Technology
Company's CaP technology has been in development as a novel vaccines
adjuvant (CaPtiVantTM)
for injection or needle-free administration, for drug delivery via mucosal
routes (e.g. oral/buccal, pulmonary), and in
aesthetic medicine as a facial "line-filler" which was licensed to Medical Aesthetics Technology Corporation (MATC). CaP has also been used to
develop an industrial process to selectively fractionate soluble milk proteins
from milk caseins. The method was applied to isolate recombinant proteins (e.g.
rhFIX, rhα1-AT) form
milk of transgenic animals in a casein-free, clear supernatant fraction that
can directly be fed into chromatography columns for further purification. CaPtivate owns the IP rights for the US Patent that was
issued for this novel process. Recent preclinical studies indicated that CaP can also be utilized as a dietary supplement (CaPliMentTM)
for calcium and phosphorus; it has properties that are superior to those of
commercially available supplements.
CaP nanoparticles
have shown to have excellent absorption capacity for bioactive molecules, are
stable for years in aqueous suspension, as gel, or as spray-dried powder. In
acute toxicity studies in Guinea pigs, CaP has been
proven safe for administration orally, into muscles, under the skin, and via
inhalation into the lungs. CAP technology has also been proven safe in human in
a Phase I "safety and toxicity" study conducted under an approved IND in the U.S. It is stable for many years when stored as
spray-dried powder or in aqueous suspension.
CaP Novel Vaccine Adjuvant
What
is Vaccine Adjuvant?
The goal of vaccination is to stimulate the immune
system of an individual to develop long term protection against an infection
caused by a pathogen (bacteria or viruses). In order to achieve this
objective, either the live but attenuated form of the pathogen, the whole
inactivated pathogen, or a purified component of the pathogen is administered
in the body. Many of the modern day vaccines are based on pure
recombinant or synthetic antigens which are inherently poorly immunogenic, thus
require the use of adjuvants to boost the immune response
to vaccine. Adjuvants, in the most
traditionally sense, are the agents that are mixed in vaccine formulations to
enhance the antigen-specific immune response in vivo. Currently in the USA and in the majority of
countries, aluminum hydroxide (alum) remains as the only compound that is
approved in human vaccines.
Demand
for New Adjuvants
The vaccine industry has
experienced significant growth over the past decade. U.S. demand for vaccines is estimated to grow
from approximately $4.9 billion in the U.S. to approximately $20 billion by
2010. The two main driving forces in the
market's growth will be entry into emerging third world countries, where
alternative delivery is particularly desirable and the development of vaccines
targeting new diseases that have not previously been covered by immunizations
such as biodefense toxins and pandemic flu. Other examples of vaccines include pediatric,
hepatitis, influenza, encephalitis, rabies, meningococcal, and veterinary
vaccines.
In spite of the critical role of adjuvants
for vaccine development, only a few new adjuvants
have been successfully incorporated into human vaccines due to the high
toxicity associated with many experimental adjuvants.
Despite being the only FDA-approved adjuvant in the US, alum has immunological
limitations that hinder our ability to produce novel or improved vaccines. Alum
mainly induces antibody (Th2) response but has little
capacity to stimulate cellular (Th1) immune responses
which are critical for protection against many pathogens. Since alum is neither
suitable nor approved for mucosal administration, alum-adjuvanted
vaccines also lack ability to induce mucosal protection thus are ineffective at
providing first line of defense to infected cells. Furthermore, being an
inflammatory chemical, it can also cause serious systemic and local allergic
reactions including eosinophilia, tissue irritation, granumolas, abscesses, or subcutaneous nodules at the site
of administration.
Consequently, the lack of choice for safer, non-toxic, and
effective adjuvants able to stimulate cellular immune
responses and suitable for mucosal administration still remains as a major
obstacle in improving current vaccines or developing new vaccines against many
life-threatening diseases. Availability of an efficacious mucosal
adjuvant to produce both systemic and mucosal immunity would enable
administration of variety of vaccine antigens using non-invasive routes.
Our
CaPtiVantTM Vaccine Adjuvant Technology
Despite the presence of many adjuvants in development that are
clearly more potent than alum, toxicity has been the single most important
impediment in introducing them in human vaccines. This need and opportunity
have been the driving forces in the development of our CaP
nanoparticle vaccine adjuvant technology (CaPtiVantTM) and we believe that
CaP has the potential to play a major role in this
growing market.
Over the years, extensive preclinical data have been generated
which show CaP's ability to enhance immunogenicity of
existing vaccines and novel vaccine antigens after administered by injection or
by mucosal routes. The safety and efficacy of CaP in
vaccines has been demonstrated using various viral and bacterial antigens, such
as seasonal flu (H3N2, H1N1), H5N1 avian flu, H1N1 swine flu, genital herpes (HSV-2),
HIV, Epstein Barr, anthrax, malaria, hepatitis B, tetanus, tuberculosis. We demonstrated that CaP-adjuvanted
vaccines can induce higher IgG and IgG2a (Th1-like) responses than
alum, can induce mucosal IgA response. CaP produces insignificant IgE
and only minimal local irritation when administered by injection or mucosal
routes. We have also shown that CaP does not
interfere with the native structure of the protein/peptide drugs and can
enhance storage stability of the active component in the formulation. We also
conducted preclinical vaccine studies as a subcontractor for the U.S.
Department of Defense and presented promising results which further validates CaP's potential as a safer and needle-free alternative to injectable alum-adjuvanted
vaccines. CaP vaccine adjuvant has also demonstrated
dose sparing potential often leading to the use of lower vaccine dosage while
maintaining or improving effectiveness and offering an improved safety profile.
Advantages of CaP
Adjuvant (CaPtiVantTM)