Proteomic screening for lysosomal storage diseases

Patent metadata

Field	Value
Publication number	US-11940448-B2
Application number	US-202117219776-A
Country	US
Kind code	B2
Filing date	Mar 31, 2021
Priority date	Mar 31, 2020
Publication date	Mar 26, 2024
Grant date	Mar 26, 2024

Abstract

Early detection of lysosomal storage diseases (LSDs) including Mucopolysaccharidosis Type I (MPS I) and Pompe Disease can greatly improve patient outcome as each disease can be fatal once symptoms emerge. Screening for MPS I and Pompe Disease using biological samples including dried blood spots (DBS), buccal swab, peripheral blood mononuclear cells (PBMCs), or white blood cells (WBCs) is described. The disclosed methods and assays provide a robust way to screen newborns for LSDs. The disclosed methods and assays can also allow rapid prediction of whether a patient with LSD will develop an immune response to enzyme replacement therapy (ERT), thus improving treatment for patients with LSDs. The disclosed methods and assays can also further reduce the number of false positives caused by pseudo deficiency cases of LSD, such as MPS I and Pompe Disease.

First claim

The invention claimed is:

1. A method of detecting one or more signature peptides of Mucopolysaccharidosis Type I (MPSI) and/or Pompe Disease in a biological sample, the method comprising:
obtaining a biological sample from a subject;
digesting proteins from the biological sample with an enzyme to yield a digested biological sample comprising peptides;
enriching the digested biological sample for the one or more signature peptides by contacting the sample with an antibody or antigen binding fragment thereof for each of the one or more signature peptides, the enriching step comprising enriching for:
(A) an alpha-L-iduronidase enzyme (IDUA) signature peptide of MPSI of SEQ ID NO: 2 with an antibody or antigen-binding fragment thereof that binds the IDUA signature peptide and comprises: a heavy chain variable (VH) domain comprising a complementarity determining region (CDR)H1 as set forth in SEQ ID NO: 22, a CDRH2 as set forth in SEQ ID NO: 23, and a CDRH3 as set forth in SEQ ID NO: 24, and a light chain variable (VL) domain comprising a CDRL1 as set forth in SEQ ID NO: 25, a CDRL2 as set forth in SEQ ID NO: 26, and a CDRL3 as set forth in SEQ ID NO: 27; and
an acid alpha-glucosidase enzyme (GAA) signature peptide of Pompe Disease of SEQ ID NO: 5 with an antibody or antigen binding fragment thereof that binds the GAA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 66, a CDRH2 as set forth in SEQ ID NO: 67, and a CDRH3 as set forth in SEQ ID NO: 68, and VL domain comprising a CDRL1 as set forth in SEQ ID NO: 69, a CDRL2 as set forth in SEQ ID NO: 70, and a CDRL3 as set forth in SEQ ID NO: 71; or
(B) a first IDUA signature peptide of MPSI of SEQ ID NO: 1 with an antibody or antigen-binding fragment thereof that binds the first IDUA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 10, a CDRH2 as set forth in SEQ ID NO: 11, and a CDRH3 as set forth in SEQ ID NO: 12, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 13, a CDRL2 as set forth in SEQ ID NO: 14, and a CDRL3 as set forth in SEQ ID NO: 15; and
a second IDUA signature peptide of MPSI of SEQ ID NO: 2 with an antibody or antigen-binding fragment thereof that binds the second IDUA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 22, a CDRH2 as set forth in SEQ ID NO: 23, and a CDRH3 as set forth in SEQ ID NO: 24, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 25, a CDRL2 as set forth in SEQ ID NO: 26, and a CDRL3 as set forth in SEQ ID NO: 27; or
(C) a first IDUA signature peptide of MPSI of SEQ ID NO: 1 with an antibody or antigen-binding fragment thereof that binds the first IDUA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 10, a CDRH2 as set forth in SEQ ID NO: 11, and a CDRH3 as set forth in SEQ ID NO: 12, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 13, a CDRL2 as set forth in SEQ ID NO: 14, and a CDRL3 as set forth in SEQ ID NO: 15;
a second IDUA signature peptide of MPSI of SEQ ID NO: 2 with an antibody or antigen-binding fragment thereof that binds the second IDUA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 22, a CDRH2 as set forth in SEQ ID NO: 23, and a CDRH3 as set forth in SEQ ID NO: 24, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 25, a CDRL2 as set forth in SEQ ID NO: 26, and a CDRL3 as set forth in SEQ ID NO: 27; and
a GAA signature peptide of Pompe Disease of SEQ ID NO: 5 with an antibody or antigen binding fragment thereof that binds the GAA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 66, a CDRH2 as set forth in SEQ ID NO: 67, and a CDRH3 as set forth in SEQ ID NO: 68, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 69, a CDRL2 as set forth in SEQ ID NO: 70, and a CDRL3 as set forth in SEQ ID NO: 71; or
(D) a first IDUA signature peptide of MPSI of SEQ ID NO: 1 with an antibody or antigen-binding fragment thereof that binds the first IDUA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 10, a CDRH2 as set forth in SEQ ID NO: 11, and a CDRH3 as set forth in SEQ ID NO: 12, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 13, a CDRL2 as set forth in SEQ ID NO: 14, and a CDRL3 as set forth in SEQ ID NO: 15;
a second IDUA signature peptide of MPSI of SEQ ID NO: 2 with an antibody or antigen-binding fragment thereof that binds the second IDUA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 22, a CDRH2 as set forth in SEQ ID NO: 23, and a CDRH3 as set forth in SEQ ID NO: 24, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 25, a CDRL2 as set forth in SEQ ID NO: 26, and a CDRL3 as set forth in SEQ ID NO: 27; and
a GAA signature peptide of Pompe Disease of SEQ ID NO: 3 with an antibody or antigen binding fragment thereof that binds the GAA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 44, a CDRH2 as set forth in SEQ ID NO: 45, and a CDRH3 as set forth in SEQ ID NO: 46, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 47, a CDRL2 as set forth in SEQ ID NO: 48, and a CDRL3 as set forth in SEQ ID NO: 49; or
(E) a first GAA signature peptide of Pompe Disease of SEQ ID NO: 3 with an antibody or antigen binding fragment thereof that binds the first GAA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 44, a CDRH2 as set forth in SEQ ID NO: 45, and a CDRH3 as set forth in SEQ ID NO: 46, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 47, a CDRL2 as set forth in SEQ ID NO: 48, and a CDRL3 as set forth in SEQ ID NO: 49; and
a second GAA signature peptide of Pompe Disease of SEQ ID NO: 5 with an antibody or antigen binding fragment thereof that binds the GAA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 66, a CDRH2 as set forth in SEQ ID NO: 67, and a CDRH3 as set forth in SEQ ID NO: 68, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 69, a CDRL2 as set forth in SEQ ID NO: 70, and a CDRL3 as set forth in SEQ ID NO: 71; or
(F) a first IDUA signature peptide of MPSI of SEQ ID NO: 1 with an antibody or antigen-binding fragment thereof that binds the first IDUA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 10, a CDRH2 as set forth in SEQ ID NO: 11, and a CDRH3 as set forth in SEQ ID NO: 12, and VL domain comprising a CDRL1 as set forth in SEQ ID NO: 13, a CDRL2 as set forth in SEQ ID NO: 14, and a CDRL3 as set forth in SEQ ID NO: 15;
a second IDUA signature peptide of MPSI of SEQ ID NO: 2 with an antibody or antigen-binding fragment thereof that binds the second IDUA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 22, a CDRH2 as set forth in SEQ ID NO: 23, and a CDRH3 as set forth in SEQ ID NO: 24, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 25, a CDRL2 as set forth in SEQ ID NO: 26, and a CDRL3 as set forth in SEQ ID NO: 27;
a first GAA signature peptide of Pompe Disease of SEQ ID NO: 3 with an antibody or antigen binding fragment thereof that binds the first GAA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 44, a CDRH2 as set forth in SEQ ID NO: 45, and a CDRH3 as set forth in SEQ ID NO: 46, and a VL domain comprising a CDRL1 as set forth in SEQ ID NO: 47, a CDRL2 as set forth in SEQ ID NO: 48, and a CDRL3 as set forth in SEQ ID NO: 49;
and a second GAA signature peptide of Pompe Disease of SEQ ID NO: 5 with an antibody or antigen binding fragment thereof that binds the GAA signature peptide and comprises: a VH domain comprising a CDRH1 as set forth in SEQ ID NO: 66, a CDRH2 as set forth in S

Assignees

• Seattle Childrens Hospital

Inventors

• Hahn Sihoun
• Collins Christopher
• Dayuha Remwilyn
• Yi Fan

Classifications

• G01N33/6854 Primary

  Immunoglobulins · CPC title

• G01N33/6848 Primary

  Methods of protein analysis involving mass spectrometry · CPC title

• G01N2800/38

  Pediatrics · CPC title

• G01N2800/04

  Endocrine or metabolic disorders · CPC title

• G01N2800/385

  Congenital anomalies · CPC title