Bispecific anti-hapten/anti-blood brain barrier receptor antibodies, complexes thereof and their use as blood brain barrier shuttles

A method for delivering a haptenylated payload across the blood brain barrier,

• wherein the haptenylated payload is comprised in a covalent conjugate comprising
• i) a bispecific antibody, which has a first binding specificity, which specifically binds to a haptenylated payload, and a second binding specificity, which specifically binds to a blood brain barrier receptor, and
• ii) a haptenylated payload,
• wherein the haptenylated payload is specifically bound by the first binding specificity,
• wherein the covalent conjugate has a covalent bond between the haptenylated payload and the first binding specificity that specifically binds to the haptenylated payload, and
• wherein the haptenylated payload is selected from the group consisting of biotinylated payloads, theophyllinylated payloads, digoxigenylated payloads, carboranylated payloads, fluoresceinylated payloads, helicarylated payloads and bromodeoxyuridinylated payloads, and
• wherein the payload of the haptenylated payload is selected from the group consisting of a label, a chemotherapeutic agent, an anti-angiogenic agent, a cytotoxin, a cytokine, a prodrug, an enzyme, a growth factor, a transcription factor, a drug, a radionuclide, a ligand, an antibody or fragment thereof, a lipsosome, a nanoparticle, and a viral particle.

A method for targeted delivery of a haptenylated payload across the blood brain barrier by a bispecific antibody,

• wherein the bispecific antibody comprises
• i) a first binding specificity, which specifically binds to the haptenylated payload, and
• ii) a second binding specificity, which specifically binds to a blood brain barrier receptor,
• wherein the haptenylated payload is selected from the group consisting of biotinylated payloads, theophyllinylated payloads, digoxigenylated payloads, carboranylated payloads, fluoresceinylated payloads, helicarylated payloads and bromodeoxyuridinylated payloads, and
• wherein the payload of the haptenylated payload is selected from the group consisting of a label, a chemotherapeutic agent, an anti-angiogenic agent, a cytotoxin, a cytokine, a prodrug, an enzyme, a growth factor, a transcription factor, a drug, a radionuclide, a ligand, an antibody or fragment thereof, a lipsosome, a nanoparticle, and a viral particle.

A method for delivering a haptenylated payload across the blood brain barrier,

• wherein the haptenylated payload is comprised in a non-covalent complex comprising
• i) a bispecific antibody, which has a first binding specificity, which specifically binds to a haptenylated payload, and a second binding specificity, which specifically binds to a blood brain barrier receptor, and
• ii) a haptenylated payload,
• wherein the haptenylated payload is specifically bound by the first binding specificity,
• wherein the haptenylated payload is selected from the group consisting of biotinylated payloads, theophyllinylated payloads, digoxigenylated payloads, carboranylated payloads, fluoresceinylated payloads, helicarylated payloads and bromodeoxyuridinylated payloads, and
• wherein the payload of the haptenylated payload is selected from the group consisting of a label, a chemotherapeutic agent, an anti-angiogenic agent, a cytotoxin, a cytokine, a prodrug, an enzyme, a growth factor, a transcription factor, a drug, a radionuclide, a ligand, an antibody or fragment thereof, a lipsosome, a nanoparticle, and a viral particle.

A method for targeted delivery of a haptenylated payload across the blood brain barrier by a bispecific antibody,

• wherein the bispecific antibody comprises
• i) a first binding specificity, which specifically binds to the haptenylated payload, and
• ii) a second binding specificity, which specifically binds to a blood brain barrier receptor,
• wherein the haptenylated payload is selected from the group consisting of biotinylated payloads, theophyllinylated payloads, digoxigenylated payloads, carboranylated payloads, fluoresceinylated payloads, helicarylated payloads and bromodeoxyuridinylated payloads,
• wherein the payload of the haptenylated payload is selected from the group consisting of a label, a chemotherapeutic agent, an anti-angiogenic agent, a cytotoxin, a cytokine, a prodrug, an enzyme, a growth factor, a transcription factor, a drug, a radionuclide, a ligand, an antibody or fragment thereof, a lipsosome, a nanoparticle, and a viral particle, and
• wherein the haptenylated payload is released within the blood brain barrier or in the brain. particle.

A method for delivering a haptenylated payload across the blood brain barrier,

• wherein the haptenylated payload is comprised in a non-covalent complex comprising
• i) a bispecific antibody, which has a first binding specificity, which specifically binds to a haptenylated payload, and a second binding specificity, which specifically binds to a blood brain barrier receptor, and
• ii) a haptenylated payload,
• wherein the haptenylated payload is specifically bound by the first binding specificity,
• wherein the haptenylated payload is selected from the group consisting of biotinylated payloads, theophyllinylated payloads, digoxigenylated payloads, carboranylated payloads, fluoresceinylated payloads, helicarylated payloads and bromodeoxyuridinylated payloads,
• wherein the payload of the haptenylated payload is selected from the group consisting of a label, a chemotherapeutic agent, an anti-angiogenic agent, a cytotoxin, a cytokine, a prodrug, an enzyme, a growth factor, a transcription factor, a drug, a radionuclide, a ligand, an antibody or fragment thereof, a lipsosome, a nanoparticle, and a viral particle, and
• wherein the haptenylated payload is released within the blood brain barrier or in the brain.