Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of...
Reexamination Certificate
2001-04-13
2004-01-20
McGarry, Sean (Department: 1635)
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
C435S320100, C536S024300, C536S024310, C536S024330
Reexamination Certificate
active
06680197
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
The present invention relates generally to therapy and diagnosis of cancer, such as breast cancer. The invention is more specifically related to polypeptides, comprising at least a portion of a breast tumor protein, and to polynucleotides encoding such polypeptides. Such polypeptides and polynucleotides are useful in pharmaceutical compositions, e.g., vaccines, and other compositions for the diagnosis and 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 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 the treatment and diagnosis of breast cancer. The present invention fulfills these needs and further provides other related advantages.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides polynucleotide compositions comprising a sequence selected from the group consisting of:
(a) sequences provided in SEQ ID NO: 1-175, 178, 180, 182-468, 474, 476, 477 479, 484, 486, 489, 504-506, 510-513 and 520-533;
(b) complements of the sequences provided in SEQ ID NO: 1-175, 178, 180, 182-468, 474, 476, 477 479, 484, 486, 489, 504-506, 510-513 and 520-533;
(c) sequences consisting of at least 20 contiguous residues of a sequence provided in SEQ ID NO: 1-175, 178, 180, 182-468, 474, 476, 477 479, 484, 486, 489, 504-506, 510-513 and 520-533;
(d) sequences that hybridize to a sequence provided in SEQ ID NO: 1-175, 178, 180, 182-468, 474, 476, 477 479, 484, 486, 489, 504-506, 510-513 and 520-533, under moderately stringent conditions;
(e) sequences having at least 75% identity to a sequence of SEQ ID NO: 1-175, 178, 180, 182-468, 474, 476, 477 479, 484, 486, 489, 504-506, 510-513 and 520-533;
(f) sequences having at least 90% identity to a sequence of SEQ ID NO: 1-175, 178, 180, 182-468, 474, 476, 477 479, 484, 486, 489, 504-506, 510-513 and 520-533; and
(g) degenerate variants of a sequence provided in SEQ ID NO: 1-175, 178, 180, 182-468, 474, 476, 477 479, 484, 486, 489, 504-506, 510-513 and 520-533.
In one preferred embodiment, the polynucleotide compositions of the invention are expressed in at least about 20%, more preferably in at least about 30%, and most preferably in at least about 50% of breast tumors samples tested, at a level that is at least about 2-fold, preferably at least about 5-fold, and most preferably at least about 10-fold higher than that for normal tissues.
The present invention, in another aspect, provides polypeptide compositions comprising an amino acid sequence that is encoded by a polynucleotide sequence described above.
The present invention further provides polypeptide compositions comprising an amino acid sequence selected from the group consisting of sequences recited in SEQ ID NO: 176, 179, 181, 469-473, 475, 485, 487, 488, 507-509, 514-519 and 534-547.
In certain preferred embodiments, the polypeptides and/or polynucleotides of the present invention are immunogenic, i. e., they are capable of eliciting an immune response, particularly a humoral and/or cellular immune response, as further described herein.
The present invention further provides fragments, variants and/or derivatives of the disclosed polypeptide and/or polynucleotide sequences, wherein the fragments, variants and/or derivatives preferably have a level of immunogenic activity of at least about 50%, preferably at least about 70% and more preferably at least about 90% of the level of immunogenic activity of a polypeptide sequence set forth in SEQ ID NOs: 176, 179, 181, 469-473, 475, 485, 487, 488, 507-509, 514-519 and 534-547 or a polypeptide sequence encoded by a polynucleotide sequence set forth in SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477 479, 484, 486, 489, 504-506, 510-513 and 520-533.
The present invention further provides polynucleotides that encode a polypeptide described above, expression vectors comprising such polynucleotides and host cells transformed or transfected with such expression vectors.
Within other aspects, the present invention provides pharmaceutical compositions comprising a polypeptide or polynucleotide as described above and a physiologically acceptable carrier.
Within a related aspect of the present invention, the pharmaceutical compositions, e.g., vaccine compositions, are provided for prophylactic or therapeutic applications. Such compositions generally comprise an immunogenic polypeptide or polynucleotide of the invention and an immunostimulant, such as an adjuvant.
The present invention further provides pharmaceutical compositions that comprise: (a) an antibody or antigen-binding fragment thereof that specifically binds to a polypeptide of the present invention, or a fragment thereof; and (b) a physiologically acceptable carrier.
Within further aspects, the present invention provides pharmaceutical compositions comprising: (a) an antigen presenting cell that expresses a polypeptide as described above and (b) a pharmaceutically acceptable carrier or excipient. Illustrative antigen presenting cells include dendritic cells, macrophages, monocytes, fibroblasts and B cells.
Within related aspects, pharmaceutical compositions are provided that comprise: (a) an antigen presenting cell that expresses a polypeptide as described above and (b) an immunostimulant.
The present invention further provides, in other aspects, fusion proteins that comprise at least one polypeptide as described above, as well as polynucleotides encoding such fusion proteins, typically in the form of pharmaceutical compositions, e.g., vaccine compositions, comprising a physiologically acceptable carrier and/or an immunostimulant. The fusions proteins may comprise multiple immunogenic polypeptides or portions/variants thereof, as described herein, and may further comprise one or more polypeptide segments for facilitating the expression, purification and/or immunogenicity of the polypeptide(s).
The present invention further provides, in other aspects, fusion proteins that comprise at least one polypeptide as described above, as well as polynucleotides encoding such fusion proteins. Exemplary fusion proteins according to the present invention comprise a first amino acid portion and a second amino acid portion wherein the first amino acid portion includes 9 or more contiguous amino acids from mammaglobin as depicted by amino acids 1-93 of SEQ ID NO: 493 (SEQ ID NO: 503); wherein the second amino acid portion includes 9 or more contiguous amino acids from B726P as depicted by SEQ ID NO: 475, SEQ ID NO: 469, or SEQ ID NO: 176; and wherein the first amino acid portion is connected to either the amino terminal or carboxy-terminal end of the second amino acid portion.
Still further embodiments of the present invention provide fusion proteins wherein said first amino acid portion is selected from the group consisting of: IDELKECFLNQTDETLSNVE (SEQ ID NO:
Dillon Davin C.
Harlocker Susan L.
Henderson Robert A.
Hepler William T.
Jiang Yuqiu
Corixa Corporation
Epps-Ford Janet L.
McGarry Sean
Seed IP Law Group PLLC
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