1. A clamping assembly for selectively retaining a stack of pages, said assembly comprising:
a bottom disk configured to be positioned proximate the stack of pages;
a tube operationally coupled to said bottom disk;
a top disk operationally coupled to said tube wherein said top disk selectively compresses the stack of pages between said top and bottom disks;
a retainer operationally coupled to said top disk wherein said retainer retains said top disk on the stack of pages; and
a release operationally coupled to said top disk wherein said release is configured to selectively release said top disk from the stack of pages; and
a shaft slidably positioned within said tube wherein a bottom end of said shaft is positioned proximate a bottom end of said tube.
2. The assembly according to claim 1 further comprising a lip coupled to and extending upwardly from a top side of said bottom disk wherein said lip is coextensive with an outer edge of said bottom disk.
3. The assembly according to claim 1 further comprising a bottom engaging disk coupled to a top edge of a lip on said bottom disk wherein an outer edge of said bottom engaging disk is coextensive with said lip on said bottom disk.
4. The assembly according to claim 1 further comprising a tube aperture extending through a top side and a bottom side of a bottom engaging disk proximate an outer edge of said bottom engaging disk.
5. The assembly according to claim 1 further comprising said tube extending downwardly through a tube aperture wherein a bottom end of said tube is coupled to a top side of said bottom disk.
6. (canceled)
7. The assembly according to claim 1 further comprising a primary spring biasing member positioned within said tube wherein said primary spring biasing member is positioned between a top side of said bottom disk and a bottom end of said shaft wherein said primary spring biasing member biases said shaft upwardly in said tube.
8. The assembly according to claim 1 further comprising:
of an outer edge of said top disk having a flat portion wherein said top disk forms a circle segment; and
a lip coupled to and extending upwardly from a top side of said top disk wherein said lip is coextensive with said outer edge of said top disk.
9. A clamping assembly for selectively retaining a stack of pages, said assembly comprising:
a bottom disk configured to be positioned proximate the stack of pages;
a tube operationally coupled to said bottom disk;
a top disk operationally coupled to said tube wherein said top disk selectively compresses the stack of pages between said top and bottom disks;
a retainer operationally coupled to said top disk wherein said retainer retains said top disk on the stack of pages;
a release operationally coupled to said top disk wherein said release is configured to selectively release said top disk from the stack of pages; and
a primary shaft aperture extending through a top side and a bottom side of said top disk proximate a flat portion of an outer edge of said top disk.
10. The assembly according to claim 9 further comprising a shaft extending upwardly through a primary shaft aperture in said top disk wherein said top disk is coupled to said shaft.
11. A clamping assembly for selectively retaining a stack of pages, said assembly comprising:
a bottom disk configured to be positioned proximate the stack of pages;
a tube operationally coupled to said bottom disk;
a top disk operationally coupled to said tube wherein said top disk selectively compresses the stack of pages between said top and bottom disks;
a retainer operationally coupled to said top disk wherein said retainer retains said top disk on the stack of pages;
a release operationally coupled to said top disk wherein said release is configured to selectively release said top disk from the stack of pages;
a rounded portion of said retainer coupled to a second end of a straight portion of said retainer wherein said retainer has a T-shape;
a first end of a straight portion of said retainer being hingedly coupled to a top side of said top disk wherein said straight portion of said retainer extends outwardly through an opening in a lip on said top disk wherein a rounded portion of said retainer is positioned outside of said lip on said top disk; and
a secondary shaft aperture extending through a top side and a bottom side of a straight portion of said retainer wherein a shaft extends upwardly through said secondary shaft aperture in said straight portion of said retainer.
12. The assembly according to claim 7, further comprising a secondary spring biasing member positioned around a shaft wherein said secondary spring biasing member is positioned between a bottom side of said retainer and a top side of said top disk wherein said secondary spring biasing member biases said retainer into a retaining position wherein an outer edge of a secondary shaft aperture in a straight portion of said retainer engages an outer surface of said shaft.
13. A clamping assembly for selectively retaining a stack of pages, said assembly comprising:
a bottom disk configured to be positioned proximate the stack of pages;
a tube operationally coupled to said bottom disk;
a top disk operationally coupled to said tube wherein said top disk selectively compresses the stack of pages between said top and bottom disks;
a retainer operationally coupled to said top disk wherein said retainer retains said top disk on the stack of pages;
a release operationally coupled to said top disk wherein said release is configured to selectively release said top disk from the stack of pages; and
a cover coupled to a top edge of a lip on said top disk wherein an outer edge of said cover is coextensive with said lip on said top disk.
14. A clamping assembly for selectively retaining a stack of pages, said assembly comprising:
a bottom disk configured to be positioned proximate the stack of pages;
a tube operationally coupled to said bottom disk;
a top disk operationally coupled to said tube wherein said top disk selectively compresses the stack of pages between said top and bottom disks;
a retainer operationally coupled to said top disk wherein said retainer retains said top disk on the stack of pages;
a release operationally coupled to said top disk wherein said release is configured to selectively release said top disk from the stack of pages;
an outer edge of said release having a flat portion wherein said release forms a circle segment;
a lip coupled to and extending upwardly from a top side of said release wherein said lip on said release is coextensive with said outer edge of said release;
said release being operationally coupled to said top side wherein said flat portion of said outer edge of said release abuts a flat portion of an outer edge of said top disk wherein said release and said top disk forms a complete circle;
a cover coupled to a top edge of said lip on said release wherein said cover is coextensive with said lip on said release; and
a rounded portion of said retainer being positioned with said release wherein an outer edge of said rounded portion of said retainer is coextensive with an inner edge of said lip on said release.
15. The assembly according to claim 1 further comprising the stack of pages being selectively positioned between said top and bottom disks wherein said top disk is urged downwardly wherein the stack of paper is compressed between a top surface of a bottom engaging disk and a bottom side of said top disk wherein said retainer is positioned in a retaining position wherein the stack of pages is retained between said top and bottom disks.
16. The assembly according to claim 7, further comprising said release being selectively depressed wherein said retainer is urged into a releasing position wherein a shaft freely moves in a secondary shaft aperture in said retainer wherein a primary spring biasing member biases said top disk upwardly away from the stack of pages wherein the stack of pages are removable from said assembly.
17. The assembly according to claim 1, further comprising:
a lip coupled to and extending upwardly from a top side of said bottom disk wherein said lip is coextensive with an outer edge of said bottom disk;
a bottom engaging disk coupled to a top edge of said lip on said bottom disk wherein an outer edge of said bottom engaging disk is coextensive with said lip on said bottom disk;
a tube aperture extending through a top side and a bottom side of said bottom engaging disk proximate an outer edge of said bottom engaging disk;
said tube extending downwardly through said tube aperture wherein a bottom end of said tube is coupled to said top side of said bottom disk;
a primary spring biasing member positioned within said tube wherein said primary spring biasing member is positioned between said top side of said bottom disk and said bottom end of said shaft wherein said primary spring biasing member biases said shaft upwardly in said tube;
said top disk comprising an outer edge of said top disk having a flat portion wherein said top disk forms a circle segment;
a lip coupled to and extending upwardly from a top side of said top disk wherein said lip is coextensive with said outer edge of said top disk;
a primary shaft aperture extending through a top side and a bottom side of said top disk proximate said flat portion of said outer edge of said top disk, said shaft extending upwardly through said primary shaft aperture in said top disk wherein said top disk is coupled to said shaft;
said retainer comprising a rounded portion of said retainer coupled to a second end of a straight portion of said retainer wherein said retainer has a T-shape, a first end of said straight portion of said retainer being hingedly coupled to said top side of said top disk wherein said straight portion of said retainer extends outwardly through an opening in said lip on said top disk wherein said rounded portion of said retainer is positioned outside of said lip on said top disk; and
a secondary shaft aperture extending through a top side and a bottom side of said straight portion of said retainer wherein said shaft extends upwardly through said secondary shaft aperture in said straight portion of said retainer;
a secondary spring biasing member positioned around said shaft wherein said secondary spring biasing member is positioned between a bottom side of said retainer and said top side of said top disk wherein said secondary spring biasing member biases said retainer into a retaining position wherein an outer edge of said secondary shaft aperture in said straight portion of said retainer engages an outer surface of said shaft;
a cover coupled to a top edge of said lip on said top disk wherein an outer edge of said cover is coextensive with said lip on said top disk;
said release comprising an outer edge of said release having a flat portion wherein said release forms a circle segment, said release being operationally coupled to said top disk wherein said flat portion of said outer edge of said release abuts said flat portion of said outer edge of said top disk wherein said release and said top disk forms a complete circle;
a lip coupled to and extending upwardly from a top side of said release wherein said lip on said release is coextensive with said outer edge of said release;
a cover coupled to a top edge of said lip on said release wherein said cover is coextensive with said lip on said release;
said rounded portion of said retainer being positioned with said release wherein an outer edge of said rounded portion of said retainer is coextensive with an inner edge of said lip on said release;
the stack of pages being selectively positioned between said top and bottom disks wherein said top disk is urged downwardly wherein the stack of paper is compressed between a top surface of said bottom engaging disk and said bottom side of said top disk wherein said retainer is positioned in a retaining position wherein the stack of pages is retained between said top and bottom disks; and
said release being selectively depressed wherein said retainer is urged into a releasing position wherein said shaft freely moves in said secondary shaft aperture in said retainer wherein said primary spring biasing member biases said top disk upwardly away from the stack of pages wherein the stack of pages are removable from said assembly.
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 method of preventing or reducing hypersensitivity or allergic reactions in a human patient undergoing taxane therapy for a taxane-responsive disease condition, comprising orally co-administering to the patient a taxane and an oral bioavailability enhancing agent comprising an inhibitor of P-glycoprotein, without prior administration of medication to prevent the hypersensitivity or allergic reactions, wherein the taxane reaches therapeutic blood or plasma levels in said patient.
2. The method of claim 1, wherein the taxane is selected from the group consisting of paclitaxel and analogs, derivatives and prodrugs thereof.
3. The method of claim 1 wherein the taxane is a analog of paclitaxel.
4. The method of claim 3, wherein the analog of paclitaxel is docetaxel.
5. The method of claim 1, wherein the enhancing agent is administered either
a) about 0.5-72 hrs. before,
b) less than 0.5 hr. before, together with or less than 0.5 hr. after, or
c) both about 0.5-72 hrs. before and again less than 0.5 hr. before, together with or less than 0.5 hr. after, the administration of the taxane.
6. The method of claim 1, wherein the taxane and the enhancing agent are administered in separate oral dosage forms.
7. The method of claim 1, wherein the taxane and the enhancing agent are administered together in a combination oral dosage form.
8. The method of claim 1, wherein the taxane is paclitaxel.
9. The method of claim 1, wherein the enhancing agent is administered in an amount of from about 0.1 to 20 mgkg of patient body weight.
10. The method of claim 8, wherein the paclitaxel and the enhancing agent are orally co-administered once a week.
11. The method of claim 10, wherein the paclitaxel is administered in a divided dose.
12. The method of claim 5, wherein the taxane is docetaxel.
13. The method of claim 1, wherein two or more doses of the taxane are administered after a single dose of the enhancing agent.
14. The method of claim 1, wherein the patient is administered about 20-1,000 mgm2 of the taxane based on patient body surface area.
15. The method of claim 14, wherein the patient is administered about 50-200 mgm2 of the taxane based on patient body weight.
16. The method of claim 1, wherein the patient is administered about 2-30 mgkg of paclitaxel based on patient body weight.
17. The method of claim 16, wherein the patient is administered about 2-6 mgkg of paclitaxel.
18. The method of claim 1, wherein the taxane, the enhancing agent or both is each administered in a dosage form selected from the group consisting of tablets, softgel capsules, hardgel capsules, caplets, gelcaps, pills, lozenges, powders, micronized particles, osmotic delivery systems, and liquid solutions, suspensions and elixirs.
19. The method of claim 8, wherein paclitaxel is administered in a formulation further comprising a polyethoxylated castor oil, alcohol or polyoxyethylated sorbitan mono-oleate.
20. The method of claim 1, wherein the disease condition is a cancer, tumor, malignancy, uncontrolled tissue or cellular proliferation secondary to tissue injury, or an inflammatory disease.
21. The method of claim 1, wherein the disease condition is selected from the group consisting of gastrointestinal tract cancers, lung cancers, pancreatic cancer, prostate cancer, hepatocellular carcinoma, liver metastases, genito-urinary and gastrointestinal tract cancers, Kaposi’s sarcoma, polycystic kidney disease and malaria.
22. The method of claim 1, wherein the disease condition is cancer.
23. The method of claim 22, wherein the taxane is paclitaxel.
24. The method of claim 23, wherein the patient is administered about 50-200 mgm2 of paclitaxel based on patient body weight.
25. The method of claim 24, wherein paclitaxel and the enhancing agent are orally co-administered about once per week.
26. The method of claim 25, wherein paclitaxel is administered in a divided dose.
27. The method of claim 1, wherein the taxane is docetaxel.
28. The method of claim 1, wherein the disease condition is lung cancer.
29. The method of claim 28, wherein the taxane is paclitaxel.
30. The method of claim 29, wherein the patient is administered about 50-200 mgm2 of paclitaxel based on patient body weight.
31. The method of claim 30, wherein paclitaxel and the enhancing agent are orally co-administered about once per week.
32. The method of claim 31, wherein paclitaxel is administered in a divided dose.
33. The method of claim 28, wherein the taxane is docetaxel.
34. The method of claim 33, wherein from about 0.1 to about 20 mgkg of the enhancing agent are orally administered to the patient.
35. The method of claim 1, wherein the disease condition is a cancer of the gastrointestinal tract.
36. The method of claim 35, wherein the taxane is paclitaxel.
37. The method of claim 36, wherein the patient is administered about 50-200 mgm2 of paclitaxel based on patient body weight.
38. The method of claim 37, wherein paclitaxel and the enhancing agent are orally co-administered about once per week.
39. The method of claim 38, wherein paclitaxel is administered in a divided dose.
40. The method of claim 35, wherein the taxane is docetaxel.
41. The method of claim 40, wherein from about 0.1 to about 20 mgkg of the enhancing agent are orally administered to the patient.
42. The method of claim 1, wherein the disease condition is ovarian cancer.
43. The method of claim 42, wherein the taxane is paclitaxel.
44. The method of claim 43, wherein the patient is administered about 50-200 mgm2 of paclitaxel based on patient body weight.
45. The method of claim 44, wherein paclitaxel and the enhancing agent are orally co-administered about once per week.
46. The method of claim 45, wherein paclitaxel is administered in a divided dose.
47. The method of claim 3, wherein the taxane is docetaxel.
48. The method of claim 47, wherein from about 0.1 to about 20 mgkg of the enhancing agent are orally administered to the patient.
49. The method of claim 1, wherein the disease condition is breast cancer.
50. The method of claim 49, wherein the taxane is paclitaxel.
51. The method of claim 50, wherein the patient is administered about 50-200 mgm2 of paclitaxel based on patient body weight.
52. The method of claim 51, wherein paclitaxel and the enhancing agent are orally co-administered about once per week.
53. The method of claim 52, wherein paclitaxel is administered in a divided dose.
54. The method of claim 49, wherein the taxane is docetaxel.
55. The method of claim 54, wherein from about 0.1 to a out 20 mgkg of the enhancing agent are orally administered to the patient.