Navidea Biopharmaceuticals, Inc. announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office for its patent application titled, “Compositions And Methods For Altering Macrophage Phenotype (US Application #16/832,620).” Broadly, this patent covers the ability of Navidea's constructs to stimulate the body's immune response against tumors through targeted delivery of payloads (e.g., doxorubicin, paclitaxel, and bisphosphonates) that change the nature of macrophages to make them more proinflammatory. These constructs have demonstrated the ability to rally an immune response against tumors and make other therapies work more effectively against those tumors in preclinical studies. If confirmed in clinical trials, the ability to increase the efficacy of cancer therapeutics by harnessing the body's immune system could bring significant benefits to patients.

The Notice of Allowance concludes the substantive examination of the patent application and is expected to result in the issuance of a U.S. patent after administrative processes are completed. When issued, this patent will protect key elements of Navidea's cancer immunotherapy product pipeline. Navidea's cancer immunotherapy product pipeline consists of a series of mannosylated-amine dextrans (MADs) that carry small molecule drug payloads that are attached to MADs by degradable linkers.

The MADs bind to CD206 receptors on tumor associated macrophages (TAMs) and related cells such as dendritic cells and myeloid derived suppressor cells. The degradable linkers are designed to release their small molecule payloads inside the CD206 expressing cells. The small molecule payloads are designed to induce proinflammatory behaviors in these cells.

In tumors, TAMs and their cellular relatives create an immunosuppressive tumor environment that prevents other types of immune cells from attacking cancer cells, thus permitting cancer cells to survive and grow. In addition, this immunosuppressive tumor environment decreases the effectiveness of a wide variety of other cancer therapies, including other cancer immunotherapies. Navidea's MAD-based cancer immunotherapies alter the behavior of macrophages to make them less immunosuppressive and more proinflammatory, or antitumor.

Studies in mouse models of cancer have shown that Navidea's MAD-based immunotherapies can enhance the effectiveness of other cancer immunotherapies and significantly reduce tumor growth. The results of these studies have been presented at the New York Academy of Sciences (2021), the Tumor Myeloid-Directed Therapies meeting (2022), and at the 2022 annual meeting of the Society for Immunotherapy of Cancer.