Claims
- 1. A polynucleotide that encodes an 103P2D6-related protein, wherein the polynucleotide is selected from the group consisting of:
(a) an isolated polynucleotide comprising the sequence as shown in FIG. 2 (SEQ ID NO: 1), wherein T can also be U; (b) a polynucleotide consisting of the sequence as shown in FIG. 2 (SEQ ID NO: 1), from nucleotide residue number 805 through nucleotide residue number 2493, wherein T can also be U; (c) a polynucleotide that encodes a 103P2D6-related protein whose sequence is encoded by a cDNA contained in the plasmid designated p103P2D6-B or p 103P2D6-2 deposited with American Type Culture Collection as Accession No. PTA-1895 and PTA-1155, respectively; (d) a polynucleotide that encodes an 103P2D6-related protein that is at least 90% identical to the entire amino acid sequence shown in FIG. 2 (SEQ ID NO: 2); and (e) a polynucleotide that is fully complementary to a polynucleotide of any one of (a)-(d).
- 2. A polynucleotide of claim 1 That encodes the polypeptide sequence shown in SEQ ID NO: 2.
- 3. An isolated fragment of a polynucleotide of claim 1 comprising:
(a) at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in FIG. 2, from nucleotide residue number 1 through nucleotide residue number 804; or, (b) at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in FIG. 2, from nucleotide residue number 977 through nucleotide residue number 1036; or, (c) at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in FIG. 2, from nucleotide residue number 1414 through nucleotide residue number 1815; or (d) a polynucleotide whose starting base is in the range of 1-804 of FIG. 2 and whose ending base is in the range of 805-2493 of FIG. 2; or (e) a polynucleotide whose starting base is in the range of 977-1036 of FIG. 2 and whose ending base is in the range of 1037-2493 of FIG. 2; or (f) a polynucleotide whose starting base is in the range of 1414-1815 of FIG. 2 and whose ending base is in the range of 1816-2493 of FIG. 2; or (g) a polynucleotide whose starting base is in the range of 805-976 of FIG. 2 and whose ending base is in the range of 977-2493 of FIG. 2; or (h) a polynucleotide whose starting base is in the range of 805-2493 of FIG. 2 and whose ending base is in the range of 2494-4727 of FIG. 2; or (i) a polynucleotide of (d-g) that is at least 10 nucleotide bases in length; or (j) a polynucleotide that selectively hybridizes under stringent conditions to a polynucleotide of (a)-(g);
wherein a range is understood to specifically disclose all whole unit positions thereof and wherein T can be U.
- 4. A polynucleotide that encodes an 103P2D6-related protein, wherein the polypeptide includes a motif-bearing amino acid sequence set forth in Table XIX.
- 5. A polynucleotide that encodes an 103P2D6-related protein, wherein the polypeptide comprises an HLA class I A1, A2, A3, A24, B7, B27, B58, B62 supermotif, or an HLA class II DR supermotif set forth in Table IV (B) or an Alexander pan DR binding epitope supermotif or an HLA DR3 motif.
- 6. A polynucleotide of any one of claims 1-4 that is labeled with a detectable marker.
- 7. A recombinant expression vector that contains a polynucleotide of any one of claims 1-4.
- 8. A host cell that contains an expression vector of claim 7.
- 9. A process for producing a 103P2D6-related protein comprising culturing a host cell of claim 8 under conditions sufficient for the production of the polypeptide and recovering the 103P2D6-related protein so produced.
- 10. A 103P2D6-related protein produced by the process of claim 9.
- 11. An isolated 103P2D6-related protein.
- 12. The 103P2D6-related protein of claim 11, wherein 103P2D6-related protein has the amino acid sequence shown in SEQ ID NO: 2.
- 13. An isolated 103P2D6-related protein of claim 11 that has an amino acid sequence which is exactly that of an amino acid sequence encoded by a polynucleotide selected from the group consisting of:
(a) a polynucleotide consisting of the sequence as shown in SEQ ID NO: 1, wherein T can also be U; (b) a polynucleotide consisting of the sequence as shown in SEQ ID NO: 1, from nucleotide residue number 805 through nucleotide residue number 2493, wherein T can also be U; (c) a polynucleotide that encodes a 103P2D6-related protein whose sequence is encoded by a cDNA contained in the plasmid designated p103P2D6-B or p103P2D6-2 deposited with American Type Culture Collection as Accession No. PTA-1895 and PTA-1155, respectively; (d) a polynucleotide that encodes an 103P2D6-related protein that is at least 90% identical to the entire amino acid sequence shown in SEQ ID NO: 2; and (e) a polynucleotide that is fully complementary to a polynucleotide of any one of (a)-(d).
- 14. An isolated 103P2D6-related protein of claim 13 encoded by a polynucleotide selected from the group consisting of:
(a) of at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in FIG. 2 (SEQ ID NO: 1), from nucleotide residue number 1 through nucleotide residue number 255; or (b) of at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in FIG. 2 (SEQ ID NO: 1), from nucleotide residue number 730 through nucleotide residue number 997; or (c) a polynucleotide whose starting base is in the range of 1-255 of FIG. 2 (SEQ ID NO: 1) and whose ending base is in the range of 256-2198 of FIG. 2 (SEQ ID NO: 1); or (d) a polynucleotide whose starting base is in the range of 1-729 of FIG. 2 (SEQ ID NO: 1) and whose ending base is in the range of 730-2198 of FIG. 2 (SEQ ID NO: 1); or (e) a polynucleotide whose starting base is in the range of 1-255 of FIG. 2 (SEQ ID NO: 1) and whose ending base is in the range of 175-1773 of FIG. 2 (SEQ ID NO: 1); or (f) a polynucleotide whose starting base is in the range of 730-997 of FIG. 2 (SEQ ID NO: 1) and whose ending base is in the range of 739-1773 of FIG. 2 (SEQ ID NO: 1); or (g) a nucleotide that starts at any of the following positions and ends at a higher position of FIG. 2 (SEQ ID NO 1): 1, 255, a range of 1-255, a range of 256-729; 730, a range of 730-997, 997, 998-1771, a range of 1771-1947, 1947, 1948, a range of 1948-2198, 2198; (h) a polynucleotide of (c-g) that is at least 10 nucleotide bases in length; or (i) a polynucleotide that selectively hybridizes under stringent conditions to a polynucleotide of (a)-(h);
wherein a range is understood to specifically disclose all whole unit positions thereof and wherein T can be U.
- 15. An antibody or fragment thereof that specifically binds to a 103P2D6-related protein.
- 16. The antibody or fragment thereof of claim 15, which is monoclonal.
- 17. A recombinant protein comprising the antigen-binding region of a monoclonal antibody of claim 16.
- 18. The antibody or fragment thereof of claim 16, which is labeled with a detectable marker.
- 19. The recombinant protein of claim 17, which is labeled with a detectable marker.
- 20. The antibody fragment of claim 15,lwhich is an Fab, F(ab′)2, Fv or Sfv fragment.
- 21. The antibody of claim 15, which is a human antibody.
- 22. The recombinant protein of claim 19, which comprises murine antigen binding region residues and human constant region residues.
- 23. A non-human transgenic animal that produces an antibody of claim 15.
- 24. A hybridoma that produces an antibody of claim 15.
- 25. A single chain monoclonal antibody that comprises the variable domains of the heavy and light chains of a monoclonal antibody of claim 16.
- 26. A vector comprising a polynucleotide encoding a single chain monoclonal antibody of claim 25 that immunospecifically binds to a 103P2D6-related protein.
- 27. An assay for detecting the presence of a 103P2D6-related protein or polynucleotide in a biological sample comprising: contacting the sample with an antibody or polynucleotide, respectively, that specifically binds to the 103P2D6-related protein or polynucleotide, respectively, and detecting the binding of 103P2D6-related protein or polynucleotide, respectively, in the sample thereto.
- 28. An assay of claim 27 or detecting the presence of an 103P2D6-related protein or polynucleotide comprising the steps of: obtaining a sample, evaluating said sample in the presence of an 103P2D6-related protein or polynucleotide, whereby said evaluating step produces a result that indicates the presence or amount of 103P2D6-related protein or polynucleotide, respectively.
- 29. An assay of claim 28 for detecting the presence of an 103P2D6 polynucleotide in a biological sample, comprising:
(a) contacting the sample with a polynucleotide probe that specifically hybridizes to a polynucleotide encoding an 103P2D6-related protein having an amino acid sequence shown in FIG. 2; and (b) detecting the presence of a hybridization complex formed by the hybridization of the probe with 103P2D6 polynucleotide in the sample, wherein the presence of the hybridization complex indicates the presence of 103P2D6 polynucleotide within the sample.
- 30. An assay for detecting the presence of 103P2D6 mRNA in a biological sample comprising:
(a) producing cDNA from the sample by reverse transcription using at least one primer; (b) amplifying the cDNA so produced using 103P2D6 polynucleotides as sense and antisense primers to amplify 103P2D6 cDNAs therein; (c) detecting the presence of the amplified 103P2D6 cDNA, wherein the 103P2D6 polynucleotides used as the sense and antisense probes are capable of amplifying the 103P2D6 cDNA contained within the plasmid as deposited with American Type Culture Collection as Accession No. PTA-1895 or PTA-1155.
- 31. A method of claim 30, for monitoring 103P2D6 gene products comprising:
determining the status of 103P2D6 gene products expressed by cells in a tissue sample from an individual; comparing the status so determined to the status of 103P2D6 gene products in a corresponding normal sample; and identifying the presence of aberrant 103P2D6 gene products in the sample relative to the normal sample.
- 32. The method of claim 31, wherein the 103P2D6 gene products are monitored by comparing the polynucleotide sequences of 103P2D6 gene products in the test tissue sample with the polynucleotide sequences of 103P2D6 gene products in a corresponding normal sample.
- 33. The method of claim 31, wherein the 103P2D6 gene products are monitored by comparing the levels 103P2D6 gene products in the test tissue sample with the levels of 103P2D6 gene products in the corresponding normal sample.
- 34. A method of diagnosing the presence of cancer in an individual comprising: performing the method of claim 32 or 33 whereby the presence of elevated 103P2D6 mRNA or protein expression in the test sample relative to the normal tissue sample provides an indication of the presence of cancer.
- 35. The method of claim 34, wherein the cancer occurs in a tissue set forth in Table I.
- 36. Use of an 103P2D6-related protein, a vector comprising a polynucleotide encoding a single chain monoclonal antibody that immunospecifically binds to an 103P2D6-related protein, an antisense polynucleotide complementary to a polynucleotide having 103P2D6 coding sequences, or a ribozyme capable of cleaving a polynucleotide having 103P2D6 coding sequences, for the preparation of a composition for treating a patient with a cancer that expresses 103P2D6.
- 37. The use of claim 36, wherein the cancer occurs in a tissue set forth in Table I.
- 38. A pharmaceutical composition comprising an 103P2D6-related protein, an antibody or fragment thereof that specifically binds to an 103P2D6-related protein, a vector comprising a polynucleotide encoding a single chain monoclonal antibody that immunospecifically binds to an 103P2D6-related protein, a polynucleotide comprising an 103P2D6-related protein coding sequence, an antisense polynucleotide complementary to a polynucleotide having an 103P2D6 coding sequences or a ribozyme capable of cleaving a polynucleotide having 103P2D6 coding sequences and, optionally, a physiologically acceptable carrier.
- 39. A method of treating a patient with a cancer that expresses 103P2D6 which comprises administering to said patient a composition of claim 38 comprising a vector that comprises a polynucleotide encoding a single chain monoclonal antibody that immunospecifically binds to an 103P2D6-related protein, such that the vector delivers the single chain monoclonal antibody coding sequence to the cancer cells and the encoded single chain antibody is expressed intracellularly therein.
- 40. A method of inhibiting the development of a cancer expressing 103P2D6 in a patient, comprising administering to the patient an effective amount of the vaccine composition of claim 38.
- 41. A method of generating an immune response in a mammal comprising exposing the mammal's immune system to an immunogenic portion of an 103P2D6-related protein of claim 38, so that an immune response is generated to 103P2D6.
- 42. A method of delivering a cytotoxic agent to a cell that expresses 103P2D6 comprising conjugating the cytotoxic agent to an antibody or fragment thereof of claim 15 that specifically binds to a 103P2D6 epitope and exposing the cell to the antibody-agent conjugate.
- 43. A method of inducing an immune response to an 103P2D6 protein, said method comprising:
providing a 103P2D6-related protein T cell or B cell epitope; contacting the epitope with an immune system T cell or B cell respectively, whereby the immune system T cell or B cell is induced.
- 44. The method of claim 43, wherein the immune system cell is a B cell, whereby the induced B cell generates antibodies that specifically bind to the 103P2D6-related protein.
- 45. The method of claim 43, wherein the immune system cell is a T cell that is a cytotoxic T cell (CTL), whereby the activated CTL kills an autologous cell that expresses the 103P2D6 protein.
- 46. The method of claim 43, wherein the immune system cell is a T cell that is a helper T cell (HTL), whereby the activated HTL secretes cytokines that facilitate the cytotoxic activity of a CTL or the antibody producing activity of a B cell.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. provisional application No. 60/184,558, filed Feb. 24, 2000, and U.S. provisional application No. 60/218,856, filed Jul. 13, 2000, the entire contents of each of which are incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60184558 |
Feb 2000 |
US |
|
60218856 |
Jul 2000 |
US |