Other Nanotemplate Engineering Applications

Molecular Imaging Agents

Molecular Imaging Agents For Use In Magnetic Resonance Imaging (MRI) 
Nanoparticles possessing accessible gadolinium (Gd) atoms can be selectively sequestered in tumors through Enhanced Permeation & Retention (EPR). NanoMed has utilized DTPA-PE to bind Gd to the surface of its novel nanoparticles, but without the need for energy-intensive microfluidization and with far less-expensive USP-grade components. Preliminary data demonstrate that these novel nanoparticles, composed of USP-grade materials and of an appropriate size range for uptake into tumors, have the potential to serve as useful contrast agents for tumor imaging by MRI. In addition, dual therapeutic/molecular imaging nanovectors can be created by entrapping chemotherapeutic agents (e.g. paclitaxel and doxorubicin) in Gd-containing nanoparticles.

Therapeutic Vaccine

Unmet Need
Approximately 40 million people worldwide are infected with HIV. Globally, there were nearly 5 million new HIV infections in 2003 and nearly 3 million deaths. To date, no prophylactic or therapeutic vaccine has demonstrated effectiveness. Current antiretroviral therapies used to treat HIV work to prevent the virus from multiplying. While antiretroviral drugs have been shown to slow the progression HIV in infected individuals, they are expensive, require complex daily dosing regimens, and are prone to resistance. NanoMed's Solution NanoMed has utilized its Nanotemplate Engineering technology to develop a dendritic cell-targeted HIV-1 therapeutic vaccine containing the conserved proteins Tat (1-72) and Gag p24. This novel therapeutic vaccine has demonstrated effective in-vivo immune responses in mice. Specifically, neutralizing antibodies to key epitopes on the Tat protein were generated. These neutralizing antibodies have been shown to inhibit Tat-induced long terminal repeat (LTR)-transactivation which is critical for HIV replication. Previous literature reports have shown that long-term non-progressors (LTNP) (e.g., HIV-infected individuals that do not progress to AIDS) have cellular immune responses and neutralizing antibodies to key Tat epitopes. Thus, NanoMed's data are highly encouraging and suggest that therapeutic immunization of HIV-infected patients with a highly conserved Tat protein may significantly delay or perhaps avoid the progression to AIDS. Moreover, this product would avoid the longer development path of a conventional prophylactic vaccine while affording significant advantages over existing antiretroviral drugs used in the current standard treatment protocol -- "highly active antiretroviral therapy" (HAART, aka "triple cocktail treatment").

Product Development

In order to develop a vaccine for controlling infection against various HIV subtypes, the candidate antigen should be immunogenic, conserved (to produce cross-reactive CTL responses), and critical in the virus lifecycle. Based upon these therapeutic principles, NanoMed has developed a dendritic cell-targeted HIV-1 therapeutic vaccine containing two conserved proteins of great interest, Tat (1-72) and Gag p24, which generates protective Th1, CTL, and neutralizing antibody responses. The company’s preliminary data demonstrate that these proteins may be delivered with novel nanoparticles to significantly enhance immune responses.  NanoMed is working to complete the preclinical development of its HIV-1 therapeutic vaccine leading to Phase I studies in healthy individuals to assess safety and immunogenicity.

The Market
The HIV market is expected to triple in size by 2007, growing from a $5 billion dollars in sales to over $13 billion in sales by 2007. Growth in the HIV market will continue to be driven by a rapidly growing HIV and AIDS population. A recent analysis by the National Institute for Health Care Management (NIHCM) Foundation found that national retail drug expenditures for antiretrovirals (alone) totaled $2.6 billion in 2001, representing an almost 21 percent increase over 2000, compared to a 17% increase for all retail prescription drug sales over the same period.

Interestingly, AIDS drugs are in human clinical trials for an average of 5 years, which is 3 years shorter than the average drug. Anti-HIV/AIDS drugs move faster through their clinical trials, with higher success rates and lower than average trial durations for Phases I and II. Anti-HIV/AIDS drugs showed the highest probability of completing the final phase of the trials (Phase III) and reaching the market.

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NanoScintillation Systems

Hazardous Environmental Waste Reduction

NanoMed has the exclusive rights to U.S. Patent 6,855,270 (“NanoScintillation Systems For Aqueous-Based Liquid Scintillation Counting”) which covers radiation-detection applications of Nanotemplate Engineering technology.

Biomedical and environmental researchers routinely employ scintillation cocktails to quantify, or “count”, the amount of radioactivity emitted by radioisotopes in samples generated during laboratory experiments. Frequently, these samples must be mixed with an organic solvent containing dissolved fluor molecules, or “scintillators”.  Although efficient, the use of organic-based LS cocktails results in the need to dispose of large quantities of mixed low-level radioactive and hazardous waste (“Mixed LLW”) generated as a byproduct of the counting process.  Results of testing by TestAmerica, Inc., (http://www.testamericainc.com/), the leading nationally certified provider of outsourced analytical laboratory, air emissions, and indoor air quality testing services, show that the NanoScintillation System was qualified as non-hazardous waste by virtue of passing tests for Toxicity Characteristic Leaching Procedure (TCLP) Extraction by EPA 1311, TCLP for Volatile Organic Compounds by EPA Method 1311/8260B, TCLP for Semi-volatile Organic Compounds by EPA Method 1311/8270C, TCLP for Metals by 6000/7000 Series Methods, Reactivity, pH, and Ignitability as specified in Subpart C of 40 CFR Part 261.  Thus, the NanoScintillation System represents an opportunity to significantly reduce hazardous environmental waste.

According to a 1990 baseline report commissioned by the Nuclear Regulatory Commission and the Environment Protection Agency titled “National Profile on Commercially Generated Low-Level Radioactive Mixed Waste” (NUREG/CR-5938), 140,000 cubic feet of mixed waste was generated by industry and academia in the United States in 1990 alone. It is estimated that the Department of Energy generates annually an additional 800,000 cubic feet of mixed organic and radioactive waste.

Additional Potential Applications

In addition to its application in routine scintillation counting in biomedical and pharmaceutical research laboratories, NanoScintillation Systems may have utility in homeland security applications; specifically, anti-nuclear terrorism of municipal and military water supplies.  Several U.S. government agencies have made nuclear preparedness recommendations that included the use of mobile methods to detect radiation, including beta-particle- or alpha-particle-emitting radioisotopes.

NanoScintillation Systems may also have applications in other areas such as in radioisotopic binding assays and in functional genomics whereby the binding of radiolabeled probes in DNA microarrays can be quantified which may be of particular interest to biomedical researchers who build their own gene chips and need high sensitivity detection.