Antibody multimerization technologies
AssigneeMemorial Sloan Kettering Cancer Center
InventorsMahiuddin Ahmed, Nai-Kong V. Cheung
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Abstract
The present invention provides, among other things, dimeric multispecific binding agents (e.g., fusion proteins comprising antibody components) that have improved properties over multispecific binding agents without the capability of dimerization.
Claims40
A bispecific binding agent comprised of two fusion proteins, wherein each of the fusion proteins comprise from N-terminus to C-terminus:
- (i) a first antibody component that binds a tumor antigen;
- (ii) a second antibody component that binds an antigen present on an immune effector cell;
- and
- (iii) a dimerization component comprising a human hepatocyte nuclear factor-1 alpha (HNF-1α) element,
- wherein the HNF-1α element comprises a sequence that is at least 90% identical to residues 1-32 of SEQ ID NO:1, and
- wherein the fusion proteins can dimerize through the dimerization component to form a homodimer.
A fusion protein comprising, from N-terminus to C-terminus, a first antibody component that binds to a tumor antigen, a second antibody component that binds to an antigen present on T cells, and a dimerization component comprising a human hepatocyte nuclear factor-1 alpha (HNF-1α) element, wherein the HNF-1α element comprises a sequence that is at least 90% identical to residues 1-32 of SEQ ID NO:1.
A bispecific binding agent comprised of two fusion proteins that each comprise, from N-terminus to C-terminus,
- a first antibody component that binds to a tumor antigen,
- a second antibody component that binds to CD3 on T cells, and
- a dimerization component comprising a sequence that is at least 90% identical to residues 1-32 of SEQ ID NO:1, such that the fusion proteins dimerize to form a homodimeric bispecific binding agent;
- wherein the homodimeric bispecific binding agent is characterized by a longer half-life as compared to an otherwise comparable bispecific binding agent that does not comprise the dimerization component.
A method of killing tumor cells, the method comprising steps of
- contacting the tumor cells with a therapeutically effective amount of a bispecific binding agent, comprised of two fusion proteins that each comprise, from—N-terminus to C-terminus, a first antibody component that binds to a tumor antigen, a second antibody component that binds to CD3 on T cells, and a dimerization component comprising a human HNF-1α element, wherein the HNF-1α element comprises a sequence that is at least 90% identical to residues 1-32 of SEQ ID NO:
- 1, such that the bispecific binding agent is capable of dimerization to form a homodimer, the contacting being performed under conditions and for a time sufficient that T cells to which the homodimer has bound mediate killing of the tumor cells.
A method of inhibiting tumor growth, the method comprising steps of
- contacting a tumor with a therapeutically effective amount of a bispecific binding agent, comprised of two fusion proteins that each comprise, from—N-terminus to C-terminus, a first antibody component that binds to a tumor antigen, a second antibody component that binds to CD3 on T cells, and a dimerization component comprising a human HNF-1α element, wherein the HNF-1α element comprises a sequence that is at least 90% identical to residues 1-32 of SEQ ID NO:
- 1, such that the bispecific antibody is capable of dimerization to form a homodimer, the contacting being performed under conditions and for a time sufficient that T cells to which the homodimer has bound inhibit growth of a tumor.
Dependencies are inferred from the claim text.