Compositions and methods for treating pancreatic cancer

• US 9,963,703 B2
• Filed: 08/04/2017
• Issued: 05/08/2018
• Est. Priority Date: 02/09/2016
• Status: Active Grant

• Current Assignee: Autotelic LLC
• Original Assignee: Autotelic LLC
• Inventors: Trieu, Vuong
• Primary Examiner(s): Chong, Kimberly
• Application Number:
  US15/669,178
• Publication Number:
  US 20170342419A1
• Time in Patent Office: 277 Days
• Field of Search: 435 6, 514 44
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/655 Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/7125 Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2320/31 Combination therapy
• CPC Class Codes: C12N 2320/35 based on a specific dosage / administration regimen

Abstract

Provided herein are composition for sensitizing tumors to anti-tumor therapies. The compositions include antisense oligonucleotides against TGFβ2, wherein the compositions sensitize tumors to anti-tumor therapies. Also provided herein are method for treating cancer using the compositions described herein.

Claims

1. A method for treating pancreatic cancer in a human subject in need thereof, comprising:

(i) selecting a subject diagnosed with stage III or stage IV pancreatic cancer;

(ii) sensitizing a pancreatic tumor to a chemotherapeutic agent comprising, administering to the subject an effective amount of Trabedersen for at least one cycle prior to administration of the chemotherapeutic agent; and

(iii) subsequently administering an effective amount of the chemotherapeutic agent to the subject,

wherein the chemotherapeutic agent is paclitaxel, dacarbazine or a combination thereof, and wherein the cycle consists of administering Trabedersen for 4 days and not administering Trabedersen for 10 days,

so as to treat pancreatic cancer in the subject.

2. The method of claim 1, wherein the Trabedersen does not reduce the IC₅₀ of a chemotherapeutic agent.

3. The method of claim 1, wherein the effective amount of the Trabedersen is any one or more of 50-100 mg/m²/day, 100-150 mg/m²/day, 150-200 mg/m²/day 200-250 mg/m²/day, 250-300 mg/m²/day, 300-350 mg/m²/day, 350-400 mg/m²/day, 400-450 mg/m²/day, 450-500 mg/m²/day or a combination thereof.

4. The method of claim 1, wherein the effective amount of the Trabedersen is administered intravenously via continuous infusion.

5. The method of claim 4, wherein the Trabedersen is administered for one, two, three, four or five cycles prior to administration of chemotherapeutic agents, radiation therapy or a combination thereof.

6. A method for treating, inhibiting, reducing the severity of and/or preventing metastasis of pancreatic cancer in a subject in need thereof, comprising:

(i) sensitizing a pancreatic tumor to a chemotherapeutic agent comprising, administering to the subject an effective amount of Trabedersen prior to administration of the chemotherapeutic agent; and

(ii) subsequently administering an effective amount of the chemotherapeutic agent to the subject,

wherein the subject is human and has been diagnosed with stage III or stage IV pancreatic cancer,

so as to treat, inhibit, reduce severity of and/or prevent metastasis of pancreatic cancer in the subject.

7. The method of claim 6, wherein Trabedersen is administered for at least one 4 days on and 10 days off cycle prior to administration of the chemotherapeutic agent.

8. The method of claim 6, wherein Trabedersen is administered for two, three, four or more of 4 days on and 10 days off cycle.

9. The method of claim 6, wherein the chemotherapeutic agent is paclitaxel, dacarbazine or a combination thereof.

10. The method of claim 6, wherein the effective amount of the Trabedersen is any one or more of 50-100 mg/m²/day, 100-150 mg/m²/day, 150-200 mg/m²/day 200-250 mg/m²/day, 250-300 mg/m²/day, 300-350 mg/m²/day, 350-400 mg/m²/day, 400-450 mg/m²/day, 450-500 mg/m²/day or a combination thereof.

11. The method of claim 6, wherein the effective amount of the Trabedersen is administered intravenously via continuous infusion.