Combined approach to treatment of cancer using a c-myc antisense oligomer

• US 20030087861A1
• Filed: 05/17/2002
• Published: 05/08/2003
• Est. Priority Date: 05/17/2001
• Status: Abandoned Application

• Current Assignee: Avi Biopharma, Inc.
• Original Assignee: Avi Biopharma, Inc.
• Inventors: Iversen, Patrick L.
• Application Number:
  US10/151,008
• Publication Number:
  US 20030087861A1
• Time in Patent Office: Days
• US Class Current: 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 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 2310/312 Phosphonates
• CPC Class Codes: C12N 2310/3145 with the nitrogen in 3' or 5'-position
• CPC Class Codes: C12N 2310/3233 Morpholino-type ring
• CPC Class Codes: C12N 2310/3341 5-Methylcytosine

Abstract

Improved therapeutic methods for treatment of cancer by a combination treatment regimen that includes an oligomer to c-myc and a standard chemotherapeutic agent are provided.

Claims

1. In an improved method for the treatment of cancer susceptible to treatment by chemotherapy, the improvement comprising:

administering an oligomer antisense to c-myc to a cancer patient in combination with a chemotherapeutic agent, wherein said oligomer antisense to c-myc and said chemotherapeutic agent is to be administered sequentially at spaced apart time intervals of several hours after administration of the chemotherapeutic agent and at least one day after administration of the oligomer antisense.

2. The method of claim 1, wherein the oligomer antisense to c-myc is between 12-25 bases in length and contains the sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, and SEQ ID NO;

11.

3. The method of claim 1, wherein the antisense oligomer is characterized by,

(a) a backbone which is substantially uncharged;

(b) the ability to hybridize with the complementary sequence of a target RNA with high affinity at a Tm greater than 50°

C.;

(c) nuclease resistance; and

(d) the capability for active or facilitated transport into cells.

4. The method of claim 3, wherein the antisense oligomer backbone has a selected from the group consisting of

5. The method of claim 1, wherein said chemotherapeutic agent is selected from the group consisting of cisplatin, etoposide (VP-16), taxol, and analogs and derivatives thereof.

6. The method of claim 1, wherein administering of the antisense oligomer to c-myc begins at least one day after administering said chemotherapeutic agent.

7. The method of claim 6, wherein the administration of said oligomer composition, followed at least one day later by the administration of the chemotherapeutic agent represents a cycle of therapy which is repeated multiple times, each cycle separated by at least one day.

8. A kit for the treatment of cancer susceptible to treatment by chemotherapy, comprising a first composition comprising an oligomer antisense to c-myc and a second composition comprising a chemotherapeutic agent, wherein the first composition and the second composition are to be administered sequentially at spaced apart time intervals of at least one day after administration of the first composition and several hours after administration of the second composition.

9. The kit of claim 8, wherein the oligomer antisense to c-myc is between 12-25 bases in length and contains the sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, and SEQ ID NO;

11.

10. The kit of claim 8, wherein the antisense oligomer is characterized by,

(a) a backbone which is substantially uncharged;

(b) the ability to hybridize with the complementary sequence of a target RNA with high affinity at a Tm greater than 50°

C.;

(c) nuclease resistance; and

(d) the capability for active or facilitated transport into cells.

11. The kit of claim 10, wherein the antisense oligomer backbone has a structure selected from the group consisting of

12. The kit of claim 8, wherein said chemotherapeutic agent is selected from the group consisting of cisplatin, etoposide (VP-16), taxol, and analogs and derivatives thereof.

13. The kit of claim 8, wherein administering of the antisense oligomer to c-myc begins at least one day after administering said chemotherapeutic agent.

14. The kit of claim 13, wherein the administration of said oligomer composition, followed at least one day later by the administration of the chemotherapeutic agent represents a cycle of therapy which is repeated multiple times, each cycle separated by at least one day.

15. An oligomer composition for the treatment of cancer in a patient currently being treated by chemotherapy, comprising an oligomer antisense to c-myc, wherein the composition is administered prior to or following administration of a chemotherapeutic agent.

16. The oligomer composition of claim 15, which is between 12-25 bases in length and contains the sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, and SEQ ID NO;

11.

17. The oligomer of claim 15, which is characterized by,

(a) a backbone which is substantially uncharged;

(b) the ability to hybridize with the complementary sequence of a target RNA with high affinity at a Tm greater than 50°

C.;

(c) nuclease resistance; and

(d) the capability for active or facilitated transport into cells.

18. The oligomer composition of claim 17, which has a structure selected from the group consisting of