What is claimed is:
1. A method for providing contrast for alignment marks after a blanket metal deposition, comprising the steps of:
providing at least one trench in a first region and at least one trench in an alignment mark region of a semiconductor wafer;
depositing a first metal on the wafer;
blocking the first metal from filling the at least one trench in the alignment mark region to maintain the at least one trench in the alignment mark region in an unfilled state;
planarizing the wafer to remove the first metal from a top surface; and
blanket depositing a second metal layer on the first region and the alignment mark region such that the at least one trench in the alignment mark region is suitable for use as a scattering alignment mark.
2. The method as recited in claim 1, wherein the step of blocking the first metal deposition includes the steps of:
forming a seed layer over the wafer;
patterning a resist layer over the seed layer such that the seed layer in the at least one trench in the alignment mark region is exposed; and
etching the seed layer from the at least one trench in the alignment mark region such that when the first metal layer leaves the at least one trench in the alignment mark region unfilled after the deposition of the first metal layer.
3. The method as recited in claim 1, further comprising the step of scanning the wafer with laserlight to determine the position of the at least one trench in the alignment mark region.
4. The method as recited in claim 3, wherein the step of scanning the wafer with laserlight includes performing a laserlight scattering alignment.
5. The method as recited in claim 1, wherein the step of blanket depositing the second metal layer includes blanket depositing the second metal layer to a thickness less than an amount needed to completely fill the at least one trench in the alignment mark region.
6. The method as recited in claim 1, wherein the step of blocking the first metal deposition includes the steps of:
forming a block layer in the first region and in the alignment mark region to fill the at least one trench; and
patterning the block layer to remove the block layer from portions of the wafer other than the at least one trench in the alignment mark region.
7. A method for providing contrast for alignment marks after a blanket metal deposition, comprising the steps of:
etching at least one trench in a first region and at least one trench in an alignment mark region of a semiconductor wafer;
forming a seed layer in the first region and the alignment mark region;
removing the seed layer from the at least one trench in the alignment mark region;
depositing a metal layer on the semiconductor wafer to fill the at least one trench in the first regions without filling the at least one trench in the alignment mark region;
planarizing the metal layer and the seed layer; and
blanket depositing a second metal layer on the first region and the alignment mark region such that the at least one trench in the alignment mark region is suitable for use as a scattering alignment mark.
8. The method as recited in claim 7, wherein the step of removing the seed layer includes the steps of:
patterning a resist layer such that the at least one trench in the alignment mark region is exposed; and
etching the seed layer from the at least one trench in the alignment mark region.
9. The method as recited in claim 7, further comprising the step of scanning the wafer with laserlight to determine the position of the at least one trench in the alignment mark region.
10. The method as recited in claim 9, wherein the step of scanning the wafer with laserlight includes performing a laserlight scattering alignment.
11. The method as recited in claim 7, wherein the step of blanket depositing the second metal layer includes blanket depositing the second metal layer to a thickness less than an amount needed to completely fill the at least one trench in the alignment mark region.
12. A method for providing contrast for alignment marks after a blanket metal deposition, comprising the steps of:
etching at least one trench in a first region and at least one trench in an alignment mark region of a semiconductor wafer;
forming a block layer in the first region and in the alignment mark region to fill the at least one trench;
patterning the block layer to remove the block layer from portions of the wafer other than the at least one trench in the alignment mark region;
depositing a metal layer on the semiconductor wafer to fill the at least one trench in the first regions, the metal layer being excluded from the at least one trench in the alignment mark region by the block layer;
planarizing the metal layer;
removing the block layer from the at least one trench in the alignment mark region; and
blanket depositing a second metal layer on the first region and the alignment mark region such that the at least one trench in the alignment mark region is suitable for use as a scattering alignment mark.
13. The method as recited in claim 12, wherein the step of depositing the metal layer includes the steps of:
forming a seed layer in the first region and the block layer in the at least one trench in the alignment mark region.
14. The method as recited in claim 12, further comprising the step of scanning the wafer with laserlight to determine the position of that the at least one trench in the alignment mark region.
15. The method as recited in claim 14, wherein the step of scanning the wafer with laserlight includes performing a laserlight scattering alignment.
16. The method as recited in claim 12, wherein the block layer includes silicon nitride.
17. The method as recited in claim 12, wherein the step of patterning the block layer includes the steps of:
forming a blocking mask by depositing a photoresist on the blocking layer;
patterning the photoresist to remain over the at least one trench in the alignment mark region; and
removing the blocking layer from portions of the wafer other than the at least one trench in the alignment mark region.
18. The method as recited in claim 17, wherein the photoresist includes a mid ultraviolet (MUV) photoresist.
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. An isolated dual-specificity antibody having specificity for both an activated erbB2 receptor and erbB1 dimers, without significant affinity for monomeric EGFr that is not activated,
wherein the antibody has the same binding specificity as an antibody produced by a cell line 8A4 having the assigned accession number PTA-4565 or a cell line A10A12 having the assigned accession number PTA-4566.
2. The isolated antibody of claim 1 wherein the antibody has an affinity for the activated erbB2 receptor that is at least about 10-fold greater than the affinity the antibody has for the erbB2 receptor that is not activated.
3. The isolated antibody of claim 1 wherein the antibody has an affinity for the activated erbB2 receptor that is at least about 100-fold greater than the affinity the antibody has for the erbB2 receptor that is not activated.
4. The isolated antibody of claim 1 wherein the antibody has specificity for one or more cystine knot regions on the activated erbB2 receptor and erbB 1 dimers.
5. The isolated antibody of claim 4 wherein the antibody has a binding constant of at least 5\xd7106 Ka for each activated erbB2 receptor and erbB 1 dimer.
6. The isolated antibody of claim 5 wherein the antibody has a binding constant of at least 1\xd7107 Ka for each activated erbB2 receptor and erbB 1 dimer.
7. The isolated antibody of claim 6 wherein the antibody has a binding constant of at least 2\xd7107 Ka for each activated erbB2 receptor and erbB 1 dimer.
8. The isolated antibody of claim 7 wherein the antibody has a binding constant of at least 1\xd7108 Ka for each activated erbB2 receptor and erbB 1 dimer.
9. The isolated antibody of claim 1 wherein the antibody is selected from the group consisting of a monoclonal antibody, a humanized antibody, a camelized antibody, a chimeric antibody, a primatized antibody, a phage-displayed antibody, a FAb fragment thereof, or a F(Ab)2 fragment thereof.
10. The isolated antibody of claim 1 wherein the antibody binds to an assembly domain of the receptor.
11. The isolated antibody of claim 10 wherein the assembly domain is a cystine knot.
12. The isolated antibody of claim 4 wherein said isolated antibody binds to sub domain IV of said activated erbB 1 receptor.
13. The isolated antibody of claim 1 wherein the antibody is produced by a cell line 8A4 having the assigned accession number PTA-4565 or a cell line A10A12 having the assigned accession number PTA-4566.
14. The isolated antibody of claim 13 wherein the antibody is produced by the cell line 8A4 having the assigned accession number PTA-4565.
15. The isolated antibody of claim 1 wherein the antibody is conjugated to a radioactive agent, a chemotherapeutic agent or an imaging agent.
16. The antibody of claim 15 wherein the radioactive agent is 47Sc, 67Cu, 90Y, 86Y, 109Pd, 123I, 125I, 131I, 186Re, 199Au, 211At, 212Pb, 18F or 212Bi.
17. The isolated antibody of claim 15 wherein the antibody is conjugated to a chemotherapeutic agent and wherein the chemotherapeutic agent is selected from the group consisting of methotrexate (amethopterin), doxorubicin (adrimycin), daunorubicin, cytosinarabinoside, etoposide, 5-4 fluorouracil, melphalan, chlorambucil, cyclophosphamide, cis-platin, vindesine, mitomycin, bleomycin, tamoxiphen, taxol, ricin, ricin A chain, Pseudomonas exotoxin (PE), diphtheria toxin (DT), Clostridium perfringens phospholipase C (PLC), bovine pancreatic ribonuclease (BPR), pokeweed antiviral protein (PAP), abrin, abrin A chain, cobra venom factor (CVF), gelonin (GEL), saporin (SAP), modeccin, viscumin and volkensin.
18. The isolated antibody of claim 15 wherein the antibody is conjugated to an imaging agent and wherein the imaging agent is 43K, 52Fe, 57Co, 67Cu, 67Ga, 68Ga, 77Br, 81Rb, 81MKr, 87MSr, 86Y, 90Y, 99MTc, 111In, 113MIn, 123I, 125I, 127Cs, 129Cs, 131I, 132I, 197Hg, 203Pb, 206Bi, 18F, a heavy metal or a positron emitter of oxygen, nitrogen, iron, carbon, or gallium.
19. The isolated antibody of claim 18 wherein the heavy metal is selected from the group consisting of a chelate of iron, gadolinium and manganese.
20. A composition comprising the isolated antibody of claim 1 and a pharmaceutically acceptable carrier, excipient, or diluent.
21. The composition of claim 20 wherein the composition is an injectable composition.
22. The composition of claim 20 further comprising a chemotherapeutic agent or an imaging agent.
23. The composition of claim 21 further comprising a therapeutically effective amount of methotrexate (amethopterin), doxorubicin (adriamycin), daunorubicin, cytosinarabinoside, etoposide, 5-4 fluorouracil, melphalan, chlorambucil, cyclophosphamide, cis-platin, vindesine, mitomycin, bleomycin, tamoxiphen, or taxol.
24. A method of treating an individual who has an erbB2erbB 1 tumor which comprises administering to said individual a pharmaceutical composition comprising the antibody according to claim 1 and a pharmaceutically acceptable excipient.
25. The method of claim 24 further comprising exposing said individual to radiation.
26. The method of claim 24 further comprising exposing said individual to a chemotherapeutic agent.
27. A method of imaging an erbB1erbB2 tumor in a patient suffering from an erbB1erbB2 tumor which comprises administering to said patient a pharmaceutical composition comprising (i) the antibody according to claim 15, said antibody being conjugated to an imaging agent, and (ii) a pharmaceutically acceptable excipient, and detecting binding of the antibody to the erbB1erbB2 tumor.
28. A method of inhibiting progression of transformation or tumorigenesis of a cell that expresses erbB 1 and erbB2 in an individual who has a predisposition for developing erbB1erbB2 tumor, who has had an erbB1erbB2 tumor removed or who has had an erbB 1erbB2 cancer enter remission, which comprises administering to said individual a pharmaceutical composition comprising the antibody according to claim 1 and a pharmaceutically acceptable excipient.
29. The method of claim 28 which comprises inhibiting said cell from becoming a transformed tumor cell.
30. A method of treating a patient suffering from an erbB tumor which comprises administering to the patient the antibody according to claim 1 and a chemotherapeutic agent.
31. The method of claim 30 wherein said antibody is administered prior to administration of said chemotherapeutic agent.
32. The method of claim 30 wherein said chemotherapeutic agent is administered prior to administration of said antibody.
33. The method of claim 30 wherein said antibody and said chemotherapeutic agent are administered concurrently.
34. A method of treating a patient suffering from an erbB tumor which comprises administering to the patient the antibody according to claim 1 and radiation.
35. The method of claim 34 wherein said antibody is administered prior to administration of radiation.
36. The method of claim 34 wherein radiation is administered prior to administration of said antibody.
37. The method of claim 34 wherein said antibody and radiation are administered concurrently.
38. The isolated antibody of claim 1, wherein the antibody specifically binds to at least one activation epitope in the extracellular region of the activated erbB2 receptor.
39. The isolated antibody of claim 1, wherein the antibody has an affinity for the activated erbB2 receptor that is at least about 5-fold greater than the affinity the antibody has for the erbB2 receptor that is not activated.