Regioselective chemical modification of monoclonal antibodies
AssigneeUniversity of Pittsburgh
InventorsGirish Ranadive, Howard S. Rosenzweig, Michael Epperly, William Bloomer
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Abstract
A method of selectively modifying an immunoglobulin having at least one Fab region and at least one Fc region, each region having an isoelectric point wherein said isoelectric point of the Fab fragment of said immunoglobulin is different than the isoelectric point of the Fc fragment of the immunoglobulin, said method comprising modification of the immunoglobulin at a pH between the respective isoelectric points of the Fab and Fc fragments of the immunoglobulin.
Claims39
A method of selectively modifying an immunoglobulin having at least one Fab region and at least one Fc region, each region having an isoelectric point wherein said isoelectric point of the Fab fragment of said immunoglobulin is different than the isoelectric point of the Fc fragment of immunoglobulin, said method comprising modification of the Fc region amino groups of the immunoglobulin at a pH between the respective isoelectric point of the Fab and Fc fragments of the immunoglobulin.
The method of enhancing the biodistribution of immunoglobulin having a Fab region and an Fc region for localization in a target, comprising exposing a mammalian subject to immunoglobulin that has been chemically modified at only the Fc region amino groups of the immunoglobulin at a pH between the isoelectric points of the Fab and Fc fragments of the immunoglobulin.
A method of producing chemically modified immunoglobulin having a Fab region and an Fc region with improved immunoreactivity comprising the steps of:
- determining the individual isoelectric points of the Fc and Fab fragments of the immunoglobulin;
- and
- performing a chemical modification of Fc region amino groups of said immunoglobulin at a pH within the range of the two isoelectric points.
A method of enhancing the sensitivity of an immunoglobulin having a Fab region and an Fc region for use in diagnostic testing using a target, said method comprising exposing the target to an immunoglobulin that has been chemically modified at only Fc region amino groups of the immunoglobulin at a pH between the isoelectric points of the Fab and Fc fragments of the immunoglobulin.
Dependencies are inferred from the claim text.