A METHIONINASE FOR METHIONINE-DEPENDENT CHEMOTHERAPY

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$486,774.00
Award Year:
1990
Program:
SBIR
Phase:
Phase II
Contract:
n/a
Award Id:
7118
Agency Tracking Number:
7118
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
5325 Metro St, San Diego, CA, 92110
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
Peter H Stern Phd
(619) 299-3250
Business Contact:
() -
Research Institution:
n/a
Abstract
NEW APPROACHES ARE NECESSARY TO IMPROVE CHEMOTHERAPY OF SOLID TUMORS. FOR THIS PURPOSE, ANTICANCER, INC. HAS TAKEN ADVANTAGE OF THE CANCER-SPECIFIC METABOLIC DEFECT OF METHIONINE DEPENDENCE, WHICH CAUSES MANY TYPES OF CANCER CELLS TO REVERSIBLY ARREST LATE IN THE S/G2 PHASE OF THE CELL CYCLE IN MEDIUM WHERE METHIONINE (MET) HAS BEEN REPLACED BY HOMOCYSTEINE (HCY) (MET-HCY+ MEDIUM). THIS APPROACH HAS BEEN TERMED "METHIONINE-DEPENDENT CHEMOTHERAPY". TO BRING METHIONINE-DEPENDENT CHEMOTHERAPY CLOSER TO CLINICAL TRIALS, ANTICANCER, INC. PROPOSES TO ISOLATE A METHIONINASE THAT, UPON ADMINISTRATION TO THE ANIMAL OR PATIENT, WILL ALLOW THE MODULATION OF CIRCULATING LEVELS OF METHIONINE. THE BACTERIA ALCALIGENES FAECALIS AND PSEUDOMONAS PSEUDOALCALIGENES, WHICH CONTAIN A METHIONINASE THAT APPARENTLY DOES NOT CLEAVE HOMOCYSTEINE, HAVE BEEN IDENTIFIED. STATE-OF-THE-ART GENETIC SELECTION AND PROTEIN PURIFICATION PROCEDURES WILL BE USED TO ISOLATE A METHIONINASE WITH A LOW KM, A LONG HALF-LIFE IN THE CIRCULATION, AND A LOW TOXICITY FOR THE EXPERIMENTAL ANIMAL OR HUMAN PATIENT. THE METHIONINE-CLEAVING PROPERTIES, HALF-LIFE, AND TOXICITY OF THE ENZYME WILL BE TESTED IN RATS. PURIFICATION AND CHARACTERIZATION OF A DESIRABLE ENZYME IN PHASE I WILL LEAD TO CLONING THE METHIONINASE GENEIN PHASE II.

* information listed above is at the time of submission.

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