Next generation antibody-drug conjugates (ADC) with unique polymer linker chemistry and high efficacy tumor targeting and minimal off-target toxicity.

ADCs are empowered antibodies designed to harness the targeting ability of monoclonal antibodies by linking them to cell-killing agents to overcome toxicity issues. One of the major limitations of ADCs is having an appropriate linker.

The proposed technology improves the linker, making it possible to create an ADC that possesses high specificity and the advantages of macromolecular therapeutics. The technology involves a controlled living polymerization technique that results in a well-defined HPMA polymer-drug conjugate, followed by specific attachment to an antibody to generate a homogenous ADC with an adjustable amount of payload. Lead ADC, RTX-P-EPI (rituximab conjugated to epirubicin) has been well characterized for high linker stability, homogenous ADC mixture, and ADC internalization.

Concept

• ADC is internalized with strong reduction in tumor burden.
• Technology allows for a high drug-to-antibody ratio (DAR)
• Stable and biodegradable HPMA linker.
• Scalable linker chemistry with rapid customization of new ADCs.

Zhang, L., Fang, Y., Kopecek, J., Yang, J. (2017). A new construct of antibody-drug conjugates for treatment of B-cell non-Hodgkin’s lymphomas. European Journal of Pharmaceutical Sciences. 103:36- 46. doi: 10.1016/j.ejps.2017.02.034.

Yang, J. and Kopecek, J. (2017). The light at the end of the tunnel – second generation HPMA conjugates for cancer treatment. Current Opinion in Colloid and Interface Science. 31:30-42. doi: 10.1016/j.cocis.2017.07.003.

Publication Number: US-2019-0216945-A1
Patent Title: Antibody-Polymer-Drug Conjugates
Jurisdiction/Country: United States
Application Type: Non-Provisional

Jason Young
(801) 587-0519
jason.r.young@utah.edu