Antibody with protein a selectivity

This application is a division of U.S. patent application Ser. No. 11/562,759, filed Nov. 22, 2006, which is incorporated herein by reference.

Staphylococcus aureus is a Gram-positive bacterium that causes a variety of suppurative (pus-forming) infections and toxinoses in humans. It causes superficial skin lesions (such as boils, styes and furunculosis), more serious infections (such as pneumonia, mastitis, phlebitis, meningitis, and urinary tract infections), and deep-seated infections (such as osteomyelitis and endocarditis). S. aureus is a major cause of hospital acquired (nosocomial) infections of surgical wounds and infections associated with indwelling medical devices. S. aureus causes food poisoning by releasing enterotoxins into food, and toxic shock syndrome by releasing superantigens into the blood stream.

S. aureus expresses a number of factors that interfere with host defense mechanisms. One such factor is Protein A. Protein A is a surface protein of S. aureus which binds the Fc region of immunoglobulins. In serum, the bacteria will bind IgG molecules in an orientation on their surface which disrupts opsonization and phagocytosis. Mutants of S. aureus lacking protein A are more efficiently phagocytosed in vitro, and mutants in infection models have diminished virulence. Protein A binds with high affinity to human IgG1, IgG2, and IgG4 as well as mouse IgG2a, IgG2b, and IgG3. Protein A binds with moderate affinity to human IgM, IgA and IgE. It does not bind with human IgG3 or IgD, nor will it bind to mouse IgM, IgA or IgE.

The present invention includes a monoclonal antibody, and antigen binding fragment thereof, wherein the monoclonal antibody inhibits the binding of monoclonal antibody 76 to Protein A from Staphylococcus aureus, wherein monoclonal antibody 76 is produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938.

The present invention also includes a monoclonal antibody, and antigen binding fragment thereof, wherein the monoclonal antibody binds to the same epitope of Protein A from Staphylococcus aureus that is recognized by monoclonal antibody 76 produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938.

Also included in the present invention is a monoclonal antibody, or antigen binding fragment thereof, wherein the monoclonal antibody includes the heavy chain variable region polypeptide sequence of the antibody 76 produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938. In some embodiments, the monoclonal antibody, or antigen binding fragment thereof, further includes the light chain variable region polypeptide sequence of monoclonal antibody 76 produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938.

The present invention also includes a monoclonal antibody, or antigen binding fragment thereof, wherein the monoclonal antibody includes the light chain variable region polypeptide sequence of the monoclonal antibody 76 produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938.

The present invention also includes a monoclonal antibody, or antigen binding fragment thereof, wherein the monoclonal antibody includes a heavy chain variable region having the complementarity determining regions (CDRs) of the heavy chain of monoclonal antibody 76 produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938. In some embodiments, the monoclonal antibody, and antigen binding fragment thereof, further includes a light chain variable region having the complementarity determining regions (CDRs) of the light chain of monoclonal antibody 76 produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938.

The present invention also includes a monoclonal antibody, or antigen binding fragment thereof, wherein the monoclonal antibody includes a light chain variable region having the complementarity determining regions (CDRS) of the light chain of monoclonal antibody 76 produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938.

In some embodiments, the antigen binding fragment thereof of the present invention is a Fab fragment, a Fab′ fragment, a F(ab)₂ fragment, or a Fv fragment.

The present invention also includes a composition having one or more of the monoclonal antibodies, or antigen binding fragments thereof, of the present invention.

The present invention also includes a kit having one or more of the monoclonal antibodies, or antigen binding fragments thereof, of the present invention.

Also included in the present invention are transformed B cell lines that produce the monoclonal antibodies, or antigen binding fragments thereof, of the present invention.

The present invention also includes the monoclonal antibody produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938, and antigen binding fragments thereof.

The present invention also includes a composition including the monoclonal antibody produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938, and antigen binding fragments thereof.

The present invention also includes hybridoma cell line 358A76.1 as deposited with the Type Culture Collection and assigned accession number PTA-7938, and progeny thereof.

The present invention also includes an isolated polynucleotide including a coding sequence for the heavy chain variable region of the monoclonal antibody produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938. In some embodiments, the isolated polynucleotide includes the coding sequence for the heavy chain of the antibody produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938.

The present invention also includes an isolated polynucleotide including a coding sequence for the light chain variable region of the monoclonal antibody produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938. In some embodiments, the isolated polynucleotide includes the coding sequence for the light chain variable region of the monoclonal antibody produced by hybridoma cell line 358A76.1 as deposited with the American Type Culture Collection and assigned accession number PTA-7938.