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Title:
COMPOSITIONS AND METHODS FOR THERAPY AND DIAGNOSIS OF OVARIAN CANCER
Document Type and Number:
WIPO Patent Application WO/2000/036107
Kind Code:
A2
Abstract:
Compositions and methods for the therapy and diagnosis of cancer, such as ovarian cancer, are disclosed. Compositions may comprise one or more ovarian carcinoma proteins, immunogenic portions thereof, polynucleotides that encode such portions or antibodies or immune system cells specific for such proteins. Such compositions may be used, for example, for the prevention and treatment of diseases such as ovarian cancer. Methods are further provided for identifying tumor antigens that are secreted from ovarian carcinomas and/or other tumors. Polypeptides and polynucleotides as provided herein may further be used for the diagnosis and monitoring of ovarian cancer.

Inventors:
MITCHAM JENNIFER L
KING GORDON E
ALGATE PAUL A
FRUDAKIS TONY N
Application Number:
PCT/US1999/030270
Publication Date:
June 22, 2000
Filing Date:
December 17, 1999
Export Citation:
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Assignee:
CORIXA CORP (US)
International Classes:
A61K31/7115; A61K35/14; A61K35/76; A61K39/00; A61K39/395; A61K48/00; G01N33/53; A61P35/00; A61P37/04; C07K14/47; C07K14/82; C07K19/00; C12N1/15; C12N1/19; C12N1/21; C12N5/07; C12N5/0783; C12N5/09; C12N5/10; C12N15/09; C12N15/12; C12Q1/68; G01N33/566; G01N33/574; G01N33/577; A61K38/00; (IPC1-7): C12N15/12; C07K14/47; C12N15/62; C12N15/11; C12Q1/68; G01N33/68; C07K16/18
Other References:
None
Attorney, Agent or Firm:
Maki, David J. (Suite 6300 701 Fifth Avenu, Seattle WA, US)
GOWSHALL, Jonathan V., Forrester & Boehmert (Münche, Germany, DE)
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Claims:
CLAIMS
1. An isolated polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigen specific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (a) polynucleotides recited in any one of SEQ ID NOs: 181,313331,359, 366,379,385387 or 391; and (b) complements of the foregoing polynucleotides.
2. A polypeptide according to claim 1, wherein the polypeptide comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (a) polynucleotides recited in any one of 366,379, 385387 or 391; and (b) complements of such polynucleotides.
3. An isolated polynucleotide encoding at least 5 amino acid residues of a polypeptide according to claim polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigen specific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (a) polynucleotides recited in any one of SEQ ID NOs: 181, 319331,359, 385387 or 391; and (b) complements of the foregoing polynucleotides.
4. A polynucleotide according to claim 3, wherein the polynucleotide encodes an immunogenic portion of the polypeptide.
5. A polynucleotide according to claim 3, wherein the polynucleotide comprises a sequence recited in any one of SEQ ID NOs: 181,319331,359,385387,391 or a complement of any of the foregoing sequences.
6. An isolated polynucleotide complementary to a polynucleotide according to claim 3.
7. An expression vector comprising a polynucleotide according to claim 3 or claim 6.
8. A host cell transformed or transfected with an expression vector according to claim 7.
9. A pharmaceutical composition comprising a polypeptide according to claim 1, in combination with a physiologically acceptable carrier.
10. A pharmaceutical composition according to claim 9. wherein the polypeptide comprises an amino acid sequence encoded by a polynucleotide that comprises a sequence recited in any one of SEQ ID NOs: 181,313331,359,366,379,385387 or 391.
11. A vaccine comprising a polypeptide according to claim 1, in combination with a nonspecific immune response enhancer.
12. A vaccine according to claim 11, wherein the polypeptide comprises an amino acid sequence encoded by a polynucleotide that comprises a sequence recited in any one of SEQ ID NOs: 181,313331,359,366, 379, 385387 or 391.
13. A pharmaceutical composition comprising: (a) a polynucleotide encoding an ovarian carcinoma polypeptide, wherein the polypeptide comprises at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 181,319 331,359,385387 or 391; and (ii) complements of the foregoing polynucleotides; and (b) a physiologically acceptable carrier.
14. A pharmaceutical composition according to claim 13. wherein the polynucleotide comprises a sequence recited in any one of SEQ ID NOs: 181,319331,359, 385387,391 or a complement of any of the foregoing sequences.
15. A vaccine comprising: (a) a polynucleotide encoding an ovarian carcinoma polypeptide, wherein the polypeptide comprises at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 181,313 331,359,366,379,385387 or 391; and (ii) complements of the foregoing polynucleotides; and.
16. A vaccine according to claim 15, wherein the polynucleotide comprises a sequence recited in any one of SEQ ID NOs: 181.319331, 359,385387 or 391.
17. A pharmaceutical composition comprising: (a) an antibody that specifically binds to an ovarian carcinoma protein, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 181,313 331,359, 366, 379,385387 or 391; and (ii) complements of such polynucleotides; and (b) a physiologically acceptable carrier.
18. A method for inhibiting the development of ovarian cancer in a patient, comprising administering to a patient an effective amount of an agent selected from the group consisting of : (a) an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391 ; and (ii) complements of such polynucleotides; (b) a polynucleotide encoding a polypeptide as recited in (a); and (c) an antibody that specifically binds to an ovarian carcinoma protein that comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of such polynucleotides; and thereby inhibiting the development of ovarian cancer in the patient.
19. A method according to claim 18, wherein the agent is present within a pharmaceutical composition according to any one of claims 9,13 or 17.
20. A method according to claim 18, wherein the agent is present within a vaccine according to any one of claims 11,15 or 18.
21. A fusion protein comprising at least one polypeptide according to claim 1.
22. A polynucleotide encoding a fusion protein according to claim 21.
23. A pharmaceutical composition comprising a fusion protein according to claim 21 in combination with a physiologically acceptable carrier.
24. A vaccine comprising a fusion protein according to claim 21 in combination with a nonspecific immune response enhancer.
25. A pharmaceutical composition comprising a polynucleotide according to claim 22 in combination with a physiologically acceptable carrier.
26. A vaccine comprising a polynucleotide according to claim 22 in combination with a nonspecific immune response enhancer.
27. A method for inhibiting the development of ovarian cancer in a patient, comprising administering to a patient an effective amount of a pharmaceutical composition according to claim 23 or claim 25.
28. A method for inhibiting the development of ovarian cancer in a patient, comprising administering to a patient an effective amount of a vaccine according to claim 23 or claim 26.
29. A pharmaceutical composition, comprising: (a) an antigen presenting cell that expresses an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of such polynucleotides; and (b) a pharmaceutically acceptable carrier or excipient.
30. A vaccine, comprising: (a) an antigen presenting cell that expresses an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391 ; and (ii) complements of such polynucleotides; and (b) a nonspecific immune response enhancer.
31. A vaccine comprising: (a) an antiidiotypic antibody or antigenbinding fragment thereof that is specifically bound by an antibody that specifically binds to an ovarian carcinoma protein that comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of such polynucleotides; and (b) nonspecific immune response enhancer.
32. A vaccine according to claim 30 or claim 31, wherein the immune response enhancer is an adjuvant.
33. A pharmaceutical composition, comprising: (a) a T cell that specifically reacts with an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: l387 or 391; and (ii) complements of such polynucleotides; and (b) a physiologically acceptable carrier.
34. A vaccine, comprising: (a) a T cell that specifically reacts with an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of such polynucleotides; and (b) a nonspecific immune response enhancer.
35. A method for inhibiting the development of ovarian cancer in a patient, comprising administering to the patient an effective amount of a pharmaceutical composition according to claim 29 or claim 33.
36. A method for inhibiting the development of ovarian cancer in a patient, comprising administering to the patient an effective amount of a vaccine according to any one of claims 30,31 or 34.
37. A method for stimulating and/or expanding T cells, comprising contacting T cells with: (a) an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of such polynucleotides; (b) a polynucleotide encoding such a polypeptide ; and/or (c) an antigen presenting cell that expresses such a polypeptide under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.
38. A method according to claim 37, wherein the T cells are cloned prior to expansion.
39. A method for stimulating and/or expanding T cells in a mammal, comprising administering to a mammal a pharmaceutical composition comprising: (a) one or more of : (i) an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and complements of such polynucleotides; (ii) a polynucleotide encoding an ovarian carcinoma polypeptide; or (iii) an antigenpresenting cell that expresses an ovarian carcinoma polypeptide; and (b) a physiologically acceptable carrier or excipient; and thereby stimulating and/or expanding T cells in a mammal.
40. A method for stimulating and/or expanding T cells in a mammal, comprising administering to a mammal a vaccine comprising: (a) one or more of : (i) an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and complements of such polynucleotides; (ii) a polynucleotide encoding an ovarian carcinoma polypeptide; or (iii) an antigenpresenting cell that expresses an ovarian carcinoma polypeptide; and (b) a nonspecific immune response enhancer; and thereby stimulating and/or expanding T cells in a mammal.
41. A method for inhibiting the development of ovarian cancer in a patient, comprising administering to a patient T cells prepared according to the method of claim 39 or claim 40.
42. A method for inhibiting the development of ovarian cancer in a patient, comprising the steps of : (a) incubating CD4+ T cells isolated from a patient with one or more of : (i) an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and complements of such polynucleotides; (ii) a polynucleotide encoding an ovarian carcinoma polypeptide; or (iii) an antigenpresenting cell that expresses an ovarian carcinoma polypeptide; such that T cells proliferate; and (b) administering to the patient an effective amount of the proliferated T cells, and therefrom inhibiting the development of ovarian cancer in the patient.
43. A method for inhibiting the development of ovarian cancer in a patient, comprising the steps of : (a) incubating CD4+ T cells isolated from a patient with one or more of : (i) an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of: polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and complements of such polynucleotides; (ii) a polynucleotide encoding an ovarian carcinoma polypeptide; or (iii) an antigenpresenting cell that expresses an ovarian carcinoma polypeptide; such that T cells proliferate; (b) cloning one or more proliferated cells; and (c) administering to the patient an effective amount of the cloned T cells.
44. A method for inhibiting the development of ovarian cancer in a patient, comprising the steps of : (a) incubating CD8+ T cells isolated from a patient with one or more of : (i) an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and complements of such polynucleotides; (ii) a polynucleotide encoding an ovarian carcinoma polypeptide; or (iii) an antigenpresenting cell that expresses an ovarian carcinoma polypeptide; such that T cells proliferate; and (b) administering to the patient an effective amount of the proliferated T cells, and therefrom inhibiting the development of ovarian cancer in the patient.
45. A method for inhibiting the development of ovarian cancer in a patient, comprising the steps of : (a) incubating CD8+ T cells isolated from a patient with one or more of : (i) an ovarian carcinoma polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigenspecific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and complements of such polynucleotides; (ii) a polynucleotide encoding an ovarian carcinoma polypeptide; or (iii) an antigenpresenting cell that expresses an ovarian carcinoma polypeptide; such that the T cells proliferate; (b) cloning one or more proliferated cells; and (c) administering to the patient an effective amount of the cloned T cells.
46. A method for identifying a secreted tumor antigen, comprising the steps of : (a) implanting tumor cells in an immunodeficient mammal; (b) obtaining serum from the immunodeficient mammal after a time sufficient to permit secretion of tumor antigens into the serum; (c) immunizing an immunocompetent mammal with the serum; (d) obtaining antiserum from the immunocompetent mammal; and (e) screening a tumor expression library with the antiserum, and therefrom identifying a secreted tumor antigen.
47. A method according to claim 46, wherein the immunodeficient mammal is a SCID mouse and wherein the immunocompetent mammal is an immunocompetent mouse.
48. A method for identifying a secreted ovarian carcinoma antigen, comprising the steps of : (a) implanting ovarian carcinoma cells in a SCID mouse; (b) obtaining serum from the SCID mouse after a time sufficient to permit secretion of ovarian carcinoma antigens into the serum; (c) immunizing an immunocompetent mouse with the serum; (d) obtaining antiserum from the immunocompetent mouse; and (e) screening an ovarian carcinoma expression library with the antiserum, and therefrom identifying a secreted ovarian carcinoma antigen.
49. A method for determining the presence or absence of a cancer in a patient, comprising the steps of : (a) contacting a biological sample obtained from a patient with a binding agent that binds to an ovarian carcinoma protein, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of the foregoing polynucleotides; (b) detecting in the sample an amount of polypeptide that binds to the binding agent; and (c) comparing the amount of polypeptide to a predetermined cutoff value, and therefrom determining the presence or absence of a cancer in the patient.
50. A method according to claim 49, wherein the binding agent is an antibody.
51. A method according to claim 50, wherein the antibody is a monoclonal antibody.
52. A method according to claim 49, wherein the cancer is ovarian cancer.
53. A method for monitoring the progression of a cancer in a patient, comprising the steps of : (a) contacting a biological sample obtained from a patient at a first point in time with a binding agent that binds to an ovarian carcinoma protein, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of the foregoing polynucleotides; (b) detecting in the sample an amount of polypeptide that binds to the binding agent; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and (d) comparing the amount of polypeptide detected in step (c) to the amount detected in step (b) and therefrom monitoring the progression of the cancer in the patient.
54. A method according to claim 53, wherein the binding agent is an antibody.
55. A method according to claim 54, wherein the antibody is a monoclonal antibody.
56. A method according to claim 53, wherein the cancer is ovarian cancer.
57. A method for determining the presence or absence of a cancer in a patient, comprising the steps of : (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes an ovarian carcinoma protein, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of the foregoing polynucleotides; (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; and (c) comparing the amount of polynucleotide that hybridizes to the oligonucleotide to a predetermined cutoff value, and therefrom determining the presence or absence of a cancer in the patient.
58. A method according to claim 57, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a polymerase chain reaction.
59. A method according to claim 57, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a hybridization assay.
60. A method for monitoring the progression of a cancer in a patient, comprising the steps of : (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes an ovarian carcinoma protein, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: l387 or 391; and (ii) complements of the foregoing polynucleotides; (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and (d) comparing the amount of polynucleotide detected in step (c) to the amount detected in step (b) and therefrom monitoring the progression of the cancer in the patient.
61. A method according to claim 60, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a polymerase chain reaction.
62. A method according to claim 60, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a hybridization assay.
63. A diagnostic kit, comprising: (a) one or more antibodies or antigenbinding fragments thereof that specifically bind to an ovarian carcinoma protein that comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of: (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of the foregoing polynucleotides.; and (b) a detection reagent comprising a reporter group.
64. A kit according to claim 63, wherein the antibodies are immobilized on a solid support.
65. A kit according to claim 63, wherein the solid support comprises nitrocellulose, latex or a plastic material.
66. A kit according to claim 63, wherein the detection reagent comprises an antiimmunoglobulin, protein G, protein A or lectin.
67. A kit according to claim 63, wherein the reporter group is selected from the group consisting of radioisotopes, fluorescent groups, luminescent groups, enzymes, biotin and dye particles.
68. A diagnostic kit, comprising: (a) an oligonucleotide comprising 10 to 40 nucleotides that hybridize under moderately stringent conditions to a polynucleotide that encodes an ovarian carcinoma protein, wherein the ovarian carcinoma protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of : (i) polynucleotides recited in any one of SEQ ID NOs: 1387 or 391; and (ii) complements of the foregoing polynucleotides; and (b) a diagnostic reagent for use in a polymerase chain reaction or hybridization assay.
Description:
INTERNATIONAL SEARCH REPORT Inten Enal Application No PCT/US 99/30270 C. (Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. A MA J ET AL :"USE OF ENCAPSULATED SINGLE CHAIN ANTIBODIES FOR INDUCTION OF ANTI-IDIOTYPIC HUMORAL AND CELLULAR IMMUNE RESPONSES" JOURNAL OF PHARMACEUTICAL SCIENCES, US, AMERICAN PHARMACEUTICAL ASSOCIATION. WASHINGTON, vol. 87, no. 11, November 1998 (1998-11), pages 1375-1378, XP000877492 ISSN: 0022-3549 the whole document A GILLESPIE A M ET AL :"MAGE, BAGE AND GAGE: TUMOUR ANTIGEN EXPRESSION IN BENIGN AND MALIGNANT OVARIAN TISSUE" BRITISH JOURNAL OF CANCER, GB, LONDON, vol. 78, no. 6, September 1998 (1998-09), pages 816-821, XP000892404 ISSN: 0007-0920 the whole document A PEOPLES G E ET AL :"OVARIAN CANCER-ASSOCIATED LYMPHOCYTE RECOGNITION OF FOLATE BINDING PROTEIN PEPTIDES" ANNALS OF SURGICAL ONCOLOGY, US, RAVEN PRESS, NEW YORK, NY, vol. 5, no. 8, December 1998 (1998-12), pages 743-750, XP000892412 ISSN: 1068-9265 the whole document A BOOKMAN M A:"BIOLOGICAL THERAPY OF OVARIAN CANCER: CURRENT DIRECTIONS" SEMINARS IN ONCOLOGY, US, BETHESDA, MD, vol. 25, no. 3, June 1998 (1998-06), pages 381-396,XP000892403 the whole document A KOEHLER S ET AL:"IMMUNTHERAPIE DES OVARIALKARZINOMS MIT DEM MONOKLONALEN ANTI-IDIOTYPISCHEN ANTIKOERPER ACA125- ERGEBNISSE DER PHASE-LB-STUDIE. IMMUNOTHERAPY OF OVERIAN CARCINOMA WITH THE MONOCLONAL ANTI-IDIOTYPE ANTIBODY ACA125-RESULTS OF THE PHASE LB STUDY" GEBURTSHILFE UND FRAUENHEILKUNDE, XX, XX, vol. 58, no. 4, April 1998 (1998-04), pages 180-186, XP000892407 ISSN: 0016-5751 the whole document 1 Inte,, honal application No. INTERNATIONAL SEARCH REPORT PCT/US 99/30270 Box I Observations where certain claims were found unsearchable (Continuation of item 1 of first sheet) This International Search Report has not been established in respect of certain claims under Article 17 (2) (a) for the following reasons: 1. i1 ; Claims Nos.: because they relate to subject matter not required to be searched by this Authority, namely: Although claims 18 to 20, 27,28,35 to 41,46 to 48 are directed to a method of treatment of the human/animal body, the search has been carried out and based on the alleged effects of the compound/composition. 2. ClaimsNos.: because they relate to parts of the International Application that do not comply with the prescribed requirements to such an extent that no meaningful International Search can be carried out, specifically : 3. g Claims Nos. : because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6.4 (a). Box 11 Observations where unity of invention is lacking (Continuation of item 2 of first sheet) This International Searching Authority found multiple inventions in this international application, as follows: 1. As all required additional search fees were timely paid by the applicant, this International Search Report covers all searchable claims. 2. As ail searchable claims could be searched without effort justifying an additional fee, this Authority did not invite payment of any additional fee. 3. n As only some of the required additional search fees were timely paid by the applicant, this International Search Report F covers only those claims for which fees were paid, specifically claims Nos.: 4.2 No required additional search fees were timely paid by the applicant. Consequently, this International Search Report is restricted to the invention first mentioned in the claims; it is covered by claims Nos.: 1-68 (partially) Remark on Protest The additional search fees were accompanied by the applicant's protest. u No protest accompanied the payment of additional search fees. International Application No. PCT/US 99/30270 FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 1. Claims: 1-68 {partially} An isolated polypeptide comprising at least an immunogenic portion of an ovarian carcinoma protein and encoded by SEQ ID NO : 1, expression vectors comprising said polynucleotide, host cells transformed by said vector, pharmaceutical compositions and vaccines comprising the polypeptide encoded by said polynuceotide according to claims 9 to 17,23 to 25 and 29 to 34, and methods of using said polynucleotides for the treatment and/or diagnosis of ovarian cancer and diagnostic kits comprising said polynucleotide.