Boundaries to patent protection
Cell and gene therapies fall at the borderlines between what is and is not acceptable subject matter for a patent. Ethical considerations like monopolising parts of the human body, preventing clinicians from implementing new approaches and modifying the human germline clash with the general principle of offering patent protection to all technical innovations.
Innovators applying for patent protection need to be aware of the boundaries applied in different parts of the world, and design their patenting strategy to fall within them. The international TRIPS Agreement requires signatory countries to make patents available in all fields of technology, but it does allow some exceptions. These include diagnostic, therapeutic and surgical methods of treatment, inventions contrary to ethical standards and plants and animals other than microorganisms. How this plays out varies between countries.
In many countries, exclusions from patentability for “discoveries” or “products of nature” mean that the patenting of gene sequences themselves is not possible. In the US, a long-running legal battle brought by patients and researchers against Myriad Genetics led to a 2013 Supreme Court ruling that naturally occurring DNA is a product of nature and so not patentable. The ruling resulted in many US patents becoming invalid. It’s worth noting that US judge-made law on patent eligibility is currently the subject of a bipartisan proposal for reform. While the proponents of the legislation do not call for the patentability of naturally occurring genes, it is unclear what the outcome of this project will be.
In Europe, specific legislation (the Biotechnology Directive, 98/44/EC) addresses the patentability of “biotechnological inventions”. This aims to clarify the boundary between what is and is not patentable. It draws a distinction between a gene sequence as it occurs in nature (not patentable) and biological material that has been isolated from its natural environment or product by means of a technical process (potentially patentable).
It also excludes from patent protection inventions that are unethical, including the use of human embryos for industrial or commercial purposes.
Gene and cell therapies
Cell and gene therapies can blur the boundary between a medicine and a method of treatment. Rather than a mass-produced medicine that is used in each patient in the same way, these therapies can involve harvesting and modifying a patient’s own cells, or making changes to the patient’s genome. Patents directed to the process of treating patients are likely to fall foul of the method of treatment restrictions. However, there are aspects of the process and resulting product that are potentially patentable.
Patents have been applied to covering modified cells engineered to express the altered surface protein, and the sequence of the modified protein itself. Other claims seek to cover the DNA vectors used in the process of altering the cells. Applications covering techniques to address toxicity, by improving tissue specificity may be available, as may be improvements to the binding specificity of the cell surface protein.
It may be easier in this field to obtain process rather than product patents. However, these can be more difficult to enforce. Proving that your proprietary process has been used is usually more difficult than proving that a product includes infringing features. This is especially so where the process is carried out in another country.
Patent filing strategies
The numbers of patent filings in both gene editing and cell therapy are increasing rapidly. A recent analysis of the patent landscape relating to CAR T-cell immunotherapy showed a rapid increase in the numbers of patent filings, beginning in 2013. Much of this activity originates in the US and China, with substantial development also coming from Switzerland, the UK, Germany and France.
Innovators under pressure to get their technology protected will need to find a balance between early filing, and developing better supporting data for the patent. Filers need to be strategic in using the time available to generate the best kinds of data to support the invention. Broad supporting data is important for platform-type inventions, in order to demonstrate that the invention can be used across a wide range of applications. For an incremental invention, more focused data may be appropriate. After the initial priority filing has been made, the patent owner can use the priority year to develop stronger supporting data, and flesh out any areas that may be weaker.
Dealing with an increasingly crowded patent landscape
As the patent landscape for gene and cell therapies becomes more crowded, those entering the field will need to assess the need to obtain licences from existing patent-owners. The ongoing battle for control of CRISPR-Cas9 genome editing technology provides a vivid example.
CRISPR-Cas9 gene editing is one of the key technologies underlying the rapid advance of cell and gene therapies. It offers a new degree of precision meaning that viral vectors and therapeutic cells can be modified to exact specifications. Numerous scientists were involved in developing the technology, and competing patent portfolios have been built up, particularly by an international team led by Jennifer Doudna of University of California, Berkeley and Emmanuelle Charpentier, and a rival group from the Broad Institute, Harvard, and MIT. The foundational patents for this technology remain in dispute in both the US and Europe. However that battle ends, users of CRISPR-Cas9 are likely to need licences from one or both groups.
The leading patent filers have established patent licensing companies (primarily Editas Medicine for the Broad Institute group, and CRISPR Therapeutics for the UC Berkeley). These control licensing of the portfolios for pharmaceutical development.
Other companies and institutions have filed their own patents relating to CRISPR, and the field is proliferating rapidly. This means that users of CRISPR-Cas9, and particularly those intending to develop medicinal products, can expect to require licences from more than one patent-holder.
Some have proposed the establishment of patent pools, akin to those established in the mobile telecoms industry. In this model, patent owners contribute relevant patents to be licensed as a package to all interested users. Once submitted to the pool, licensing of a particular patent can no longer be separately controlled, but it has the advantage of providing a substantial revenue stream to the patent owner. The share of licensing revenue that any patent owner receives normally depends on the numbers of patents contributed. This incentivises filers to aim for quality rather than quantity, and can lead to further complexity and muddying of the waters.
The cell and gene therapy patent landscape is becoming increasingly crowded. This makes it more difficult for innovators to obtain protection for their own work, and acquire the necessary licences to use existing patent portfolios.
Innovators will need to develop a patenting strategy that balances building appropriate experimental support for their applications with the need to file as early as possible. Tracking the increasingly complex patent landscape, and obtaining suitable licences, is likely to be a necessary part of product development.
Written by Mark Pearce.