A cure for the pharma R&D blues

Pharmaceutical companies are laboring under an overall decline in R&D productivity. It is a headache that has plagued the industry for the past three decades and shows no signs of letting up. And with the growing pressure from the public need for (and demand for) improved healthcare and quality of life, the widening gap between R&D results and market demand is well on its way to becoming a migraine.

Most of the difficulties in pharmaceutical R&D (and the lion’s share of a company’s allocated R&D resources) are focused on the pre-clinical stages: finding a novel compound for development, developing a stable formulation and then testing it in vitro and in vivo. Despite the heroic investments by scores of competent R&D teams, statistics show that only a fraction of these new compounds ever reach the stage of clinical trials, and those that succeed in getting that far have no guarantee of delivering the promised potential, unless they can maintain stability under the full range of clinical testing.

The natural chemicals used in the pharmaceutical industry are perfectly structured and suited for the environment in which they are meant to exist and interact. What if technology were able to deliberately replicate the ideal circumstances for novel compounds and create a ‘natural’ stability for them, rather than hoping for a stroke of good luck?

Reinventing water
The ability of water to dissolve more substances than any other liquid gave it the moniker ‘the Universal Solvent’. However, the 20th and 21st centuries have seen the creation and application of an increasing variety of hydrophobic compounds, and their love-hate relationship with water has been the culprit behind many frustrating R&D obstacles.

Do-Coop Technologies Ltd, a private company that has researched the best way to break through this ‘water barrier’ at a molecular level, has developed a cGMP-compliant production method for a new water-based nanotechnology, appropriately dubbed Neowater.

Neowater is distinguished from natural water by a clear shift in physical properties and a proprietary structure that is remarkably stable. Its unique molecular organization, derived from its interaction between water, large surface area exhibited by minute amounts of nano-particle’s and carbon dioxide, results in better solubility of hydrophobic drugs, higher stability of proteins and cell cultures, enhanced biological in vitro and in vivo reactions and a reduced need for the introduction of stabilizers and detergents.

New properties
The Neowater nanotechnology breakthrough harnesses the surface effect produced by a minute amount of particles (10 to the 15th power particles per liter) and an elevated amount of insoluble carbon dioxide to compete on the free bulk water, reducing the entropy of the bulk. The payoff is a new colloidal structure within the water, which has been proven by Zeta potential measurements, unique near infrared signature, ultrasound propagations and ITC.

Neowater was demonstrated to be nontoxic in a toxicology test performed recently and a Type IV Drug Master File has been submitted to the FDA. These factors provide an immediate advantage in streamlining any R&D project that initiates clinical studies for compounds formulated with Neowater: there is no need for a separate Neowater toxicity control group.

A new stream of scientific discoveries
From the moment of its invention, Neowater attracted intense interest from the scientific community, which investigated it for its revolutionary properties. The findings in turn have provided new insights into modern physics, water science and biological processes.

In 2007, the laboratory team of Prof. Eshel Ben-Jacob (Tel Aviv University, Israel) published an article dealing with the effect of radio-frequency (RF) irradiation on the physio-chemical properties of RF-treated natural water compared with Neowater.

Previous studies showed that RF irradiation generates nano-bubble formation in water and aqueous solutions, which may lead to ordered shells and a structure of water molecules around them for a transient period. The researchers demonstrated that, unlike regular water pretreated with RF irradiation, Neowater sustains the effects and properties shown by the radiation for several years after production.

Scanning electron microscopy of electrochemical deposition (ECD) samples showed a difference in the structure formation of dendrite branching morphology (DBM) between regular water (which lacks ordered branch formation) and Neowater (exhibiting orderly DBM formation), a finding that further strengthens the hypothesis of a radically new ordered water-molecule structure. Further electron microscopy research is being done at the Alexander King Laboratory (Purdue University, USA) in order to further evaluate Neowater’s nanoparticle structure and its formation at the atomic level.

Recently, another research group headed by Dr. Leslie Lobell (Ben Gurion University in the Negev, Israel) published an article describing the effect of Neowater on Hybridoma formation and secretion, and on the proliferation of immortal and fibroblast cells. The group reported that the Neowater-based media elevated the clone-ability of the basic clones, Hybridoma yield and its secretion capabilities. One of the most interesting findings is that Neowater-based media enhanced the proliferation of the CHO cell line, while it slowed the growth rate of the human primary fibroblasts without reducing their total population doublings. This finding indicates an elevation in cells sensitivity to the secreted factor when grown in Neowater, as well as the power to enhance the stabilization, activity and proliferation of cells which in turn leads to higher antibody secretion.

The fact that Neowater promises to enhance and improve established processes in the pharmaceutical industry is supported by Dr. Furtune Cohen (Weizmann Institute of Science, Israel), who in a recent publication in The American Chemical Society cited the ability of Neowater to solvate her highly hydrophobic compounds. The secret is in the highly concentrated carbon dioxide content (up to 100 times more than natural water), conferring on it hydrophobic characteristics that serve to solvate hydrophobic compounds like novel and generic APIs, while also imparting to the compounds a greater stability and higher bioavailability. Neowater also eliminates the need for complicated logistics solutions in long-distance distribution of thermal-sensitive biomaterials.

Then there is the recent (yet to be published) work on protein and enzyme stabilization, which hints at the ability of Neowater to stabilize and maintain enzyme activity even at room temperatures, opening the way for long-term consistency and better bioavailability.

With an improved balance between toxicity and efficacy, new horizons come into view for more cost-effective and efficient drug development using Neowater, as well as an extended shelf life, IP extension, superior drug delivery and solubility. Other pharmaceutical applications that harness the new capacity for Hybridoma formation and antibody production/secretion (mentioned above) can also benefit from the nanostructure and molecular order of Neowater.

A new wave of R&D breakthroughs?
The availability of Neowater for use in R&D processes has far-reaching implications for pure science (the study of water) and for applied research. Many novel therapeutic substances could improve our quality of life, if it were not for the drawbacks of regular water being only partially successful in passing itself off as intracellular water. To conquer the natural and basic barrier of water molecules would mean to unlock the potential of a great number of ‘great ideas’ that have failed to cross the R&D watershed from promising theory to practical solution. Neowater gives the pharma and healthcare industries a uniquely stable water-based environment that is more similar than ever to the water that supports life itself.

About Dr. Ohad Karnieli
- Director of R&D at Docoop technologies since 2004
- Founder and VP of R&D of the Molecular and Biotechnology division at “Karnieli Ltd, Medicine and Biotechnology”, a leading Israeli human endocrinology clinic and molecular diagnosis and innovation company
- Former junior faculty of the Tel Aviv university school of medicine, department of molecular medicine and human genetics