REGARDING THE SYBIOL PATENT
The patent includes mention of every type of cell that has ever been considered for use in an "extracorporeal" liver assist device. My guess is that this is to stop anyone from claiming they're not violating the patent by stealing the design and plugging in porcine or other mammalian cells.
And an interesting add-on to the above is specifically mentioning genetically altered porcine cells to be used in the machine to be compatible with a liver genetically designed to be transplanted in place of a "real" human liver. I don't know how that field is going, but should any of the people receiving a human liver substitute from a pig need a liver assist, Sybiol is there for them.
There is mention of the "preferred embodiment" of the device--meaning they had to include descriptions of earlier machines and methods so no one can take one of the early versions and say it's new and their's, etc. But what they get around to claiming is that in the revised and improved model under discussion, they are using liver cells that are unattached to any substrate: freely floating in the sustaining medium. This is in contrast to prevailing wisdom, and is important because it eliminates steps in the handling of the cells after harvest (time/money consuming work) and also serves to protect the cells from injury when being handled in making them cohere to the substrate--AND means that there is more total surface area of the hepatocytes available to interact with toxins, metabolites, etc.--the actual function of the device. However, they have developed a method of introducing the hepatocytes to the mixing chamber that promotes the joining together of hepatocytes into "aggregated hepatocytes" working as a team to remain funcional longer than isolated hepatocytes.
Addressing the area of (probably, in my understanding) the greatest potential drawback to the therapeutic value of any such device, they say they have a means of letting through larger molecules like proteins, some of which are valuable and need returning to the treated blood before it is transfered back to the patient's blood stream--which allows them to apply the machine to extracting antibodies in the blood plasma (red blood cells are not exposed to the functions of the machine). These are antibodies which may be in the blood already (remember the transplants of whole organs--they have a tendency to provoke massive rejection if the immune system is not notched down) as well as antibodies formed through the contact (mediated by membranes) with the hepatocytes of the device. It sounds as if they have surmounted the device-killer: the immune system's sensitivity to exposure to any non-body cells. Antibodies are isolated from plasma or from the sustaining medium and not allowed to enter the processed plasma.
There is a lot of stuff about flow and contra-flow, maintaining temperature within an insulated chamber, oxigenating the sustaining media to promote forming those aggregated hepatocytes, all the variables involved with the sequences of different sized tubes with different sized holes, how to add on the commonly used filters of renal dialysis and red blood cell extraction, and how to maximize contact of hepatocyte and toxin within the 6 hours it takes to do one filtration run of blood--so that the device is a veritable swiss army knife of basic functions and sometimes necessary add ons.
In short, if it works as they imply they know it does, it's a winner, and nobody else is in the same ballpark to compete.
Upon re-reading the patent, I was struck by the obvious: They have to include the use of porcine cells in the description because they are going to have to run animal studies at some point in the gauntlet of Phases in a FDA approved study, so the patent has to say the device uses pig cells even if the "preferred embodiment" of the device will use MUCL's hepatocytes.
One of the innovative thoughts is applied to a "less preferred" iteration of the machine. To achieve good circulation of hepatocytes that ARE linked to a substrate, not "aggregated" in suspension, there is a method where beads with a magnetic center are made to move about by generation of an magnetic field in the sustaining medium. The main concerns are to get adequate closeness of hepatocyte and toxin through circulation, and the problem can be banging the cells into the chamber walls if circulation is done with a centrofuge or given too large a push by a mechanical circulator. A lot of balancing has to be achieved to get the filtration of toxins without over exposure of blood to the extracorporeal hepatocyte.
Count me as one who doesn't think Mr. Newmin is spending a lot of time scratching his head to figure out what to do next. He's had a long time to ponder this.
AI
