Auteur : hsors

Depending on the blood group, human red blood cells are covered with antigens A (blood group A), or antigens B (blood group B), or a mix of antigens A and B (blood group AB) or no A nor B antigen at all (blood group O). Line 1 of the table below is showing these four different cases.

Human blood plasma from one individual contains antibodies to the antigens not present on the corresponding red cells. That is:

• Plasma of group A contains anti B antibodies
• Plasma of group B contains anti A antibodies
• Plasma of group AB doesn’t contain anti A nor anti B antibodies
• Plasma of group O contains both anti A and anti B antibodies

The idea of producing blood group A & B carbohydrate antigens able to fix anti A & anti B antibodies and use them to eliminate these antibodies from the plasma is not a new one and has already been patented a long time ago (Those patents have been in the public domain for already a very long time). However, the ability to produce in volume and in economically satisfactory conditions enough group A & B antigen sugars and graft them on the ad hoc support enabling efficient utilization in plasma or blood, did not exist until now.

Thanks to GlycoBAR patented technology, it is now possible to produce those blood group antigen sugars in volume at a price that is low enough to envision a world where only universal plasma, injectable to any patient would exist. Economy for hospital would be huge and risk of miss match with recipient blood group would be eliminated.

There are two ways of managing plasma.

The first and most commonly used one is by using individual bags of plasma coming from individual donors (one donor = one bag). When plasma is collected, it is frozen, which is the reason why the name of this type of plasma is « FFP » for Fresh Frozen Plasma. With GlycoBAR technology, it is perfectly possible to design a filter to be included in the blood collection bag system so that antibodies are captured before the plasma is frozen.

The second one is by pool. This is when plasmas coming from thousands different donors are mixed in a pool of up to thousands liters, ready for an industrial treatment in a pharmaceutical environment. In such a case, there are two possibilities of removing blood group antibodies from such a plasma pool. The first one is to use a chromatographic column where GlycoBAR antigen sugars are grafted on a chromatographic resin. The plasma goes through this column, blood group antibodies are captured in the column thanks to their affinity with the antigen ligands and after each pool the column is washed with an ad hoc solution in order to be reused for the next batch. Another option is to use our disposable BAR product, which is a cellulosic support on which the antigen sugars are immobilized. When mixed with the plasma, BAR product captures the blood group antibodies and is then filtered out and thrown away.

Issue statement :

A recipient can accept only transplanted organs compatible with his ABO blood group otherwise his ABO antibodies will kill the transplanted organ. The donor to recipient compatibility matrix is represented here below and is showing a great number of incompatibilities:

As a result of the limited donors-recipient compatibility matrix, there is currently a huge shortage of available organs for transplant. Blood group mismatch is a big issue and providing a product allowing to resolve that issue is utmost important for saving lives.

Existing Solutions

• GlycoBAR partners are able to propose extra corporal devices that filter the recipient blood so that blood group antibodies are eliminated. After treatment the recipient’s blood is becoming compatible with a wider diversity of organs. GlycoBAR is supplying its blood group antigen sugars to companies willing to propose such a filtration solution. One partner company is already proposing such a filtration device

• Alternatively, recipient’s plasma can be entirely changed (this implies full plasmapheresis, which is an expensive and cumbersome process) so that the new one is free of antibodies not compatible with the transplanted organ

GlycoBAR liquid solution

GlycoBAR can provide a fully injectable solution that can neutralize all the ABO blood group antibodies from the recipient’s plasma. The solution remains in the blood stream from several weeks so that the newly generated ABO antibodies are continuously neutralized. This is a very comfortable and significantly less costly solution, which provides full compatibility between donors and recipients.

Plasma fractionation industry producing so called IVIG products (Intra Venous Immuno globulin type G) are also facing serious challenges with the presence of anti A and anti B antibodies in their products (hemolysis accidents are more and more frequent and regulation will probably shortly impose complete removal of isoagglutinins). GlycoBAR offers several convenient and easy to use solutions to purify these IVIG from blood group antibodies.

The first one is by using a traditional chromatographic column with a resin grafted with GlycoBAR ligands. By adding a very simple and well known chromatographic purification step in their IVIG production process, IVIG suppliers can now eliminate completely isoagglutinins from their products and therefore provide a such safer solution to hospital for treating immune deficient patients. GlycoBAR has a partnership with a leading chromatographic resin supplier which is taking care of the grafting process and offer a turn-key solution to IVIG suppliers

Another option to eliminate isoagglutinins from IVIG is using a GlycoBAR ready to use and disposable solution. We can indeed propose our antigen sugars grafted on a cellulosic support that can be mixed with IVIG. A simple filtration process after a short incubation time would allow to obtain an IVIG product fully purified from blood group antibodies. GlycoBAR fermentation process needed to obtain the blood group antigens is so inexpensive that a such a simple and disposable solution is economically perfectly acceptable.

The worldwide IVIG market is planned to be around 20 tons in 2020.

Until mad cow crisis, hospitals were using a so called “AB substance” which allowed them to neutralize anti-A and anti-B antibodies from patient’s blood in many difference prescription cases.

This AB substance was extracted from bovine intestines and had been therefore forbidden after the mad cow crises because of potential prion presence in this substance that was deemed prone to trigger Creutzfeldt-Jakob encephalopathy.

It is now possible to use again such a liquid solution that GlycoBAR can provide to neutralize anti-A and anti-B antibodies thus preventing hemolysis risk in many prescription cases.