Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,...
Reexamination Certificate
2000-07-20
2003-03-04
McGarry, Sean (Department: 1635)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
C530S387100
Reexamination Certificate
active
06528054
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 may be used in compositions for prevention and treatment of breast cancer, and for the diagnosis and monitoring of such cancers.
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
Briefly stated, the present invention provides compositions and methods for the diagnosis and therapy of cancer, such as breast cancer. In one aspect, the present invention provides polypeptides comprising at least a portion of a breast tumor protein, or a variant thereof. Certain portions and other variants are immunogenic, such that the ability of the variant to react with antigen-specific antisera is not substantially diminished. Within certain embodiments, the polypeptide comprises a sequence that is encoded by a polynucleotide sequence selected from the group consisting of: (a) sequences recited in SEQ ID NO: 1-175, 178, 180, 182-468, 474, 476, 477 479, 484, 486 and 489; (b) variants of a sequence recited in SEQ ID NO: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489; and (c) complements of a sequence of (a) or (b). In specific embodiments, the polypeptides of the present invention comprise at least a portion of a tumor protein that includes an amino acid sequence selected from the group consisting of sequences recited in SEQ ID NO: 176, 179, 181, 469-473, 475, 485, 487 and 488, and variants thereof.
The present invention further provides polynucleotides that encode a polypeptide as described above, or a portion thereof (such as a portion encoding at least 15 amino acid residues of a breast tumor protein), 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, immunogenic compositions, or vaccines for prophylactic or therapeutic use are provided. Such compositions comprise a polypeptide or polynucleotide as described above and an immunostimulant.
The present invention further provides pharmaceutical compositions that comprise: (a) an antibody or antigen-binding fragment thereof that specifically binds to a breast tumor protein; 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. Antigen presenting cells include dendritic cells, macrophages, monocytes, fibroblasts and B cells.
Within related aspects, immunogenic compositions, or vaccines, 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. 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; 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 (amino acids 59-78 of SEQ ID NO: 493); TTNAIDELKECFLNQ (amino acids 55-69 of SEQ ID NO: 493); SQHCYAGSGCPLLENVISKTI (amino acids 13-33 of SEQ ID NO: 493); EYKELLQEFIDDNATTNAID (amino acids 41-60 of SEQ ID NO: 493); KLLMVLMLA (amino acids 2-10 of SEQ ID NO: 493); QEFIDD
N
ATTNAI (amino acids 47-59 of SEQ ID NO: 493); and LKECFL
N
QTDETL (amino acids 62-74 of SEQ ID NO: 493).
Alternative embodiments provide fusion proteins wherein the second amino acid portion includes 9 or more contiguous amino acids encoded by (1) the combined upstream and downstream open reading frame (ORF) of B726P as depicted in SEQ ID NO: 475; (2) the upstream ORF of B726P as depicted in from SEQ ID NO: 469; and (3) the downstream ORF of B726P as depicted in SEQ ID NO: 176. Fusion proteins according to the present invention may also comprise a second amino acid portion that includes 9 or more contiguous amino acids from the amino acid sequence depicted by amino acids 1-129 of SEQ ID NO: 475. Still additional exemplary fusion proteins are depicted herein by SEQ ID NO: 493; SEQ ID NO: 494; and SEQ ID NO: 495.
Fusion proteins are provided wherein the mammaglobin amino acid portion is connected to the amino-terminus of the B726P amino acid portion while other fusion proteins are provided wherein the mammaglobin amino acid portion is connected to the carboxy-terminus of the B726P amino acid portion. The connection between the mammaglobin amino acid portion and the B726P portion may be a covalent bond. Additionally, a stretch of amino acids either unrelated or related to either mammaglobin and/or B726P may be incorporated between or either amino- or carboxy-terminal to either the mammaglobin and/or B726P amino acid portion.
The present invention also provides isolated polynucleotides that encode any of the fusion proteins that are specifically disclosed herein as well as those fusion proteins that may be accomplished with routine experimentation by the ordinarily skilled artisan.
Within related aspects, pharmaceutical compositions comprising a fusion protein, or a polynucleotide encoding a fusion protein, in combination with a physiologically acceptable carrier are provided.
Compositions are further provided, within other aspects, that comprise a fusion protein, or a polynucleotide encoding a fusion protein, in combination with an immunostimulant.
Within further aspects, the present invention provides methods for inhibiting the development of a cancer in a patient, comprising administering to a patien
Dillon Davin C.
Harlocker Susan L.
Hepler William T.
Jiang Yuqiu
Mitcham Jennifer L.
Corixa Corporation
Epps Janet
McGarry Sean
Seed Intellectual Property Law Group PLLC
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