GlycoBAR will be attending the tenth Plasma Product Biotechnology Meeting that will be held in Malta from May 15th, 2017 to May 18th, 2017, with a poster presentation called “Removal of Isoagglutinins at Large Scale using an Innovative & Patented Oligosaccharides Production Process”
The poster can be downloaded from this link:
GlycoBAR has received a special award from the European Commission called “Seal of excellence”. This award is recognizing the high potential of GlycoBAR technology in its targeted market.
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.
The other GlycoBAR flagship product is the BAR molecule (BAR stands for Blood-group Antibody Remover). This is tetraose blood group antigen sugars immobilized on a cellulosic support. It exists under two versions: BAR-A and BAR-B; the BAR molecule is represented here below in it’s A version:
This product has been designed to be disposable (once the blood group antibodies are captured and fixed on the BAR molecule, the product of interest is filtered and the used BAR product is thrown away. This approach is made possible by the low cost approaches that have been chosen in the product design and the high scale production of the sugars themselves. Note however that BAR can be recycled thanks to 1M NaOH washing solution.
Those are the core products proposed by GlycoBAR. The standard form is with an amine termination and a linker arm giving to the molecule approximately the same length as the hexa-saccharide blood group antigen sugars corresponding to the natural antigens attached to erythrocytes .
Our two core products are represented here below and are available in any quantity at a price that is a small fraction of the competition price for a tri-saccharide. Please contact us for more information.
- Blood group A antigen tetra-saccharide with linker arm and NH2 termination:
- Blood group B antigen tetra-saccharide with linker arm and NH2 termination:
GlycoBAR is also able to propose a lot of other blood group antigen sugars:
- Blood group A tri-saccharide antigen
- Blood group B tri-saccharide antigen
- Blood group A hexa-saccharide antigen (following molecule is the bare sugar version; amine termination is also available)
- Blood group B hexa-saccharide antigen (following molecule is the bare sugar version; amine termination is also available)
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.
- 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.
GlycoBAR can also customize its products for specific applications involving blood group antibodies removal such as designing a specific filters, tubing, columns or cartridges.
We also have a diagnostic project going on and will shortly be able to propose a new, innovative and inexpensive solution able to identify blood group type and to titer the concentration of blood group antibody at the same time
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.
The most important and key competitive advantage that GlycoBAR is owning is our ability to produce blood group antigens by biofermentation, whereas competition is producing corresponding carbohydrates by chemical synthesis, which is an expensive process, very difficult to scale-up.
CERMAV, a CNRS organization located in Grenoble/France has patented this principle for creating complex sugar and has developed a very strong know-how to GlycoBAR, which is now capable of producing high quantity of these sugars using CERMAV technology.
The blood group antigen carbohydrate which is the closest to the one present on the red blood cell is the hexa-saccharide, which is almost impossible to produce by chemical synthesis. GlycoBAR has been able to produce this complex sugar using CERMAV bacteria strain and has done a lot of experiment with it. In summary, we have been able to determine that the same efficacy can be obtained with tetra-saccharides with an appropriate linker arm giving to the resulting molecule approximately the same length that hexa-saccharides.
GlycoBAR has developed an optimized process to give to the tetra-saccharide the ad-hoc length. Instead of doing chemistry on the tetra-saccharide, at the risk of losing some proportion of a very valuable product, chemistry is done on the lactose bacteria acceptor, a very inexpensive product, in order to add to it the ad-hoc linker arm. The result is a very cost effective product, easy to produce with an easy scalable process.
Thanks to the NH2 termination of our sugars (other options are possible), grafting process on almost any support is standard and easy to perform with classical equipment.
|Low scale process||high scale process
GlycoBAR mission is to help the pharma industry to eliminate hemolytic antibodies from plasma and plasma derivative products. Initially we are targeting specifically blood group anti A and anti B antibodies purification from blood, plasma and plasma fractionation products.
GlycoBAR is located in one of the most important Glyco-science Research Clusters worldwide, called Glyco-Alps, comprising seventeen research labs and hundreds of carbohydrates researchers. We are especially close to CERMAV, a CNRS organization which created the technology that GlycoBAR uses.