Targeting intracellular target-binding determinants with intracellular antibodies
View Patent ↗The invention provides a method for inhibiting an intracellular target in a cell with a bispecific antibody comprising contacting the cell with a bispecific antibody having a first Fv fragment with a cell-penetrating determinant and a second Fv fragment with an intracellular target-binding determinant under suitable conditions so that the first Fv fragment causes the bispecific antibody to enter the cell and the second Fv fragment binds the intracellular target in the cell and thereby inhibiting the intracellular target.
1. A bispecific antibody comprising a first Fv fragment, wherein the first Fv fragment comprises a heavy chain variable domain comprising: a) a complementarity determining region (CDR) CDRH1 comprising SEQ ID NO: 11, b) a CDRH2 comprising SEQ ID NO: 13 and c) a CDRH3 comprising SEQ ID NO: 15; and, a light chain variable domain comprising: a) a CDRL1 comprising SEQ ID NO: 5, b) a CDRL2 comprising SEQ ID NO: 7, and c) a CDRL3 comprising SEQ ID NO: 9; and a second Fv fragment, wherein the second Fv fragment comprises a heavy chain variable domain comprising: a) a CDRH1 comprising SEQ ID NO: 23, b) CDRH2 comprising SEQ ID NO: 25 and c) CDRH3 comprising SEQ ID NO: 27; and, a light chain variable domain comprising: a) CDRL1 comprising SEQ ID NO: 17, b) CDRL2 comprising SEQ ID NO: 19, and c) CDRL3 comprising SEQ ID NO: 21.
2. The bispecific antibody of claim 1 , wherein the bispecific antibody has the amino acid sequence of SEQ ID NO: 3.