30 April 2014Europe

Patients in a test tube: Horizon Discovery's IP strategy

Editing the genome

As a better understanding of how genes function in disease is developing, personalised medicine is becoming a reality for more patients.

Since the 1990s, advances in technology have allowed the manipulation, or ‘editing’, of the human genome so that the function of certain genes and how genetic mutations cause the onset of disease can be studied.

There are several varieties of this so-called ‘genome editing’. One of the most recent methods, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system, uses a bacterially-derived protein and synthetic guide ribonucleic acid (RNA) to make breaks in targeted parts of the genome.

UK-based Horizon Discovery uses a combination of genome editing methods to create cell lines—what it calls ‘patients in a test tube’—which model the genetic anomalies found in patients with cancer and other diseases, for use by companies in the business of drug discovery and development, as well as in clinical diagnostic development.

“Gene editing allows Horizon Discovery to manipulate the genome,” explains Eric Rhodes, vice president of research and development, and chief technology officer at the company. “We can essentially recreate patient populations.

“As long as you have a unique patient population for a disease, you can recreate that disease in a cell and use that to test drugs to see if they have an effect.”

Personalised medicine

The technology’s potential application as a research tool in the development of personalised medicine is clear. It is an approach that can stop patients receiving treatments that will not work for them, while reducing the chance of an adverse effect.

Horizon Discovery brings together CRISPR, another genome editing method called Zinc Finger Nucleases, and its own proprietary recombinant adeno-associated virus (rAAV) technology to make gene point mutations, knockouts, deletions and insertions on the genome, and create a variety of different cell lines. Drug development companies can use them to see how a population will respond to a medicine before introducing it to a patient.

As gene function is often a factor in the development of cancer, Horizon Discovery has been focusing on creating research tools to assist in the development of treatments for the disease, although it is not limiting itself to oncology.

“Outside oncology there are other things you can do, such as modify cells to make them resemble monogenic diseases, such as Huntington’s or cystic fibrosis.

“Different types of gene editing are used to make specific cells, such as a cell that is typical of a certain type of cancer,” Rhodes explains.

“For example we may take a kidney cell and recreate kidney cancer by mutating a gene. We sell the non-mutated version of the cell next to the mutated version, so researchers can do studies to see the difference between the two when they’re treated with a drug.”

“You may file for one patent at the US Patent and Trademark Office, then end up with ten different smaller patents because the office imposes limits.”

These isogenic cell lines are called X-MAN (gene X–mutated and normal) and they model the genetic anomalies that are often responsible for the development of cancer, among other diseases. These cell lines are used by researchers to identify the effects of individual genetic anomalies on drug activity, patient responsiveness, and resistance.

Since its establishment in 2005, Horizon Discovery has been augmenting its portfolio with cell lines developed in many academic institutions based in the US, and some in Europe. It now holds a library of more than 550 genetically defined cell lines.

A defined technology

While many of its technologies have been in-licensed from other companies, part of Horizon Discovery’s strategy is to create IP of its own. “We’ve created patents ourselves—some technology patents and some that are focused on disease-specific applications,” Rhodes explains, estimating the company holds between 50 and 70 patents.

The company uses its own platform for drug discovery. Upon finding targets that look as though they have potential in the treatment of cancers, Horizon Discovery will sometimes develop chemical compounds and patent those as well.

However, Rhodes says, there can be delays patenting technologies and compounds in the crowded field of genome editing, as patents multiply.

“You may file for one patent at the US Patent and Trademark Office, then end up with ten different smaller patents because the office imposes limits,” Rhodes says.

“Often you file a patent on a broad idea, and the patent office asks you to be more specific. For example, in cancer, we found that patients with a particular mutation are more likely to be treated with a certain class of drug, so in our application we might name something very broad like ‘patients who have lung cancer’—and the office will come back to you and ask ‘what do you mean by lung cancer?’.

“You have to be more defined, so then you start breaking it down.”

Patent offices require applications to be more specific. “You can’t say ‘any one of these 100 genes causes lung cancer’. The office limits you to saying in any single patent that one gene or up to five cause the cancer,” Rhodes says.

“Patents can be general in some ways, such as in applications for methods, but they have to be very specific when it comes to genes.”

As more innovators are citing gene function in their patent claims, the patent office has “got wiser” over the last 20 years on how to deal with patents that mention genes in their claims, Rhodes says. “They’ve realised the difference between genetic information and the value of it.”

Looking forward

While protecting its technologies may be one obstacle—a slow process that, Rhodes says, is getting faster—Horizon Discovery’s biggest challenge is staying ahead in such a competitive sector. “Gene editing is highly competitive right now so there are lots of academics involved,” Rhodes says.

“The patent office is probably inundated with applications related to these new technologies, and it’s going to take some time to tease all of these things apart.”

He likens the situation to the influx of new technologies that followed the discovery of small interfering RNA’s (siRNA) potential use in genome regulation. First reported in 1999, siRNA can be used to stop the expression of, or ‘silence’, certain genes in the genome.

“There was a flood of different patent applications from various directions, and it took many years to sort it all out,” Rhodes says.

He estimates there are about ten other established companies involved in gene editing. What is the company’s plan as the field develops?

“We’re continuing to look into the genetic editing space and trying to develop technology there. That is the main focus for us right now,” he says.

Does its unique position as the sole licensee of rAAV technology give Horizon Discovery an edge? “Ten years ago, there was only one gene editing technology. Now there are at least four commonly accepted gene editing technologies—maybe even five.”

He says that CRISPR’s relative simplicity, compared with the other technologies, means that many academics, biotechs and pharmaceutical companies are taking a ‘do-it-yourself ’ approach with the technology, rather than licensing from other companies with expertise.

“It’s simple enough, at least to approach—that’s why there’s so much competition. The patents are so new that many of them haven’t been published yet,” he says, though he predicts that once the patents start to be published, and companies are required to take licences to use the technologies, things will settle down, and the level of competition will subside.

Until then, however, “it’s a sort of free-for-all and a commercial game right now”.

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