Technology

  1. The HIV/AIDS Pandemic
  2. The Company’s Technology
  3. CLONE 3’s Effectiveness Has Been Verified by 5 Independent Laboratories
  4. Clinical Evidence Substantiates that CLONE 3 will be Effective in Humans
  5. Experts Have Concluded that Monoclonal Antibodies will be Needed to Control HIV/AIDS
  6. CLONE 3 Antibody Has the Capacity to Neutralize 98% of the HIV Strains Identified Around the World.
  7. Applying Bioclonetics Discoveries
  8. Market Statistics
  9. Management / Scientific Advisory Board
 

The HIV/AIDS Pandemic

To understand the full impact of the HIV/AIDS pandemic, all one needs to know is that 1,000 children die each day from HIV/AIDS.  This is three times the number who die from cancer.

Today, there are 42 million people in the world with HIV/AIDS.  Five (5) million people are newly infected each year with HIV (14,000 each day), and 3 million die (8,000 each day).  Twenty five (25) million people have died of HIV-related medical issues since 1981, and there are currently 15 million HIV/AIDS-related orphans worldwide. The number of HIV/AIDS-related orphans is expected to surpass 25 million by 2015. The human tragedy continues unchecked internationally.

In the United States, 1.2 million individuals are infected with HIV/AIDS, and 44,000 more individuals in the U.S. are infected each year.

Despite significant medical advances, including the use of additional anti-retroviral drugs and fast-tracked Federal Drug Administration (FDA) approval of protease inhibitors, the number HIV/AIDS cases continues to advance unrestrained, regardless of cultures, geography, and borders without boundaries.  The continued increase in multi-drug cross-resistant HIV viral strains, which spawn pathogenic “super-viruses”, highlights the fact that current and new drug therapies against HIV/AIDS are not an effective long term medical solution.  Although these chemotherapeutics have extended lives, they are not able to prevent viral infectivity from person-to-person and have done little to slow the advance of HIV/AIDS globally.

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The Company’s Technology

BioClonetics has created a human cell line that produces a human antibody, identified as CLONE 3, which neutralizes HIV, the virus known to cause AIDS, rendering it inactive.

In in vitro tests conducted in five independent laboratories, CLONE 3 has been tested against 41 clinical HIV isolates (strains) of the virus. CLONE 3 has demonstrated that it successfully neutralizes 37 of them.

Presently, CLONE 3 is the only human monoclonal antibody found to neutralize the Clade C isolate found in Africa, China and India.  CLONE 3 also neutralizes the Clade B isolate that is predominate in North America and Europe. In view of these test results, the Company is moving forward with animal and human trials to establish CLONE 3 as a significant means for treatment of those that have HIV/AIDS and to produce a vaccine against HIV.

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CLONE 3’s Effectiveness Has Been Verified by 5 Independent Laboratories

The neutralizing capacity of CLONE 3 has been established in tests conducted by five independent research groups. In tests conducted at the University of California – San Francisco (by Jay Levy, M.D.), CLONE 3 Antibody was shown to have in vitro neutralization effect against geographically distinct clinical HIV (primary) isolates. Research conducted at four additional international institutes has confirmed these results of in vitro neutralization. In total, the neutralizing capabilities of CLONE 3 have been verified at the following 5 laboratories:

  • University of California, San Francisco, CA, USA (Jay Levy, M.D.)
  • University of South Florida, Tampa, FL, USA (Kenneth Ugen, Ph.D.)
  • Polymun, Vienna, Austria, (Hermann Katinger, Ph.D.)
  • Duke University, Durham, NC, USA (David Montefiori, Ph.D.)
  • Dana Farber Cancer Institute, Boston, MA, USA, (Ruth Ruprecht, M.D., Ph.D.)
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The research conducted at the University of South Florida that validated CLONE 3 antibody as having in vitro neutralization capacity was funded by a six year $1.4 million USD NIH grant to University of South Florida (USF) in Tampa, FL, USA (Kenneth Ugen, Ph.D., principal investigator) and BioClonetics (Joseph Cotropia, M.D. co-principal investigator).

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Clinical Evidence Substantiates that CLONE 3 will be Effective in Humans

The following independent studies provide overwhelming clinical evidence that CLONE 3 will be effective in Humans to both neutralize HIV and serve as an effective vaccine.

  • P.A. Broliden, et al. reported in AIDS September 1989, that in a group of HIV-infected infants born to HIV+ mothers, those infants who lacked the presence of CLONE 3 antibodies had a rapid progression to symptomatic AIDS.
  • Vanini, et al. reported in AIDS, February 1993, that decreasing concentration of CLONE 3 antibodies directly correlated with HIV disease progression.
  • Loomis-Price, et al., in Journal of Infectious Diseases volume 178, pp. 1306-1316, November 1998, also demonstrated that high antibody reactivity to the peptide containing the CLONE 3 immunogen epitope [LIC] is associated with slow progression to AIDS.
  • The National Institute of Health (NlH) studies, conducted by Anthony Fauci et al., Director of the National Institute of Allergies and Infectious Diseases (NIAID) at the NIH., and published in Nature Medicine November 2001, provide further validation of the efficacy of this linear amino acid epitope, LIC, as a protective active vaccine immunogen.

    As background for understanding how tests conducted by Dr. Fauci demonstrate that CLONE 3 will be effective in Humans, one must understand how CLONE 3 works to neutralize the HIV virus.  Through collaboration with the Karolinska Institute in Stockholm, Sweden (Britta Wahren, M.D., Professor of Microbiology), the Company identified the linear minimal essential “core” epitope on the virus to which CLONE 3 binds. As published in Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology in 1996, this minimal core eptitope is defined as the amino acid sequence “KLIC”, located on the portion of the virus designated as gp41.

    In Dr. Fauci’s primate phage-display peptide vaccine studies, primates were vaccinated with a peptide immunogen represented as the linear KLVC rather than KLIC. KLVC is a linear peptide having a conservative amino acid substitution of valine (V) for isoleucine (I). KLIC occurs in the native HIV gp41 amino acid sequence.

    The vaccinated primates produced an antibody [anti-KLVC] that is cross-reactive with linear peptide KLIC--an amino acid sequence on HIV gp41 (and SHIV gp41). When the primates were challenged with the SHIV virus [having the gp41 amino acid sequence KLIC], the vaccinated primates--although infected with SHIV--were infected at a lower SHIV viral set-point than the SHIV challenged non-vaccinated control primate. Moreover, the vaccinated primates retained normal T4 cell counts while the non-vaccinated control primate’s T4 cell counts decreased and progressed to frank AIDS and death within 6 months of SHIV challenge. The KLVC vaccinated primates’ health status were that of a Long-Term Non-Progressor.

    These tests demonstrate that the CLONE 3 active vaccine component prevented progression to AIDS-like illness, and also supports the conclusion that the peptide of the CLONE 3 epitope (KLIC) will be effective as an active vaccine against HIV.
  • Ursula Dietrich, Ph.D., et al., from the Georg-Speyer-Haus Institute for Biomedical Research at the University of Frankfurt in Germany, also validated the significance of the CLONE 3 epitope by reporting the presence of anti-KLlC CLONE 3 human antibodies identified in HIV+ blood plasma obtained from Long-Term Non-Progressors (LTNPs) who had normal T-cell counts, no opportunistic infections and were not taking any prescribed adjunct chemotherapeutics or anti-retroviral drugs. These findings were reported at the 16th International Conference on AIDS in Toronto, August 2006.
  • Cano, et al., in an article published in Immunology Letters, September 2004, cited the BioClonetics publications on CLONE 3 Antibody, noting that the human monoclonal anti-gp41 antibody was a neutralizing anti-HIV antibody that recognizes (binds preferentially to) a linear peptide in the immunodominant region.  In the article, Cano, et al. went on to state that "we found here a correlation between the presence of anti-linear peptide antibodies and endurance of infection."

    In other words, those HIV-seropositive individuals who are Long-Term Non-Progressors (LTNPs) have endogenously produced during the natural course of HIV exposure and infection, neutralizing (and therefore protective) anti-gp41 HIV antibodies, e.g. CLONE 3 Antibodies, that recognize (bind to) the linear peptide KLIC.

    These six (6) collective independent clinical studies validate that CLONE 3 antibody will be therapeutic against HIV/AIDS when used in a “passive immunotherapy”.  Likewise, the CLONE 3 epitope will be an effective immunogen in an active prophylactic vaccine that will elicit CLONE 3 antibody production to prevent HIV infections.

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Experts Have Concluded that Monoclonal Antibodies will be Needed to Control HIV/AIDS

Experts in the field also see human monoclonal antibodies as being the likely way to control HIV/AIDS. At the 2004 Proceedings of the National Academy of Sciences (USA), vaccinologist Maurice Hilleman wrote that any vaccine based upon cellular immunity was unlikely to be effective.  In contrast, the CLONE 3 immunogen is a peptide-based HIV vaccine that elicits a humoral protective novel human antibody. Thus, CLONE 3 technology has a clear scientific advantage over DNA-based HIV vaccines which elicit cellular immunity vaccines only.

In 2005, Anthony Fauci, M.D., Director of NIAID, stated that a successful vaccine against HIV/AIDS will require inducing the production of a neutralizing antibody.  Significantly, the pharmaceutical industry has disregarded this scientific truth that a neutralizing antibody will be necessary to produce a successful vaccine, and has instead focused primarily on DNA-based cellular immunity vaccines, none of which have succeeded.

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CLONE 3 Antibody Has the Capacity to Neutralize 98% of the HIV Strains Identified Around the World.

A review of the HIV data reported to the Los Alamos HIV Clinical Database (July 2006), reveals that CLONE 3 antibody has the capacity to neutralize 3471 of 3548 (or 98%) of HIV strains identified in the 7 regions of the world.

The reason CLONE 3 is so effective is understood by examining the portion of the HIV virus to which it binds. The human CLONE 3 antibody binds to a portion of the gp41 molecule on the viral surface containing the highly conserved amino acid peptide sequence Leucine-Isoleucine-Cysteine (LIC) that is a part of the viral protein coat of the virus. The U.S. Government’s HIV Clinical Database at Los Alamos currently records 3548 clinical HIV isolates with their amino acid surface composition mapped and sequenced.

By searching the amino acid surface composition of these 3548 isolates, it is seen that 2835 have an exact match for the minimal essential “core” epitope (LIC) to which CLONE 3 antibody binds.  Another 636 of clinical HIV isolates have a conservative match to CLONE 3’s epitope to which CLONE 3 would bind.  Thus, 3471 (2835+636) clinical HIV isolates have an amino acid sequence [epitope] that is bound by the CLONE 3 antibody, leaving only twenty (77) clinical HIV isolates that do not have an identical or conserved amino acid sequence (epitope) that is capable of being bound by the CLONE 3 antibody (paratope).

Thus, CLONE 3 antibody expectedly will neutralize 98% (3471/3548) of all HIV strains around the world.

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APPLYING BIOCLONETICS’ DISCOVERIES

Immunotherapeutic Treatment and Production of a Prophylactic Vaccine

The CLONE 3 technology can be applied to HIV/AIDS infection in two ways:

  1. As a neutralizing human antibody, CLONE 3 can be used as effective therapy for those HIV+ individuals who have the HIV virus. CLONE 3 can neutralize HIV and therefore prevent viral infectivity from individual-to-individual. Prevention of HIV transmission has not been achieved by any chemotherapeutic drugs to date.
  2. The CLONE 3 epitope (the active vaccine immunogen – namely amino acid sequence KLIC) which is the biological component that triggers the production of the protective CLONE 3 human antibody in the body (in vivo), has also been identified by BioClonetics. With this novel discovery, an active prophylactic vaccine against the virus can be produced which can provide a protective immune status against HIV exposure.

These goals will be accomplished in the following steps:

  1. Completion of primate and human trials leading to FDA approval of use of CLONE 3 antibody as a passive immunotherapyto treat those infected with HIV/AIDS. Trials will be conducted to demonstrate that CLONE 3:
    1. Is effective therapeutically in treating (passive immunotherapy) those who are HIV+.
    2. Protects (prophylactically) those exposed to HIV from advancing to full blown AIDS; and
  2. Prepare and test an active prophylactic vaccine against HIV/AIDS using the neutralizable immunogen of CLONE 3, which has already been demonstrated in primates to elicit the protective CLONE 3 antibody and provide a protective immune status against HIV/AIDS.

Advancement of the use of CLONE 3 in passive immunotherapy and as an active vaccine will be carried out by BioClonetics in conjunction with the University of Texas Southwestern Medical Center, Dallas, Texas, under the direction of Dr. Ellen S. Vitetta.  Dr. Vitetta is the Director of the Cancer Immunology Center and is a member of the National Academy of Sciences (USA). The pediatrics protocols and research will be conducted at the David Geffen School of Medicine at University of California at Los Angeles (UCLA), California, under the direction of Dr. Yvonne J. Bryson.  Dr. Bryson is the Chief, Division of Pediatric Infectious Diseases as well as Chairman, International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group for perinatal maternal HIV transmission. Both Dr. Vitetta and Dr. Bryson are scientific advisors to BioClonetics.

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Market Statistics

BioClonetics’ CLONE 3 immunotherapeutics can benefit all 1.2 million U.S. residents infected with HIV. All 300 million U.S. residents could benefit from an active prophylactic vaccine against HIV exposure and infection.

There are 45 million HIV-infected individuals worldwide. CLONE 3’s therapeutic capacity is critical to the successful treatment of these individuals.  The world’s population of 6.6 billion individuals could benefit from an active prophylactic vaccine against HIV/AIDS. With 5 million individuals being infected each year, there is an urgent need for an effective therapy and a vaccine against HIV.

Pharmaceutical manufacturer’s gross annual profits from anti-retroviral drug chemotherapeutics for 2005 was in excess of $127 billion. An antibody therapy and vaccine is a preferable and superior substitute for these anti-retroviral drugs now being used to treat HIV/AIDS patients.

Passive and active CLONE 3 immunotherapies would benefit patients worldwide. Given the enormity of the health issues presented by HIV, an effective therapy will produce significant sales revenue.  The large projected gross revenue and profits that will flow from an effective therapy and vaccine are reflective of the enormity of the HIV epidemic and the need for an effective treatment. The Company is glad to discuss projections regarding revenue and profit potential with interested collaborators and partners.

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