Patent Document ID: 9335321
Application ID: 12302732
Patent Flag: 1

Claim One:
1. A biological method of screening an agent having angiogenic modulating activity, which is carried out by a hierarchical 3-tier biological screening assay system comprising: (i) in the first tier, (a) treating teleost embryos with a test agent at different concentrations covering seven orders of magnitude, while simultaneously, testing a control group (b) observing the vascular system of said embryos, wherein said embryos are at least 3-day old embryos, for any alteration in the constant number of intersegmental vessels at the different concentrations of the test agent; wherein any observed alteration in the constant number of intersegmental vessels in the teleost embryo treated with the test agent will lead to a conclusion that the test agent is an angiogenic modulating agent and the agent will proceed to the second tier for further testing; (ii) in the second tier, (a) plotting a dose response curve to show the dose response relationship of the test agent as compared to a control; (b) determining the highest concentration at which there are no statistically significant increases in the percentage of adverse effects on teleost embryos between the group exposed to the test agent and the control group, wherein said adverse effects include death or malformation of the teleost embryos; wherein said highest concentration is determined to be the no observed adverse effect concentration (NOAEC) and the test agent will proceed to the third tier for further testing; (iii) in the third tier, (a) determining whether the test agent at the level of NOAEC induces adverse effects at the organ level and cellular level in teleost embryos thereby resulting in an evaluation of the safety of said test agent, and (b) determining the parameters of the angiogenic modulating activity of said test agent at the level of NOAEC.