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Under each of the below headings, you fill find the conversations we had with these stakeholders which integrated into our final product. Please enjoy reading through our journey!   
 
Under each of the below headings, you fill find the conversations we had with these stakeholders which integrated into our final product. Please enjoy reading through our journey!   
 
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Revision as of 23:59, 28 October 2017

About Our Integrated Human Practices

We spent a considerable amount of time looking out into the real world to figure out how our project would best solve the issues of insulin unaffordability and inaccessibility. Key advisors and stakeholders aided the decisions we made along the way. Not only did our project integrate with the advice of individual people, but these individuals became integrated into a big conversation between us all. Specifically, these conversations were around how we Apply the design, the Project Design itself and ultimately how we best present this project to the real world as a business.

Under each of the below headings, you fill find the conversations we had with these stakeholders which integrated into our final product. Please enjoy reading through our journey!

Project Design

To: Project Design
Anthony (Counter Culture Labs)
We need an Open Source Insulin! We need a team to be able to start investigating methods that could be used to increase the yield, and decrease the post-expression processing steps currently required to produce insulin.
Meow
I've got a team in mind.
Nick
USYD iGEMers- what do you think?
Team DISCO
We can do that! iGEM is an international competition where teams across the world create and deposit genetic sequences into an open source registry, so that the global community can follow on from a single team’s work.
Meow
That’s fantastic! Keep me updated throughout the project, I’m more than happy to help with this process if I can. Also, good luck with the competition!
After researching insulin a little further, we’ve come to realise that there are a few issues we’d like to address.

Firstly, Human insulin purification takes a long time and, depending on the method used, can be very expensive. We investigated alternatives to this process, and we came up with a few expression systems that could be used to improve the folding of insulin inside Escherichia coli and Bacillus subtilis.

Secondly, insulin is currently stored at 4°C to preserve its activity. Keeping insulin at this temperature in cold storage chains while it’s being transported is incredibly difficult. This is especially so in lower economic countries, where we hope our insulin will be able to be sold.

So we thought, what if we designed our own, single chain, open source insulin that is also thermostable?
Neil
Hi! As a part of the not-for-profit group Insulin for Life, I currently work to export insulin from Australia to all corners of the globe. We haven’t had any issues with the activity of the insulin we distribute, even though we don’t use any cold chain transportation. I think that any insulin you design, just like the human insulin you’re looking to produce, will be thermostable enough for global transportation without cold storage.
Team DISCO
Oh wow! Thanks Neil for your input. That gives us a lot of confidence to say that our insulins should be able to be distributed without cold chain transportation!
Jeri
Also, just be careful with how much you adapt the insulin you design. Endocrinologists are hesitant to put their patients on biosimilars because they can never be taken off that specific biosimilar. Generally, if a person is taken off one insulin biosimilar and put on a different analogue, they will suffer from an allergic reaction to the new insulin!
Team DISCO
Well we’d better make sure that our insulin is classified as an analogue, not a biosimilar. Unfortunately, Human Insulin will be classified as a biosimilar, but we have designed it to be exactly the same as the human form. Since there aren’t any ‘other’ bits on Human insulin like His-tags or TEV digestion sites, we hypothesise that there will be no adverse reactions or allergies brought on by Human Insulin.
Len
Would you like some quick tips on how to figure out if the insulin you’ve designed is ‘new to market,’ or whether you’re unintentionally infringing an active patent?
Team DISCO
Yes please! We have designed a single chain insulin with a 12 amino acid length linker between the A and B chains, and have made no changes to the human insulin A chain. We have added a glycine to the B chain, as this immensely increases stability.
Len
After checking whether or not your patient is currently active and, if so, where it is active, the main thing you need to read is the claims. If your product fits 100% of the key criteria outlined in a single claim, then you are infringing the patent and could be open to a law suit. However, if your product differs from that claim at all, then you are outside the scope of that claim and are not infringing on it.
Team DISCO
Which patents should we be looking at to figure out whether we are infringing or not?
Len
If I were you, I’d consider all the insulins on the market, particularly focusing on single chain Insulins. We already know that human insulin itself is off patent, but you may want to check that subsequent patents on insulin production methodology weren’t filed and are still active today. Checking method patents in general, especially for your Bacillus expression system, would be important too. Inventive steps in methods are generally patented.
Team DISCO
We definitely need to design our insulin after we check all of the relevant patents for single chain insulins. Expression systems and methodology should then follow. How long would it take, and about how much would it cost for your firm to investigate this for us?
Len
Investigating whether or not a product is “new” would generally take a full year, and cost about AU$100,000.
Team DISCO
Ah, that’s a lot of money and time!
Edwina
Also, if I had to choose between short or long acting, I would probably go for a short acting insulin for someone living in a developing country. Long acting insulins wouldn’t stabilise blood sugar levels in people who only eat sparse meals.
Team DISCO
Wow, that’s so helpful! Since you can’t have the same insulin being short AND long acting, its good to aim to create an insulin that’s one or the other. Ruby will be able to do some cool modelling to predict whether our Winsulin will be short-acting or long-acting!!
Ultimately, we have two insulin products. Our first insulin, Human Insulin, will be exactly the same as the one we produce in our human beta cells. Our other insulin, our newly designed insulin Winsulin, will have the same A and B chains as Human Insulin, but contains a smaller, 12 amino acid length C peptide linker.

From our predictive modelling, we predict the Winsulin will be a short acting insulin, as advised. We also believe that our Winsulin will not fall into the ‘biosimilar’ category, as it is not simply an adaptation on a current market therapy, but an entirely new design altogether.

Applied Design

To: Applied Design
We’ve done a little research into how we could approach the issues of insulin accessibility and affordability, but we aren’t quite sure how we should be approaching them.
Dr David Beran
In my opinion, coaxing generic manufacturers to produce your insulin will be a hard feat considering the impassable barriers to entry, including a Good Manufacturing Practice certification for insulin production.
Team DISCO
We can do that! iGEM is an international competition where teams across the world create and deposit genetic sequences into an open source registry, so that the global community can follow on from a single team’s work.
Dr David Beran
Good Manufacturing Practice, or GMPs for short, are licenses required by a manufacturing plant to produce a therapeutic drug to be sold commercially. This makes sure that the processes used by a plant are meeting quality standards and product specifications. These generally cost around US$100M for a manufacturing plant to receive. This barrier is restricting a considerable amount of small businesses from entering the biosimilar insulin market.
Team DISCO
Wow! That’s a high market-entry expense that we really need to consider! We must consider how we would raise those kind of funds, if we were to eventually build a manufacturing plant in the future!
Len
– But hold on, you guys have something that could be considered a ‘new to market’ drug, which means you could patent this yourselves and raise money through investors who are comfortable that your company will function to produce profits, rather than a single insulin.
George
We just raised $16, 656 through some crowd funding though, which is 227% of what we needed to kick start our lab work. If anything, this shows that when moneys needed to be raised, we can raise what we need and more!
Team DISCO
And I guess we wouldn’t really need to ‘build’ a large manufacturing plant. We’d be providing the methods and cells ready to go, so really all a manufacturing plant would need would be the GMP.
Dr David Beran
Yeah, you guys really are the proof of concept the industry needs to start seriously looking into insulin production.
Team DISCO
Our YNCM tagged insulins in Bacillus should also provide a much simpler purification process that could be turned into a continuous system with the right optimisations. We should make sure that we spend a little more time making sure that we can compare methodologies between protein extraction when we get up to this stage.
Team DISCO
But wait, hold on. Why are we even pursing to produce an open source insulin, when there might be other alternatives to enter into the market that aren’t the more traditional routes? Could we potentially make an open insulin pump?
Dr David Beran
you could, but because of the way that the current pumps are made for a specific insulin analogue, you’d have a hard time selling it without your own insulin. It also wouldn’t really aid the issue of inaccessibility that are currently felt in many places in the world.
Edwina
Hi everyone! As a diabetic myself, I am quite accustomed to injecting myself with insulin, so I wouldn’t worry too much about not having a pump, especially in dire circumstances.
Team DISCO
Len, you’ve said before it would take about a full year and approx. AU$AU100 000 to fully prepare our Winsulin for patenting.
Len
Yes. It’s a rough estimate and highly dependent on the product, but generally that’s our rule of thumb.
Team DISCO
We are already starting to see just how costly these kinds of endeavours are, without even including the biosimilar trial and clinical trials required for both of our insulins. Surely there are some other alternatives? Could we not just start producing insulin in bathtubs all around the world?
Nick
Guys, that’s a great idea, but we have GMPs for a reason. Safety is more paramount than simply meeting demand. Regulating something like that would be way more of a nightmare than it’s worth.
Team DISCO
Yeah, we guess you’re right. Recombinant methods of production of an open source insulin seems like our best option moving forward. Market hurdles included! We should probably investigate how an open-source business would function though with a few more experts.

Entrepreneurship

To: Entrepeneurship
We’re at the point where we’re pretty sure we have a couple of awesome products, but we need to make sure that our project will be effective in the future and doesn’t simply mimic another business or open-source project out there that wasn’t successful!
Mike
In order to make a global impact, you really need to build a business around your products, patents and all. Raising funds will be a lot easier when you start a start-up in conjunction with us, as many businesses with much less appeal have made millions of dollars after just a few years here.
Team DISCO
Wow that’s amazing! It would definitely be easier to raise the funds as a company. Much of the price of insulin comes from manufacturers and patent holders adding huge mark ups on the product that the governments and consumers then must face. If we were to design a business, obviously we wouldn’t impose those kinds of mark ups.
Narcyz
Hey guys, slow down a little. In my research, I’ve found that on average, 85% of clinical trial costs are from government investment, rather than from profits made from the business. Though it’s never been done before, there could be great opportunities for an open source research group to use government grants and funding to support a clinical trial process.
Team DISCO
We hadn’t considered that. I guess that we need to think about all the potential options for funding that doesn’t necessarily involve us making it directly to fund the project.
Mike
You should also start thinking about how the initial manufacturing plant begins. If I were you, I’d find a country that has a high demand for insulin and is currently very undersupplied. Build your plant there, following the regulatory guidelines required for that country. Once your Human Insulin production starts making a profit, you can begin phasing in your Winsulin. Get Winsulin off the ground with your human insulin production.
Neil
This might be a nice way to start. We currently have a large amount of processes that we have to go through in order to transport insulin from one country to another. Custom imports are different between countries, some of which are time and resource intensive to manoeuvre through. Localising your operation in one location may be a better way of organising this before expanding.
Mike
Would you have anywhere specifically in mind?
Neil
We have had a huge demand for insulin in Tanzania. Their diabetic population is quite large and is expected to grow significantly as better diagnostic tools are implemented, as estimated 2/3rds of their diabetic population are currently undiagnosed in Africa alone.
Mike
So, maybe Tanzania or somewhere similar would work? You should strongly consider forming a start-up, and withhold Winsulin from the open source sphere to pursue this. Global impacts require profit margins and intellectual protection.
Team DISCO
These are all such great insights. We really need to consider our options.
Upon later reflection and planning, we’ve decided that the open source option is the most applicable moving forward.

Our international connections and global traction make us confident that our work will be continued in various laboratories across the world.

With this global force, we hope that the grass-roots approach will ultimately work to provide all corners of the globe the insulin they all need to survive.