US2009118205A2PendingUtilityA2

Antisense Oligonucleotides Directed to Ribonucleotide Reductase R2 and uses Thereof in the Treatment of Cancer

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Assignee: LORUS THERAPEUTICS INCPriority: Feb 10, 2003Filed: Aug 10, 2005Published: May 7, 2009
Est. expiryFeb 10, 2023(expired)· nominal 20-yr term from priority
Inventors:Jim A. WrightAiping H. Young
A61P 35/02A61K 31/7048A61P 35/00A61K 31/7072A61K 31/573A61K 31/704A61K 31/4745C12N 2310/315A61K 38/00C12N 15/1137A61K 31/19
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Claims

Abstract

The present invention provides antisense oligonucleotides directed to a mammalian ribonucleotide reductase R2 gene and combinations of the antisense oligonucleotides with one or more chemotherapeutic agents for use in the treatment of cancer.

Claims

exact text as granted — not AI-modified
161 . A dosage unit formulation comprising an antisense oligonucleotide of between about 7 and 100 nucleotides in length comprising at least 7 consecutive nucleotides of a sequence as set forth in SEQ ID NO: 1 in an amount effective to provide a dose of between about 2 mg/kg/day and 10 mg/kg/day to a human.  
     
     
         162 . The dosage unit formulation according to  claim 161 , wherein said dosage unit formulation is for the treatment of leukemia in said human.  
     
     
         163 . The dosage unit formulation according to  claim 162 , wherein said leukemia is acute myeloid leukemia.  
     
     
         164 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide is in an amount effective to provide a dose of between about 3 mg/kg/day and 8 mg/kg/day to said human.  
     
     
         165 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide is in an amount effective to provide a dose of between about 3 mg/kg/day and 5 mg/kg/day to said human.  
     
     
         166 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide is in an amount effective to provide a dose of about 3.5 mg/kg/day of said antisense oligonucleotide to said human.  
     
     
         167 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide is in an amount effective to provide a dose of about 5 mg/kg/day of said antisense oligonucleotide to said human.  
     
     
         168 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide is between about 7 and 50 nucleotides in length.  
     
     
         169 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide is between about 15 and 25 nucleotides in length.  
     
     
         170 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide is between about 20 and 100 nucleotides in length.  
     
     
         171 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide comprises the sequence as set forth in SEQ ID NO: 1.  
     
     
         172 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide consists of the sequence as set forth in SEQ ID NO: 1.  
     
     
         173 . The dosage unit formulation according to  claim 161 , wherein said dosage unit formulation is formulated for intravenous administration.  
     
     
         174 . The dosage unit formulation according to  claim 161 , wherein said dosage unit formulation is an injectable formulation.  
     
     
         175 . The dosage unit formulation according to  claim 162 , wherein said dosage unit formulation is administered in combination with one or more chemotherapeutic agents.  
     
     
         176 . The dosage unit formulation according to  claim 175 , wherein at least one of said one or more chemotherapeutic agents is cytarabine.  
     
     
         177 . The dosage unit formulation according to  claim 175 , wherein said one or more chemotherapeutic agents is cytarabine.  
     
     
         178 . The dosage unit formulation according to  claim 177 , wherein said cytarabine is administered to said human at a dose of between about 5 mg/m 2 /day and 3000 mg/m 2 /day.  
     
     
         179 . The dosage unit formulation according to  claim 177 , wherein said cytarabine is administered to said human at a dose of between about 1500 mg/m 2 /12 hours and 2000 mg/m 2 112 hours.  
     
     
         180 . The dosage unit formulation according to  claim 177 , wherein said cytarabine is administered to said human at a dose of between about 2000 mg/m 2 /12 hours and 3000 mg/m 2 /12 hours.  
     
     
         181 . The dosage unit formulation according to  claim 177 , wherein said cytarabine is administered intravenously.  
     
     
         182 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide is a modified or substituted oligonucleotide.  
     
     
         183 . The dosage unit formulation according to  claim 161 , wherein said antisense oligonucleotide is a phosphorothioated oligonucleotide.  
     
     
         184 . A method of treating cancer in a human comprising administering to said human an effective amount of the dosage unit formulation according to  claim 161 .  
     
     
         185 . The method according to  claim 184 , wherein said cancer is leukemia.  
     
     
         186 . The method according to  claim 185 , wherein said leukemia is acute myeloid leukemia.  
     
     
         187 . The method according to  claim 184 , wherein said antisense oligonucleotide is in an amount effective to provide a dose of between about 3 mg/kg/day and 8 mg/kg/day to said human.  
     
     
         188 . The method according to  claim 184 , wherein said antisense oligonucleotide is in an amount effective to provide a dose of between about 3 mg/kg/day and 5 mg/kg/day to said human.  
     
     
         189 . The method according to  claim 184 , wherein said antisense oligonucleotide is in an amount effective to provide a dose of about 3.5 mg/kg/day to said human.  
     
     
         190 . The method according to  claim 184 , wherein said antisense oligonucleotide is in an amount effective to provide a dose of about 5 mg/kg/day to said human.  
     
     
         191 . The method according to  claim 184 , wherein said antisense oligonucleotide is between about 7 and 50 nucleotides in length.  
     
     
         192 . The method according to  claim 184 , wherein said antisense oligonucleotide is between about 15 and 25 nucleotides in length.  
     
     
         193 . The method according to  claim 184 , wherein said antisense oligonucleotide is between about 20 and 100 nucleotides in length.  
     
     
         194 . The method according to  claim 184 , wherein said antisense oligonucleotide comprises the sequence as set forth in SEQ ID NO: 1.  
     
     
         195 . The method according to  claim 184 , wherein said antisense oligonucleotide consists of the sequence as set forth in SEQ ID NO: 1.  
     
     
         196 . The method according to  claim 184 , wherein said antisense oligonucleotide is a modified or substituted oligonucleotide.  
     
     
         197 . The method according to  claim 184 , wherein said antisense oligonucleotide is a phosphorothioated oligonucleotide.  
     
     
         198 . The method according to  claim 184 , wherein said dosage unit formulation is administered parenterally.  
     
     
         199 . The method according to  claim 184 , wherein said dosage unit formulation is administered intravenously.  
     
     
         200 . The method according to  claim 188 , wherein said dosage unit formulation is administered by continuous intravenous infusion for between 144 hours and 168 hours.  
     
     
         201 . The method according to  claim 184 , wherein said dosage unit formulation is administered in combination with one or more chemotherapeutic agents.  
     
     
         202 . The method according to  claim 201 , wherein said dosage unit formulation is administered prior to administration of said one or more chemotherapeutic agents.  
     
     
         203 . The method according to  claim 201 , wherein said dosage unit formulation is administered concurrently with said one or more chemotherapeutic agents.  
     
     
         204 . The method according to  claim 201 , wherein said dosage unit formulation is administered after administration of said one or more chemotherapeutic agents.  
     
     
         205 . The method according to  claim 201 , wherein at least one of said one or more chemotherapeutic agents is cytarabine.  
     
     
         206 . The method according to  claim 201 , wherein said one or more chemotherapeutic agents is cytarabine.  
     
     
         207 . The method according to  claim 206 , wherein said cytarabine is administered to said human at a dose of between about 5 mg/m 2 /day and 3000 mg/m 2 /day.  
     
     
         208 . The method according to  claim 206 , wherein said cytarabine is administered to said human at a dose of between about 1500 mg/m 2 112 hours and 2000 mg/m 2 /12 hours.  
     
     
         209 . The method according to  claim 206 , wherein said cytarabine is administered to said human at a dose of between about 2000 mg/m 2 /12 hours and 3000 mg/m 2 /12 hours.  
     
     
         210 . The method according to  claim 206 , wherein said cytarabine is administered intravenously.

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