Claims
- 1. An antibody that specifically binds MUC-1, said antibody comprising a domain having the amino acid sequence of a polypeptide selected from the group consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8), a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 2. The antibody of claim 1, wherein said antibody is a single chain antibody.
- 3. The antibody of claim 1, wherein said antibody comprises a variable light domain selected from the group consisting of:
a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8); and a variable heavy domain selected from the group consisting of a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 4. The antibody of claim 3, wherein said antibody comprises a 12E variable heavy domain (SEQ ID NO:1) and a 12E variable light domain (SEQ ID NO:2).
- 5. The antibody of claim 3, wherein said antibody comprises a 3D variable heavy domain (SEQ ID NO:3) and a 3D variable light domain (SEQ ID NO:4).
- 6. The antibody of claim 3, wherein said antibody comprises an A5 variable heavy domain (SEQ ID NO:5) and an A5 variable light domain (SEQ ID NO:6).
- 7. The antibody of claim 3, wherein said antibody comprises a C4 variable heavy domain (SEQ ID NO:7) and a C4 variable light domain (SEQ ID NO:8).
- 8. The antibody of any one of claim 4, 5, 6, or 7, wherein said antibody is a single chain antibody.
- 9. The antibody of claim 8, wherein said antibody is an scfv antibody.
- 10. The antibody of any one of claim 4, 5, 6, or 7, wherein said antibody comprises a diabody.
- 11. The antibody of any one of claim 4, 5, 6, or 7, wherein said antibody is a human antibody.
- 12. The antibody of any one of claim 4, 5, 6, or 7, wherein said antibody is a humanized antibody.
- 13. The antibody of any one of claim 4, 5, 6, or 7, wherein said antibody is a chimeric antibody.
- 14. A nucleic acid that encodes an antibody that specifically binds MUC-1, said nucleic acid comprising a nucleotide sequence encoding an amino acid sequence selected from the group consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8), a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 15. The nucleic acid of claim 14, wherein said nucleic acid encodes a variable light domain selected from the group consisting a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8); and
a variable heavy domain selected from the group consisting of a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 16. The nucleic acid of claim 15, wherein said nucleic acid encodes a 12E variable heavy domain (SEQ ID NO:1) and a 12E variable light domain (SEQ ID NO:2).
- 17. The nucleic acid of claim 15, wherein said nucleic acid encodes a 3D variable heavy domain (SEQ ID NO:3) and a 3D variable light domain (SEQ ID NO:4).
- 18. The nucleic acid of claim 15, wherein said nucleic acid encodes an A5 variable heavy domain (SEQ ID NO:5) and an A5 variable light domain (SEQ ID NO:6).
- 19. The nucleic acid of claim 15, wherein said nucleic acid encodes a C4 variable heavy domain (SEQ ID NO:7) and a C4 variable light domain (SEQ ID NO:8).
- 20. The nucleic acid of any one of claims 16, 17, 18, or 19, wherein said nucleic acid encodes an scfv antibody.
- 21. The nucleic acid of any one of claims 16, 17, 18, or 19, wherein said nucleic acid encodes a human antibody.
- 22. The nucleic acid of any one of claims 16, 17, 18, or 19, wherein said nucleic acid encodes a component of a diabody.
- 23. A chimeric molecule comprising an antibody attached to an effector, wherein:
said antibody is an antibody that specifically binds MUC-1, said antibody comprising a domain having an amino acid sequence of a polypeptide selected from the group consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8), a 12E variable heavy domain (SEQ ID NO: 1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7); and said effector is selected from the group consisting of an epitope tag, a second antibody, a label, a cytotoxin, a liposome, a radionuclide, a drug, a prodrug, a liposome, and a chelate.
- 24. The chimeric molecule of claim 23, wherein said antibody is a single chain antibody.
- 25. The chimeric molecule of claim 23, wherein said antibody comprises a variable light domain selected from the group consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8); and a variable heavy domain selected from the group consisting of, a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 26. The chimeric molecule of claim 23, wherein said antibody comprises a 12E variable heavy domain (SEQ ID NO:1) and a 12E variable light domain (SEQ ID NO:2).
- 27. The chimeric molecule of claim 23, wherein said antibody comprises a 3D variable heavy domain (SEQ ID NO:3) and a 3D variable light domain (SEQ ID NO:4).
- 28. The chimeric molecule of claim 23, wherein said antibody comprises an A5 variable heavy domain (SEQ ID NO:5) and an A5 variable light domain (SEQ ID NO:6).
- 29. The chimeric molecule of claim 23, wherein said antibody comprises a C4 variable heavy domain (SEQ ID NO:7) and a C4 variable light domain (SEQ ID NO:8).
- 30. The chimeric molecule of claims 26, 27, 28, or 29, wherein said antibody is a single chain antibody.
- 31. The chimeric molecule of claim 30, wherein said antibody is an scfv antibody.
- 32. The chimeric molecule of claim 30, wherein said effector is an epitope tag selected from the group consisting of an avidin, and a biotin.
- 33. The chimeric molecule of claim 30, wherein said effector is a cytotoxin selected from the group consisting of a Diphtheria toxin, a Pseudomonas exotoxin, a ricin, an abrin, and a thymidine kinase.
- 34. The chimeric molecule of claim 30, wherein said effector is a chelate comprising a metal isotope selected from the group consisting of 99Tc, 203Pb, 67Ga, 68Ga, 72As, 111In, 113mIn, 97Ru, 62Cu, 641Cu, 52Fe, 52mMn, 51Cr, 186,Re, 188Re, 77As, 90Y, 67Cu, 169Er, 121Sn, 127Te, 142Pr, 143Pr, 198Au, 199Au, 161Tb, 109Pd, 165Dy, 149Pm, 151Pm, 153Sm, 157Gd, 159Gd, 166Ho, 172Tm, 169Yb, 175Yb, 177Lu, 105Rh, and 111Ag.
- 35. The chimeric molecule of claim 30, wherein said effector is a chelate comprising DOTA.
- 36. A method of detecting a cell bearing a MUC-1 antigen, said method comprising:
contacting a cell bearing a MUC-1 antigen with a chimeric molecule comprising an anti-MUC-1 antibody attached to an epitope tag, wherein said antibody comprises a domain having an amino acid sequence of a polypeptide selected from the group consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8), a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7); contacting said chimeric molecule with a chelate comprising a detectable moiety whereby said chelate binds to said epitope tag thereby associating said detectable moiety with said chelate; and detecting said detectable moiety.
- 37. The method of claim 36, wherein said antibody comprises a variable light domain selected from the group consisting of:
a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8); and a variable heavy domain selected from the group consisting of a 12E variable heavy domain (SEQ ID NO: 1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 38. The method of claim 36, wherein said antibody comprises a 12E variable heavy domain (SEQ ID NO:1) and a 12E variable light domain (SEQ ID NO:2).
- 39. The method of claim 36, wherein said antibody comprises a 3D variable heavy domain (SEQ ID NO:3) and a 3D variable light domain (SEQ ID NO:4).
- 40. The method of claim 36, wherein said antibody comprises an A5 variable heavy domain (SEQ ID NO:5) and an A5 variable light domain (SEQ ID NO:6).
- 41. The method of claim 36, wherein said antibody comprises a C4 variable heavy domain (SEQ ID NO:7) and a C4 variable light domain (SEQ ID NO:8).
- 42. The method of claim 36, wherein said detectable moiety is a radionuclide.
- 43. The method of claim 36, wherein said detectable moiety is selected from the group consisting of a gamma-emitter, a positron-emitter, an x-ray emitter, and a fluorescence-emitter.
- 44. The method of claim 36, wherein said cell is a cancer cell.
- 45. The method of claim 36, wherein said detecting comprises external imaging.
- 46. The method of claim 36, wherein said detecting comprises internal imaging.
- 47. The method of claim 36, wherein said detectable moiety comprises a metal isotope selected from the group consisting of 99Tc, 203Pb, 67Ga, 68Ga, 72As, 111In, 113mIn, 97Ru, 62Cu, 641Cu, 52Fe, 52mMn, 51Cr, 186,Re, 188Re, 77As, 90Y, 67Cu, 169Er, 121Sn, 127Te, 142Pr, 143Pr, 198Au, 199Au, 161Tb, 109Pd, 165Dy, 149Pm, 151Pm, 153Sm, 157Gd, 159Gd, 166Ho, 172Tm, 169Yb, 175Yb, 177Lu, 105Rh, and 111Ag.
- 48. The method of claim 36, wherein said chelate comprises DOTA.
- 49. The method of claim 36, wherein said epitope tag is an avidin or a biotin.
- 50. A method of detecting a cell bearing a MUC-1 antigen, said method comprising:
contacting a cell bearing a MUC-1 antigen with a chimeric molecule comprising an anti-MUC-1 antibody attached to a detectable label; and detecting said detectable label.
- 51. The method of claim 50, wherein said antibody comprises a domain having the amino acid sequence of a polypeptide selected from the group consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8), a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 52. The method of claim 50, wherein said antibody is a single chain antibody.
- 53. The method of claim 50, wherein said antibody comprises a variable light domain selected from the group consisting of:
a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8); and a variable heavy domain selected from the group consisting of a 12E variable heavy domain (SEQ ID NO: 1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 54. The method of claim 50, wherein said antibody comprises a 12E variable heavy domain (SEQ ID NO: 1) and a 12E variable light domain (SEQ ID NO:2).
- 55. The method of claim 50, wherein said antibody comprises a 3D variable heavy domain (SEQ ID NO:3) and a 3D variable light domain (SEQ ID NO:4).
- 56. The method of claim 50, wherein said antibody comprises an A5 variable heavy domain (SEQ ID NO:5) and an A5 variable light domain (SEQ ID NO:6).
- 57. The method of claim 50, wherein said antibody comprises a C4 variable heavy domain (SEQ ID NO:7) and a C4 variable light domain (SEQ ID NO:8).
- 58. The method of claim 50, wherein said detectable label is a radionuclide.
- 59. The method of claim 50, wherein said detectable label is a selected from the group consisting of a gamma-emitter, a positron-emitter, an x-ray emitter, and a fluorescence-emitter.
- 60. A method of inhibiting growth or proliferation of a cell bearing a MUC-1 antigen, said method comprising:
contacting said cell bearing a MUC-1 antigen with a chimeric molecule comprising an anti-MUC-1 antibody attached to an effector selected from the group consisting of a cytotoxin, a radionuclide, a liposome comprising an anti-cancer drug, a prodrug, and an anti-cancer drug. said antibody comprising a domain having the amino acid sequence of a polypeptide selected from the group consisting of a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8), a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 61. The method of claim 60, wherein said antibody is a single chain antibody.
- 62. The method of claim 60, wherein said antibody comprises a variable light domain selected from the group consisting of:
a 12E variable light domain (SEQ ID NO:2), a 3D variable light domain (SEQ ID NO:4), an A5 variable light domain (SEQ ID NO:6), a C4 variable light domain (SEQ ID NO:8); and a variable heavy domain selected from the group consisting of a 12E variable heavy domain (SEQ ID NO:1), a 3D variable heavy domain (SEQ ID NO:3), an A5 variable heavy domain (SEQ ID NO:5), and a C4 variable heavy domain (SEQ ID NO:7).
- 63. The method of claim 60, wherein said antibody comprises a 12E variable heavy domain (SEQ ID NO:1) and a 12E variable light domain (SEQ ID NO:2).
- 64. The method of claim 60, wherein said antibody comprises a 3D variable heavy domain (SEQ ID NO:3) and a 3D variable light domain (SEQ ID NO:4).
- 65. The method of claim 60, wherein said antibody comprises an A5 variable heavy domain (SEQ ID NO:5) and an A5 variable light domain (SEQ ID NO:6).
- 66. The method of claim 60, wherein said antibody comprises a C4 variable heavy domain (SEQ ID NO:7) and a C4 variable light domain (SEQ ID NO:8).
- 67. An antibody that specifically binds MUC-1 at an epitope specifically bound by a single-chain antibody selected from the group consisting of 12E (SEQ ID NO:9), 3D(SEQ ID NO:10), A5 (SEQ ID NO:11), and C4 (SEQ ID NO:12).
- 68. An antibody that specifically binds MUC-1 at an epitope specifically bound by a single-chain antibody said antibody comprising the amino acid sequence of a variable heavy chain and a variable light chain of an antibody selected from the group consisting of 12E (SEQ ID NO:9), 3D(SEQ ID NO:10), A5 (SEQ ID NO:11), and C4 (SEQ ID NO:12), or conservative substitutions thereto.
- 69. A kit comprising a container containing an antibody of claim 1.
- 70. The kit of claim 69, further comprising an effector.
- 71. The kit of claim 70, wherein said effector comprises a chelate.
- 72. The kit of claim 69, wherein said antibody is in a pharmacologically acceptable excipient.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims benefit of and priority to U.S. Ser. No. 60/280,721, filed on Mar. 30, 2001 which is incorporated herein by reference for all purposes.
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
[0002] This work was supported by National Cancer Institute Grant CA-47829, California Breast Cancer Research Program Postdoctoral Fellowship Grant 5FB-0023, and Society of Nuclear Medicine Education and Research Fellowship. The Government of the United States of America may have certain rights in this invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60280721 |
Mar 2001 |
US |