ANTI-ACETAMINOPHEN ANTIBODIES AND ACETAMINOPHEN PROTEIN ADDUCTS

• US 20200131278A1
• Filed: 01/10/2020
• Published: 04/30/2020
• Est. Priority Date: 12/03/2014
• Status: Active Grant

• Current Assignee: Arkansas Children'S Research Institute, Bioventures, LLC
• Original Assignee: Arkansas Children'S Research Institute, Bioventures, LLC
• Inventors: Roberts, Dean W., James, Laura, Hinson, Jack
• Granted Patent: US 11,566,081 B2
• Time in Patent Office: Days
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: C07K 19/00 Hybrid peptides , i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/9486 Analgesics, e.g. opiates, aspirine

Abstract

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

Claims

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

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

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

9. The immunoassay 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.