Do-Coop Technologies - A revolutionary cure for protein instability

An ordered aqueous solution that mimics in-vivo conditions may prove to be the cure for the instability and reduced bioactivity that afflicts many protein-based therapeutic formulations.

The development of protein-based pharmaceuticals is plagued by the "bio-monsters" of instability and reduced activity. Too many compounds cannot retain the protein's therapeutic properties long enough to benefit patients. We all know why. the protein's structural stability is undermined during the stringent purification required for vaccine and protein production, while thermostability issues make the compound vulnerable to damage from normal shipping temperatures.

The protein's biological clock begins ticking as soon as it debuts in the lab. The process of developing the therapeutic compound, sending it through the market distribution chain and preparing it for clearance in the patient is a race against time and nature. The industry's response has been to "stop the clock" by adding salts, sugars and other chemicals to the protein buffer solution, and by stabilising the protein through refrigeration/freezing. But these solutions have led to other problems: degradation with reduced activity, undesirable side-effects from additives, painful injections due to a viscous solution, and the risk of tissue necrosis. And despite the costly stabilising efforts, the short-lived efficacy of suspensions has necessitated recalls of vaccine batches that fell below required potency levels.


The ideal answer would be to provide proteins with the environment that they need: an aqueous solution that mimics in-vivo conditions.

Do-Coop Technologies has investigated the unique properties of water together with the physical principles of in-vivo conditions. The result is a patented water-based nanotechnology branded as Neowater.

The unique molecular organisation of Neowater is derived from the interaction of the water, carbon dioxide and a minute amount of suspended insoluble nanoparticles arranged in clusters. Neowater harnesses the resulting surface effect to create structure within the water that is a superior environment for biological reactions.

Various studies have demonstrated that Neowater confers increased stability on proteins at elevated temperatures, as well as at 4°C. é-Galactosidase (é-gal), alkaline phosphatase (AP), restriction enzymes and Taq polymerase are just some of the proteins that showed greater stability at elevated temperatures in Neowater.

A Neowater environment not only induces thermostability in proteins, but the ordered aqueous environment also maintains and enhances protein bioactivity in pharmaceutical formulations. Moreover, the reduced need for additives lowers the viscosity of a Neowater-based formulation, improving vaccination procedures.

Study results

One evaluation study, conducted by Do-Coop Technologies and a leading European pharmaceutical company, examined the in-vitro binding activity of a commercial antibody when solvated with Neowater. The results demonstrated better binding affinity to an antigen, under various storage conditions and at elevated temperatures. Not only that, but exposure of the therapeutical agent to body temperature (37°C) showed a threefold increase in antigen binding capability, a result that strongly suggests that Neowater contributes to antibody activity under in-vivo conditions.

The revolutionary nature of Neowater in mirroring intracellular water allows companies to accelerate and improve biological reactions with minimal customisation, and enables in-vivo responses closer to those of living organisms. Companies can move from in-vitro development to in-vivo delivery, and from early laboratory experiments to late-stage studies in humans, more smoothly and cost-effectively, with more confidence of success. The achievement of all these benefits simply by switching to a Neowater solution is reality. It's just good science, good sense, and good news for an industry plagued by faltering R&D pipelines. And, who knows? Perhaps the next protein rescued by Do-Coop's nanotechnology will be the blockbuster drug of the decade.

Revolutionary water-based nanotechnology

Do-Coop's Neowater solution for hydrating poorly performing drug compounds opens and widens the therapeutic window, allowing the entry of poorly soluble compounds into the intellectual properties portfolio, solving one of the major challenges the pharma industry faces. The company's Eran Gabbai and Regina Nadborny explore the product's benefits.

The pharma industry is facing a major challenge during the discovery and development stages. Hundreds, if not thousands, of compounds with proven activity have been stranded in development because of formulation problems. Billions of dollars have already been spent, with no possible ROI. The problem is how to formulate a hydrophobic API with as few additives and as minimal toxicity as possible without hindering biological activity.

The solubility challenge

New APIs frequently get stuck within the drug development cycle because 40-50% of all drug compounds are hydrophobic. This becomes even more critical given that there are few new APIs, forcing scientists to find different techniques to overcome the formulation barriers that not only pose health risks, but also affect profitability.

Cell-based living organisms consist of at least 70% water, a hydrophilic environment, while site receptors are composed of lipids and are hydrophobic. This equilibrium between hydrophobic and hydrophilic regions is what creates the challenge of effective drug delivery and release. Understanding water Do-Coop Technologies Ltd, a private IP company based in Israel, has developed a solution for hydrating poorly performing drug compounds.

Neowater, a proprietary water-based nanotechnology, offers the potential to release these compounds back into the drug development chain. It is a natural, safe, costeffective delivery agent that can be deployed throughout the development cycle - from initial compound formulation to human ingestion. Neowater offers increased bioavailability and stability and an enhanced ability to deliver hydrophobic and hydrophilic compounds. Neowater is distinguished from ordinary water by a shift in the physical and chemical properties, with a structure that is remarkably stable under extreme and standard conditions. The unique organisation of the water molecules in Neowater is derived from interaction among the water, carbon dioxide and a suspended minute amount of nanoparticles arranged in clusters. This combination provides a much greater surface area and more closely resembles naturally occurring water in biological organisms. These characteristics assist in overcoming the barriers of reintroducing hydrophobic compounds into living systems.

From toxicity to safety

Today's toxic delivery agents affect bioavailability, metabolism of the drugs themselves, and uptake and excretion. Neowater provides a natural, non-toxic solution that can be widely deployed with minimal customisation. Formulating compounds with Neowater maintains or enhances the efficacy of compounds without the risks of toxicity - moving drugs more rapidly through the development cycle. Do-Coop has successfully formulated numerous compounds with Neowater, dramatically reducing the levels of toxic agents while maintaining or enhancing compound efficacy.

Reformulation with Neowater

Cyclosporine A is an effective immunosuppressive, antiinflammatory and antiparasitic agent widely used for dry-eye syndrome. It was successfully formulated with Neowater, replacing large concentrations of Cremophor EL, maintaining efficacy and lowering toxicity while increasing the production of natural tears. This formulation is eligible for new IP. Do-Coop is in the early stages of examining the commercialisation of the formulation with a third party.

A licensing agreement signed between Champion Biotechnology Inc and Do-Coop deals with SG410, a novel benzoyl-phenylureasulfur analogue, which was found to be efficient as an anti-pancreatic cancer drug candidate via its use as a cancer cell proliferation inhibitor. However, it could only be deployed in a highly toxic solvent, unfit for clinical trials. Formulating SG410 with Neowater maintains its in vitro efficacy and mechanism of action with sharply reduced toxicity for in vivo use.With Neowater, pharma companies can regain their investments in existing compounds, reduce time to market, enhance delivery and maintain or increase exclusive market penetration.

Company profile

Do-Coop Technologies Ltd, founded in 1997, is a private intellectual property company based in Israel, specialising in the manufacture and commercialisation of its novel and proprietary water-based nanotechnology.

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