What is claimed is:
1. A hapten represented by the following structure:
11
where n is greater than or equal to 2 and less than or equal to 8.
2. A hapten according to claim 1 that mimics the transition state of an aldol reaction as found in Class I aldolases.
3. A hapten according to claim 1 wherein n is greater than or equal to 4 and less than or less than or equal to 6.
4. A hapten according to claim 1 wherein n is five.
5. A transition state immunoconjugate represented by the following structure:
12
where n is greater than or equal to 2 and less than or equal to 8.
6. A transition state immunoconjugate according to claim 5 wherein n is greater than or equal to 4 and less than or equal to 6.
7. A transition state immunoconjugate according to claim 5 wherein n is five.
8. A transition state immunoconjugate according to claim 5 wherein the carrier protein is keyhole limpet hemocyanin (KLH).
9. A process for producing a catalytic monoclonal antibody for catalyzing an aldol reaction, the process comprising the following steps:
Step A: eliciting an immune response within an immune responsive subject by injecting a sterile solution of a hapten-carrier protein, said hapten-carrier protein including a sulfone -diketone hapten; then
Step B: isolating and cloning an antibody producing cell from the immune responsive subject of said Step A which expresses a catalytic antibody for catalyzing the aldol reaction; and then
Step C: isolating the aldolase catalytic antibody expressed by the antibody producing cell isolated and cloned in said Step B.
10. A process for producing a catalytic monoclonal antibody according to claim 9 wherein the hapten-carrier protein is represented by the following structure:
13
where n is greater than or equal to 2 and less than or equal to 5.
11. A process for producing a catalytic monoclonal antibody according to claim 9 wherein n is 5.
12. Antibody molecules or molecules containing antibody combining site portions that catalyze an aldol addition reaction produced according to the following method:
Step A: eliciting an aldolase immune response within an immune response subject by vaccination with a sterile solution containing the appropriate concentration of an aldol transition state immunoconjugate, said aldol transition state immunoconjugate including a sulfone -diketone hapten; then
Step B: isolating and cloning an antibody producing cell from the immune responsive subject of said Step A which expresses a catalytic aldolase antibody; and then
Step C: isolating the catalytic aldolase antibody expressed by the antibody producing cell isolated and cloned in said Step B.
13. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the aldol transition state immunoconjugate is represented by the following structure:
14
where n is greater than or equal to 2 and less than or equal to 8.
14. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein n of the aldol transition state immunoconjugate is 5.
15. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the antibody producing cell of said Step B is hybridoma 85A2, having ATCC accession number HB ______.
16. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the antibody producing cell of said Step B is hybridoma 85C7, having ATCC accession number HB ______.
17. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the antibody producing cell of said Step B is hybridoma 92F9, having ATCC accession number HB ______.
18. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the antibody producing cell of said Step B is hybridoma 93F3, having ATCC accession number HB ______.
19. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the antibody producing cell of said Step B is hybridoma 84G3, having ATCC accession number HB ______.
20. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the antibody producing cell of said Step B is hybridoma 84G11, having ATCC accession number HB ______.
21. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the antibody producing cell of said Step B is hybridoma 84H9, having ATCC accession number HB ______.
22. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the antibody producing cell of said Step B is hybridoma 85H6, having ATCC accession number HB ______.
23. Antibody molecules or molecules containing antibody combining site portions according to claim 12 wherein the antibody producing cell of said Step B is hybridoma 90G8, having ATCC accession number HB ______.
24. An antibody producing cell which secretes antibody molecules or molecules containing antibody combining site portions that catalyze an aldol addition reaction, the antibody producing cell being produced according to the following method:
Step A: eliciting an aldolase immune response within an immune response subject by vaccination with a sterile solution containing the appropriate concentration of the aldol transition state immunoconjugate, said aldol transition state immunoconjugate including a sulfone -diketone hapten; and then
Step B: isolating and cloning the antibody producing cell from the immune responsive subject of said Step A which expresses a catalytic aldolase antibody.
25. An antibody producing cell according to claim 24 wherein the aldol transition state immunoconjugate is represented by the following structure:
15
where n is greater than or equal to 2 and less than or equal to 8
26. The antibody producing cell of claim 24 that is a hybridoma.
27. A hybridoma according to claim 24 having ATCC accession number HB ______ which is capable of expressing antibody 85A2.
28. A hybridoma according to claim 24 having ATCC accession number HB ______ which is capable of expressing antibody 85C7.
29. A hybridoma according to claim 24 having ATCC accession number HB ______ which is capable of expressing antibody 92F9.
30. A hybridoma according to claim 24 having ATCC accession number HB ______ which is capable of expressing antibody 93F3.
31. A hybridoma according to claim 24 having ATCC accession number HB ______ which is capable of expressing antibody 84G3.
32. A hybridoma according to claim 24 having ATCC accession number HB ______ which is capable of expressing antibody 84G11.
33. A hybridoma according to claim 24 having ATCC accession number HB ______ which is capable of expressing antibody 84H9.
34. A hybridoma according to claim 24 having ATCC accession number HB ______ which is capable of expressing antibody 85H6.
35. A hybridoma according to claim 24 having ATCC accession number HB ______ which is capable of expressing antibody 90G8.
36. An improved process for catalyzing an aldol reaction between aldehyde and a ketone reactants, wherein the improvement comprises contacting said aldehyde and ketone reactants with antibody molecules or molecules containing antibody combining site portions that catalyze an aldol addition reaction produced according to the following method:
Step A: eliciting an aldolase immune response within an immune response subject by vaccination with a sterile solution containing the appropriate concentration of an aldol transition state immunoconjugate, said aldol transition state immunoconjugate including a sulfone -diketone hapten; then
Step B: isolating and cloning an antibody producing cell from the immune responsive subject of said Step A which expresses a catalytic aldolase antibody; and then
Step C: isolating the catalytic aldolase antibody expressed by the antibody producing cell isolated and cloned in said Step B.
37. An improved process for catalyzing an aldol reaction according to claim 36 wherein the aldol transition state immunoconjugate of said Step A is represented by the following structure:
16
where n is greater than or equal to 2 and less than or equal to 8.
38. An improved process for catalyzing an aldol reaction according to claim 36 wherein the ketone is selected from a group consisting of members represented by the following structures:
17
39. An improved process for catalyzing, an aldol reaction according to claim 36 wherein the aldehyde is selected from a group consisting of members represented by the following structures:
18
40. An improved process for catalyzing an aldol reaction between aldehyde and ketone reactants, wherein the improvement comprises contacting said aldehyde and ketone reactants with antibody molecules selected from a group consisting of 85A2, 85C7, 92F9, 93F3, 84G3, 84G11, 84H9, 85H6 and 90G8.
41. An improved process for catalyzing an aldol reaction according to claim 40 wherein the ketone is selected from a group consisting of members represented by the following structures:
19
42. An improved process for catalyzing an aldol reaction according to claim 40 wherein the aldehyde is selected from a group consisting of members represented by the following structures:
20
43. An improved kinetic resolution of -hydroxyketones from a racemic mixture by means of a retro-aldol reaction, wherein the improvement comprises catalyzing said retro-aldol reaction with antibody molecules or molecules containing antibody combining site portions that catalyze an aldol addition reaction produced according to the following method:
Step A: eliciting an aldolase immune response within an immune response subject by vaccination with a sterile solution containing the appropriate concentration of an aldol transition state immunoconjugate, said aldol transition state immunoconjugate including a sulfone -diketone hapten; then
Step B: isolating and cloning an antibody producing cell from the immune responsive subject of said Step A which expresses a catalytic aldolase antibody; and then
Step C: isolating the catalytic aldolase antibody expressed by the antibody producing cell isolated and cloned in said Step B.
44. An improved kinetic resolution of -hydroxyketone according to claim 43 wherein the aldol transition state immunoconjugate of said Step A is represented by the following structure:
21
where n is greater than or equal to 2 and less than or equal to 8
wherein the acemic mixture is treated with a catalytic amount of the antibody in an aqueous buffer to give a simple ketone, an aldehyde containing a phenyl ring and an enantiomerically enriched -hydroxyketone.
45. An improved kinetic resolution of -hydroxyketones from a racemic mixture by means of a retro-aldol reaction, wherein the improvement comprises catalyzing said retro-aldol reaction with antibody molecules selected from a group consisting of 85A2, 85C7, 92F9, 93F3, 84G3, 84G11, 84H9, 85H6 and 90G8.
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 minimally invasive system for preparing tissue associated with a spinal facet joint space targeted for receiving an implant, the spinal facet joint space including a superior facet joint surface and an inferior facet joint surface, the spinal facet joint space opening in a posterior direction immediately adjacent a superior lateral mass and an inferior lateral mass, the system comprising:
a decorticator comprising a proximal portion, a distal portion opposite the proximal portion and a hollow body extending between the proximal and distal portions, the distal portion distally terminating in a decorticating surface comprising at least one of an abrasive surface or a plurality of teeth; and
a guide tool comprising a proximal region, a distal region opposite the proximal region and an elongated member extending between the proximal and distal regions, the distal region including a first chamfered tip,
wherein the decorticator and guide tool are each further configured such that, when the first chamfered tip is positioned in the spinal facet joint space between the superior and inferior facet joint surfaces and the elongated member of the guide tool extends through the hollow body of the decorticator, the decorticator can be rotated about a longitudinal axis of the elongated member and the decorticating surface brought into decorticating contact with at least one of the superior lateral mass or the inferior lateral mass.
2. The system of claim 1, wherein the distal portion of the decorticator terminates at a sloped angle relative to a longitudinal axis of the hollow body.
3. The system of claim 2, wherein, when the decorticator is rotated about the elongated member in a first orientation, the sloped angle allows the decorticating surface to contact the superior lateral mass without contacting the inferior lateral mass, and, when the decorticator is rotated about the elongated member in a second orientation opposite the first orientation, the sloped angle allows the decorticating surface to contact the inferior lateral mass without contacting the superior lateral mass.
4. The system of claim 2, wherein the sloped angle is between approximately 10 degrees to approximately 80 degrees relative to the longitudinal axis of the hollow body.
5. The system of claim 2, wherein the sloped angle is between approximately 30 degrees to approximately 60 degrees relative to the longitudinal axis of the hollow body.
6. The system of claim 2, wherein the sloped angle is approximately 45 degrees relative to the longitudinal axis of the hollow body.
7. The system of claim 1, wherein an inner diameter of the hollow body of the decorticator is substantially equal to an outer diameter of the elongated member and a difference between the inner diameter and the outer diameter is such that the hollow body can slide over and rotate about the elongated member.
8. The system of claim 1, wherein the first chamfered tip comprises a first fork and a second fork offset from the first fork by a distance transverse to a longitudinal axis of the elongated member.
9. The system of claim 8, wherein the first fork distally tapers towards a distal point.
10. The system of claim 1, wherein the elongated body comprises a lumen extending between the proximal and distal regions.
11. The system of claim 10, wherein the first chamfered tip comprises a first fork and a second fork offset from the first fork by a distance transverse to a longitudinal axis of the elongated member, the system further comprising:
a rasp comprising a proximal aspect, a distal aspect opposite the proximal aspect and a shaft extending between the proximal and distal aspects, the distal aspect distally terminating in a rasp configuration,
wherein the rasp and guide tool are further configured such that, when the first chamfered tip is positioned in the spinal facet joint space between the superior and inferior facet joint surfaces and the shaft of the rasp extends through the lumen of the guide tool such that the rasp configuration is positioned in the spinal facet joint space, the rasp configuration is positioned between the first and second forks.
12. The system of claim 11, wherein the rasp can be longitudinally displaced within the lumen to cause the rasp configuration to rasp against at least one of the inferior facet joint surface or the superior facet joint surface.
13. The system of claim 11, wherein a longitudinal cross section of the rasp configuration is generally similar to a longitudinal cross section of the first chamfered tip.
14. The system of claim 13, wherein the first chamfered tip and rasp configuration are both double chamfered.
15. The system of claim 11, wherein an inner diameter of the lumen of the guide tool is substantially equal to an outer diameter of the shaft and a difference between the inner diameter and the outer diameter is such that the shaft can slide through the lumen.
16. The system of claim 15, wherein the proximal aspect of the rasp includes a first structure and the proximal region of the guide tool includes a second structure configured to matingly engage with the first structure, such that, when the first and second structures are matingly engaged, the longitudinal cross section of the first chamfered tip is generally aligned with the longitudinal cross section of the rasp configuration.
17. The system of claim 11, wherein the rasp configuration comprises a chevron rasp pattern.
18. The system of claim 11, wherein rasp configuration and the first chamfered tip both comprise complementary transverse holes that generally align when the rasp configuration and first chamfered tip are generally aligned to generally form a combined chamfered tip.