Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus
Reexamination Certificate
1998-12-23
2001-09-04
Clark, Deborah J. R. (Department: 1633)
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
Genetically modified micro-organism, cell, or virus
C435S069100, C435S320100, C435S325000, C536S023100, C536S023500
Reexamination Certificate
active
06284241
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to compositions and methods for the treatment and diagnosis of colon cancer. The invention is more specifically related to nucleotide sequences that are preferentially expressed in colon tumor tissue, together with polypeptides encoded by such nucleotide sequences. The inventive nucleotide sequences and polypeptides may be used in vaccines and pharmaceutical compositions for the treatment and diagnosis of colon cancer.
BACKGROUND OF THE INVENTION
Colon cancer is the second most frequently diagnosed malignancy in the United States as well as the second most common cause of cancer death. An estimated 95,600 new cases of colon cancer will be diagnosed in 1998, with an estimated 47,700 deaths. The five-year survival rate for patients with colorectal cancer detected in an early localized stage is 92%; unfortunately, only 37% of colorectal cancer is diagnosed at this stage. The survival rate drops to 64% if the cancer is allowed to spread to adjacent organs or lymph nodes, and to 7% in patients with distant metastases.
The prognosis of colon cancer is directly related to the degree of penetration of the tumor through the bowel wall and the presence or absence of nodal involvement, consequently, early detection and treatment are especially important. Currently, diagnosis is aided by the use of screening assays for fecal occult blood, sigmoidoscopy, colonoscopy and double contrast barium enemas. Treatment regimens are determined by the type and stage of the cancer, and include surgery, radiation therapy and/or chemotherapy. Recurrence following surgery (the most common form of therapy) is a major problem and is often the ultimate cause of death. In spite of considerable research into therapies for the disease, colon cancer remains difficult to diagnose and treat.
Accordingly, there remains a need in the art for improved vaccines, treatment methods and diagnostic techniques for colon cancer.
SUMMARY OF THE INVENTION
Briefly stated, the present invention provides compounds and methods for the therapy and diagnosis of colon cancer. In a first aspect, isolated polynucleotide molecules encoding colon tumor polypeptides are provided, such polynucleotide molecules comprising one of the following nucleotide sequences: (a) sequences provided in SEQ ID NO: 2, 8, 15, 16, 22, 24, 30, 32-34, 36, 38, 40, 41, 46-49, 52, 54, 59, 60, 65-69, 79, 89, 90, 93, 99-101 and 109-111; (b) sequences complementary to a sequence provided in SEQ ID NO: 2, 8, 15, 16, 22, 24, 30, 32-34, 36, 38, 40, 41, 46-49, 52, 54, 59, 60, 65-69, 79, 89, 90, 93, 99-101 and 109-111; and (b) sequences that hybridize to a sequence of (a) or (b) under moderately stringent conditions.
In a second aspect, isolated polypeptides are provided that comprise at least an immunogenic portion of a colon tumor protein or a variant thereof. In specific embodiments, such polypeptides comprise an amino acid sequence encoded by a polynucleotide molecule comprising one of the following nucleotide sequences: (a) sequences recited in SEQ ID NO: 2, 8, 15, 16, 22, 24, 30, 32-34, 36, 38, 40, 41, 46-49, 52, 54, 59, 60, 65-69, 79, 89, 90, 93, 99-101 and 109-111; (b) sequences complementary to a sequence provided in SEQ ID NO: 2, 8, 15, 16, 22, 24, 30, 32-34, 36, 38, 40, 41, 46-49, 52, 54, 59, 60, 65-69, 79, 89, 90, 93, 99-101 and 109-111; and (c) sequences that hybridize to a sequence of (a) or (b) under moderately stringent conditions.
In related aspects, expression vectors comprising the inventive polynucleotide molecules, together with host cells transformed or transfected with such expression vectors are provided. In preferred embodiments, the host cells may be
E. coli
, yeast and mammalian cells.
In another aspect, fusion proteins comprising a first and a second inventive polypeptide or, alternatively, an inventive polypeptide and a known colon tumor antigen, are provided.
The present invention further provides pharmaceutical compositions comprising one or more of the above polypeptides, fusion proteins or polynucleotide molecules and a physiologically acceptable carrier, together with vaccines comprising one or more such polypeptides, fusion proteins or polynucleotide molecules in combination with an immune response enhancer.
In related aspects, the present invention provides methods for inhibiting the development of colon cancer in a patient, comprising administering to a patient an effective amount of at least one of the above pharmaceutical compositions and/or vaccines.
Additionally, the present invention provides methods for immunodiagnosis of colon cancer, together with kits for use in such methods. Polypeptides are disclosed which comprise at least an immunogenic portion of a colon tumor protein or a variant of said protein that differs only in conservative substitutions and/or modifications, wherein the colon tumor protein comprises an amino acid sequence encoded by a polynucleotide molecule having one of the following nucleotide sequences recited in SEQ ID NO: 1-112, and variants thereof Such polypeptides may be usefully employed in the diagnosis and monitoring of colon cancer.
In one specific aspect of the present invention, methods are provided for detecting colon cancer in a patient, comprising: (a) contacting a biological sample obtained from a patient with a binding agent that is capable of binding to one of the above polypeptides; and (b) detecting in the sample a protein or polypeptide that binds to the binding agent. In preferred embodiments, the binding agent is an antibody, most preferably a monoclonal antibody.
In related aspects, methods are provided for monitoring the progression of colon cancer in a patient, comprising: (a) contacting a biological sample obtained from a patient with a binding agent that is capable of binding to one of the above polypeptides; (b) determining in the sample an amount of a protein or polypeptide that binds to the binding agent; (c) repeating steps (a) and (b); and comparing the amounts of polypeptide detected in steps (b) and (c).
Within related aspects, the present invention provides antibodies, preferably monoclonal antibodies, that bind to the inventive polypeptides, as well as diagnostic kits comprising such antibodies, and methods of using such antibodies to inhibit the development of colon cancer.
The present invention further provides methods for detecting colon cancer comprising: (a) obtaining a biological sample from a patient; (b) contacting the sample with a first and a second oligonucleotide primer in a polymerase chain reaction, at least one of the oligonucleotide primers being specific for a polynucleotide molecule that encodes one of the above polypeptides; and (c) detecting in the sample a polynucleotide sequence that amplifies in the presence of the first and second oligonucleotide primers. In a preferred embodiment, at least one of the oligonucleotide primers comprises at least about 10 contiguous nucleotides of a polynucleotide molecule, such as those sequences from SEQ ID NO: 1-112.
In a further aspect, the present invention provides a method for detecting colon cancer in a patient comprising: (a) obtaining a biological sample from the patient; (b) contacting the sample with an oligonucleotide probe specific for a polynucleotide molecule that encodes one of the above polypeptides; and (c) detecting in the sample a polynucleotide sequence that hybridizes to the oligonucleotide probe. Preferably, the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a polynucleotide molecule comprising a partial sequence from any of the following: SEQ ID NO: 1-112.
In related aspects, diagnostic kits comprising the above oligonucleotide probes or primers are provided.
In yet a further aspect, methods for the treatment of colon cancer in a patient are provided, the methods comprising obtaining PBMC from the patient, incubating the PBMC with a polypeptide of the present invention (or a polynucleotide that encodes such a polypeptide) to provide incubated T cells and administering the incubated T cells to the patient. Th
Chen Shin-Lin
Clark Deborah J. R.
Corixa Corporation
Seed Intellectual Property Law Group PLLC
LandOfFree
Compounds for immunotherapy and diagnosis of colon cancer... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compounds for immunotherapy and diagnosis of colon cancer..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds for immunotherapy and diagnosis of colon cancer... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2545728