to be products resulting from direct human intervention that could not possibly occur under natural conditions; they are thus also subject to protection.

As for the chimeric/humanised antibodies that are also subject to patent protection, their characterisation requires the presentation of a SEQ ID NO: X containing an amino acid sequence of the variable portion of the antibody and the definition of the other elements (Fc portion) (Item 6.4.6.3 of Resolution 144), as exemplified as follows:

• “humanised antibody against a-actin, characterised by comprising the murine variable region which consists of SEQ ID NO: X and human y chain regions”; and
• “humanised antibody against a-actin, characterised 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”.

As mentioned above, the INPI is likely to raise objections to any definition comprising binding, encoding and neutralising features, as well as therapeutic and identity or homology functions (regardless of how high the identity or homology is).

For foreign applications filed in Brazil, the applicant may submit a separate claim set for Brazilian prosecution, where the claims are more relevant to the national practice. Nevertheless, it may be more strategic not to restrict the claims by excessive limitations upon filing and instead await the INPI’s position on patentability during examination of the application. In the end, correct delimitation of the scope of protection will always depend on the concepts behind the invention and, in many cases, commercial strategies.