Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of...
Reexamination Certificate
1998-07-17
2002-04-30
Caputa, Anthony C. (Department: 1642)
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
C536S023500, C536S023100, C435S252330, C435S252800, C435S254200, C435S320100, C435S352000, C435S358000, C435S363000, C435S365000, C435S366000
Reexamination Certificate
active
06379951
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to compositions and methods for the treatment of breast cancer. The invention is more particularly related to polypeptides comprising at least a portion of a protein that is preferentially expressed in breast tumor tissue and to DNA molecules encoding such polypeptides. Such polypeptides may be used in vaccines and pharmaceutical compositions for treatment of breast cancer.
BACKGROUND OF THE INVENTION
Breast cancer is a significant health problem for women in the United States and throughout the world. Although advances have been made in detection and treatment of the disease, breast cancer remains the second leading cause of cancer-related deaths in women, affecting more than 180,000 women in the United States each year. For women in North America, the life-time odds of getting breast cancer are now one in eight.
No vaccine or other universally successful method for the prevention or treatment of breast cancer is currently available. Management of the disease currently relies on a combination of early diagnosis (through routine breast screening procedures) and aggressive treatment, which may include one or more of a variety of treatments such as surgery, radiotherapy, chemotherapy and hormone therapy. The course of treatment for a particular breast cancer is often selected based on a variety of prognostic parameters, including an analysis of specific tumor markers. See, e.g., Porter-Jordan and Lippman,
Breast Cancer
8:73-100 (1994). However, the use of established markers often leads to a result that is difficult to interpret, and the high mortality observed in breast cancer patients indicates that improvements are needed in the treatment, diagnosis and prevention of the disease.
Accordingly, there is a need in the art for improved methods for therapy and diagnosis of breast cancer. The present invention fulfills these needs and further provides other related advantages.
SUMMARY OF THE INVENTION
The present invention provides compounds and methods for immunotherapy of breast cancer. In one aspect, isolated polypeptides are provided comprising at least an immunogenic portion of a breast tumor protein or a variant of said protein that differs only in conservative substitutions and/or modifications, wherein the breast tumor protein comprises an amino acid sequence encoded by a DNA molecule having a partial sequence selected from the group consisting of (a) nucleotide sequences recited in SEQ ID NOS: 3, 10, 17, 24, 45-52 and 55-67, (b) complements of said nucleotide sequences and (c) sequences that hybridize to a sequence of (a) or (b) under moderately stringent conditions.
In related aspects, isolated DNA molecules encoding the above polypeptides are provided. In specific embodiments, such DNA molecules have partial sequences provided in SEQ ID NOS: 3, 10, 17, 24, 45-52 and 55-67. The present invention further provides expression vectors comprising the above DNA molecules and host cells transformed, or transfected with such expression vectors. In preferred embodiments, the host cells are selected from the group consisting of
E. coli,
yeast and mammalian cells.
In another aspect, the present invention provides fusion proteins comprising a first and a second inventive polypeptide or, alternatively, an inventive polypeptide and a known breast antigen.
The present invention also provides pharmaceutical compositions comprising at least one of the above polypeptides, or a DNA molecule encoding such a polypeptide, and a physiologically acceptable carrier, together with vaccines comprising at least one or more such polypeptide or DNA molecule in combination with a non-specific immune response enhancer. Pharmaceutical compositions and vaccines comprising one or more of the above fusion proteins are also provided.
In related aspects, pharmaceutical compositions for the treatment of breast cancer comprising at least one polypeptides and a physiologically acceptable carrier are provided, wherein the polypeptide comprises an immunogenic portion of a breast tumor protein or a variant thereof, the breast tumor protein being encoded by a DNA molecule having a partial sequence selected from the group consisting of: (a) nucleotide sequences recited in SEQ ID NOS: 1, 2, 4-9, 11-16, 18-23, 25-44, 53 and 54, (b) complements of said nucleotide sequences, and (c) sequences that hybridize to a sequence of (a) or (b) under moderately stringent conditions. The invention also provides vaccines for the treatment of breast cancer comprising such polypeptides in combination with a non-specific immune response; enhancer, together with pharmaceutical compositions and vaccines comprising at least one DNA molecule having a partial sequence provided in SEQ ID NOS: 1, 2, 4-9, 11-16, 18-23, 25-44, 53 and 54.
In yet another aspect, methods are provided for inhibiting the development of breast cancer in a patient, comprising administering an effective amount of at least one of the above pharmaceutical compositions and/or vaccines.
These and other aspects of the present invention will become apparent upon reference to the following detailed description. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.
DETAILED DESCRIPTION OF THE INVENTION
As noted above, the present invention is generally directed to compositions and methods for the immunotherapy of breast cancer. The inventive compositions are generally isolated polypeptides that comprise at least a portion of a breast tumor protein. Also included within the present invention are molecules (such as an antibody or fragment thereof) that bind to the inventive polypeptides. Such molecules are referred to herein as “binding agents.”
In particular, the subject invention discloses polypeptides comprising at least a portion of a human breast tumor protein, or a variant thereof, wherein the breast tumor protein includes an amino acid sequence encoded by a DNA molecule including a sequence selected from the group consisting of: nucleotide sequences recited in SEQ ID NOS: 1-67, the complements of said nucleotide sequences, and variants thereof. As used herein, the term “polypeptide” encompasses amino acid chains of any length, including full length proteins, wherein the amino acid residues are linked by covalent peptide bonds. Thus, a polypeptide comprising a portion of one of the above breast proteins may consist entirely of the portion, or the portion may be present within a larger polypeptide that contains additional sequences. The additional sequences may be derived from the native protein or may be heterologous, and such sequences may be immunoreactive and/or antigenic.
As used herein, an “immunogenic portion” of a human breast tumor protein is a portion that is capable of eliciting an immune response in a patient inflicted with breast cancer and as such binds to antibodies present within sera from a breast cancer patient. Such immunogenic portions generally comprise at least about 5 amino acid residues, more preferably at least about 10, and most preferably at least about 20 amino acid residues. Immunogenic portions of the proteins described herein may be identified in antibody binding assays. Such assays may generally be performed using any of a variety of means known to those of ordinary skill in the art, as described, for example, in Harlow and Lane,
Antibodies: A Laboratory Manual
, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1988. For example, a polypeptide may be immobilized on a solid support (as described below) and contacted with patient sera to allow binding of antibodies within the sera to the immobilized polypeptide. Unbound sera may then be removed and bound antibodies detected using, for example,
125
I-labeled Protein A. Alternatively, a polypeptide may be used to generate monoclonal and polyclonal antibodies for use in detection of the polypeptide in blood or other fluids of breast cancer patients. Methods for preparing and identifying immunogenic portions of antigens of known sequence are well known in
Reed Steven G.
Xu Jiangchun
Canella Karen A.
Caputa Anthony C.
Corixa Corporation
Seed Intellectual Property Law Group PLLC
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