Therapeutic annexin composition of reduced off-target effects
DKFZ has patented a novel annexin-formulation of enhanced receptor-mediated effects.
Annexins are currently under investigation for their therapeutic potential in diseases like chronic inflam-matory and autoimmune disorders, allergy and cancer vaccination as well as cardiovascular diseases. Com-mon to most of these therapeutic annexin applications is the use of a soluble annexin-preparation. How-ever, in addition to desired binding to specific re-ceptor(s), soluble annexin is known to bind to nega-tively charged phospholipids such as phosphatidylser-ine. Thus, high background binding and off-target effects are often observed for soluble annexin preparations when when administered in vivo due to PS expression on various cellular and vascular sur-faces. Soluble annexin typically binds randomly to membranes comprising negatively charged phospho-lipids and does not selectively bind to target receptors on target cells. These off-target effects reduce the ef-fective annexin concentration drastically, prompting the administration of very high annexin doses. More-over, high annexin dosages often lead to undesired side effects, e.g. induction of vascular leakage by re-duced coagulation.
In the field of therapeutic use of annexins our formu-lation raises the effective concentration. With a more precise dosage of the drug and fewer side effects the patient suffers less, and production costs can be re-duced.We expect that annexin doses can be reduced up to 10,0000x when applied in the provided compo-sition.