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
Life of this patent
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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.
Claims10
1-17. (canceled)
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
- 3E8 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QSSYSLI (SEQ ID NO:5), a CDRH1 region comprising the amino sequence LSYYSM (SEQ ID NO:6), a CDRH2 region comprising the amino acid sequence SISPYYGYTY (SEQ ID NO:7), and a CDRH3 region comprising the amino acid sequence RGGAYYFGYYGSGSYAMD (SEQ ID NO:8);
- 3G9 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QHYYYSPWPI (SEQ ID NO:17), a CDRH1 region comprising the amino sequence LYSYYI (SEQ ID NO:18), a CDRH2 region comprising the amino acid sequence SISPYYSSTY (SEQ ID NO:19), and a CDRH3 region comprising the amino acid sequence RSSYSYAGMD (SEQ ID NO:20);
- 2C11 Fab, having a light chain comprising a CDR L1, a CDRL2, and a CDRL3 region comprising the amino acid sequence QSYVSPI (SEQ ID NO:21), a CDRH1 region comprising the amino sequence ISSYYI (SEQ ID NO:22), a CDRH2 region comprising the amino acid sequence SISSYYSSTY (SEQ ID NO:23), and a CDRH3 region comprising the amino acid sequence RVSYGHAYVGYSSGMD (SEQ ID NO:24);
- 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 RSFGYGWAFD (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 CDRH3 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 CDRH1 region 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.