Synthetic antibodies to bax and uses thereof
AssigneesAlbert Einstein College of Medicine, The Governing Council of the University of Toronto
InventorsEvripidis Gavathiotis, Jonathan R. Lai, Sachdev Sidhu
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Abstract
Synthetic fragment antigen-binding (Fab) antibodies are disclosed that bind to an N-terminal activation site of BCL-2-associated X-protein (BAX) and inhibit BAX activation. Also disclosed are methods of using the Fabs for measuring inactive monomeric BAX levels, screening for small molecules that bind to an N-terminal activation site of BAX, inhibiting apoptotic cell death, and predicting the ability of a cancer therapy to promote apoptotic cell death.
Claims9
A synthetic fragment antigen-binding (Fab) antibody that binds to an N-terminal activation site of BCL-2-associated X-protein (BAX) and inhibits BAX activation, wherein the synthetic fragment antigen-binding (Fab) antibody is selected from the group consisting of:
- 3H4 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QSWYYSYPI (SEQ ID NO:25), a CDRH1 region comprising the amino sequence LSYSSM (SEQ ID NO 26), a CDRH2 region comprising the amino acid sequence SISSYYSYTS (SEQ ID NO:27), and a CDRH3 region comprising the amino acid sequence RYYGYGGGID (SEQ ID NO-28);
- 2A6 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QSAGGYPLI (SEQ ID NO:29), a CDRH1 region comprising the amino sequence IYYSSM (SEQ ID NO-30), a CDRH2 region comprising the amino acid sequence SISPYSSYTS (SEQ ID NO:31), and a CDRH3 region comprising the amino acid sequence RSFGYCWAFD (SEQ ID NO:32);
- 3H1 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QHSYPI (SEQ ID NO:33), a CDRH1 region comprising the amino sequence ISYSSI (SEQ ID NO:34), a CDRH2 region comprising the amino acid sequence SIYSYSGSTY (SEQ ID NO 35), and a CDRH3 region comprising the amino acid sequence RYGAMD (SEQ ID NO:36);
- 2A2 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QYYYPI (SEQ ID NO:37), a CDRH1 region comprising the amino sequence ISSSSI (SEQ ID NO:38), a CDRH2 region comprising the amino acid sequence SIYSYYGYTY (SEQ ID NO:39), and a CDRH3 region comprising the amino acid sequence RYSAMD (SEQ ID NO:40);
- 3G3 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QGAWSGGHLI (SEQ ID NO 41), a CDRH1 region comprising the amino sequence LSYSSM (SEQ ID NO:42), a CDRH2 region comprising the amino acid sequence YISPYYGYTY (SEQ ID NO:43), and a CDRH3 region comprising the amino acid sequence RGWAYYYGYWGPSGLD (SEQ ID NO:44);
- 2D5 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QWGYSHSHLI (SEQ ID NO:45), a CDRH1 region comprising the amino sequence ISYSS (SEQ ID NO:46), a CDRH2 region comprising the amino acid sequence SISPYYGSTY (SEQ ID NO:47), and a CDR-13 region comprising the amino acid sequence RSHFGALD (SEQ ID NO:48),
- 2D2 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QSYYWVSPF (SEQ ID NO:49), a CDRH1 region comprising the amino sequence LYYSSI (SEQ ID NO:50), a CDRH2 region comprising the amino acid sequence SIYPYSGSTY (SEQ ID NO:51), and a CDRH3 region comprising the amino acid sequence RSYGYAMD (SEQ ID NO:52);
- and
- 2A5 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QYHYWYYPI (SEQ ID NO 53), a CDRH1region comprising the amino sequence ISYYSM (SEQ ID NO:54), a CDRH2 region comprising the amino acid sequence SISPYYGSTY (SEQ ID NO:55), and a CDRH3 region comprising the amino acid sequence RAGAMD (SEQ ID NO:56).
Dependencies are inferred from the claim text.