Scientific Origins
Oligasis' technology has its origins in:
- Fundamental work studying water structuring, notably the
unusual properties of very tightly bound water by zwitterionic
molecules which maintain a balanced positive and negative charge
(i.e. net neutral)
- Applied work commercializing zwitterion-containing polymers
as biocompatibility coatings for devices (Medtronic's Endeavor
drug-eluting coronary stent, CooperVision's Proclear soft
contact lenses, Sorin's PrimoO2X oxygenators and perfusion
tubing systems)
- Lessons learned from attachment of first-generation
hydrophilic polymers to pharmaceuticals (including PEGylation)
Zwitterion-containing polymers, particularly those constructed of
certain naturally occurring zwitterions (such as phosphorylcholine),
bind water molecules so tightly that the water is no longer
available for exchange with bulk water. When applied to
medical devices, this unique property has translated into multiple
benefits:
- No protein adsorption (Proclear/Endeavor)
- No dehydration under arid conditions (Proclear)
- Lowest late-stage thrombosis rate 3+ years out (Endeavor)
From Medical Devices to Pharmaceuticals
In moving from medical devices to pharmaceuticals, traditional
polymer manufacturing approaches such as conventional free radical
polymerization are not suitable. They do not provide control
of molecular weight. They do not contain functional groups
(for specific attachment to pharmaceuticals), and generally employ
weak hydrophobic or ionic attachment to surfaces as opposed to
specific covalent attachment.
Optimal polymers for pharmaceutical use require the following
attributes:
- The presence of well-defined and reproducible
α-functional groups to facilitate covalent
attachment to pharmaceuticals
- Multi-arm architectures (through controlled branching)
- Stoichiometric random and block copolymerization
(multi-functional and multi-format)
- Tight control of molecular weight, polydispersity,
α-functional group, and
reproducibility
Intersecting Disciplines: Putting the Pieces in Place
In order to provide biopolymers for attachment to
pharmaceuticals, Oligasis has brought together the following key
disciplines:
- Extreme biocompatibility monomers
- Controlled "living" free radical polymerization
- Protein friendly aqueous conjugation chemistries
- Regulatory acceptance of polydisperse pharmaceuticals
- Copolymerization: multi-function and multi-format
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