本院覽號:12A-870326
創作人:羅傅倫、陳基旺、呂玉玲
智財權:獲證專利 US6,043,367
摘要:
A glucuronide prodrug of 9-aminocamptothecin was invented that displays high water solubility, low toxicity and good stability. This prodrug is activated by beta-glucuronidase. It displays potent antitumor activity against human tumors in nude mice. It can also be selectively activated at tumor cells after injection of an antibody-glucuronidase conjugate that binds to tumor-associated antigens. This type of treatment can cure solid human xenografts in nude mice.
可能的應用範圍:
Therapy of human cancers by monotherapy (injection of the glucuronide prodrug alone) or by ADEPT (injection of an antibody-glucuronidase conjugate followed by injection of the prodrug).
此項發明的優點:
Camptothecin diplays potent antitumor activity but in very water insoluble. Currently, two water-soluble derivatives of camptothecin have been approved for use in humans. These are CPT-11 and topotecan. Our prodrug displays excellent water solubility and low toxicity. It can be converted to 9-aminocamptothcin by beta-glucuronidase present at the tumor site. Tumor selectivity is thereby achieved. It has demonstrated as good as well as much better activity than CPT-11 against human tumor xenografts. This prodrug may therefore be superior to current drugs in clinical use. In addition, the new prodrug can be employed for antibody-directed enzyme prodrug therapy of cancer. An immunoenzyme composed of a targeting antibody and beta glucuronidase is first injected. This allows accumulation of enzyme at the tumor. The glucuronide prodrug is then injected whereby it is selectively converted to 9-aminocamptothecin at the tumor cells. Selectivity of cancer therapy can be greatly enhanced by this strategy, reducing side-effects of therapy. ●formulation improved (water soluble) ●low toxicity ●tumor selective ●potent antitumor activity
智財技轉處聯絡人:李梅芳 / 02-2787-2503 / mflee@gate.sinica.edu.tw
智財權:獲證專利 US6043367