A treatment regimen based on a newly discovered endogeneous fragment of Histidine-rich glycoprotein (HRGP). A 35mer peptide derived thereof has been identified and shown to significantly inhibit tumor vascularization and growth of experimental tumors

Angiogenesis is a multistep process with several essential intermediate steps, including capillary endothelial cell activation, proliferation, and migration. Based on these physiological definable intermediate stages, a number of surrogate in vitro and in vivo assays and models have been established, which are routinely used to evaluate the activity of putative angiogenesis stimulators and inhibitors in preclinical studies. We have studied the effect of purified human plasma and recombinant HRGP, as well as selected fragments thereof and HRGP derived peptides in:

• migration assays, in which chemotaxis of capillary endothelial cells towards angiogenic growth factors has been measured.
• chick chorioallantoic membrane (CAM) assays that measure blood vessel formation and growth in the developing chicken embryo.
• established experimental animal models measuring treatment effect on tumor vascularisation and tumor growth.

The work has been carried out partly in the academic setting, and partly by independently employed CRO companies.

In repeated in vitro analyses, HRPG and HRPG330 have been shown to inhibit endothelial cell chemotaxis towards FGF-2 or VEGF. Chemotaxis by peripheral human monocytes towards VEGF-ligands is also inhibited by HRGP whereas fibroblast migration towards FGF-2 is not affected. Endothelial cell proliferation measured as incorporation of [3H]thymidine or as increase in cell number, is not altered in the presence of HRGP.

Moreover, we have shown that adhesion of endothelial cells to the avb3 integrin ligand vitronectin is attenuated by HRGP330. Therefore, current data strongly indicate that HRGP interfere with integrin functions. Whether integrins, e.g. the avb3 integrin, serves as a receptor for HRGP is not proven at present. Current efforts in the Claesson-Welsh laboratory, are aimed to identify a receptor for HRGP using the yeast two-hybrid methodology.

Preclinical

Following the acquisition of the exclusive worldwide IP rights associated with the invention, Innoventus Project AB has pursued a proactive and structured patent strategy to obtain strong IPR protection both technically and geographically. Today, the patent portfolio consists of two patent families.

Innoventus' role and competence is, and will remain, in early stage project development and in this project partnering is essential, in order to develop a candidate drug and carry it through clinical trials and eventually to the market.

For that reason Innoventus is seeking an industrial partner, which has the desire and resources to manage the project during its subsequent phases.