Chemical Liposuction Protein Product

I. Background

As peoples’ living standards improve, obesity becomes a very serious problem. Additionally, obesity causes lethal diseases, including cardiovascular diseases, paralysis (really?), and diabetes. Obese people attempt to lose weight with any method available, such as dieting, exercise, and weight-loss medication, but the results are usually unsatisfying. Thus more and more obese people choose to use liposuction to get rid of excess fat under their skin. Liposuction uses a physical method to vacuum out excess fat, but this surgery easily causes infection, bruises, and severe mechanical damage to tissue under the skin. Sometimes because the vacuum process cannot be carried out evenly, the skin is uneven after the operation. Even with so many shortcomings, liposuction is undertaken by 800,000 people in the US each year, commanding an annual market size in the billion-dollar range.

II. Oulian’s Product

We have identified, cloned and purified a mutant form of a certain type of bacterial collagenase with the desired activity to melt animal fat. Our purified protein melts subcutaneous fat tissues of fat rats in our animal testing experiments, with very few side effects. We have set up a collaboration with a well-known university in China to produce a large quantity of our protein product. Initial production and purification of our product has already been performed successfully.

Theory

Native collagenase degrades collagen that links fat cells (adipocytes) together. When collagen around the fat cells is degraded, the fat cells are detached from the support matrix and subsequently removed by natural metabolism. Native human collagenases and bacterial collagenases both can degrade collagen. So far the commercial preparation of native collagenase is from a bacteriumstrain called Clostridium histolyticum. The drawbacks for using this type of collagenase for fat-meltingare as follows: 1) It is an impure mixture, thus it is hard to control batch-to-batch consistency; 2) native collagenase degrades collagen too fast, and thus causes excessive bleeding; 3) native collagenase is not stable, and is easily degraded by numerous proteases in our body.

Using our years of experience in protein three-dimensional structuralanalysis and protein chemistry, we have designed a series of collagenase mutants (from Clostridium histolyticum), which have perceptably lower activity and better stability. Monitoring fat-melting effects in rats as a testing platform, we selected one mutant that has the desired quality.

Experimental Results

Oulian’s mutant is around one-fifth as active as the native collagenase, according to established collagenase activity assay. The potency assay of mutant collagenaseis based on the digestion of un-denatured collagen (from bovine tendon) at pH 7.2 and 37.degree. C. for 5 hours ( a protocol from Worthington Biochem).


Oulian’s mutant is more stable than native collagenase, as shown in the Trypsin (protease) digestion experiments[IM1].

[Fig. 2] Oulian’s mutant protein melts fat, yet induces very little bleeding, as shown in the left figure.

Oulian’s mutant collagenase should be safe for human use. The injection grade native collagenase from Clostridium histolyticum (Joy Pharmaceutical Co.) is approved by SDA in China for herniated disk at waist level. Our product has one residue change in the active site of a collagenase, thus it will not change the structure of the collagenase, and thus is unlikely to change its safety. In addition, our mutant has lower activity than the native form, and thus it would have less disturbance for epithelialcells[IM2].

As shown in our fat rat experiments, Joy’s product induced excessive bleeding in our fat rat experiment. This proves the point that native collagenase has too high activity and induces excessive bleeding.

III. Competitors

Biospecific Biotechnology Co.

This company is using native collagenase mixture from Clostridium histolyticum to melt fat and undergo clinical trials for lipoma patients. As we pointed out earlier, native collagenase induces excessive bleeding.

In China we have no competitors.

IV. Timeline for the product development

Lipoma is a small field, but we will use the Lipoma patients to get our product approved by the FDA/Chinese SDA in a short time and with lower cost. After this drug is approved, we can apply it to the off-label chemical liposunction field (similar to the Botox story).

Jan. 2004US patent applied.

Mar. 2004Finish large-scale production and quality control of our product in Shanghai.

Jan. 2005Finish our pre-clinical testing in China.

Jun. 2005Start human trial of lipoma patients in China.

Sep. 2005Finish phase I trial in China.

Oct. 2005IND clinical trial application in the US.

Feb. 2006Finish Phase II trial in China.

Apr. 2006Start human trial on lipoma patients in the US.

Oct. 2006Finish phase III trial in China, and start marketing (lipoma and off-label usage, chemical liposuction).

Dec. 2006Finish phase I/II trial in the US, and start strategic alliance with large pharmaceutical company in the US.

V. Market

Our product’s ease of use, effectiveness, and less side effects would be the major drive for sale.

The liposuction market is in the billion-dollar range in the US. We have raised $120,000 from angel investors to work on this project. We are in need of $0.5 million for our pre-clinical animal testing in China and $2 million to complete human testing in China. This sum is approximately 1/10th what it would cost to do similar work in the US.

[IM1]1I don’t understand the description of this diagram.

[IM2]1I don’t understand the relationship between the Joy Pharmaceutical product and Oulian’s product from this brief description.