An isolated bi-valent binding agent of Formula I A-a':a-S-b:b'-B (Formula I) capable of binding a posttranslationally phosphorylated target polypeptide, the bi-valent binding agent comprising exactly two monovalent binders A and B of different specificity that are linked to each other via a linker, wherein a) - represents a covalent bond, b) a-S-b is the linker having a length between 10 nm and 50 nm, wherein S is a spacer, c) a':a and b:b' are binding pairs consisting of hybridizing nucleic acid sequences each forming a stable duplex via multiple base pairing, wherein the sequences of the binding pair a':a do not bind to the sequences of the binding pair b:b', respectively, and vice versa, d) the first monovalent binder A is a molecule interacting with the target polypeptide at a single binding site, wherein the first monovalent binder binds to a polypeptide epitope of said target polypeptide, and wherein the polypeptide epitope is not subject to a posttranslational modification, e) the second monovalent binder B binds to a posttranslational phosphorylation, wherein the Kdiss of the second monovalent binder is at least 20 times lower for a polypeptide carrying the posttranslational phosphorylation as compared to the same non-posttranslationally phosphorylated polypeptide, f) each monovalent binder is selected from the group consisting of a single chain antibody, a Fab-fragment of a monoclonal antibody, and a Fab'-fragment of a monoclonal antibody, g) each monovalent binder has a Kdiss in the range of 5x10 -3 /sec to 10 -4 /sec, determined by biosensor-based surface plasmon resonance spectroscopy, and h) the bi-valent binding agent has a Kdiss of 3x10 -5 /sec or less, determined by biosensor-based surface plasmon resonance spectroscopy. a) - represents a covalent bond, b) a-S-b is the linker having a length between 10 nm and 50 nm, wherein S is a spacer, c) a':a and b:b' are binding pairs consisting of hybridizing nucleic acid sequences each forming a stable duplex via multiple base pairing, wherein the sequences of the binding pair a':a do not bind to the sequences of the binding pair b:b', respectively, and vice versa, d) the first monovalent binder A is a molecule interacting with the target polypeptide at a single binding site, wherein the first monovalent binder binds to a polypeptide epitope of said target polypeptide, and wherein the polypeptide epitope is not subject to a posttranslational modification, e) the second monovalent binder B binds to a posttranslational phosphorylation, wherein the Kdiss of the second monovalent binder is at least 20 times lower for a polypeptide carrying the posttranslational phosphorylation as compared to the same non-posttranslationally phosphorylated polypeptide, f) each monovalent binder is selected from the group consisting of a single chain antibody, a Fab-fragment of a monoclonal antibody, and a Fab'-fragment of a monoclonal antibody, g) each monovalent binder has a Kdiss in the range of 5x10 -3 /sec to 10 -4 /sec, determined by biosensor-based surface plasmon resonance spectroscopy, and h) the bi-valent binding agent has a Kdiss of 3x10 -5 /sec or less, determined by biosensor-based surface plasmon resonance spectroscopy.