Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2000-03-29
2004-06-22
Carlson, Karen Cochrane (Department: 1653)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C530S350000, C536S023500, C435S254210, C435S320100, C435S252300, C435S007100, C435S069700
Reexamination Certificate
active
06753314
ABSTRACT:
FIELD OF THE INVENTION
The invention relates generally to polypeptides and complexes of two or more polypeptides, as well as to methods of use thereof.
BACKGROUND OF THE INVENTION
Most, if not all, biologically important activities are mediated at the tissue, cellular, and subcellular level at least in part by interactions between one or more proteins. These biologically important activities can include, e.g., cell division, cell differentiation, anabolic activities, and catabolic activities. Interacting proteins or polypeptides can form a complex. Accordingly, failure to form a given polypeptide complex can result in deleterious consequences to a cell or individual. Conversely, the inappropriate formation of a given polypeptide complex can likewise be undesirable.
The identification of protein complexes associated with specific biological activities can be used to identify or prevent conditions associated with the absence or presence of these complexes.
SUMMARY OF THE INVENTION
The invention is based, in part, upon the identification of protein-protein interactions in the yeast
S. cerevisiae
and humans. Interacting proteins present in complexes according to the invention are shown in, e.g., Table 3.
In one aspect, the invention provides a purified complex including a first polypeptide that includes the amino acid sequence encoded by the open reading frame (“ORF”) listed in Table 3, column 1, and a second polypeptide that includes the amino acid sequence of the corresponding polypeptide encoded by the ORF recited in column 5 of Table 3. Gene names for the ORFs recited in Table 3, column 1, and Table 3, column 5 are provided in Table 3, columns 2 and 6, respectively.
In another aspect, the invention provides a purified complex including a first polypeptide and a second polypeptide selected from, or including, the human polypeptides recited in Table 7, column 2, and the corresponding polypeptides recited in Table 7, column 6. Complexes of polypeptides including the binding domains of such polypeptides, and complexes having labeled polypeptide, are also provided.
The invention also provides purified complexes of a first and a second polypeptide. The first polypeptide is a polypeptide functionally classified in the MIPS database as a Cell/Growth/Cell Division/DNA Synthesis protein; a Cell Rescue/Cell Defense/Cell Death and Aging Protein; a Cellular Biogenesis protein; a Cellular Organization protein; a Classification Not-Yet Clear Cut protein; an Energy Protein; an Intracellular Transport protein; an Ionic Homeostasis protein, a Metabolism protein; a Protein Destination protein; a Protein Synthesis protein; a Retrotransposon/Plasmid protein; a Signal Transduction protein; a Transcription protein; a Transport Facilitation protein, or an Unclassified protein. The second polypeptide is the corresponding polypeptide recited in Table 3, column 5 or Table 7, column 6, respectively.
The invention also provides a purified complex of a first and second polypeptide, where at least one of the polypeptides is a microtubule or microtubule-associated protein, a heme biosynthesis protein, or a cell wall or cell-wall synthesis protein.
The invention further provides purified chimeric complexes including a yeast polypeptide and a human ortholog polypeptide. In some embodiments the yeast polypeptide includes the amino acid sequence of the polypeptides recited in Table 7, column 1, and the human polypeptide includes the amino acid sequence of the corresponding polypeptides recited in Table 7, column 6. In other embodiments the yeast polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 5, and the human ortholog polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 2.
In a further aspect, the invention provides chimeric polypeptides having six or more amino acids of a first polypeptide covalently linked to six or more amino acids of a second polypeptide. In some embodiments, the chimeric polypeptides are yeast-yeast chimeras, while in others the chimeric polypeptides are human-human or yeast-human chimera. In some embodiments, the first polypeptide is selected from the polypeptides recited in Table 3, column 1, and the second polypeptide is selected from the polypeptides recited in Table 3, column 5. In other embodiments, the first polypeptide is selected from polypeptides recited in Table 7, columns 1 or 2, and the second polypeptide is selected from the polypeptides recited in Table 7, columns 5 or 6. Nucleic acids encoding chimeric polypeptides, and vectors and cells containing the same, are also provided.
In yet another aspect, the invention provides an antibody which specifically binds polypeptide complexes according to the invention. The antibody preferably binds to a complex comprising one or more polypeptides with greater affinity than its affinity for either polypeptide that is not present in the complex.
Also provided by the invention are kits containing reagent which can specifically detect the complexes of the invention. In one embodiment, the reagent is a complex-specific antibody, while in other embodiments the reagent is an antibody specific for the first or second polypeptides of the complex.
In another aspect, the invention provides pharmaceutical compositions including the complexes described herein. Such compositions are formulated to be suitable for therapeutic administration in the treatment of deficiencies or diseases involving altered levels of the complexes of the invention.
In still another aspect, the invention provides methods of identifying an agent which disrupts a polypeptide complex by providing a complex described herein, contacting the complex with a test agent, and detecting the presence of a polypeptide displaced from the complex. In certain embodiments, the complex includes at least one polypeptide comprising a microtubule or microtubule-associated protein, a heme biosynthesis protein, or a cell wall or cell-wall synthesis protein.
In a further aspect, the invention provides a method for inhibiting the interaction of a protein with a ligand by contacting a complex of the protein and ligand with an agent that disrupts the complex. In certain embodiments, the protein is a microtubule or microtubule associated protein, a heme biosynthesis protein, or a cell wall or cell-wall synthesis protein, and the ligand is a corresponding interacting polypeptide described herein.
In yet another aspect, the invention provides a method of identifying a polypeptide complex in a subject by providing a biological sample from the subject and detecting, if present, the level of a complex, described herein, in the subject.
Also provided by the invention is a method for detecting a polypeptide in a biological sample by providing a biological sample containing a first polypeptide, and contacting the sample with a second polypeptide under conditions suitable to form a polypeptide complex.
In another aspect, the invention provides a method for removing a first polypeptide from a biological sample by providing a biological sample including the first polypeptide, contacting the sample with a second polypeptide under conditions suitable for formation of a polypeptide complex, and removing the complex, thereby effectively removing the first polypeptide. In certain embodiments, the first polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 2, and the second polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 6. In another embodiment, the first polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 6, and the second polypeptide is selected from, or includes, the polypeptides recited in Table 7, column 2.
In a further aspect, the invention provides a method for determining altered expression of a polypeptide in a subject by providing a biological sample from the subject, measuring the level of polypeptide complex in the sample, and comparing the level of the complex in the sample to the level of complex in a reference sample with a
Giot Loic
Mansfield Traci A.
Carlson Karen Cochrane
CuraGen Corporation
Elrifi, Esq. Ivor R.
Kam Chih-Min
Mintz Levin Cohn Ferris Glovsky & Popeo P.C.
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