Antibodies and methods of using thereof

Patent metadata

Field	Value
Publication number	US-2024425572-A1
Application number	US-202218701201-A
Country	US
Kind code	A1
Filing date	Oct 15, 2022
Priority date	Oct 15, 2021
Publication date	Dec 26, 2024
Grant date	—

Abstract

Provided herein are antibodies that specifically bind to a peptide antigen. Also provided are methods of detecting, isolating or quantifying the peptide antigen. In some embodiments, the peptide antigen is released from dystrophin or microdystrophin by protease digestion. Also provided are methods for detecting or quantifying microdystrophin or dystrophin in a sample using the antibodies. In some embodiments, a method described herein is used to monitor the expression of microdystrophin in a subject that has been administered a nucleic acid based therapy.

First claim

What is claimed is:

1 . An isolated antibody or antigen binding fragment thereof capable of binding to a polypeptide comprising the amino acid sequence of SEQ ID NO: 1.

2 . The antibody or antigen binding fragment thereof of claim 1 , wherein the amino acid sequence of the polypeptide consist of SEQ ID NO: 1.

3 . The antibody or antigen binding fragment thereof of claim 1 or claim 2 that does not bind to a peptide consisting of the amino acid of SEQ ID NO: 2.

4 . The antibody or antigen binding fragment thereof of any one of claims 1 to 3 , wherein the antibody is a polyclonal antibody.

5 . The antibody or antigen binding fragment thereof of any one of claims 1 to 3 , wherein the antibody is a monoclonal antibody.

6 . An isolated antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein the VH comprises VH complementarity determining region 1 (CDR1), CDR2 and CDR3 and the VL comprises VL CDR1, CDR2 and CDR3, wherein the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 comprises
a) the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 of the 130D2-1 antibody, respectively, independently comprising 0, 1, 2, 3, 4 or 5 substitutions; b) the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 of the 133E10-1 antibody, respectively, independently comprising 0, 1, 2, 3, 4 or 5 substitutions; or c) the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 of the 75A2-1 antibody, respectively, independently comprising 0, 1, 2, 3, 4 or 5 substitutions.

7 . An isolated antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein the VH comprises VH complementarity determining region 1 (CDR1), CDR2 and CDR3 and the VL comprises VL CDR1, CDR2 and CDR3, wherein the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 comprises
a) the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 of the 130D2-1 antibody, respectively; b) the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 of the 133E10-1 antibody, respectively; or c) the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 of the 75A2-1 antibody, respectively.

8 . The isolated antibody or antigen binding fragment thereof according to claim 6 or claim 7 , wherein the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 of 130D2-1, 133E10-1 and 75A2-1 are according to Kabat.

9 . An isolated antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein the VH and VL comprises
a) an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 95%, at least 97% or 100% identity with the VH and VL of the 130D2-1 antibody, respectively; b) an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 95%, at least 97% or 100% identity with the VH and VL of the 133E10-1 antibody, respectively; or c) an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 95%, at least 97% or 100% identity with the VH and VL of the 75A2-1 antibody, respectively.

10 . An isolated antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein the VH and VL comprises
a) the VH and VL of the 130D2-1 antibody, respectively; b) the VH and VL of the 133E10-1 antibody, respectively; or c) the VH and VL of the 75A2-1 antibody, respectively.

11 . An isolated antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein the VH comprises VH complementarity determining region 1 (CDR1), CDR2 and CDR3 and the VL comprises VL CDR1, CDR2 and CDR3, wherein the
a) the VH CDR1 comprises an amino acid sequence of SEQ ID NO: 8 comprising 0, 1, 2, 3, 4 or 5 substitutions; b) the VH CDR2 comprises an amino acid sequence of SEQ ID NO: 9 comprising 0, 1, 2, 3, 4 or 5 substitutions; c) the VH CDR3 comprises an amino acid sequence of SEQ ID NO: 10 comprising 0, 1, 2, 3, 4 or 5 substitutions; d) the VL CDR1 comprises an amino acid sequence of SEQ ID NO: 11 comprising 0, 1, 2, 3, 4 or 5 substitutions; e) the VL CDR2 comprises an amino acid sequence of SEQ ID NO: 12 comprising 0, 1, 2, 3, 4 or 5 substitutions; and f) the VL CDR3 comprises an amino acid sequence of SEQ ID NO: 13 comprising 0, 1, 2, 3, 4 or 5 substitutions.

12 . An isolated antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein the VH comprises VH complementarity determining region 1 (CDR1), CDR2 and CDR3 and the VL comprises VL CDR1, CDR2 and CDR3, wherein the
a) the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 8; b) the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 9; c) the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 10; d) the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 11; e) the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 12; and f) the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 13.

13 . An isolated antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein
a) the VH comprises an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 95%, at least 97% or 100% identity with SEQ ID NO: 4; and b) the VL comprises an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 95%, at least 97% or 100% identity with SEQ ID NO: 5.

14 . An isolated antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein
a) the VH comprises the amino acid sequence of SEQ ID NO: 4; and b) the VL comprises the amino acid sequence of SEQ ID NO: 5.

15 . The antibody or antigen binding fragment thereof of any one of claims 6 to 14 capable of binding to a polypeptide comprising the amino acid sequence of SEQ ID NO: 1.

16 . The antibody or antigen binding fragment thereof of claim 15 , wherein the amino acid sequence of the polypeptide consist of SEQ ID NO: 1.

17 . The antibody or antigen binding fragment thereof of any one of claims 6 to 16 that does not bind to a peptide consisting of the amino acid of SEQ ID NO: 2.

18 . An isolated antibody or antigen binding fragment thereof capable of binding to a polypeptide comprising the amino acid sequence of SEQ ID NO: 3.

19 . The antibody or antigen binding fragment thereof of claim 18 , wherein the amino acid sequence of the polypeptide consist of SEQ ID NO: 3.

20 . The antibody or antigen binding fragment thereof of claim 18 or claim 19 , wherein the antibody is a polyclonal antibody.

21 . The antibody or antigen binding fragment thereof of claim 18 or claim 19 , wherein the antibody is a monoclonal antibody.

22 . An isolated antibody or antigen binding fragment thereof comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein the VH comprises VH complementarity determining region 1 (CDR1), CDR2 and CDR3 and the VL comprises VL CDR1, CDR2 and CDR3, wherein the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 comprises
a) the VH CDR1, CDR2 and CDR3 and the VL CDR1, CDR2 and CDR3 of the 112E4-1 antibody, respectively, independently comprising 0, 1, 2, 3, 4 or 5 substitutions; b

Assignees

• Regenxbio Inc

Inventors

• Fiscella Michele
• Yang Lin
• Wu Zhuchun
• Patel Hiren
• Wang Hua

Classifications

• G01N2800/2885

  Duchenne dystrophy · CPC title

• G01N2458/15

  Non-radioactive isotope labels, e.g. for detection by mass spectrometry · CPC title

• G01N33/6887

  from muscle, cartilage or connective tissue · CPC title

• G01N33/6848

  Methods of protein analysis involving mass spectrometry · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title