Anti-acetaminophen antibodies and acetaminophen protein adducts

11566,081

16/740030

January 10, 2020

The present disclosure provides isolated antibodies that bind to acetaminophen-protein adducts that are useful in the detection and diagnosis of acetaminophen-induced toxicity.

BioVentures, LLC (Little Rock, AR, US); Arkansas Children's Research Institute (Little Rock, AR, US)

BioVentures, LLC (Little Rock, AR, US), Arkansas Children's Research Institute (Little Rock, AR, US)

1. A composition for an immunoassay, the composition comprising at least one isolated antibody which specifically binds an acetaminophen-protein adduct but does not specifically bind free acetaminophen, wherein the antibody comprises: (a) a light chain CDR1 amino acid sequence of SEQ ID NO:21; (b) a light chain CDR2 amino acid sequence of SEQ ID NO:22; (c) a light chain CDR3 amino acid sequence of LGh; wherein h is a hydrophobic amino acid; (d) a heavy chain CDR1 amino acid sequence of YXI, wherein X is any amino acid; (e) a heavy chain CDR2 amino acid sequence of SEQ ID NO:23; and (f) a heavy chain CDR3 amino acid sequence of SEQ ID NO:24.

2. The composition of claim 1 , wherein the immunoassay is a competitive or a non-competitive immune assay.

3. The composition of claim 1 , wherein the immunoassay is selected from the group consisting of an enzyme linked immunosorbent assay (ELISA), a lateral flow assay, a sandwich immunoassay, a radioimmunoassay, an immunoblot or Western blot, flow cytometry, immunohistochemistry, and an antibody array.

4. A composition for an immunoassay, the composition comprising at least one isolated antibody which specifically binds an acetaminophen-protein adduct but does not specifically bind free acetaminophen, wherein the antibody comprises: (a) a light chain CDR1 amino acid sequence of SEQ ID NO:21; (b) a light chain CDR2 amino acid sequence of SEQ ID NO:22; (c) a light chain CDR3 amino acid sequence of LGh; wherein h is a hydrophobic amino acid; (d) a heavy chain CDR1 amino acid sequence of YXI, wherein X is any amino acid; (e) a heavy chain CDR2 amino acid sequence of SEQ ID NO:23; and (f) a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:6 with zero to two amino acid substitutions or SEQ ID NO:12 with zero to two amino acid substitutions.

5. The composition of claim 4 , wherein the immunoassay is a competitive or a non-competitive immune assay.

6. The composition of claim 4 , wherein the immunoassay is selected from the group consisting of an enzyme linked immunosorbent assay (ELISA), a lateral flow assay, a sandwich immunoassay, a radioimmunoassay, an immunoblot or Western blot, flow cytometry, immunohistochemistry, and an antibody array.

7. A composition for an immunoassay, the composition comprising at least one isolated antibody which specifically binds an acetaminophen-protein adduct but does not specifically bind free acetaminophen, wherein the antibody comprises: (a) a light chain CDR1 amino acid sequence of SEQ ID NO:21; (b) a light chain CDR2 amino acid sequence of SEQ ID NO:22; (c) a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:3 with zero to two amino acid substitutions or SEQ ID NO:9 with zero to two amino acid substitutions; (d) a heavy chain CDR1 amino acid sequence of YXI, wherein X is any amino acid; (e) a heavy chain CDR2 amino acid sequence of SEQ ID NO:23; and (f) a heavy chain CDR3 amino acid sequence of SEQ ID NO:24.

8. The composition of claim 7 , wherein the immunoassay is a competitive or a non-competitive immune assay.

9. The composition of claim 7 , wherein the immunoassay is selected from the group consisting of an enzyme linked immunosorbent assay (ELISA), a lateral flow assay, a sandwich immunoassay, a radioimmunoassay, an immunoblot or Western blot, flow cytometry, immunohistochemistry, and an antibody array.

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