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OLIGONUCLEOTIDES AS PRODRUGS FOR ANTICANCER DRUGS

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
60008
Program Year/Program:
2002 / SBIR
Agency Tracking Number:
CA091678
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
RELIABLE BIOPHARMACEUTICAL CORPORATION
RELIABLE BIOPHARMACEUTICAL CORP. BOX 2517, 1945 WALTON RD ST. LOUIS, MO 63114
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2002
Title: OLIGONUCLEOTIDES AS PRODRUGS FOR ANTICANCER DRUGS
Agency: HHS
Contract: 1R43CA091678-01A1
Award Amount: $100,000.00
 

Abstract:

DESCRIPTION (provided by applicant): The overall objected is to develop an easy controlled method of delivery for anticancer nucleoside drugs [cytarabine (araC); cladribine] in their polymeric form as oligonucleotides. The monomer drugs, currently are delivered slowly through continuous infusion in a hospital to avoid doses-related toxicities. They are phosphorytlated in the cytoplasm to the monophosphate the active metabolite. We have shown that poly araC, an oligonucleotide prodrug is degraded by nucleases to cytarabine monophosphate [araCMP] and that chimeric oligonucleotides [the prodrug] containing cytarabine and 2'O-alkyl nucleoside "speed bumps" degrade slower. Also, poly-araC, when transfected into HL-60 cells was degraded to araCMP and caused cell death. The specific aim in Phase I is to prepare various chimeric prodrug oligonucleotides with araC and 2'OMe-araU and study the rates of degradation in vitro and in HL6O and araC-resistant HL-60 cells. We expect to show that the araC-resistant cells are susceptible to araCMP, the metabolite from our prodrug oligonucleotides. We intend to show that the degradation is dependent upon 2'OMe-araU, the "speed bump nucleoside" used and that will be indicative of a controlled release version of these drugs. In Phase ll, the pharmacology, toxicology and efficacy of these oligonucleotide prodrugs in animals will be studied. PROPOSED COMMERCIAL APPLICATION: The proposed anticancer nucleoside prodrugs will localize inside the cytoplasm and in a controlled or timed release manner, degrade directly to the active metabolite {nucleoside monophosphate} in therapeutically relevant concentrations and thus reduce the cost of therapy by reducing the dose and the toxicity-related risks.

Principal Investigator:

Umashanker Sampath
3144297700
USAMPATH@RELIABLEBIOPHARM.COM

Business Contact:

Joseph Toce
3144297700
JTOCE@RELIABLEBIOPHARM.COM
Small Business Information at Submission:

RELIABLE BIOPHARMACEUTICAL CORPORATION
RELIABLE BIOPHARMACEUTICAL CORP. BOX 2517, 1945 WALTON RD ST. LOUIS, MO 63114

EIN/Tax ID: 430959527
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No