Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Reexamination Certificate
1998-03-23
2002-08-27
Caputa, Anthony C. (Department: 1642)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
C530S387100, C530S387700, C530S388100, C435S007100, C435S007200, C435S007210, C435S007230
Reexamination Certificate
active
06441143
ABSTRACT:
The invention relates to certain anti-p185
-HER-2
eu
antibodies and the use of said antibodies in assays for the determination of HER-2
eu expression levels in biological samples. The antibodies of the invention are accurate indicators of HER-2
eu overexpression in human cancerous tissue using immunocytochemical or immunohistochemical assays. These reagents are useful for identifying cancer patients who have the greatest probability of relapse and/or the least likelihood of survival and, as a result, may be likely to benefit from adjuvant therapy.
BACKGROUND OF THE INVENTION
Prognostic factors often help predict relapse and survival in patients suffering from cancer. The presence of certain factors that are indicative of a greater probability of relapse and/or a low probability of survival may suggest that adjuvant therapy is appropriate. High-dose chemotherapy or autologous bone marrow transplantation are possible treatment regimens after surgery. The existence of reliable prognostic factors to predict relapse and survival are important since aggressive cancer therapy is costly and is frequently accompanied by toxic side effects. Likewise, the absence of such factors may indicate that less intensive therapy is required. Prognostic factors that have been used to predict relapse in breast cancer patients include tumor size (Carter et al. Cancer 63, 181-187 (1989)), number of lymph nodes involved (Carter et al., supra), histologic grade (Henson et al. Cancer 68, 2142-2149 (1991)), and the presence of estrogen or progesterone receptors (Osborne, in
Breast Diseases
, Harris, J. R. et al., eds. 2nd ed. J. B. Lippincott, pp. 301-325 (1991)). Recently, a variety of molecular markers have shown potential as prognostic factors for identifying cancer patients, particularly those suffering from breast and ovarian cancer, that are most likely to benefit from aggressive cancer therapy. Molecular markers that may be important include measurements of DNA content, cell proliferation and oncogene expression. Oncogene expression has received some attention by investigators in view of the apparent correlation between expression of the HER-2
eu oncogene and poor prognosis in patients with breast cancer. However, as explained below, this correlation has not been observed by all investigators or has been observed in only a subset of patients examined.
The HER-2
eu oncogene encodes a membrane-associated glycoprotein referred to as p185
HER-2
eu
having extracellular, transmembrane and intracellular domains, with the extracellular domain having homology to that of the epidermal growth factor receptor. The human gene, designated as c-erbB-2, HER-2, or neu , was reported by Semba et al. (Proc. Natl. Acad. Sci. USA 82, 6497-6501 (1985)); Coussens et al. (Science 230, 1132-1139 (1985)) and King et al. (Science 229, 974-976 (1985)). A related rat gene was reported by Schecter et al (Science 229, 976-978 (1985)).
Increased expression of the HER-2
eu oncogene in tumor cells and cell lines has been reported by several groups (Coussens et al., supra; King et al., supra). The increased expression of HER-2
eu results from gene amplification or increased expression of the single copy gene. These observations suggested that HER-2
eu may be overexpressed in human cancer tissue. Slamon and colleagues (Slamon et al. Science 235, 177-182 (1987); Slamon et al. Science 244, 707-712 (1989)) examined HER-2
eu expression levels in tumors taken from a large sample of breast and ovarian cancer patients. It was found that nearly 30% of those patients had amplification of the HER-2
eu gene, that the amplification was associated with overexpression, and that overexpression of HER-2
eu was associated with a poor clinical outcome (increased relapse and low survival rate) particularly in node-positive breast cancer patients. The correlations reported by Slamon have been confirmed in a number of studies (see, for example, Ro et al. Cancer Res. 49, 6941-6944 (1989); Walker et al. Brit. J. Cancer 60, 426-429 (1989); Wright et al. Cancer Res. 49, 2087-2090 (1989); Berchuck et al. Cancer Res 50, 4087-4091 (1990); Kallioniemi et al. Int. J. Cancer 49, 650-655 (1991); Rilke et al. Int. J. Cancer 49, 44-49 (1991)). However, other investigators have not found a significant correlation between prognosis and HER-2
eu overexpression in breast and ovarian cancer (see, for example, Van de Vijver et al. N. Engl. J. Med. 319, 1239-1245 (1988); Zhou et al. Oncogene 4, 105-108 (1989); Clark et al. Cancer Res. 51, 944-948 (1991); Kury et al. Eur. J. Cancer 26, 946-949 (1990); Rubin et al. Am. J. Obstet. Gynecol. 168, 162-169 (1993)). Presently, it is not clear in the art as to the reliability of HER-2
eu overexpression as a prognostic factor in breast and other cancers.
Most studies reported to date that have examined HER-2
eu expression levels in human breast cancer tissue specimens have employed immunohistochemical analysis of fixed paraffin-embedded tissue samples. A variety of anti-p185
HER-2
eu
antibodies have been generated and used in evaluating HER-2
eu expression (see, for example, van de Vijver et al. Cancer Cells 7, 385-391 (1989); Gullick et al. Int. J. Cancer 40, 246-254 (1987); Corbett et al. J. Path. 161, 15-25 (1990); Fendly et al. Cancer Res. 50, 1550-1558 (1990); Slamon et al. Cancer Cells 7, 371-380 (1989)). In view of the contradictory conclusions regarding the predictive value of HER-2
eu expression levels in breast cancer tissue, Press et al. (Cancer Res. 54, 2771-2777 (1994)) undertook a systematic evaluation of 28 different anti-p185
HER-2
eu
antibodies using multi-tumor tissue blocks. They observed significant variability in the detection of HER-2
eu expression levels in the same tissue samples by different antibodies. It has become apparent that the antibody used in the analysis of HER-2
eu expression is a crucial reagent that can significantly affect the reliability of HER-2
eu expression as a prognostic tool.
U.S. Pat. No. 4,968,603 discloses methods for screening patients suffering from breast and ovarian cancer for HER-2
eu expression or amplification. Expression of the HER-2
eu gene can be measured in one instance by immunohistochemical staining using an antibody raised against part or all of the HER-2
eu polypeptide. This disclosure does not provide anti-p185
HER-2
eu
antibodies nor does it suggest the variability with which different anti-p185
HER-2
eu
antibodies may react with p185
HER-2
eu
protein in biological samples. PCT Application No. WO89/10412 discloses antibodies to HER-2
eu protein generated by using NIH 3T3 cells transfected with a HER-2
eu full-length cDNA clone as the immunogen. Also disclosed are methods for detecting HER-2
eu overexpression using anti-p185
HER-2
eu
antibodies. PCT Application No. WO89/06692 discloses antibodies raised to NIH 3T3 cells transfected with full-length HER-2
eu cDNA clone and discloses methods for detecting tumors expressing HER-2
eu using anti-p185
HER-2
eu
antibodies. PCT Application No. WO93/03741 discloses antibodies raised to SK-BR-3 human breast cancer cells as an immunogen. None of these applications describe the reaction of anti-p185
HER-2
eu
antibodies with human cancer tissue samples. In addition, none of these applications address the problem of variable reactivity of anti-p185
HER-2
eu
antibodies with HER-2
eu protein in tissue samples.
It has been recently reported (Muss et al. N. Engl. J. Med. 330, 1260-1266 (1994)) that node-positive breast cancer patients treated with high-dose chemotherapy had significantly longer time to relapse and longer survival time if their tumors had HER-2
eu overexpression, while patients with little or no HER-2
eu expression showed no significant benefit to increased dosage.
In view of the potential importance of HER-2
eu overexpression in predicting response to treatment in certain cancers, it is desirable to identify reagents which will accurately and reliably measure levels of HER-2
eu expression. In particular, it is desirable to develop anti-p185
HER-2
eu
antibodies whic
Amgen INC
Caputa Anthony C.
Finnegan Henderson Farabow Garrett & Dunner L.L.P.
Hunt Jennifer
LandOfFree
Methods and compositions for determining HER-2/neu expression does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods and compositions for determining HER-2/neu expression, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and compositions for determining HER-2/neu expression will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2897230