Technology

GATT NHS-POx: the Science

GATT NHS-POxThe GATT platform technology is based on a synthetic polymer having excellent hemostatic and/or sealant characteristics, obtained by reacting an electrophilic activated polyoxazoline (NHS-POx) with a nucleophilic cross-linking agent.  The cross-linked polymer has tissue-adhesive properties due to the fact that it contains NHS groups. These NHS groups are already used in the PEG tissue adhesive technology approved in NHS-PEG sealant products.

The NHS groups, bound to- and stabilized by POx, are capable of forming covalent bonds with nucleophile-containing components naturally present on tissue and in blood. NHS-PEG contains reactive groups capable of cross-linking and/or protein binding on the end-chains of its polymer, NHS-POx also contains these groups on its side-chains. This, in combination with the more versatile synthesis of the polymer, makes NHS-POx a potentially stronger adhesive that can be tuned within a more varied range to fit technical functionalities of different product formulations. The adhesiveness of the cross-linked polymer can be manipulated effectively by controlling the level and nature of alkyl side chain and/or end-group functionalization and the polymer chain length. The NHS-POx cohesiveness is determined largely by the number/density of cross-links within the polymer. The number of cross-links in the polymer can be varied within wide ranges by incorporating different amounts of activated groups in the alkyl side chains of the POx. Controlling the adhesiveness and cohesiveness is of major importance to be able to create product formulations with optimal effectiveness.

GATT has developed a fully synthetic polyoxazoline (POx) polymer that stabilizes pendant NHS groups. This is unique.

 

GATT NHS-POx: ease of use and tailor-made versatile efficacy

Enabled and driven by synthetic NHS-technology, the market of high demanding hemostats and sealants is shifting to faster hemostatic, stronger adhesive and significantly more cost-effective, medical devices. These will replace current expensive fibrin based medicine products and will enable/drive a much broader use.

Additionally, to the advantages of NHS-PEG used in existing and new hemostatic and sealant medical devices, NHS-POx has a multitude of technological advantages:

  • stronger and faster hemostasis and adhesion properties:
    POx side chain activated NHS-ester contains 4 times the number of NHS groups compared to 4-arm NHS-PEG based products, resulting in faster and stronger tissue adhesion and cross-linking to (anti-coagulated)blood, body fluids, water.
  • versatile properties better tuneable for specific clinical applications:
    The GATT technology enables exact fine-tuning of the number of tissue adhering groups and fine-tuning of the biodegradation rate. Both features open a vast new set of clinical applications as for some procedures, it might be obligatory that a GATT product does not decompose in the body – while for other applications, it should have a fast biodegradability and very strong tissue adhering properties.
  • non-brittle: POx side chain activated NHS-ester is very stable unlike many other side chain activated NHS ester (bio-) polymers.
  • it allows for the incorporation of functional additives, such as, for instance, antimicrobial agents, coagulation factors and growth factors.
  • products are able to stick on product, by adding POx-amine to the formulation (GATT-Tape’s unique feature)

These general functional characteristics enable specific advantages for the intended specific GATT hemostatic and sealant products

 

GATT NHS-POx: safety

Instead of the NHS-PEG technology, GATT’s platform technology is based on NHS-POx-technology.  NHS-PEG technology originated in the pharmaceutical industry for PEGylation (drug delivery). The same goes for NHS-POx technology (POZylation). The GATT NHS-POx platform uses polyoxazoline derivatives that closely resemble those proven to be safe in pharmaceutical applications, and uses identical NHS tissue adhering groups, as the ones used in other already approved NHS-PEG-sealant products.

 

GATT NHS-POx: scalable cost effective production

GATT NHS-POx technology also allows for very cost-effective and robust, scalable production due to the low cost synthetic components. GATT has established proof of very cost-effective, scalable production for the GATT-Patch and the GATT-Tape.

 

GATT NHS-POx: strong IP portfolio covering the full product spectrum

GATT has used all hemostat and sealing product principles known from the NHS-PEG IP as a “mirror”, to set claims as wide as possible for its NHS-POx IP.

The GATT technology and patent portfolio is geared at a complete as possible versatile platform, tunable per important parameter, superior or equal at all important parameters compared to existing NHS-PEG sealant based products.

GATT Technology is the sole owner of GATT’s intellectual property rights.

An extensive external search confirmed that there is very little prior art addressing the innovative POx-based polymers that form the building blocks of GATT

 

The GATT patents

WO 2012/057628

Cross-linked polymers and implants derived from electrophilically activated polyoxazoline

WO 2013/137736

Cross-linked polymers and medical products derived from nucleophilically activated polyoxazoline

WO 2016/056901

tissue-adhesive porous hemostatic product

 

GATT has an exclusive license agreement with Ghent University regarding patent:

WO 2013/103297
Polyoxazoline polymers and methods for their preparation, conjugates of these polymers and medical uses thereof