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Dec 1, 2006 (Vol. 26, No. 21)

Gauging Nanobiotech's Promise Realistically

Biotech and Pharma Firms Are Taking a Wait-and-See Approach

  • Biotech products based on nanotechnology are becoming more widespread, but not without first encountering substantial challenges. According to a report issued by the ETC Group (www.etcgroup.org/en), the major pharmaceutical companies generally have been taking a wait-and-see attitude on nanotechnology.

    According to the report, and confirmed by a number of presentations at the “2006 NanoBio Technology Conference,” held recently at MIT, Big Pharma has not invested heavily on research but has been collaborating with small biotechnology companies, entering into licensing agreements, relying on government and academic research, and biding their time as the technology develops and the regulatory climate becomes clearer.

    This sentiment is shared by Al Kolb, Ph.D., president of Key Tech Solutions (www.keytechsolutions.com). “It would not be unusual for governments to fund initial research that may be risky, with industry later picking up product development. The early days of the NASA space program could be an analogy. No company would have funded this, because of the long time frame for payback.”

    Safety is another unknown and source of uncertainty. “The jury is still out on safety,” Dr. Kolb states. “There are so many forms of nanodevices to be considered that it’s not possible to generalize regarding their potential hazards. Some nanoparticles are biological, such as dendrimers and a number of diagnostic and drug delivery methods, and have already been approved by the FDA. The biological behavior of carbon nanotubes can change dramatically depending on how they are derivatized. While I don’t believe safety concerns are a disincentive to investment, it is a factor to consider.”

  • Assessment of the Industry

    Nanotechnology has received a lot of attention in the media in recent years, causing what may be an overhype effect. Dr. Kolb has little sympathy for the obsessive need for instant results in our society. “Often the overhype comes from venture capitalists who want a large, short-term return,” he suggests. “It has to be successful immediately or it’s considered a failure. That doesn’t make the science bad. Some things take a long time to develop, some never pay off. That doesn’t mean we don’t try new things. Simple product development based solely on theory is risky and difficult. In the development of a new field of science it is going to be hard to predict what the impact will be or in what time frame.”

    Scott Livingston, managing director of The Livingston Group of Axiom Capital Management, senses a maturation of investment trends in nanotechnology. “Recent data indicate that venture investment in nanotechnology has slowly increased, while internal corporate R&D efforts at large companies have expanded as technologies move through the pipeline to actual product offerings. Governments, on the other hand, can invest in research projects that don’t necessarily have immediate benefits and are not subject to the same portfolio management demands as venture investing,” he told the MIT conference attendees.

    “I would say that large companies are carefully studying the environmental and health effects of nanotechnologies,” Livingston continues, “but there is no reliable data, so the debate is still very much open.”

    Livingston does not feel that nanotechnology has been overhyped. “Comparing nano with other recent technologies, I recall the predictions for Internet adoption and the Internet’s impact on consumer behavior, political discourse, and advertising back in the 90s, and I think that many of those prophecies have been surpassed.

    “I might even take the other side of that argument, and offer that telling people that nano is overhyped may itself be an overhyped concept. It may be that this is the greatest scientific wave of discovery in history, and it is not being hyped enough. But from our point of view as investment counselors, we advise investors to be skeptical of everything they hear and do their own due diligence.”

    Livingston points out that nanomedicine has already been introduced in drug delivery and diagnostics products, achieving milestones with the FDA and generating significant price moves in the stocks of public companies.

    “Pre-Sarbanes-Oxley [a public company accounting reform and investor protection act], you would have had more companies going to the public markets to finance their growth at an earlier stage, and milestones would be more visible because you would have stock prices moving based on this news,” he says. “Post-SarbOx it is much more difficult for companies to go public, so great progress doesn’t show up on the financial websites.”

    Yet given these numerous concerns, Livingston observes that money is flowing into some nanomedicine companies because the potential is huge. “Right now interest is continuing to focus on delivery and diagnostics, but we also see investors alert to certain diseases that respond to nanotechnology-based therapies.

    “There has been a lot of negativity directed toward nanotechnology in the press and in the public markets, some with good reason,” Livingston concludes. “I do see transformative science pushing technology forward and market and customer needs pulling for new technologies. Investment cycles will come and go, but the bridge is being built between the basic science and the customer demands. My sense is that important partnerships, discoveries, and patents are happening now, and that people interested in being on the front end of these stories will be in a position to act on their knowledge. I am more enthusiastic about the field than many others.”

  • Higher Performance Protein Binding

    Inanovate (www.inanovate.com) is developing nanostructured biochip substrates, according to David Arslanian, COO and cofounder and another presenter at the MIT meeting. “Our substrates are used by biopharmaceutical companies as high-performance surfaces. These materials permit deposition of capture agents (usually proteins) developed by our clients.”

    Classically, protein binding chips are coated with gold or other materials in order to facilitate protein binding. The Inanovate technology uses gold nanoparticles of precise dimensions in order to provide defined binding in which the molecules are all oriented in the same direction. Thus the nanoparticles are all exactly the same size and dimensions, and all are tethered to the surface in precisely the same fashion. The result is a consistent surface assuring that the percentage of protein molecules attached to the chip will be many times greater than with conventional colloidal gold particles.

    The Inanovate technology deals with a variety of problems presented by conventional attachment surfaces: (1) The surface binds the material so poorly that it is lost; (2) the target molecules attach, but are misaligned so their active areas are hidden; (3) the molecules clump together, shielding their active areas; (4) the biomolecules are oriented incorrectly, so the active area faces the surface; (5) the molecules denature and do not retain their original function.

    Accordingly, only a small percentage of the biomolecules deposited onto existing biochips can be recognized by antibodies or other capture reagents. This leads to sensitivity and consistency problems, which may overwhelm existing protein biochip systems. Thus the Inanovate technology avoids spurious results that can, in the case of drugs pushed forward in development based on inaccurate information, result in hundreds of millions of dollars lost.

    The Inanovate platform, designed to be compatible with existing standard hardware, provides companies with an application-specific, biochip available for drug development and testing procedures, according to Arslanian. The technology will be in the marketplace in the next year.

    “At the nanoscale, physical structures take on unusual properties, and we can exploit these properties using carbon nanotubes,” says Peter Antoinette, CEO and cofounder at NanoComp Technologies (NCTI; www.nanocomptech.com).

    “Electrons and photons at these dimensions are guided by quantum constraints, and the nanotube materials may behave as insulators, conductors, or transmitters,” he explained to the MIT audience.

    NanoComp is one of a number of companies investigating these structures that look like chicken-wire cylinders, but with a diameter as small as DNA. The company seeks to leverage its technology for the production of long carbon nanotubes together with the ability to fabricate them into physically strong, lightweight, electro-thermally conductive yarns and felts for use as structural materials and electro-energy devices.

    Carbon nanotubes possess extraordinary properties with a wealth of industrial applications. They are extremely strong (100 times stronger than steel), are lightweight (30% lighter than aluminum), display superb electrical conductivity, (comparable to copper), and exhibit thermal properties of heat transfer and retention superior to metals. However, a serious shortcoming of available competitive commercial manufacturing processes is that they generally produce only short carbon nanotubes, usually tens of microns long, with the result that the product is much like a powder.

    Antoinette and his colleagues recognized that longer nanotubes mean greater strength, higher conductivity, easier handling, and greater product safety. Moreover, today’s nanotubes are also quite expensive—usually too expensive for use in volume industrial applications. This is a result of the significant amounts of impurities generated in their manufacture that are difficult and costly to remove. NCTI’s patent-pending process produces long, pure, continuous carbon nanotubes at high growth rates that require no post-growth purification, according to the company. Nanocomp is pursuing a number of applications of its long nanotubes.

  • Nanoproduction of Drugs

    Another application of nanotechnology is the efficient separation of chiral molecules, says Robert Pucciariello, CEO of Evolved Nanomaterial Sciences (www.ensbio.com) and one of the speakers at the MIT nanobiotech conference.

    “Many leading pharmaceuticals are based on chiral molecules. In fact, about $250 billion, or half of all drug revenues, were based on chiral molecules last year. This percentage is likely to increase, as 80% of all drugs in the development pipeline are chiral.”

    Conventional chemical synthesis of pharmaceutical compounds typically produces both of the mirror-image twins, referred to as optical isomers or enantiomers.

    Although chemically identical, they react differently biologically by binding to receptors in the body that have a specific 3-D shape. Thus, only one of the enantiomers will preferentially bind and create the desired therapeutic effect. The unneeded twin may even cause catastrophic side effects.

    There are a number of chemical methods for separating enantiomorphs, but they are expensive and time-consuming. Evolved Nanomaterial Sciences is based on the concept of a cost-effective, nano-based solution for chiral separations. The core technology is a 3-D physical filter. Made from self-assembling polymers, this filter has 11-nm corkscrew-like pores allowing only one of the two enantiomers to pass through. The size of the pore is large enough to permit entry of pharmaceutically relevant molecules, but small and chirally curved enough to create a nanoenvironment where one of the enantiomeric molecular shapes will always be favored over the other. The unwanted enantiomer will be excluded.

    “This physical filtering approach can be scaled from milligrams to kilograms to provide any sample quantity,” says Pucciariello. “And because chiral shape is a far more general way of looking at molecules than the numerous highly specific chiral chemistry types, our nanotechnology-based chiral materials can separate out a broad range of enantiomers.”

    Although biological pharmaceuticals are highly touted these days by the pharma industry, they carry with them notable drawbacks. Protein-based drugs are technically challenging to produce; certified generics are not readily available; and protein drugs are generally injectables, making them difficult to administer.

    For this reason many biotechs are diversifying their candidate therapeutics portfolios and using their biotechnology expertise to discover and detect chiral small molecules. However, the selection of suitable candidates requires chiral separation in a high-throughput environment in order to avoid commitment to unsuitable candidate molecules.

    A striking feature of nanomedicine companies is their product diversity. The applications of these structures to a range of biotech challenges, including therapeutics, diagnostics, structural materials, and electrical devices, is striking. Provided that environmental and safety concerns can be addressed in a meaningful and open fashion, there seems little doubt that this technology, after years of incubation, will finally accrue long sought-after benefits for its promoters.

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