Conformer-specific antibodies and method of use, thereof
AssigneeProsetta Corporation
InventorsVishwanath Lingappa, Mahadevappa Prasad, William Hansen, Joshua Lehrer-Graiwer, Carsten Korth
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Abstract
A number of polypeptides exist in different three-dimensional conformations, or “conformers,” which have different biological functions despite having the same or substantially the same primary polypeptide sequences. The existence of different polypeptide conformers underlies to a variety of disease states, which may be assessed using antibody that is specific for a given conformer. Thus, such antibody thus is useful for identifying or detecting certain conformers within a mixed population of conformers.
Claims19
A method for producing an antibody specific for a polypeptide conformer, the method comprising:
- isolating from a polyclonal antibody, which is produced in an animal and raised against a polypeptide preparation enriched for a polypeptide conformer of interest, an antibody specific for the polypeptide conformer of interest;
- determining the polypeptide sequence of the antibody specific for the polypeptide conformer of interest;
- using the polypeptide sequence to design one or more degenerate oligonucleotides comprising nucleotide sequences corresponding to polynucleotides encoding the antibody specific for the polypeptide conformer of interest;
- and
- using the one or more degenerate oligonucleotides to identify polynucleotides encoding the antibody specific for the polypeptide conformer of interest.
A method for immunizing a patient against a disease mediated by a polypeptide conformer of interest, the method comprising administering to the patient an immunogenic amount of a polypeptide composition enriched for a polypeptide conformer of interest.
An isolated conformer-specific antibody obtained from a polyclonal antibody raised against a polypeptide preparation comprising a conformer of interest, comprising:
- identifying amino acid sequences of conformer-specific antibodies present in the polyclonal antibody, using the amino acid sequences to produce polynucleotides encoding the conformer-specific antibody, expressing the conformer-specific antibody encoded by the polynucleotides in an organism or a cell free translation system, and isolating the conformer-specific antibody so expressed.
A conformer-specific antibody isolated from a polyclonal antibody raised against a conformer of interest by incubating the polyclonal antibody in the presence of a conformer of interest, isolating antibody-conformer of interest complexes, determining the amino acid sequence of antibodies present in the complexes, and designing polynucleotides for expression of such conformer-specific antibodies.
Dependencies are inferred from the claim text.