Reagents and methods useful for detecting diseases of the breast

• US 20050153373A1
• Filed: 11/18/2004
• Published: 07/14/2005
• Est. Priority Date: 10/31/1996
• Status: Abandoned Application

• Current Assignee: Edward N. Granados, John C. Russell, Jon D. Kratochvil, Julian Gordon, Lisa Roberts-Rapp, Maurice Cohen, Michael R. Klass, Patricia A. Billing-Medel, Paula N. Friedman, Stephen D. Stroupe, Steven C. Hodges, Tracey L. Colpitts
• Original Assignee: Edward N. Granados, John C. Russell, Jon D. Kratochvil, Julian Gordon, Lisa Roberts-Rapp, Maurice Cohen, Michael R. Klass, Patricia A. Billing-Medel, Paula N. Friedman, Stephen D. Stroupe, Steven C. Hodges, Tracey L. Colpitts
• Inventors: Klass, Michael R., Granados, Edward N., Gordon, Julian, Roberts-Rapp, Lisa, Friedman, Paula N., Kratochvil, Jon D., Stroupe, Stephen D., Billing-Medel, Patricia A., Hodges, Steven C., Russell, John C., Cohen, Maurice, Colpitts, Tracey L.
• Application Number:
  US10/991,681
• Publication Number:
  US 20050153373A1
• Time in Patent Office: Days
• US Class Current: 435/7.230
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 16/3015 Breast
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 33/57415 of breast

Abstract

A set of contiguous and partially overlapping RNA sequences and polypeptides encoded thereby, designated as BS106 and transcribed from breast tissue is described. These sequences are useful for the detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, or determining the predisposition of an individual to diseases and conditions of the breast such as breast cancer. Also provided are antibodies which specifically bind to BS106-encoded polypeptide or protein, and agonists or inhibitors which prevent action of the tissue-specific BS106 polypeptide, which molecules are useful for the therapeutic treatment of breast diseases, tumors or metastases.

Claims

1. A purified multimeric polypeptide antigen (MPA) comprising at least one BU106 polypeptide said polypeptide having at least 50% identity to the polypeptides in SEQ ID NOS:

20-33, and at least other polypeptide together forming a molecular weight of at least 200 Kd.

2. The MPA of claim 1, wherein said polypeptides are complexed via a disulfide bond.

9. An antibody which will specifically bind to the MPA of claim 1.

3. A purified multimeric polypeptide antigen (MPA) comprising at least one BS106 polypeptide said polypeptide having at lest 50% identity to the polypeptides in SEQ ID NOS:

20-33 complexed with another peptide to form a non-reductable complex having a molecular weight of approximately 120 Kd.

10. An antibody which will specifically bind to the MPA of claim 3.

4. A method of detecting the presence of a multimeric polypeptide antigen (MPA) in a test sample suspected of containing said MPA, wherein said MPA comprises at least one BU106 polypeptide and, at least, one other polypeptide, wherein said MPA has a molecular weight greater than 200 Kd, said method comprising the steps of:

(a) contacting said test sample with at least one antibody specific for at least one epitope of said MPA for a time and under conditions sufficient to allow the formation of antigen/antibody complexes; and

(b) detecting said complexes, wherein presence of said complexes wherein said detection indicates the presence of said MPA in said test sample.

15. The method of claim 4, wherein said detection of said complex is indicative of breast disease.

5. A method of detecting the presence of a multimeric polypeptide antigen (MPA) in a test sample suspected of containing said MPA, wherein said MPA comprises at least one BU106 polypeptide and, at least, one other polypeptide, wherein said MPA has a molecular weight greater than approximately 120 Kd, said method comprising the steps of:

(a) contacting said test sample with at least one antibody specific for at least one epitope of said MPA for a time and under conditions sufficient to allow the formation of antigen/antibody complexes; and

(b) detecting said complexes, wherein detection of said complexes indicates the presence of said MPA in said test sample.

16. The method of claim 5, wherein said detection of said complex is indicative of breast disease.

6. A purified polypeptide antigen comprising BUS 106 polypeptide, said polypeptide having at least 50% identity to those polypeptides selected from the group consisting of SEQ ID NOS:

20-33 with at least two carbohydrate covalently linked at multiple sites, said sites selected from the group consisting of serine residue sites and threonine residue sites.

11. An antibody which will specifically bind to the antigen of claim 6.

7. A purified polypeptide antigen comprising BS106 polypeptide, said polypeptide having at least 50% identity to those polypeptides selected from the group consisting of SEQ ID NOS:

20-33 and at least one carbohydrate.

12. An antibody which will specifically bind to the antigen of claim 7.

8. A purified multimeric polypeptide antigen (MPA) comprising at least one BU106 polypeptide and at least one other polypeptide together forming a complex, said complex having molecular weight of approximately 50 to 80 kD.

13. An antibody which will specifically bind to the antigen of claim 8.

14. The cell line designated 106C1.

17. A diagnostic kit comprising a panel of breast markers comprising:

at least one BS106 marker and at least one other breast-specific marker.

18. An antibody which specifically binds to a BU106 polypeptide wherein said BU106 polypeptide has at least 50% identity to SEQUENCE ID NOS. 20-33.

19. A method of detecting BU106 comprising:

(a) providing a patient sample;

(b) analyzing said sample for a polypeptide having a molecular weight selected from the group consisting of approximately 200 Kd and 120 Kd;

(c) detecting the presence of said polypeptide have said molecular weight.

20. A method for detecting cancer cells, if present, in a tissue sample from a human patient, the method comprising contacting a tissue sample from a patent with a recognition agent for BU106, and detecting binding of the recognition agent to BU106 protein in the prepared sample as an indication of the presence of cancer cells in the tissue sample.

21. A method according to claim 20 which includes the steps of obtaining from a patient a tissue sample to be tested for the presence of cancer cells;

and producing a prepared sample in a sample preparation process;

prior to contacting the prepared sample with a recognition agent that reacts with BU106 protein.

22. The method of claim 21 wherein binding of said recognition agent to BU106 protein in sample is detected by immunohistochemical analysis.

23. The method of claim 22, wherein the sample preparation process comprises contacting the tissue with fixative and producing a thin seciton suitable for immunohistochemical analysis.

24. The method of claim 20 wherein said BU106 is in complexed form.