Thanks to generous funding from the Department of Defense and the National Institutes of Health via Small Business Innovative Research (SBIR) grants, Abzyme have developed a number of antibody candidates for treating human diseases besides cancer. We have developed VHH antibodies that function similar to Brain-Derived Neurotrophic Factor (BDNF) to stimulate the nerve growth. We have also developed very potent VHH antibodies capable of inhibiting the enzymatic activity of the complement component C1q. VHH antibodies against nerve growth stimulant, BDNF, are now being evaluated in animal models for treatment of multiple sclerosis. These studies are sponsored by NIH.
We also have a number of antibodies to targets mediating angiogenesis. Among them are antibodies targeting VEGF, ANGPTL4 and CD147. Targeting angiogenesis is a way to kill cancer cells by blocking the formation of blood vessels supplying nutrition to the tumors. Blocking abnormal blood vessel formation is also the strategy for treatment of age-related macular degeneration (AMD).
The antibody half-life in the human body not only affects the therapeutic efficacy but also the frequency of dosing. VHH antibodies, as well as other biologics with low molecular weight, have short half-lives. We have developed different strategies to extend the half-life of our biologics. One such strategy is to fuse anti-albumin VHH to the biologic, as it will extend the serum half-life of the biologic. Another half-life modulator Abzyme has developed is a 12-amino acid peptide that binds to hyaluronic acid (HA). Hyaluronic acid is found throughout our body in different concentrations. Tissues containing the highest amount of HA are the umbilical cord, joint fluid, vitreous body of the eye and skin. VHH antibodies fused with the 12-amino acid HA-binding peptides are retained in the HA-matrix even after several weeks of incubation, while VHH antibodies without the peptide quickly diffused.
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