Methods and compositions for the treatment of cancer

• US 10,385,343 B2
• Filed: 08/28/2015
• Issued: 08/20/2019
• Est. Priority Date: 08/29/2014
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Lieberman, Judy, Gilboa-Geffen, Adi, Wheeler, Lee Adam
• Primary Examiner(s): Poliakova-Georgantas, Ekaterina
• Application Number:
  US15/506,010
• Publication Number:
  US 20170275629A1
• Time in Patent Office: 1,453 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/5152 Tumor cells
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/16 Aptamers
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/3519 Fusion with another nucleic acid
• CPC Class Codes: C12N 2310/3533 Halogen

Abstract

Described herein are methods and compositions relating to the treatment of cancer, e.g., breast cancer, using, e.g., aptamer-siRNA chimera molecules.

Claims

1. A method of treating cancer, the method comprising administering a chimeric molecule comprising an EPCAM binding aptamer domain and an inhibitory nucleic acid domain,

wherein the inhibitory nucleic acid inhibits the expression of Plk1

and wherein the chimeric molecule is an aptamer-siRNA chimera (AsiC) comprising the sequence of SEQ ID NO:

1 or SEQ ID NO;

3.

2. The method of claim 1, wherein the cancer is an epithelial cancer, breast cancer or triple-negative breast cancer.

3. The method of claim 1, wherein the administration is subcutaneous.

4. The method of claim 1, wherein the subject is further administered an additional cancer treatment.

5. The method of claim 4, wherein the cancer treatment is paclitaxel.

6. The method of claim 1, wherein the 3′

end of the chimeric molecule comprises dTdT.

7. The method of claim 1, wherein the chimeric molecule comprises at least one 2′

-F pyrimidine.