Irofulven and Novel Derivatives for Cancer Treatment
Tech ID: 22048 / UC Case 2005-D37-0
Background
In randomized Phase II clinical trials, the IND-approved drug, irofulven, produced a significant increase in both median lifespan and landmark survival rate in patients with taxane-refractory prostate cancer when compared to the patient population receiving the standard chemotherapy regimen for this disease. In contrast, other experimental agents for prostate cancer (OGX-11, Provenge) have not been effective against this form of prostate cancer. Furthermore, manageable toxicity in this refractory and difficult-to-treat, elderly patient population puts irofulven as the lead in a pipeline of analogs and derivatives, which are at various stages of development.Technology Description
In a continuing effort to improve target and site selectivity, UC San Diego researchers have synthesized numerous, novel derivatives of the acylfulvene, irofulven. Irofulven has progressed through Phase II clinical trials and newer compositions have been assessed in terms of pre-clinical, in vivo efficacy, structure–activity correlations, and mechanism of action.Applications
- Treatment of taxane-refractory prostate cancer.
- NCEs for treatment of other solid tumors, including hepatoma, colorectal, endometrial cancer, sarcoma, and thyroid cancer.
- Demonstrated activity as monotherapy and in-combination therapy with other agents, including cisplatin, capecitabine, prednisone, and oxaliplatin.
Advantages
- Parent compound, irofulven, safe in numerous clinical trials for various indications.
- Validated leads for follow-on INDs supported by xenograft data.
- Improved therapeutic window for new derivatives (preclinical validation).
- Improved bio-stability and reduced reactivity with thiols.
- Ease of synthesis.
- Extensive portfolio of patents, claiming compositions of matter and methods of use, in U.S., Europe, and worldwide.
State Of Development
In vivo studies in a demanding, murine xenograft model of metastatic lung carcinoma identify several analogs that induce tumor shrinkage at doses that are non-toxic to the animal. In vitro experiments show increased target specificity and reduced cytotoxicity to non-target cells.Intellectual Property Info
Published U.S. patent/applications include 20080306147, 7,629,380, 7,141,603, 6,987,193, 6,908,918, 6,855,696, 6,717,017, 6,639,105, 6,548,679, 6,469,184, 6,380,403, 6,323,181, 6,252,093, 6,160,184, 5,932,553, 5,723,632.Patent Status
| Country | Type | Number | Dated | Case |
| United States Of America | Issued Patent | 7,713,939 | 05/11/2010 | 1996-D35 |
| United States Of America | Issued Patent | 7,655,695 | 02/02/2010 | 2005-D37 |
| United States Of America | Issued Patent | 7,629,380 | 12/08/2009 | 1998-C59 |
| United States Of America | Issued Patent | 7,141,603 | 11/28/2006 | 1998-C59 |
| United States Of America | Issued Patent | 6,987,193 | 01/17/2006 | 1996-D35 |
| United States Of America | Issued Patent | 6,855,696 | 02/15/2005 | 1998-C59 |
| United States Of America | Issued Patent | 6,639,105 | 10/28/2003 | 1996-D35 |
| United States Of America | Issued Patent | 6,548,679 | 04/15/2003 | 1998-C59 |
| United States Of America | Issued Patent | 6,469,184 | 10/22/2002 | 1996-C68 |
| United States Of America | Issued Patent | 6,380,403 | 04/30/2002 | 1996-D35 |
| United States Of America | Issued Patent | 6,160,184 | 12/12/2000 | 1996-C68 |
| United States Of America | Issued Patent | 5,932,553 | 08/03/1999 | 1996-D35 |
| United States Of America | Issued Patent | 5,723,632 | 03/03/1998 | 1996-C68 |
| United States Of America | Issued Patent | 5,523,490 | 06/04/1996 | 1988-B96 |
Related Materials
- McMorris et. al., "Structure−Activity Studies of Urea, Carbamate, and Sulfonamide Derivatives of Acylfulvene" (2010), J. Med. Chem. e-published January 12, 2010.
- Alexandre J. et al., A Phase I and Pharmacokinetic Study of Irofulven and Capecitabine Administered Every 2 Weeks in Patients with Advanced Solid Tumors. (2007) Invest New Drugs. 25(5):453-62.
- Senzer N. et al., Irofulven Demonstrates Clinical Activity Against Netastatic Hormone-Refractory Prostate Cancer in a Phase 2 Single-Agent Trial. (2005) Am J Clin Oncol. 28(1):36-42.
- Woynarowska B.A. et al., Targeting Apoptosis by Hydroxymethylacylfulvene in Combination with Gamma Radiation in Prostate Tumor Cells. (2000) Radiat Res. 154(4):429-38.
- Berger Prostate 2B Results ASCO 2007 #5068.
- Falcon-Lizaraso P1 Iro Mono in HCC ASCO 2004 #4083.
- Goldwasser P1 Iro + Oxal HCC Responders Abstract 14082 ASCO 2006.
- Stuart P2 Iro HCC ASCO 2003 #1107.
- Hart P2 Actual Presentation of Irofulven Combinations in HRPC Abstract 299 Proc EORTC-NCI-AACR 2006.
Other Information
Categorized As
Related cases
2005-D37-0, 1998-C59-0, 1996-D35-0, 1988-B96-0, 1996-C68-0
Keywords
acylfulvene, analog, Illudin, oncology, prostate, solid tumors, tumor, NCE, new chemical entity, composition of matter, combination, cisplatin, capecitabine, prednisone, oxaliplatin, taxane-refractory,, methods of use, synthesis, therapeutic, hepatoma, colorectal, endometrial cancer, sarcoma, thyroid cancer
Contact
University of California, San Diego Technology Transfer Office / invent@ucsd.edu / tel: View Phone Number. Please reference Tech ID #22048.
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