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Details for Patent: 6,699,843

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Details for Patent: 6,699,843

Title: Method for treatment of tumors using nucleic acid ligands to PDGF
Abstract:A method is provided for treating solid tumors comprising administering a composition comprising a PDGF aptamer and a cytotoxic agent. In a preferred embodiment the PDGF aptamer is identified using the SELEX process for the Systematic Evolution of Ligands by Exponential enrichment. A method is also provided for reducing the interstitial fluid pressure (IFP) of a solid tumor comprising administering a PDGF aptamer. Finally, a method is provided for increasing the uptake of cytotoxic agents into a tumor comprising administering a composition comprising a PDGF aptamer and a cytotoxic agent.
Inventor(s): Pietras; Kristian (Uppsala, SE), Ostman; Arne (Uppsala, SE), Heldin; Carl-Henrik (Uppsala, SE), Rubin; Kristofer (Uppsala, SE)
Assignee: Gilead Sciences, Inc. (Foster City, CA)
Filing Date:May 17, 2001
Application Number:09/859,724
Claims:1. A method for treating tumors comprising administering to a host having a tumor a therapeutically effective dose of a composition comprising a platelet-derived growth factor (PDGF) aptamer and a cytotoxic agent, whereby tumors are treated.

2. The method of claim 1 wherein said PDGF aptamer is identified according to a method comprising: a) preparing a candidate mixture of nucleic acids; b) contacting the candidate mixture of nucleic acids with PDGF, wherein nucleic acids having an increased affinity to PDGF relative to the candidate mixture may be partitioned from the remainder of the candidate mixture; c) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; and d) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids enriched for nucleic acids with relatively higher affinity and specificity for binding to PDGF, whereby a nucleic acid ligand of PDGF may be identified.

3. The method of claim 1 wherein said PDGF aptamer is SEQ ID NO:1.

4. The method of claim 1 wherein said cytotoxic agent is selected from the group consisting of Bleomycin, Cisplatin, and Pt analogues; Carboplatin and Iproplatin, Cyclophosphamide, Daunorubicin, Doxofluoridine, Doxorubicin, Etoposide, Epirubicin, 5-Flurouracil, Gemzar, Ifosfamide, Melphalan, Methotrexate, Mithramycin, Mitomycin C, Mitoxanthrone, Streptozotocin, Taxol and Taxotere, Vincristine, Vinblastine, Vindesine, Vinorelbine, Topotecan and CPT-11.

5. A method for reducing the interstitial fluid pressure (IFP) of a tumor comprising administering a PDGF aptamer to a host having a tumor, whereby the intestinal fluid pressure of a tumor is reduced.

6. The method of claim 5 wherein said PDGF aptamer is identified according to a method comprising: a) preparing a candidate mixture of nucleic acids; b) contacting the candidate mixture of nucleic acids with PDGF, wherein nucleic acids having an increased affinity to PDGF relative to the candidate mixture may be partitioned from the remainder of the candidate mixture; c) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; and d) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids enriched for nucleic acids with relatively higher affinity and specificity for binding to PDGF, whereby a nucleic acid ligand of PDGF may be identified.

7. The method of claim 5 wherein said PDGF aptamer is SEQ ID NO:1.

8. A method for increasing the uptake of cytotoxic agents into a tumor comprising administering to a host having a tumor a composition comprising a PDGF aptamer and a cytotoxic agent, whereby the uptake of cytotoxic agents into the tumor is increased.

9. The method of claim 8 wherein said PDGF aptamer is identified according to a method comprising: a) preparing a candidate mixture of nucleic acids; b) contacting the candidate mixture of nucleic acids with PDGF, wherein nucleic acids having an increased affinity to PDGF relative to the candidate mixture may be partitioned from the remainder of the candidate mixture; c) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; and d) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids enriched for nucleic acids with relatively higher affinity and specificity for binding to PDGF, whereby a nucleic acid ligand of PDGF may be identified.

10. The method of claim 8 wherein said PDGF aptamer is SEQ ID NO:1.

11. The method of claim 8 wherein said cytotoxic agent is selected from the group consisting of Bleomycin, Cisplatin, and Pt analogues; Carboplatin and Iproplatin, Cyclophosphamide, Daunorubicin, Doxofluoridine, Doxorubicin, Etoposide, Epirubicin, 5-Flurouracil, Gemzar, Ifosfamide, Melphalan, Methotrexate, Mithramycin, Mitomycin C, Mitoxanthrone, Streptozotocin, Taxol and Taxotere, Vincristine, Vinblastine, Vindesine, Vinorelbine, Topotecan and CPT-11.
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