1. A method of fabricating an integrated circuit transistor comprising:
forming in an integrated circuit substrate, a first active area including a first insulated gate thereon and a second active area including a second insulated gate thereon;
selectively forming an implant-blocking mask on the second active area;
implanting extension dopants into the first active area on opposite sides of the first insulated gate to form source and drain extension regions while the implant-blocking mask blocks the dopants from the second active area;
forming an anti-reflective coating on the first active area;
directionally etching the anti-reflective coating on the first active area to form anti-reflective coating sidewall spacers on opposite sidewalls of the first insulated gate, while retaining the implant-blocking mask on the second active area;
implanting sourcedrain dopants into the first active area on opposite sides of the first insulated gate to form source and drain regions while the implant-blocking mask blocks the sourcedrain dopants from the second active area and the anti-reflective coating sidewall spacers block at least some sourcedrain dopants from the first active area beneath the anti-reflective coating sidewall spacers and the source and drain extension regions remain beneath the anti-reflective coating sidewall spacers; and
removing the implant-blocking mask and the anti-reflective coating sidewall spacers.
2. A method according to claim 1 wherein selectively forming an implant-blocking mask on the second active area comprises:
blanket forming an implant-blocking layer on the first and second active areas; and
removing the implant-blocking layer from the first active area.
3. A method according to claim 1:
wherein forming an implant-blocking mask is preceded by forming oxide sidewall spacers on sidewalls of the first and second insulated gates;
wherein implanting extension dopants into the first active area on opposite sides of the first insulated gate to form source and drain extension regions comprises implanting extension dopants into the first active area at an oblique angle to extend the source and drain extension regions beneath the oxide sidewall spacers; and
wherein directionally etching the anti-reflective coating on the first active area comprises directionally etching the anti-reflective coating on the first active area to form anti-reflective coating sidewall spacers on the oxide sidewall spacers on opposite sidewalls of the first insulated gate, while retaining the implant-blocking mask on the second active area.
4. A method according to claim 3:
wherein removing the implant-blocking mask and the anti-reflective coating sidewall spacers comprises removing the implant-blocking mask and the anti-reflective coating sidewall spacers while retaining the oxide sidewall spacers; and
wherein removing the implant-blocking mask and the anti-reflective coating sidewall spacers is followed by forming nitride sidewall spacers on the oxide sidewall spacers that were retained.
5. A method according to claim 1 wherein the implant-blocking mask comprises photoresist.
6. A method according to claim 5 wherein directionally etching the anti-reflective coating on the first active area to form anti-reflective coating sidewall spacers on opposite sidewalls of the first insulated gate, while retaining the implant-blocking mask on the second active area, comprises selectively directionally etching the anti-reflective coating relative to the photoresist.
7. A method according to claim 1:
wherein forming an anti-reflective coating on the first active area comprises blanket forming an anti-reflective coating on the first active area and on the implant-blocking mask on the second active area; and
wherein directionally etching the anti-reflective coating on the first active area comprises directionally etching the anti-reflective coating on the first active area while simultaneously removing at least some of the anti-reflective coating from the implant-blocking mask on the second active area to form the anti-reflective coating sidewall spacers on opposite sidewalls of the first gate and while retaining the implant-blocking mask on the second active area.
8. A method of fabricating an integrated circuit transistor comprising:
forming in an integrated circuit substrate, a first active area including a first insulated gate thereon and a second active area including a second insulated gate thereon;
selectively forming an implant-blocking mask on the second active area;
forming an anti-reflective coating on the first active area;
directionally etching the anti-reflective coating on the first active area to form anti-reflective coating sidewall spacers on opposite sidewalls of the first insulated gate, while retaining the implant-blocking mask on the second active area;
implanting sourcedrain dopants into the first active area on opposite sides of the first insulated gate to form source and drain regions while the implant-blocking mask blocks the sourcedrain dopants from the second active area and the anti-reflective coating sidewall spacers block at least some sourcedrain dopants from the first active area beneath the anti-reflective coating sidewall spacers; and
removing the implant-blocking mask and the anti-reflective coating sidewall spacers.
9. A method according to claim 8 wherein selectively forming an implant-blocking mask on the second active area comprises:
blanket forming an implant-blocking layer on the first and second active areas; and
removing the implant-blocking layer from the first active area.
10. A method according to claim 8:
wherein forming an implant-blocking mask is preceded by forming oxide sidewall spacers on sidewalls of the first and second insulated gates; and
wherein directionally etching the anti-reflective coating on the first active area comprises directionally etching the anti-reflective coating on the first active area to form anti-reflective coating sidewall spacers on the oxide sidewall spacers on opposite sidewalls of the first insulated gate, while retaining the implant-blocking mask on the second active area.
11. A method according to claim 10:
wherein removing the implant-blocking mask and the anti-reflective coating sidewall spacers comprises removing the implant-blocking mask and the anti-reflective coating sidewall spacers while retaining the oxide sidewall spacers; and
wherein removing the implant-blocking mask and the anti-reflective coating sidewall spacers is followed by forming nitride sidewall spacers on the oxide sidewall spacers that were retained.
12. A method according to claim 8 wherein the implant-blocking mask comprises photoresist.
13. A method according to claim 12 wherein directionally etching the anti-reflective coating on the first active area to form anti-reflective coating sidewall spacers on opposite sidewalls of the first insulated gate, while retaining the implant-blocking mask on the second active area, comprises selectively directionally etching the anti-reflective coating relative to the photoresist.
14. A method according to claim 8:
wherein forming an anti-reflective coating on the first active area comprises blanket forming an anti-reflective coating on the first active area and on the implant-blocking mask on the second active area; and
wherein directionally etching the anti-reflective coating on the first active area comprises directionally etching the anti-reflective coating on the first active area while simultaneously removing the anti-reflective coating from the implant-blocking mask on the second active area to form anti-reflective coating sidewall spacers on opposite sidewalls of the first insulated gate and while retaining the implant-blocking mask on the second active area.
15. A method of fabricating an integrated circuit transistor comprising:
forming in an integrated circuit substrate, an active area including an insulated gate thereon;
forming an anti-reflective coating on the active area;
directionally etching the anti-reflective coating on the active area to form anti-reflective coating gate sidewall spacers on opposite sidewalls of the insulated gate; and
implanting dopants into the active area on opposite sides of the insulated gate while the anti-reflective coating gate sidewall spacers block at least some dopants from the active area beneath the anti-reflective coating sidewall spacers.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A compound to selectively kill a target cell in a patient with reduced systemic toxicity, which comprises a compound of the formula:
W-Z-X
wherein,
X is a therapeutical agent selected from the group consisting of chemotherapeutic agent, antiviral agent, antibacterial agent, antifungal agent and enzyme inhibitor agent;
W is a molecule which is adapted to selectively bind said target cell directly or indirectly; and
Z is a breakable linker which covalently links W and X together, wherein said linked W remains available for binding to said target cell, whereby said breakable linker releases said therapeutical agent into said target cell.
2. The compound of claim 1, wherein said compound when bound to said target cell is internalized into said target cell.
3. The compound of any one of claims 1 and 2, wherein said linker is breakable by pH modification, reduction or enzymatic hydrolysis.
4. The compound of any one of claims 1 to 3, wherein said chemotherapeutic agent is selected from the group of taxanes, taxanes derivatives, anthracyclines, anthracyclines derivatives, doxorubicin, daunomycin, daunorubicin, adriamycin, methotrexate, mitomycin, epirubicin, nucleoside analogs, DNA damaging agents and tyrphostins.
5. The compound of any one of claims 1 to 4, wherein said therapeutical agent is selected from the group of antisense oligonucleotide and cDNA for a gene.
6. The compound of claim 4 wherein said taxane is paclitaxel.
7. The compound of any one of claims 1 to 3, wherein said chemotherapeutic agent is doxorubicin.
8. The compound of claim 1 wherein said molecule is selected from the group of antibody and mimicking molecules thereof, peptides, peptidomimetics, growth factors, hormones, adhesion molecules, viral proteins and functional fragments thereof.
9. The compound of claim 8 wherein said antibody is a monoclonal antibody.
10. The compound of claim 8, wherein said antibody binds to a specific receptor on said target cell.
11. The compound of claim 9 wherein said monoclonal antibody is selected from the group of MC192, 5C3 and a-IR3.
12. The compound of claim 1, wherein said compound further comprises a spacer between W and Z andor between Z and X.
13. The compound of claim 12, wherein when W is a primary biologically active molecule indirectly binding to said target cell, said compound further comprises W which is a secondary biologically active molecule selectively bound to W and adapted to selectively bind said target cell.
14. The compound of claim 13 wherein said primary andor said secondary biologically active molecules is an antibody.
15. The compound of claim 14 wherein a primary antibody is of a species and a secondary antibody is of a different species.
16. The compound of any one of claims 14 or 15, wherein said antibody is a monoclonal antibody.
17. The compound of claim 13 wherein said secondary biologically active molecule is a rabbit-antimouse antibody.
18. The compound of claim 1, wherein said compound is of the formula:
6
wherein Y is a spacer selected from the group of alkene, alkyl, methyl, ethyl ester, ethyl glycol and H(CH2CH2O)nOH, n being between 1 and 90.
19. The compound of claim 18, wherein said spacer is (CH2)3.
20. The compound of claim 1, wherein said compound is of the formula I,
7
21. The compound of claim 1, wherein Z is
8
22. The compound of claim 1, wherein said compound is of the formula II,
9
23. The compound of claim 1, wherein said compound is of the formula III,
10
24. A therapeutical composition, which comprises a therapeutically effective amount of a compound of any of claims 1 to 23 in association with a pharmaceutically acceptable carrier.
25. An anti-cancer composition, which comprises a therapeutically effective amount of a compound of any of claims 1 to 23 in association with a pharmaceutically acceptable carrier, wherein said therapeutical agent is a chemotherapeutic agent.
26. A method for treating cancer with reduced effects in a patient, said method consisting in administering a therapeutically effective amount of a compound of any of claims 1 to 23 to a patient, wherein said therapeutical agent is a chemotherapeutic agent.
27. Use of the compound of any one of claims 1 to 23 for the manufacture of a medicament for the treatment of cancer with reduced effects in a patient, wherein said therapeutical agent is a chemotherapeutic agent.
28. A method for decreasing toxic side effects and increasing selectivity of a chemotherapeutic agent for tumor cells, said method comprising the step of administering to a patient a conjugate comprising a chemotherapeutic agent conjugated to a molecule which is adapted to selectively bind said target cell directly or indirectly, wherein said compound when bound to said target cell is internalized into said cell and to a breakable linker which covalently links said molecule and said chemotherapeutic agent together, wherein said linked molecule remains available for binding said target cell, whereby said breakable linker releases said chemotherapeutic agent into said target cell.
29. Use of a chemotherapeutic agent conjugated to a molecule for decreasing toxic side effects and increasing selectivity of a chemotherapeutic agent for tumor cells, said molecule being adapted to selectively bind said target cell directly or indirectly, wherein said compound when bound to said target cell is internalized into said cell and to a breakable linker which covalently links said molecule and said chemotherapeutic agent together, wherein said linked molecule remains available for binding said target cell, whereby said breakable linker releases said chemotherapeutic agent into said target cell.
30. A method for by-passing resistance of tumor cells by p-glycoprotein pump (PGP), said method comprising the step of administering the compound of claim 1 to a patient in need of such a treatment whereby said biologically active molecule is a monoclonal antibody and said compound is avoiding membrane diffusion andor permeability route to enter into said cells.
31. A compound to selectively protect a target cell which comprises a compound of the formula:
W-Z-X
wherein,
X is a protective agent to cells selected form the group consisting of: enzyme inhibitors, ligands of nuclear receptors, vitamin D, vitamin E and analogs thereof, estrogen and analogs thereof and inhibitors of the apoptotic cascase;
W is a biologically active molecule which is adapted to selectively bind said target cell directly or indirectly; and
Z is a linker which covalently links W and X together, wherein said linked W remains available for binding said target cell, whereby said linker releases said therapeutical agent into said cell and whereby said compound is providing a patient with a reduced systemic toxicity.
32. The compound of claim 31, wherein said protective agent is an enzyme inhibitor agent.
33. The compound of claim 32, wherein said enzyme inhibitor agent is a caspase inhibitor agent.
34. A method for decreasing toxic side effects to non-tumor cells, said method comprising the step of administering to a patient a conjugate comprising a protective agent conjugated to a molecule which is adapted to selectively bind said non-tumor target cell directly or indirectly, wherein said compound when bound to said non-tumor target cell and to a breakable linker which covalently links said molecule and said protective agent together, wherein said linked molecule remains available for binding said target cell, whereby said breakable linker releases said protective agent into said cell and whereby said protective agent internalized in said cell is protecting said cell from subsequent toxicity by a chemotherapeutic agent which is therefore decreasing toxic side effects.