Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Reexamination Certificate
1998-02-09
2001-07-17
Caputa, Anthony C. (Department: 1642)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
C514S002600, C514S012200, C530S324000
Reexamination Certificate
active
06261562
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to compositions and methods for the treatment of prostate cancer. The invention is more particularly related to polypeptides comprising at least a portion of a prostate protein and to DNA molecules encoding such polypeptides. Such polypeptides may be used in vaccines and pharmaceutical compositions for treatment of prostate cancer.
BACKGROUND OF THE INVENTION
Prostate cancer is the most common form of cancer among males, with an estimated incidence of 30% in men over the age of 50. Overwhelming clinical evidence shows that human prostate cancer has the propensity to metastasize to bone, and the disease appears to progress inevitably from androgen dependent to androgen refractory status, leading to increased patient mortality. This prevalent disease is currently the second leading cause of cancer death among men in the U.S.
In spite of considerable research into therapies for the disease, prostate cancer remains difficult to treat. Commonly, treatment is based on surgery and/or radiation therapy, but these methods are ineffective in a significant percentage of cases. Two previously identified prostate specific proteins—prostate specific antigen (PSA) and prostatic acid phosphatase (PAP)—have limited therapeutic and diagnostic potential. For example, PSA levels do not always correlate well with the presence of prostate cancer, being positive in a percentage of non-prostate cancer cases, including benign prostatic hyperplasia (BPH). Furthermore, PSA measurements correlate with prostate volume, and do not indicate the level of metastasis.
Accordingly, there remains a need in the art for improved vaccines and treatment methods for prostate cancer.
SUMMARY OF THE INVENTION
The present invention provides compounds and methods for immunotherapy of prostate cancer. In one aspect, polypeptides are provided comprising at least an immunogenic portion of a prostate tumor protein or a variant of said protein that differs only in conservative substitutions and/or modifications, wherein the prostate tumor protein comprises an amino acid sequence encoded by a DNA molecule having a sequence selected from the group consisting of nucleotide sequences recited in SEQ ID NO: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, the complements of said nucleotide sequences and variants thereof.
In related aspects, DNA molecules encoding the above polypeptides are provided. In specific embodiments, such DNA molecules include sequences provided in SEQ ID NO: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177. 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 prostate antigen.
The present invention also provides pharmaceutical compositions comprising one or more of the above polypeptides, or a DNA molecule encoding such polypeptides, and a physiologically acceptable carrier, together with vaccines comprising one or more of such polypeptide or DNA molecules in combination with a non-specific immune response enhancer.
In related aspects, pharmaceutical compositions for the treatment of prostate cancer comprising one or more polypeptides and a physiologically acceptable carrier are provided, wherein the polypeptide comprises an immunogenic portion of a prostate tumor protein or of a variant of said protein that differs only in conservative substitutions and/or modifications, the prostate tumor protein being encoded by a DNA molecule having a sequence selected from the group consisting of nucleotide sequences recited in SEQ ID NO: 5-7, 30-40, 46, 53, 66-69, 71, 72, 75-78, 80, 82-86, 88, 89, 91, 94-96, 98-102, 105, 106 and 161-170, the complements of said nucleotide sequences and variants thereof. The invention also provides vaccines for the treatment of prostate cancer comprising such polypeptides in combination with a non-specific immune response enhancer, together with pharmaceutical compositions and vaccines comprising one or more DNA molecules having a sequence provided in SEQ ID NO: 5-7, 30-40, 46, 53, 66-69, 71, 72, 75-78, 80, 82-86, 88, 89, 91, 94-96, 98-102, 105, 106 and 161-170. Pharmaceutical compositions and vaccines comprising one or more of the above fusion proteins are also provided.
In yet another aspect, methods are provided for inhibiting the development of prostate 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 and attached drawings. 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 prostate cancer. The inventive compositions are generally polypeptides that comprise at least a portion of a prostate 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 prostate tumor protein, or a variant of such a protein that differs only in conservative substitutions and/or modifications, wherein the prostate tumor protein includes an amino acid sequence encoded by a DNA molecule having a sequence selected from the group consisting of nucleotide sequences recited in SEQ ID NO: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111 and 115-160, 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 prostate 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 prostate tumor protein is a portion that is capable of eliciting an immune response in a patient inflicted with prostate cancer and as such binds to antibodies present within sera from a prostate cancer patient. Immunogenic portions of the proteins described herein may thus 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 prostate cancer patients.
The compositions and methods of the present invention also encompass variants of the above polypeptides and DNA molecules. A polypeptide
Dillon Davin C.
Xu Jiangchun
Caputa Anthony C.
Corixa Corporation
Nichols Jennifer
Seed Intellectual Property Law Group PLLC
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