Claims
- 1. A method for identifying a phenotypically active binding agent, comprising:
(a) contacting a first cell with a first binding agent, wherein said first cell comprises a binding target; (b) detecting binding of said first binding agent to said first cell; (c) preparing a second binding agent, wherein said second binding agent is derived from said first binding agent; (d) contacting a second cell with said second binding agent; wherein said second cell comprises said binding target; (e) detecting a phenotypic change in said second cell in response to said contact with said second binding agent; wherein said phenotypic change in said second cell is in response to said contact with said second binding agent; whereby said second binding agent is identified as a phenotypically active binding agent.
- 2. The method of claim 1, wherein said first cell is a neural cell.
- 3. The method of claim 2, wherein said second cell is a neural cell.
- 4. The method of claim 2, wherein said first binding agent is a protein or a peptide.
- 5. The method of claim 4, wherein the second binding agent comprises a peptide, wherein said peptide comprises a sequence of contiguous amino acids that is substantially identical to a region of contiguous amino acids in the first binding agent.
- 6. The method of claim 5, wherein said peptide comprises a sequence of at least 3 contiguous amino acids identical to a region of contiguous amino acids in said first binding agent.
- 7. The method of claim 5, wherein said peptide comprises a sequence of at least 4 contiguous amino acids identical to a region of contiguous amino acids in said first binding agent.
- 8. The method of claim 5, wherein said peptide comprises a sequence of at least 5 contiguous amino acids identical to a region of contiguous amino acids in said first binding agent.
- 9. The method of claim 5, wherein said peptide comprises a sequence of at least 9 contiguous amino acids identical to a region of contiguous amino acids in said first binding agent.
- 10. The method of claim 2, wherein said first binding agent is an antibody molecule or fragment thereof.
- 11. The method of claim 2, wherein said first binding agent is a monoclonal antibody or fragment thereof.
- 12. The method of claim 11, wherein said second binding agent comprises the complementarity determining region of said first binding agent, or a fragment thereof.
- 13. The method of claim 2, wherein the first binding agent is a fragment of an antibody expressed on a phage particle.
- 14. The method of claim 2, wherein the detection of binding of said first binding agent of (b) occurs by a method comprising detecting a phenotypic change in said first cell in response to contact with said binding agent.
- 15. The method of claim 2, wherein said second binding agent is a peptidomimetic.
- 16. The method of claim 2, wherein said second binding agent comprises a sequence of contiguous amino acids that is substantially identical to a retro-inverso peptide corresponding to a region of contiguous amino acids in said first binding agent.
- 17. The method of claim 2, wherein said second binding agent is prepared by a method comprising isolating a nucleic acid encoding the first binding agent.
- 18. The method of claim 17, wherein the first binding agent is expressed by a hybridoma cell.
- 19. The method of claim 18, wherein said nucleic acid is a fragment of genomic DNA isolated from said hybridoma cell.
- 20. The method of claim 18, wherein said nucleic acid is a fragment of cDNA prepared from the mRNA of said hybridoma cell.
- 21. The method of claim 2, wherein said binding target is a cell-surface receptor.
- 22. The method of claim 21, wherein said cell-surface receptor is an ion channel gate.
- 23. The method of claim 21, wherein said cell-surface receptor is the N-methly-D-aspartate receptor.
- 24. The method of claim 2, wherein said phenotypic change in second cell comprises induction of long-term potentiation.
- 25. The method of claim 2, wherein the second binding agent is an organic molecule.
- 26. A method for identifying a phenotypically active binding agent, comprising:
(a) identifying a binding target; (b) contacting a first cell with a first binding agent, wherein said first cell comprises said binding target; (c) detecting binding of said first binding agent to said first cell; (d) preparing a second binding agent, wherein said second binding agent is derived from said first binding agent; (e) contacting a second cell with said second binding agent; wherein said second cell comprises said binding target; (f) detecting a phenotypic change in said second cell in response to said contact with said second binding agent; wherein said phenotypic change in said second cell is in response to said contact with said second binding agent; whereby said second binding agent is identified as a phenotypically active binding agent.
- 27. A method for identifying a phenotypically active binding agent, comprising:
(a) identifying a first binding agent, wherein first binding agent binds to a binding target, (b) preparing a second binding agent, wherein said second binding agent is derived from said first binding agent; (c) contacting a cell with said second binding agent; wherein said cell comprises said binding target; (d) detecting a phenotypic change in said cell in response to said contact with said second binding agent; wherein said phenotypic change in said second cell is in response to said contact with said second binding agent; whereby said second binding agent is identified as a phenotypically active binding agent.
- 28. The method of claim 27, wherein said cell is a neural cell.
- 29. The method of claim 28, wherein said first binding agent is a protein or a peptide.
- 30. The method of claim 28, wherein said second binding agent comprises a peptide, wherein said peptide comprises a sequence of contiguous amino acids that is substantially identical to a region of contiguous amino acids in said first binding agent.
- 31. The method of claim 28, wherein said first binding agent is a monoclonal antibody.
- 32. The method of claim 28, wherein said second binding agent is a peptidomimetic.
- 33. The method of claim 28, wherein said binding target is a cell-surface receptor.
- 34. The method of claim 33, wherein said cell-surface receptor is the N-methyl-D-aspartate receptor.
- 35. The method of claim 28, wherein said phenotypic change in said second cell comprises induction of long-term potentiation.
- 36. A method for identifying a phenotypically active binding agent, comprising:
(a) contacting a first cell with a first binding agent, wherein said first cell comprises a binding target and wherein said first binding agent is encoded by a nucleic acid; (b) detecting binding of said first binding agent to said first cell; (c) preparing a nucleic acid library, wherein said nucleic acid library comprises said nucleic acid encoding said first binding agent, or a fragment thereof; (d) preparing a second binding agent, wherein said second binding agent is prepared by utilizing said nucleic acid library; (e) contacting a second cell with said second binding agent; wherein said second cell comprises said binding target; (f) detecting a phenotypic change in said second cell in response to said contact with said second binding agent; wherein said phenotypic change in said second cell is in response to said contact with said second binding agent; whereby said second binding agent is identified as a phenotypically active binding agent.
- 37. The method of claim 36, wherein said first cell is a neural cell.
- 38. The method of claim 37, wherein said nucleic acid library is derived from a genomic library of a hybridoma cell that expresses a monoclonal antibody.
- 39. The method of claim 37, wherein said nucleic acid library is derived from a cDNA library of a hybridoma cell that expresses a monoclonal antibody.
- 40. The method of claim 37, wherein said nucleic acid library is a phage display library.
- 41. The method of claim 37, wherein said nucleic acid library comprises a stochastically generated library.
- 42. The method of claim 37, wherein said nucleic acid library is modified by gene shuffling.
- 43. The method of claim 37, wherein said second binding agent is prepared by gene shuffling said nucleic acid library.
- 44. The method of claim 37, wherein said second binding agent is a peptidomimetic.
- 45. A phenotypically active binding agent identified by the method of claim 2.
- 46. A phenotypically active binding agent identified by the method of claim 5.
- 47. A phenotypically active binding agent identified by the method of claim 12.
- 48. A phenotypically active binding agent identified by the method of claim 15.
- 49. A phenotypically active binding agent identified by the method of claim 18.
- 50. A phenotypically active binding agent identified by the method of claim 21.
- 51. A phenotypically active binding agent identified by the method of claim 23.
- 52. A phenotypically active binding agent identified by the method of claim 24.
- 53. A phenotypically active binding agent identified by the method of claim 26.
- 54. A phenotypically active binding agent identified by the method of claim 28.
- 55. A phenotypically active binding agent identified by the method of claim 30.
- 56. A phenotypically active binding agent identified by the method of claim 31.
- 57. A phenotypically active binding agent identified by the method of claim 32.
- 58. A phenotypically active binding agent identified by the method of claim 33.
- 59. A phenotypically active binding agent identified by the method of claim 34.
- 60. A phenotypically active binding agent identified by the method of claim 35.
- 61. A phenotypically active binding agent identified by the method of claim 37.
- 62. A phenotypically active binding agent identified by the method of claim 40.
- 63. A phenotypically active binding agent identified by the method of claim 44.
RELATED APPLICATION
[0001] This application claims the benefit of priority of U.S. Provisional Application No. 60/307,740 filed Jul. 25, 2001, which is incorporated by reference herein in its entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60307740 |
Jul 2001 |
US |