Symbol of the Government of Canada


Patent Document Number: 2771099

(54) English Title: CANCER CELL APOPTOSIS

(54) French Title: APOPTOSE DE CELLULES CANCEREUSES


Claims:

Note: Claims are shown in the official language in which they were submitted.



Claims

1. A therapeutic agent capable of directly or indirectly having an effect on
the
proteins N-methyl-D-aspartate (NMDA), Cyclooxygenase-2 (COX-2), Tumour
Necrosis factor alpha (TNF-a), Nuclear factor-kappa B(NF .kappa. B), Cyclin-
dependent
kinases, e.g. CDK2/A and CDK5/p25, Histone acetyltransferase (HAT) and
Farnesyltransferase, simultaneously, sequentially or separately

2. A therapeutic agent according to claim 1 wherein the therapeutic agent is
dexanabinol or a derivative thereof.

3. A therapeutic agent according to claims 1 or 2 for the apoptosis of cancer
cells
wherein the cancer cells are selected from one or more of primary cancer,
breast
cancer, colon cancer, prostate cancer, non-small cell lung cancer,
glioblastoma,
lymphoma, mesothelioma, liver cancer, intrahepatic bile duct cancer,
oesophageal
cancer, pancreatic cancer, stomach cancer, laryngeal cancer, brain cancer,
ovarian
cancer, testicular cancer, cervical cancer, oral cancer, pharyngeal cancer,
renal cancer,
thyroid cancer, uterine cancer, urinary bladder cancer, hepatocellular
carcinoma,
thyroid carcinoma, osteosarcoma, small cell lung cancer, leukaemia, myeloma,
gastric
carcinoma and metastatic cancers.

4. A therapeutic agent according to any preceding claim for the apoptosis of
cancer cells wherein the cancer cells are selected from one or more of
pancreatic
carcinoma, glioblastoma, gastric carcinoma, oesophageal carcinoma, ovarian
carcinoma, renal carcinoma and thyroid carcinoma.


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5. A therapeutic agent according to anyone of claims 1 to 3 for the apoptosis
of
cancer cells wherein the cancer cells are selected from one or more of primary
cancer,
breast cancer, colon cancer, prostate cancer, non-small cell lung cancer,
glioblastoma,
lymphoma, and metastatic cancers.

6. Dexanabinol, or a derivative thereof, for the apoptosis of cancer in a
patient,
wherein the cancer cells are selected from one or more of primary cancer,
breast
cancer, colon cancer, prostate cancer, non-small cell lung cancer,
glioblastoma,
lymphoma, mesothelioma, liver cancer, intrahepatic bile duct cancer,
oesophageal
cancer, pancreatic cancer, stomach cancer, laryngeal cancer, brain cancer,
ovarian
cancer, testicular cancer, cervical cancer, oral cancer, pharyngeal cancer,
renal cancer,
thyroid cancer, uterine cancer, urinary bladder cancer, hepatocellular
carcinoma,
thyroid carcinoma, osteosarcoma, small cell lung cancer, leukaemia, myeloma,
gastric
carcinoma and metastatic cancers.

7. Dexanabinol, or a derivative thereof, according to claim 6 for the
apoptosis of
cancer cells wherein the cancer cells are selected from one or more of
pancreatic
carcinoma, glioblastoma, gastric carcinoma, oesophageal carcinoma, ovarian
carcinoma, renal carcinoma and thyroid carcinoma.

8. Dexanabinol, or a derivative thereof, according to claim 6 wherein the
cancer
cells are selected from one or more of primary cancer, breast cancer, colon
cancer,
prostate cancer, non-small cell lung cancer, glioblastoma, lymphoma, and
metastatic
cancers.





9. Dexanabinol, or a derivative thereof, according to anyone of claims 6 to 8
which comprises a therapeutically effective amount sufficient for apoptosis of
a
cancer cell.

10. Dexanabinol, or a derivative thereof, according to anyone of claims 6 to 9

wherein the dexanabinol, or a derivative thereof, directly or indirectly has
an effect
on the proteins N-methyl-D-aspartate (NMDA), Cyclooxygenase-2 (COX-2), Tumour
Necrosis factor alpha (TNF-a), Nuclear factor-kappa B(NF .kappa. B), Cyclin-
dependent
kinases, e.g. CDK2/A and CDK5/p25, Histone acetyltransferase (HAT) and
Farnesyltransferase, simultaneously, sequentially or separately.

11. Dexanabinol, or a derivative thereof, according to anyone of claims 6 to
10
which comprises a therapeutically effective amount of dexanabinol, or a
derivative
thereof, sufficient to inhibit tumourigenesis of a cancer cell.

12. Dexanabinol, or a derivative thereof, according to anyone of claims 6 to
11 in
combination with another cancer treating therapeutic agent.

13. Dexanabinol, or a derivative thereof, according to claim 12 in combination

with another cancer treating therapeutic agent wherein the other cancer
treating
therapeutic agent is suitable for inhibition of tumourigenesis, inhibition of
cell
proliferation, or induction of cytotoxicity.

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14. Dexanabinol, or a derivative thereof, according to anyone of claims 6 to
11
wherein the cancer to be treated is premalignant, malignant, metastatic, or
multidrug-
resistant, and combinations thereof.

15. Dexanabinol, or a derivative thereof, according to claim 14 wherein the
cancer
is one or more metastatic cancers.

16. A method of treating cancer wherein the method comprises the apoptosis of
the cancer, which comprises the administration of a therapeutically effective
amount
of an agent capable of directly or indirectly having an effect on to the
proteins N-
methyl-D-aspartate (NMDA), Cyclooxygenase-2 (COX-2), Tumour Necrosis factor
alpha (TNF-a), Nuclear factor-kappa B(NF .kappa. B), Cyclin-dependent kinases,
e.g.
CDK2/A and CDK5/p25, Histone acetyltransferase (HAT) and Farnesyltransferase,
simultaneously, sequentially or separately wherein the cancer cells are
selected from
one or more of primary cancer, breast cancer, colon cancer, prostate cancer,
non-small
cell lung cancer, glioblastoma, lymphoma, mesothelioma, liver cancer,
intrahepatic
bile duct cancer, oesophageal cancer, pancreatic cancer, stomach cancer,
laryngeal
cancer, brain cancer, ovarian cancer, testicular cancer, cervical cancer, oral
cancer,
pharyngeal cancer, renal cancer, thyroid cancer, uterine cancer, urinary
bladder
cancer, hepatocellular carcinoma, thyroid carcinoma, osteosarcoma, small cell
lung
cancer, leukaemia, myeloma, gastric carcinoma and metastatic cancers.

17. A method according to claim 16 for the apoptosis of cancer cells wherein
the
cancer cells are selected from one or more of pancreatic carcinoma,
glioblastoma,

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gastric carcinoma, oesophageal carcinoma, ovarian carcinoma, renal carcinoma
and
thyroid carcinoma.

18. A method according to claim 16 wherein the cancer cells are selected from
one or more of primary cancer, breast cancer, colon cancer, prostate cancer,
non-small
cell lung cancer, glioblastoma, lymphoma, and metastatic cancers.

19. A method according to anyone of claim 16 to 18 which comprises the
administration of a single therapeutic agent for directly or indirectly having
an effect
on the proteins N-methyl-D-aspartate (NMDA), Cyclooxygenase-2 (COX-2), Tumour
Necrosis factor alpha (TNF-a), Nuclear factor-kappa B (NF .kappa. B), Cyclin-
dependent
kinases, e.g. CDK2/A and CDK5/p25, Histone acetyltransferase (HAT) and
Farnesyltransferase, simultaneously, sequentially or separately.

20. A method according to anyone of claim 16 to 19 wherein the method
comprises administration of a therapeutically effective amount of dexanabinol,
or a
derivative thereof, to a patient in need of such a therapy.

21. A method according to claim 20 wherein the method comprises administration

of a therapeutically effective amount of dexanabinol, or a derivative thereof,
sufficient
to inhibit tumourigenesis of a cancer cell.

22. A method according to claim 20 wherein the method comprises administration

of a therapeutically effective amount dexanabinol, or a derivative thereof,
sufficient to
induce cytotoxicity in the cancer cell.

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23. A method according to claim 17 wherein the method comprises administration

of dexanabinol, or a derivative thereof, wherein the amount administered to a
patient
is sufficient to achieve a plasma concentration of dexanabinol from 10 to 20
然.

24. A method according to claim 17 wherein the method comprises administration

of an effective amount of dexanabinol, or a derivative thereof, sufficient to
achieve a
plasma concentration of at least 10 然 of therapeutic agent and is
maintained for at
least 2 hours in the patient.

25. A method according to claims 14 or 17 wherein the cancer cells are
premalignant, malignant, metastatic or multidrug-resistant and combinations
thereof.
26. A method according to claim 17 which comprises administration of
dexanabinol, or a derivative thereof, in combination with another cancer
treating
therapeutic agent a derivative thereof, separately, simultaneously or
sequentially.

27. A method according to claim 23 in combination with another cancer treating

therapeutic agent wherein the other cancer treating therapeutic agent is
suitable for
inhibition of tumourigenesis, inhibition of cell proliferation, or induction
of
cytotoxicity.

28. A method according to claim 23 wherein the other therapeutic agent
comprises
a chemotherapeutic agent, immunotherapeutic agent, gene therapy or radio
therapeutic agent.

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29. A method of simultaneously, sequentially or separately directly or
indirectly
having an effect on proteins N-methyl-D-aspartate (NMDA), Cyclooxygenase-2
(COX-2), Tumour Necrosis factor alpha (TNF-a), Nuclear factor-kappa B(NF
.kappa. B),
Cyclin-dependent kinases, e.g. CDK2/A and CDK5/p25, Histone acetyltransferase
(HAT) and Famesyltransferase, which comprises the administration of an
effective
amount of dexanabinol, or a derivative thereof.

30. A method according to claim 17 wherein the dexanabinol, or a derivative
thereof, is administered topically, transdermally, subcutaneously,
intravenously, or
orally.

31. A method according to claim 27 wherein the dexanabinol, or a derivative
thereof, is administered topically.

32. The use of dexanabinol, or a derivative thereof, in the manufacture of a
medicament for the apoptosis of cancer in a patient, wherein the cancer cells
are
selected from one or more of primary cancer, breast cancer, colon cancer,
prostate
cancer, non-small cell lung cancer, glioblastoma, lymphoma, mesothelioma,
liver
cancer, intrahepatic bile duct cancer, oesophageal cancer, pancreatic cancer,
stomach
cancer, laryngeal cancer, brain cancer, ovarian cancer, testicular cancer,
cervical
cancer, oral cancer, pharyngeal cancer, renal cancer, thyroid cancer, uterine
cancer,
urinary bladder cancer, hepatocellular carcinoma, thyroid carcinoma,
osteosarcoma,
small cell lung cancer, leukaemia, myeloma, gastric carcinoma and metastatic
cancers.





33. The use according to claim 32 wherein the cancer cells wherein the cancer
cells are selected from one or more of pancreatic carcinoma, glioblastoma,
gastric
carcinoma, oesophageal carcinoma, ovarian carcinoma, renal carcinoma and
thyroid
carcinoma.

34. The use according to claim 32 wherein the cancer cells are selected from
one
or more of primary cancer, breast cancer, colon cancer, prostate cancer, non-
small cell
lung cancer, glioblastoma, lymphoma, and metastatic cancers.

35. The use according to anyone of claims 32 to 34 wherein the amount of
dexanabinol, or a derivative thereof, administered to a patient is sufficient
to achieve a
plasma concentration of dexanabinol from 10 to 20 然.

36. The use according to claim 29 wherein the amount of dexanabinol, or a
derivative thereof, sufficient to achieve a plasma concentration of at least
10 然 of
therapeutic agent and is maintained for at least 2 hours in the patient.

37. A pharmaceutical composition comprising dexanabinol, or a derivative
thereof, wherein the amount of dexanabinol, or a derivative thereof, present
is
sufficient to achieve a plasma concentration of dexanabinol from 10 to 20
然.

38. A pharmaceutical composition comprising dexanabinol, or a derivative
thereof, wherein the amount of dexanabinol, or a derivative thereof,
sufficient to
achieve a plasma concentration of at least 10 然 of dexanabinol and is
maintained for
at least 2 hours in the patient.

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39. A compound, method, composition or the use substantially as hereinbefore
described with reference to the accompanying examples.



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