Waiting to inhale: MannKind's diabetes strategy

In January this year, US researchers reported a shocking rise in childhood type 1 diabetes. The number of under-fives diagnosed in the state of Philadelphia rose 70 percent between 1985 and 2004, and in older children, diagnoses increased 29 percent.

The cause of this surge is unclear—less exercise, more sugar and increasingly sterile environments leading to a less resistant immune system have all been identified as possible contributing factors. But whatever the reason, it’s a trend that is spreading across the US, the UK and Europe: there are now more than 366 million diabetics worldwide and by 2030, the World Health Organization predicts it will be the seventh most common cause of death.

There is no known cure for diabetes, so both type 1 and 2 patients rely on medication to manage their illness. For type 1 sufferers, this is a daily injection of insulin to avoid fatigue, headaches and hypoglycaemia. For type 2 diabetics, it’s a mix of exercise, healthy eating and oral medication.

With cases of this lifelong ailment on the rise, pharmaceutical companies large and small are spending billions on pioneering tools, treatments, gizmos and gadgets to make diabetics lives’ easier; from electronic glucose monitors to touch-screen insulin pumps that look more like an iPod than a medical device. By 2018, financial analysts Standard & Poor’s estimate the industry will be worth $58 billion.

One company dedicated to developing diabetes medication is California-based MannKind Corporation. A development stage company, MannKind’s lead product is Afrezza—inhalable insulin that could remove the need to face needles on a daily basis. Afrezza uses MannKind’s Technosphere technology; a dry powder delivery system that is designed to deliver insulin doses as quickly and effectively as a syringe would.

The product has twice received non-approval from the US Food and Drug Administration, which has demanded further clinical trials, but MannKind is submitting a third application in October which it hopes will be more successful. If it is accepted, the inhaler could be on the market by 2014.

“As a company, our main focus is getting our insulin product to market. If we accomplish that, we’d like to develop our dry particle and inhaler technology for other uses. We also run some oncology programmes, but the Afrezza insulin inhaler is our main focus,” explains David Diamond, MannKind’s vice president of intellectual property.

If MannKind proves Afrezza is an effective alternative to injections, the product will have an international reach. To ensure the company is prepared for this, Diamond says MannKind is in “constant discussions” with a range of bigger players that could help them go global. “It would be a lot easier than doing it ourselves,” he says.

As MannKind and its predecessors (the insulin arm of the company has been operating since 1990) have been working on Afrezza for more than 20 years, one of the biggest challenges Diamond and his colleagues face is ensuring the product is protected throughout its development.

“The first patents on our dry powder technology expired in the US this year, so it’s been a real challenge to keep an effective patent protection scheme in place,” he says. “As we’ve learned more about the technology, we’ve been able to patent particular aspects of it so that the particle technology itself is now protected by a series of patents dating out to 2031. Along the way, we’ve also developed an improved inhaler."

The bulk of MannKind’s IP enforcement work is done in-house, explains Diamond. Along with two colleagues, he is responsible for drafting initial applications and reviewing all IP activity. “But we let outside counsel do the heavy lifting— the filing and prosecuting,” he says.

"The first patents on our dry powder technology expired in the US this year, so it's been a real challenge to keep an effective patent protection scheme in place."

Worldwide, Diamond estimates that MannKind holds around 200 Afrezza-related patents, with another 300 pending. “We have a variety of design patents around the world for the inhaler, and now we’re working on prosecuting utility patents. We’d like to see utility patents on the current inhaler granted in the US later this year, which would give us protection until 2030,” he says.

The company also holds two to three hundred patents related to its immunotherapy and oncology programmes, but as Diamond points out, this is less of a priority. As MannKind’s products are all in the development stages, there have been few challenges to the company’s patents. But this is something Diamond expects to change as its success grows.

“As far as we know, there is no-one out there with a product that infringes our patents. I like to think our patents haven’t been challenged because they’re so strong, but the real explanation is probably that we don’t have a product on the market yet, so there’s not a big motivation for someone else to challenge it. If we’re successful, it’s very conceivable this will happen, and we’ll respond appropriately,” he adds.

Small biopharmaceutical companies like MannKind don’t face the same threat of infringement, generic competition and counterfeit production that global corporations do. Instead, Diamond and his team are focussed on ensuring that MannKind’s products are as widely and comprehensively protected as possible, in as many locations as time and money will allow.

“Our priority is making sure everything’s protected. We have patents on our inhaler, we have patents on the particle technology it uses, and have patents on methods of using that technology. The insulin also has an ultra-rapid kinetic profile, which impacts how it could optimally be used, so we have begun drafting patents for medical uses for that profile and the kinds of uses it enables,” he says.

Some of MannKind’s patents are exclusive to the US, but the company is also targeting key and emerging markets, including Europe, Canada, Japan, Mexico, Russia, Korea, Argentina and Israel. “Understanding the various patent laws around the world is certainly a challenge— what you can patent is very different from the US to Europe, to Japan, China and India, where they just won’t allow some of our patents at all,” he explains.

And an even bigger challenge, says Diamond, is making sure applications are tailored appropriately to meet the requirements in each of these jurisdictions. “In some countries, examinations are closely tied to Patent Cooperation Treaty search report results. In other countries, they’re more independent. Perhaps the most difficult part of our work is working out what language and format will fly in each of the various jurisdictions you are dealing with,” he adds.

In the US, the recent switch from a first to- invent to a first-to-file patent system has caused panic among major pharmaceutical brands. But for MannKind, this simply means doing in the US what they have already done abroad.

“Big pharmaceutical companies have very cumbersome processes: you have to submit an idea to a committee, and the committee decides whether or not to develop that idea, and then eventually, the company decides whether or not to file a patent application. That takes a lot of time, and is a serious concern in a competitive first-to-file jurisdiction. But for us, as soon as something looks valuable enough and ready for patenting, we just go ahead and write the application.”

A bigger change, says Diamond, would be the possible introduction of a unitary patent system in Europe. “For us, this would make patenting our products much easier. We would prefer to be able to patent across Europe without having to pay for protection in more than 20 countries. The devil’s in the detail of how it’s put together, but it’s something we’re rooting for, as it would presumably lead to reduced attorney fees, translation costs and attorney effort,” he says.

Producing potentially revolutionary products in a fiercely competitive and rapidly growing market is an arduous and delicate task. Protecting those inventions even more so. But by maintaining a proactive approach to enforcement and navigating jurisdictional differences, Diamond hopes the company will be able to bring a unique product to market that will help millions of patients worldwide.

“We certainly think we can make a difference to diabetics,” he says. “Aside from the patient convenience aspect, we believe Afrezza is a superior treatment for glucose control that will make it easier and more useful for people to start insulin treatment. Because of that, it will change diabetics’ lives.”