Symbol of the Government of Canada


Patent Document Number: 2408535

(54) English Title: COMPOSITIONS COMPRISING DENDRIMER COMPLEXES

(54) French Title: COMPOSITIONS COMPRENANT DES COMPLEXES DE DENDRIMERES


Claims:

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


CLAIMS:
1. A composition comprising a dendrimer complex, said
dendrimer complex comprising a first dendrimer comprising a
first agent and a second dendrimer comprising a second
agent, wherein said first agent is a therapeutic agent and
said second agent is a targeting agent, and wherein said
first dendrimer is different than said second dendrimer with
regard to the number of layers and/or polymer chemistry.

2. The composition of claim 1, wherein said first or
second dendrimer comprises acetymide capping.

3. The composition of claim 1, wherein said first
dendrimer is covalently linked to said second dendrimer.
4. The composition of claim 1, further comprising a
third dendrimer, wherein said third dendrimer is covalently
linked to said first and said second dendrimers.

5. The composition of claim 4, wherein said first
dendrimer is not covalently linked to said second dendrimer.
6. The composition of claim 4, further comprising a
third agent complexed with said third dendrimer.

7. The composition of claim 4, further comprising a
fourth dendrimer comprising a third agent, wherein said
fourth dendrimer is covalently linked to said third
dendrimer.

8. The composition of claim 7, further comprising a
fifth dendrimer comprising a fourth agent, wherein said
fifth dendrimer is complexed with said third dendrimer.

9. The composition of claim 1, wherein said
therapeutic agent is selected from a chemotherapeutic agent,
an anti-oncogenic agent, an antivascularizing agent, and an
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expression construct comprising a nucleic acid encoding a
therapeutic protein.

10. The composition of claim 1, wherein said
therapeutic agent is protected with a protecting group
selected from photo-labile, radio-labile, and enzyme-labile
protecting groups.

11. The composition of claim 9, wherein said
therapeutic agent is a chemotherapeutic agent selected from
platinum complex, verapamil, podophyllotoxin, carboplatin,
procarbazine, mechlorethamine, cyclophosphamide,
camptothecin, ifosfamide, melphalan, chlorambucil, bisulfan,
nitrosurea, dactinomycin, daunorubicin, doxorubicin,
bleomycin, plicomycin, mitomycin, etoposide, tamoxifen,
paclitaxel, transplatinum, 5-fluorouracil, vincristin,
vinblastin, and methotrexate.

12. The composition of claim 9, wherein said
therapeutic agent is an anti-oncogenic agent comprising an
antisense nucleic acid.

13. The composition of claim 12, wherein said
antisense nucleic acid comprises a sequence complementary to
an RNA of an oncogene.

14. The composition of claim 13, wherein said oncogene
is selected from abl, Bcl-2, Bcl-x1, erb, fms, gsp, hst,
jun, myc, neu, raf, ras, ret, src, and trk.

15. The composition of claim 9, wherein said
therapeutic agent is an expression construct comprising a
nucleic acid encoding a therapeutic protein, wherein said
nucleic acid encodes a factor selected from a tumor
suppressor, cytokine, receptor, inducer of apoptosis, and
differentiating agent.



16. The composition of claim 15, wherein said factor
is a tumor suppressor selected from BRCA1, BRCA2, C-CAM,
p16, p21, p53, p73, Rb, and p27.

17. The composition of claim 15, wherein said factor
is a cytokine selected from GMCSF, IL-1, IL-2, IL-3, IL-4,
IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL12, IL-13, IL-
14, IL-15, .beta.-interferon, y-interferon, and TNF.

18. The composition of claim 15, wherein said factor
is a receptor selected from CFTR, EGFR, estrogen receptor,
IL-2 receptor, and VEGFR.

19. The composition of claim 15, wherein said factor
is an inducer of apoptosis selected from AdE1B, Bad, Bak,
Bax, Bid, Bik, Bim, Harakid, and ICE-CED3 protease.

20. The composition of claim 1, wherein said
therapeutic agent comprises a short-half life radioisotope.
21. The composition of claim 1, wherein said targeting
agent is selected from an antibody, receptor ligand,
hormone, vitamin, and an antigen.

22. The composition of claim 21, wherein said
targeting agent is an antibody specific for a disease
specific antigen.

23. The composition of claim 22, wherein said disease
specific antigen comprises a tumor specific antigen.

24. The composition of claim 21, wherein said
targeting agent is a receptor ligand selected from a ligand
for CFTR, EGFR, estrogen receptor, FGR2, folate receptor,
IL-2 receptor, glycoprotein, and VEGFR.

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25. The composition of claim 4, wherein said first and
second dendrimers comprise PAMAM dendrimers and wherein said
third dendrimer comprises a POPAM dendrimer.

26. The composition of claim 1, wherein said first
dendrimer comprises a first nucleic acid linker and said
second dendrimer comprises a second nucleic acid linker,
wherein said first nucleic acid linker is hybridized to said

second nucleic acid linker.

27. The composition of claim 26, wherein a duplex
formed from hybridization of said first linker to said
second linker comprises a cleavage site.

28. The composition of claim 27, wherein said cleavage
site comprises a nuclease recognition site.

29. The composition of claim 28, wherein said nuclease
recognition site comprises a restriction endonuclease
recognition site.

30. A composition comprising a plurality of
dendrimers, said dendrimers comprising acetymide capping,
wherein said dendrimers are conjugated to a therapeutic or
targeting agent.

31. Use of a composition according to any one of
claims 1 to 30 for treating a cell.

32. Use of a composition according to any one of
claims 1 to 30 in the manufacture of a medicament for
treating a cell.

33. The use according to claim 31 or 32, wherein said
cell is present in a subject.

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34. The use according to claim 33, wherein said
subject has a disease.

35. The use according to claim 34, wherein said
disease is selected from the group consisting of cancer,
cardiovascular disease, inflammatory disease, and prion-type
disease.

36. The use according to claim 33, wherein said
therapeutic agent is in an inactive form and is rendered
active following administration of said composition to said
subject.

37. The use according to claim 33, wherein said
subject has a tumor.

38. The use according to claim 33, wherein said
composition is used endoscopically, intratracheally,
intralesionally, percutaneously, intravenously,
subcutaneously, or intratumorally.

39. The use according to claim 35, wherein said
disease is cancer, and said cancer is selected from lung,
breast, melanoma, colon, renal, testicular, ovarian,
prostate, hepatic, germ cancer, epithelial, head and neck,
pancreatic cancer, glioblastoma, astrocytoma,
oligodendroglioma, ependymomas, neurofibrosarcoma, meningia,
spleen, lymph node, small intestine, stomach, thyroid,
endometrium, skin, esophagus, and bone marrow cancer.

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