Sorting the sperm from the chaff

Most people in the Australian life sciences community will remember Gradipore, the company that produced the Gradiflow-branded electrophoresis instruments for protein separation.

Gradipore has morphed into the plasma-focused biotech Life Therapeutics and has now produced NuSep, a bioseparations specialist that has quite a few strings to its bow.

Gradiflow is a technology that many life scientists would be familiar with. A membrane-based process for large-scale protein separations, it is able to separate target macromolecules from complex biological solutions based on their size and electrical charge.

Gradipore also manufactured and marketed a range of electrophoresis gels under various brands, but while the company had several distributors, it was unable to sell licences to its technology, which is where the real money is.

In March 2004, Gradipore changed its name to Life Therapeutics and set out on an ambitious plan to change the company's focus to the development of plasma-based therapeutics, purchasing first 10 and then another five plasma collection centres in the United States.

The company has since closed down some and opened up others and now has 14 centres in the US with another four or five on the drawing board. Life is the largest independent plasma collection company in the world, excluding of course the major players, and has recently entered an agreement with Italian fractionation specialist Kedrion.

That agreement will see Kedrion purchase 12 of the existing collection centres and two of the new ones in return for up to a 15 per cent stake in the company, worth about $115 million to Life.

Life Therapeutics will then concentrate on its profit making diagnostics business but will keep a hand in the plasma collection area by retaining control of the higher margin plasma products from two of the centres.

In the meantime, there was the Gradiflow technology and the range of electrophoresis gels, waiting for someone to pay attention to them.

Someone is now, with a new company called NuSep established to pick up this particular ball and run with it, which its CEO, John Manusu, certainly plans on doing.

Manusu is keen to iterate that NuSep is a separate company from Life Therapeutics, although NuSep has taken over part of Life's impressive facilities at Sydney's French's Forest and Manusu was an executive on Life Therapeutics' board.

The new company plans to continue to develop and market the laboratory scale Gradiflow and retains the range of electrophoresis gels. It also has plans to introduce quite a lot more to the product portfolio.

"Once Life completed those acquisitions and we had all those US centres, the whole business was in the US," Manusu says. "We then had this small gels business back here, which was going nowhere because we had no focus on it.

"So we had a look at the business and realised that there was a real history with the gels - they couldn't get the gels to polymerise and they had other manufacturing problems, problems we have since sorted. So I thought, let's take the gel business out, let's get the laboratory scale versions of Gradiflow out and we've got a business there."

Gels and plasma

Manusu has some very definite plans for the new company, including making overseas acquisitions to extend NuSep's portfolio of products. It listed on the stock exchange in May and has begun selling two lines of electrophoresis gels - one a premium product called iGels and the other a budget product called NuBlu.

"It is about a $50million market in the US and there are two major players, so if you are the new kid on the block how you going to break into it? We have some advantages in our existing product, called the iGels, in which a researcher loads a sample straight into the gel.

"It has the convenience factor. Then the NuBlu range is a cheaper version of that. We've reduced our manufacturing cost by leaving the comb in and pass this saving onto the customer.

"So in Australia the iGel will be about $15 and the NuBlu $10, which is a significant difference. Our approach is to offer both products - you can have the more expensive product with more ease of use but higher manufacturing costs, or the cheaper product which doesn't have the added extras. That's been going for about two months now and the interest is converting into sales."

Manusu has devised a very intelligent distribution network centred on the internet. The company's manufacturing base and headquarters will remain in Sydney and will cover the Asia-Pacific region.

He has also set up offices in Atlanta US to sell into the US market and just outside of Munich in Germany to cover the European market. "But we also want to add more," he says. "Customers see the gels and then ask, what else have you got. We're not really a research company anymore - we are mainly a consumables supply company in the life sciences market."

To add to the portfolio NuSep has decided to use the advantages of its relationship with Life Therapeutics and has begun manufacture of plasma products for the research market.

"This is where Gradiflow comes in," he says. "We got all of this plasma from Life Therapeutics and said let's start to fractionate some of that and sell that to the researchers. This is not for the therapeutic area - it is purely for the research market, so the volumes are small. But we have our first product out now, IgG, we have albumin coming along soon and there will be a few more beyond that."

Recently, NuSep took a strategic stake in its neighbour Minomic International (see page 52) to extend its offering of biological products. Minomic uses proteomics methods to identify biomarkers and is well down the road to commercialising a diagnostic kit for prostate cancer.

"The biological products area is where our future lies - gels are going to be a nice little consumable line and low maintenance, but using the Gradiflow is where our future lies. And we have the ability to expand by acquisition. We are well down the approach of looking at several different companies in the US and are very active in the research monoclonal antibodies area.

"Most of the companies we are looking at have between 400 and 1000 different monoclonals - that sounds like a lot but the total turnover for those sorts of companies is between one and $2 million - not a big market individually but they all sell to the same customer base. So our salespeople will have more in their kitbag."

Clinical trials

NuSep also has a further string to its bow, the laboratory based Gradiflow instruments. The company is developing two different instruments, one for proteomics called the MF10, which should be on sale early next year, and the Sperm Sorter, for IVF and related applications, which is currently undergoing clinical trials and should be available about a year after the MF10.

NuSep's chief scientific officer, Dr John Andrews, says the technology for both instruments is the same, the original membrane separation technology known as Gradiflow. The MF10 utilises internal membranes of appropriate pore size to separate proteins.

"By setting up a gradation of pore sizes and appropriate charges through the buffer we can get separation of proteins based on size and charge," Andrews says. "Within the unit, the operator will have a selection of colour-coded molecular weight cut-off membranes in the range they want to separate.

"It will run between three and eight separations and will be quite small - basically a 200 microlitre sample. This will be aimed at the proteomics market, a complementary pre-fractionation system prior to the downstream analysis of a 2D gel electrophoresis or mass spectrometry."

Then there is the wondrously named Sperm Sorter, which does exactly what its name suggests. Andrews says the main idea for this came from Professor John Aitken of the University of Newcastle, who has collaborated with NuSep through the patent process and still performs troubleshooting R&D.

"The Sperm Sorter separates a population of sperm that generally has higher quality characteristics - higher motility, higher viability. The major advantage we are getting is that there appears to be lower DNA damage [in the higher quality sperm].

"Pretty well all cells carry a negative charge, so it uses a membrane of the appropriate pore size to allow some differentiation of sperm, which are smaller than most other cells in the semen sample."

The Sperm Sorter is planned for use in standard assisted reproductive therapies but down the track the company is hoping it will be used for more difficult samples of male infertility, such as testicular biopsy, Andrews says.

A clinical trial is currently underway at the Westmead Fertility Centre at Westmead Hospital to assess the efficacy and safety of the instrument as a sperm preparation technique for IVF treatment. Other studies will look at its potential use in intracytoplasmic sperm injection (ICSI) and intra-uterine insemination (IUI).