Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,...
Reexamination Certificate
1995-11-20
2004-05-11
Caputa, Anthony C. (Department: 1642)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
C424S133100, C424S141100, C424S155100, C424S156100
Reexamination Certificate
active
06733752
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to methods of preventing the transformation of normal mammalian cells into tumor cells.
BACKGROUND OF THE INVENTION
Huge amounts of time and money have been spent to better understand cancer and searching for ways to prevent and cure cancer. The results of these research efforts have provided a greater understanding of the biological and biochemical events that participate in the formation of tumors.
Tumor cells display a variety of characteristics that distinguish them from normal cells. Recent studies in the molecular genetics of cancer indicate that certain genes known as oncogenes may play a role in the transformation of some cells from their normal condition to a cancerous condition.
An oncogene which encodes a protein that exposes antigenic sites on the surface of transformed cells has been identified by transfection of DNA from ethyl nitrosourea-induced rat neuroblastomas into NIH3T3 cells. This oncogene has been termed neu. The neu gene has been found to be amplified in some human tumors, particularly those of the breast, suggesting that this gene may play a role in the etiology of human cancer.
The neu oncogene encodes a cell surface protein on rat cells transformed by it. The protein encoded by the neu oncogene is a 185 kDa transmembrane glycoprotein with tyrosine kinase activity, generally known by the name p185. The neu gene is closely related to the epidermal growth factor (EGF) receptor gene in structure.
The neu oncogene and p185 have also been found active in human adenocarcinomas including breast, lung, salivary gland and kidney adenocarcinomas, as well as prostate neuroblastoma. In human primary breast cancers, amplification of the neu oncogene was found in about 30% of all malignant tumors examined. Increased stage of malignancy, characterized by large tumor size and increased number of positive lymph nodes as well as reduced survival time and decreased time to relapse, was directly correlated with an increased level of amplification of the neu gene. The neu protooncogene is expressed at low levels in normal human tissues. Further, neu has been associated with 100% of the ductal carcinomas studied in situ, Lodato, R. F., et al. (1990)
Modern Pathol
. 3(4):449.
While changes in diet and behavior can reduce the likelihood of developing cancer, it has been found that some individuals have a higher risk of developing cancer than others. Further, those individuals who have already developed cancer and who have been effectively treated face a risk of relapse and recurrence.
Advancements in the understanding of genetics and developments in technology as well as epidemiology allow for the determination of probability and risk assessment an individual has for developing cancer. Using family health histories and/or genetic screening, it is possible to estimate the probability that a particular individual has for developing certain types of cancer. Those individuals that have been identified as being predisposed to developing a particular form of cancer can take only limited prophylactic steps towards reducing the risk of cancer. There is no currently available method or composition which can chemically intervene with the development of cancer and reduce the probability a high risk individual will develop cancer.
Similarly, those individuals who have already developed cancer and who have been treated to remove the cancer or are otherwise in remission are particularly susceptible to relapse and reoccurrence.
There is a need for improved preventative agents for individual with a high risk to develop cancer and for individuals who have had cancer enter remission or be removed. In cases where the type of cancer the individual is at risk to develop, such as tumors associated with neu, there is a need for specific agents which can be administered to reduce the probability that a predisposed individual will develop cancer or that a patient in remission will suffer a relapse.
SUMMARY OF THE INVENTION
The present invention provides methods for the prevention of tumor cells which express a translation product of the neu oncogene on their surfaces. In accordance with the invention, a prophylactic amount of an antibody that specifically binds to p185 is administered to an individual.
The present invention provides methods of preventing the transformation of normal human cells into tumors cells which express a translation product of the neu oncogene on their surfaces. In accordance with the invention, a prophylactic amount of an antibody that specifically binds to p185 is administered to an individual.
The present invention provides methods for the prevention of the origination of genetically induced mammalian tumor cells which express a translation product of the neu oncogene on their surfaces by interfering with a transforming event. In accordance with the invention, a prophylactic amount of an antibody that specifically binds to p185 is administered to an individual.
DETAILED DESCRIPTION OF THE INVENTION
As used herein, the terms “neu-associated cancer” and “neu-associated tumors” are meant to refer to tumor cells and neoplasms which express the neu gene to produce p185.
The translation product of the neu oncogene is p185, a transmembrane glycoprotein having tyrosine kinase activity and a molecular weight of about 185,000 daltons as determined by carrying out electrophoresis on the glycoprotein and comparing its movement with marker proteins of known molecular weight. Experiments have shown that administration of an antibody binding to p185 results in the reduced incidence of neu-associated tumors in a population susceptible to such tumors. Anti-p185 antibodies selectively inhibit the neoplastic development in animals susceptible to developing neu transformed tumors.
The occurrence of mammalian tumors cells which express a translation product of the neu oncogene on their surfaces can be prevented by administration of antibodies which bind to p185. In accordance with the invention, a prophylactic amount of an antibody that specifically binds to p185 is administered to an individual who is identified as being susceptibleto neu-associated tumors.
The present invention is particularly useful to prophylactically treat an individual who is predisposed to develop neu-associated tumors or who has had neu-associated tumors and is therefore susceptible to a relapse or recurrence.
As used herein, the term “high risk individual” is meant to refer to an individual who has had a neu-associated tumor either removed or enter remission and who is therefore susceptible to a relapse or recurrence. As part of a treatment regimen for a high risk individual, the individual can be prophylactically treated against the neu-associated tumors that they have been diagnosed as having had in order to combat a recurrence. Thus, once it is known that an individual has had cancer characterized by tumor cells with p185 on their cell surfaces, the individual can be treated according to the present invention to prevent normal cells from transforming into tumor cells.
Prophylactic compositions for prevention of neu-associated tumors comprise an antibody specific for the p185 molecule and a pharmaceutically acceptable carrier. According to preferred embodiments, the prophylactic compositions for prevention of neu-associated tumors are injectable. The compositions comprise an antibody specific for the p185 molecule and a pharmaceutically acceptable carrier or injection vehicle.
The antibodies are chosen from antibodies made according to the procedures described in detail below or other conventional methods for producing monoclonal antibodies. The carrier be selected from those well known to persons having ordinary skill in the art. An example of a carrier is sterile saline.
Antibodies Specific for Rat and Human p185
Those having ordinary skill in the art can produce monoclonal antibodies which specifically bind to p185 and are useful in prophylactic anti-tumor compositions using standard techniques and readily available starting materials. The techniques for producing mo
Greene Mark I.
Katsumato Makoto
Caputa Anthony C.
Darby & Darby
Davis Minh Tam
The Trustees of the University of Pennsylvania
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