Antigen binding complex having agonistic activity and methods of use
AssigneeGenentech, Inc.
InventorsGreg LAZAR, Jeong KIM, Jing ZHU, Yanli YANG, Randall BREZSKI
Life of this patent
Estimating the term…
Abstract
Provided herein are antigen binding polypeptides and complexes thereof having agonist activity. Also provided are methods for screening for complexes or polypeptides having agonist activity, enhancing the agonist activity of a polypeptide, and for agonizing a cell surface receptor using the complexes and polypeptide described herein.
Claims164
A hexameric antigen binding complex having agonist activity comprising six subunits, wherein each subunit comprises at least one antigen binding polypeptide comprising at least one antigen binding region for a cell surface receptor and a modified Fc region that enhances hexamer formation, and wherein the complex has agonist activity for a cell surface receptor bound by the complex.
An antigen binding polypeptide comprising an antigen binding region for a cell surface receptor and a modified Fc region, wherein the modified Fc region comprises (i) a modification that enhances hexamer formation of the antigen binding polypeptides, and (ii) a modification that attenuates effector function.
An antigen binding polypeptide comprising an antigen binding region for a cell surface receptor and a modified Fc region, wherein the modified Fc region comprises a modification that enhances intermolecular interactions between Fc domains upon binding to the cell surface receptor.
A method of increasing agonist activity of an antigen binding polypeptide, comprising:
- (a) providing an antigen binding polypeptide which comprises an antigen binding region for a cell surface receptor and a Fc region, and
- (b) introducing a modification into the Fc region, wherein the modification enhances intermolecular interactions between Fc domains upon binding to a cell surface receptor, and wherein the antigen binding polypeptide has increased agonist activity for a cell surface receptor bound by the antigen binding polypeptide as compared to the same antigen binding polypeptide not having the Fc region modification.
A method of increasing agonist activity of an antigen binding polypeptide, comprising:
- (a) providing an antigen binding polypeptide which comprises an antigen binding region for a cell surface receptor and a Fc region, and
- (b) introducing a modification into the Fc region, wherein the modification enhances hexamer formation of the antigen binding polypeptide, and wherein the hexamer has increased agonist activity for a cell surface receptor bound by the antigen binding polypeptide as compared to an individual subunit of the hexamer.
A method of identifying an antigen binding polypeptide having agonist activity for a cell surface receptor, comprising:
- (a) providing a plurality of antigen binding polypeptides, wherein each antigen binding polypeptide comprising at least one antigen binding region and a modified Fc region that enhances intermolecular interactions between Fc domains upon binding to the cell surface receptor,
- (b) screening the antigen binding complexes against a cell surface receptor, and
- (c) selecting antigen binding complexes having agonist activity for the cell surface receptor.
A method of identifying an antigen binding polypeptide having agonist activity for a cell surface receptor, comprising:
- (a) providing a plurality of hexameric antigen binding complexes, wherein each complex comprises six subunits each comprising an antigen binding polypeptide comprising at least one antigen binding region and a modified Fc region that enhances hexamer formation,
- (b) screening the antigen binding complexes against a cell surface receptor, and
- (c) selecting antigen binding complexes having agonist activity for the cell surface receptor.
A hexameric antigen binding complex having agonist activity comprising six subunits, wherein each subunit comprises at least one antigen binding polypeptide comprising at least one antigen binding region for a cell surface receptor and a modified Fc region that enhances hexamer formation, wherein the modified Fc region further comprises a modification for diminished C1q binding and/or Complement Dependent Cytotoxicity (CDC), and wherein the complex has agonist activity for a cell surface receptor bound by the complex.
Dependencies are inferred from the claim text.