1. An isolated polynucleotide which will encode CDK4I or a biologically active fragment thereof.
2. A polynucleotide according to claim 1 having the nucleotide sequence contained in SEQUENCE ID Nos. 1-2.
3. A recombinant expression vector containing at least one of the polynucleotides of claim 1.
4. CDK4I or biologically active fragments thereof expressed by the recombinant expression vector of claim 3.
5. Isolated, substantially pure CDK4I or biologically active fragments thereof.
6. An isolated polypeptide having an amino acid sequence expressed by at least one of the polynucleotide sequences contained in SEQUENCE ID Nos. 3-5.
7. Isolated, functional variants of the polypeptide of claim 6.
8. The polynucleotide according to claim 2 wherein the polynucleotide contains a polymorphism.
9. The polynucleotide according to claim 8 wherein the polymorphism consists of the deletion or substitution of at least one base pair.
10. The polynucleotide according to claim 9 wherein the cytosine at position 166 of the mRNA corresponding to SEQUENCE ID.Nos.: 1-2 is substituted with thymine.
11. The polynucleotide according to claim 9 wherein the deletion includes a deletion of the base pairs from about position 180 to position 198 of SEQUENCE ID.No.: 1.
12. Oligonucleotides which will specifically hybridize to the polynucleotides of claim 1.
13. Oligonucleotides which will specifically hybridize to the polynucleotides of claim 2.
14. Antibodies which will specifically bind CDK4I or biologically active fragments thereof.
15. Antibodies which will specifically bind the polypeptide of claim 6.
16. Antibodies which will specifically bind at least one of the polypeptides of claim 7.
17. A pharmaceutical composition containing substantially pure CDK4I or biologically active fragments thereof and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition comprising the polypeptide of claim 4 in substantially pure form and a pharmaceutically acceptable carrier.
19. A pharmaceutical composition comprising the polypeptide of claim 6 in substantially pure form and a pharmaceutically acceptable carrier.
20. A pharmaceutical composition comprising at least one of the polypeptides of claim 7 in a substantially pure form and a pharmaceutically acceptable carrier.
21. A method for diagnosing a cancer condition in a human comprising detecting all or a polynucleotide encoding all or part of CDK4I in a biological cell sample from the human.
22. The method according to claim 21 wherein the biological cell sample comprises one or more somatic cells.
23. The method according to claim 21 wherein the biological cell sample comprises one or more germline cells.
24. The method according to claim 21 wherein the cancer condition comprises melanomas, gliomas, non-small cell lung cancers and leukemias.
25. The method according to claim 21 wherein the method further comprises detecting a polynucleotide which encodes all or a part of MTAse.
26. The method according to claim 21 wherein the PCR is used to amplify all or a part of the gene for CDK4I, if present, in the biological cell sample.
27. The method according to claim 26 wherein the PCR is competitive PCR.
28. The method according to claim 27 wherein any CDK4I polynucleotide is detected by ELISA.
29. A method for diagnosing a cancer condition in a human comprising detecting CDK4I in a biological cell sample from the human which sample is suspected of containing premalignant or malignant cells.
30. The method according to claim 29 wherein the CDK4I is detected by immunoassay.
31. A method for determining susceptibility to a cancer condition comprising detecting polymorphisms in the gene for CDK4I which polymorphisms cause a reduction in the biological activity of CDK4I.
32. The method according to claim 31 wherein the biological cell sample comprises one or more somatic cells.
33. The method according to claim 31 wherein the biological cell sample comprises one or more germline cells.
34. The method according to claim 31 wherein the cancer condition comprises melanomas, gliomas, non-small cell lung cancers and leukemias.
35. The method according to claim 31 wherein the method further comprises detecting a polynucleotide which encodes all or a part of MTAse.
36. The method according to claim 31 wherein the PCR is used to amplify all or a part of the gene for CDK4I, if present, in the biological cell sample.
37. The method according to claim 36 wherein the PCR is competitive PCR.
38. The method according to claim 37 wherein any CDK4I polynucleotide is detected by ELISA.
39. The method according to claim 31 wherein the polymorphism consists of a nonsense substitution of at least one base pair in a CDK4I gene exon.
40. The method according to claim 39 wherein the cancer condition is dysplastic nevus syndrome.
41. The method according to claim 31 wherein the polymorphism consists of a deletion of at least one base pair in a CDK4I gene exon.
42. The method according claim 41 wherein the cancer condition is leukemia.
43. A method for inhibiting CDK4 activity in human cells in need of such inhibition comprising administering a therapeutically effective amount of CDK4I to a human.
44. A method for inhibiting CDK4 activity in human cells in need of such inhibition comprising administering a polynucleotide which encodes CDK4I to a human in a form wherein the gene will express CDK4I in vivo in the human cells.
45. A method according to claim 43 wherein the polynucleotide will replace any wild-type CDK4I in the human cells.
46. A method according to claim 43 wherein the human cells contain a wild-type polynucleotide of SEQUENCE ID Nos. 1-2 which polynucleotide contains a polymorphism, wherein the method further comprises administering at least one antisense polynucleotide to the human, which antisense polynucleotide will inhibit the expression of an mRNA transcribed from the wild-type polynucleotide.
47. A kit for use in performing the method according to claim 21 comprising reagants and reactants useful in the method.
48. A kit for use in performing the method according to claim 31 comprising reagants and reactants useful in the method.
49. A kit for use in performing the method according to claim 43 comprising reagants and reactants useful in the method.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A coated implantable medical device comprising a coating configured to release a taxane agent adhered to a surface of the medical device, the coating comprising:
a first layer comprising a taxane agent, wherein the taxane agent is paclitaxel comprising at least one of amorphous paclitaxel and anhydrous paclitaxel and at least 40% dihydrate paclitaxel; and
a second layer positioned over the first layer and comprising biodegradable elastomer, the biodegradable elastomer having a molecular weight of 50-500 kDa, and being present in an amount between 1 and 20 times the weight of the therapeutic agent in the first layer.
2. The coated implantable medical device of claim 1, wherein the biodegradable elastomer is poly(lactic acid).
3. The coated implantable medical device of claim 1, wherein the taxane agent comprises at least 60% dihydrate paclitaxel.
4. The coated implantable medical device of claim 1 comprising a radially-expandable vascular stent.
5. A coated implantable medical device comprising a coating configured to release a taxane agent adhered to a surface of the medical device, the coating comprising:
a first layer comprising a taxane agent, wherein the taxane agent is paclitaxel comprising at least one of amorphous paclitaxel and anhydrous paclitaxel and at least 20% dihydrate paclitaxel; and
a second layer positioned over the first layer and comprising a biodegradable elastomer, the biodegradable elastomer being present in an amount between 1 and 20 times the weight of the taxane agent in the first layer.
6. The coated implantable medical device of claim 5, wherein the dihydrate paclitaxel comprises at least 40% of the taxane agent.
7. The coated implantable medical device of claim 6, wherein the dihydrate paclitaxel comprises at least 60% of the taxane agent.
8. The coated implantable medical device of claim 5, wherein the biodegradable elastomer is poly(lactic acid).
9. A coated implantable medical device comprising a coating configured to release a taxane agent adhered to a surface of the medical device, the coating comprising:
a first layer comprising paclitaxel in a first solid form and a second solid form, wherein the first solid form is dihydrate paclitaxel, wherein the second taxane solid form is selected from the group consisting of amorphous paclitaxel and anhydrous paclitaxel, and wherein at least 10% of the paclitaxel is in the first solid form; and
a second layer positioned over the first layer and comprising a biodegradable elastomer, the biodegradable elastomer having a molecular weight of 50-500 kDa, and being present in an amount between 1 and 20 times the weight of the therapeutic agent in the first layer.
10. The coated implantable medical device of claim 9, wherein the biodegradable elastomer is poly(lactic acid).
11. The coated implantable medical device of claim 9, wherein the coated implantable medical device is a balloon.
12. The coated implantable medical device of claim 9, wherein the paclitaxel comprises at least 20% dihydrate paclitaxel.
13. The coated implantable medical device of claim 12, wherein the paclitaxel comprises at least 40% dihydrate paclitaxel.
14. The coated implantable medical device of claim 13, wherein the paclitaxel comprises at least 60% dihydrate paclitaxel.
15. The coated implantable medical device of claim 14, wherein the paclitacel comprises at least 80% dihydrate paclitaxel.
16. The coated implantable medical device of claim 1, wherein the coated implantable medical device is a balloon.
17. The coated implantable medical device of claim 16, wherein the balloon is for use in the peripheral arteries.
18. The coated implantable medical device of claim 17, wherein the balloon is for use in the superficial femoral artery.
19. The coated implantable medical device of claim 1, wherein the coated implantable medical device is a radially-expandable vascular stent for use in the peripheral arteries.
20. The coated implantable medical device of claim 19, wherein the radially-expandable vascular stent is for use in the superficial femoral artery.