Panacea Pharmaceuticals issued U.S. patent for anti-HAAH antibodies

Sep 3 2008

Panacea Pharmaceuticals, Inc. has announced the issuance of U.S. Patent Number 7,413,737 covering antibodies against human aspartyl (asparaginyl) beta-hydroxylase (HAAH), a proprietary human cancer biomarker and therapeutic target.

These antibodies were developed in collaboration with the Massachusetts Institute of Technology (MIT) and Panacea has exclusive, worldwide rights to this patent for development of human cancer diagnostics and therapeutics. Panacea is developing PAN-622, an all-human sequence anti-HAAH monoclonal antibody covered under this patent, as a cancer therapeutic antibody drug and anticipates the start of Phase 1 clinical trials in early 2009.

HAAH is a cancer molecular marker that has been detected by immunohistochemical staining in a broad range of cancers; this marker was originally discovered at the Rhode Island Hospital / Brown University. Research done both at Panacea and in collaboration with Brown University / Rhode Island Hospital has established HAAH as an excellent drug target for cancer therapy as well as a marker for cancer diagnosis. HAAH over-expression has been observed in more than twenty different cancers, and HAAH has been shown to be highly specific for cancer and absent in adjacent non-affected tissue as well as tissue from cancer-free individuals. In cancer, HAAH is found on the cell surface and in normal cells found in minute quantities inside the cell. As such, HAAH is an excellent therapeutic target. Panacea has demonstrated the efficacy of PAN-622, an all-human sequence anti-HAAH monoclonal antibody, in animal models of cancer. In these experiments PAN-622 inhibited tumor growth in 90 percent of animals, with 40 percent showing no visible tumor. Tumors did not re-grow beyond the period of drug administration. Due to its all human sequence, PAN-622 is anticipated to have low toxicity in humans. And PAN-622 is currently being manufactured under cGMP at high yields. Clinical trials of PAN-622 will be initiated in early 2009, with an initial indication for the treatment of liver cancer. In addition, the presence of HAAH protein in serum has been demonstrated to be highly sensitive and specific for cancer in hundreds of patients with a range of cancer types, and Panacea has developed serum diagnostic tests measuring HAAH for prostate lung, breast and colon cancer.

PAN-622 and other antibodies covered under U.S. Patent Number 7,413,737 were developed in collaboration with MIT using a proprietary yeast display technology. More detailed information is included in Yeung YA, Finney AH, Koyrakh IA, Lebowitz MS, Chanbari HA, Wands JR, Wittrup KD. Isolation and characterization of human antibodies targeting human aspartyl (asparaginyl) beta-hydroxylase. Hum Antibodies, 16(3-4):163-176, 2007.

"We are excited about receiving notice of the issuance of the patent covering antibodies against HAAH, and particularly PAN-622, our all-human sequence monoclonal antibody against HAAH," noted Hossein Ghanbari, Ph.D., Chairman, CEO and CSO at Panacea Pharmaceuticals. "We are quickly advancing PAN-622 toward clinical trials and we are confident that this monoclonal antibody will prove to have tremendous potential as a cancer therapeutic agent."

"HAAH is an excellent target for monoclonal antibody cancer therapeutics, and we have developed several high affinity antibodies against HAAH with good promise as cancer therapeutics," commented K. Dane Wittrup, Ph.D., Carbon P. Dubbs Professor of Chemical Engineering & Bioengineering at the Massachusetts Institute of Technology. "PAN-622 as an all-human sequence monoclonal antibody is particularly exciting, and its efficacy in preclinical mouse models of cancer is quite encouraging."

In addition to PAN-622, Panacea is developing an antibody-toxin conjugate utilizing PAN-622. Panacea has demonstrated that anti-HAAH antibodies are internalized upon binding to the cell surface of cancer cells. In addition, cytotoxicity as measured by a cell proliferation assay has been demonstrated following internalization of a PAN-622-toxin conjugate. This fact, coupled with the exclusivity of the surface expression of HAAH to cancer cells, suggests the potential clinical utility of PAN-622 for the specific delivery of cytotoxic agents to cancer cells.