Careful planning – Cell and gene therapy IP strategy

It is clear that this field is rapidly evolving and expanding. However, in this increasingly competitive field, there are a number of aspects that should be considered at an early stage to ensure a robust IP portfolio and strategy.

Common pitfalls

Patentability

In the cell and gene therapy field, there are a number of issues that can arise in prosecution due to exceptions to patentability which differ between jurisdictions. Notably, at the European Patent Office (EPO), inventions relating to stem cells derived from the destruction of human embryos are not patentable. Methods of treatment by therapy or surgery of the human body are also not allowed, although different claim language may be used to overcome this exclusion. In the US, in order for natural phenomena or products to be patentable, they must demonstrate characteristics which are “markedly different” from their natural counterpart. As such, careful drafting of applications is required to maximise protection of commercially important embodiments, taking into account the specific requirements in each different jurisdiction.

Furthermore, the cell and gene therapy field is broad and comprises various different therapeutics as well as the processes and methods that are used to develop these products. Any company working in this field should have a clear process in place to identify key areas where innovation may occur. Generally, the therapeutic product is likely to be at the core of an IP portfolio. However, it is important to bear in mind that it is also possible to protect the methods, processes and devices that are used, for example, to culture, manipulate, modify or even store and transfer the cells. This protection may come in the form of patent applications, but in some cases may be better protected via trade secrets. There is also the potential to protect a device, such as culture vessel, by using design rights. 

It is imperative to have a clear IP strategy in place at an early stage of developing products and methods in this field to capture and protect innovations.

Timing

The timing of filing a patent application can be critical. There is often a drive to get an early filing date for a patent application in order to reduce the chance of third parties either publishing results or filing a patent application related to a similar technology or to secure investment. However, in the field of therapeutics, there is a need to balance the desire for an early filing date with the need to include sufficient data to support the application.  

At the EPO, it is critical to show that it is plausible that the invention performs as claimed and solves the technical problem it is purported to do.  Under US law, the written description requirement states that the subject matter of the claims must be supported by the disclosure in the description so that it can be carried out by a skilled person without undue burden. In the therapeutic field, data is often required to meet these criteria, for example in vitro or in vivo model data demonstrating efficacy.

However, the assessment of how much data is required is not always straightforward. Furthermore, the need for experimental data can further complicate the timing of a patent filing if there are clinical trials involved. Clinical trials are essential in the development of therapeutics. However, the publication of a trial protocol is a public disclosure. Depending on the content of the disclosure it is possible that the trial protocol could be prejudicial to a later patent filing. Therefore, the timing of a patent filing around a clinical trial should always be carefully considered.

A recent case which highlights the importance of data is Juno Therapeutics, Inc. v. Kite Pharma, Inc. This case centred around the CAR-T therapy Yescarta®, which works by engineering a chimeric antigen receptor (CAR) into a patient’s T cells, the CAR allows the cells to better target cancer cells. Juno sued Kite for infringement of its patent US 7,446,190 (‘190 patent) through the sale of Yescarta ® and Kite countersued for invalidity. The recent Court of Appeal decision found that the ‘190 patent did not meet the written description requirement. This decision turned on the fact that the ‘190 patent related to a T-cell receptor which comprised an scFv as a binding domain, however only two examples of said scFv were provided and no amino acid sequences were provided. The court found that scFv that would work within the invention were not sufficiently described in the patent. Therefore, the patent was found to be invalid. This decision overturned the earlier decision and also overturned the $1.2 billion fine on Kite Pharma for infringement that was previously granted to Juno Therapeutics.

Evidently, there are many factors that play into when to file a patent application. A balance between the commercial objectives of the company, the need to obtain data to demonstrate that the invention works and reduce the chance of prejudicial publications occurring is sometimes difficult to achieve.

Ownership and Inventorship

As with any project from which intellectual property might arise it is always a good idea to consider ownership and inventorship at a very early stage. If ownership and inventorship are not considered carefully this can have huge consequences for a patent application later down the line. A key example of this occurred in the long running CRISPR battle.

The Broad Institute, MIT and Harvard (‘Broad’) obtained the first granted European patent (EP‘468) directed to CRISPR-Cas9 gene editing using single guide RNA in eukaryotic cell.  However, this application was opposed and revoked.

This decision came down to the fact there were discrepancies between the inventors listed on two of the priority documents and the later filed PCT application. Eight inventors were listed on two of the priority documents however one of these inventors was  not listed on the later PCT application. Due to this discrepancy, the priority claim was not valid. This resulted in a journal article which was published during the priority year to become citable and was found to be novelty destroying.    

Cell and gene therapy projects are often highly collaborative. In these types of projects, where different parties may be innovating together on a common project, there is a need to clearly identify any background IP that is brought to the project along with identifying any potential foreground IP that might be developed during the course of the project. Ownership should be clearly set out in any agreement to avoid subsequent disputes. 

Freedom to operate (FTO)

The cell and gene therapy market is becoming increasingly crowded and is likely to grow further given the significant investment in the field and the value of the therapeutics. The increase in granted patents in the US and at the EPO may also lead to an increase in litigation and EPO oppositions related to these technologies. The stakes are high, demonstrated by the amount of damages that were initially awarded in Juno Therapeutics, Inc. v. Kite Pharma, Inc. Therefore, especially companies starting out in this field should assess whether they have freedom to operate, to help mitigate any business risks.

Cell and gene therapies are at the forefront of cutting-edge innovation. At the same time, the patent landscape is becoming more and more complex. However, by considering the common pitfalls discussed herein at an early stage and designing an appropriate IP strategy, it is possible to develop a robust IP portfolio to achieve commercial goals.