US 2024/0294632 A1 · ANTIBODIES SPECIFIC FOR STRUCTURALLY DISORDERED SEQUENCES

Abstract

The present invention relates to a method for generating and/or obtaining specific binding moieties against intrinsically disordered proteins (IDPs) and/or intrinsically disordered protein domains which tend to be immunologically inert and lack immunogenicity in animals, in particular in mammals. The present invention also relates to such specific binding moieties, in particular to antibodies and/or to antigen binding fragments thereof, specifically binding to structurally disordered and/or intrinsically disordered sequences, in particular to Pro/Ala-rich sequences (PAS). These binding moieties, antibodies, antigen binding fragments are first in class since they bind to/recognize disordered peptides or polypeptide fragments as also comprised in such “intrinsically disordered proteins”, in particular PAS polypeptides. The inventive binding moieties, antibodies, antigen binding fragments are, without being limiting, particularly useful in diagnostic settings as well as research tools. The present invention relates to a method for generating and/or obtaining specific binding moieties against intrinsically disordered proteins (IDPs) and/or intrinsically disordered protein domains which tend to be immunologically inert and lack immunogenicity in animals, in particular in mammals. The present invention also relates to such specific binding moieties, in particular to antibodies and/or to antigen binding fragments thereof, specifically binding to structurally disordered and/or intrinsically disordered sequences, in particular to Pro/Ala-rich sequences (PAS). These binding moieties, antibodies, antigen binding fragments are first in class since they bind to/recognize disordered peptides or polypeptide fragments as also comprised in such “intrinsically disordered proteins”, in particular PAS polypeptides. The inventive binding moieties, antibodies, antigen binding fragments are, without being limiting, particularly useful in diagnostic settings as well as research tools.

Claims23

Dependent claims

A method for generating an antigen binding molecule, preferably an antibody or an antigen-binding fragment thereof, directed against intrinsically disordered peptides/proteins and/or intrinsically disordered peptide/protein domains, said method comprising the step of immunizing a non-human mammal with an antigen

wherein said antigen is a conjugate of an immunoadjuvant and one or more P/A peptides,
wherein each P/A peptide is independently a peptide consisting of about 5 to about 100 amino acid residues, wherein at least 60% of the amino acid residues of said peptide are independently selected from proline and alanine, and wherein a protecting group RN is attached to the N-terminal amino group of said peptide.

An antigen-binding molecule, wherein said antigen-binding molecule is selected from the group consisting of:

a) an antibody or an antigen-binding fragment thereof, comprising
a variable heavy (VH) chain comprising
the CDR-H1 as defined in SEQ ID NO:
35 [anti-PA(S) MAb 1.1],
the CDR-H2 as defined in SEQ ID NO:
36 [anti-PA(S) MAb 1.1], and
the CDR-H3 as defined in SEQ ID NO:
37 [anti-PA(S) MAb 1.1];
and/or
a variable light (VL) chain comprising
the CDR-L1 as defined in SEQ ID NO:
38 [anti-PA(S) MAb 1.1],
the CDR-L2 as defined in SEQ ID NO:
39 [anti-PA(S) MAb 1.1], and
the CDR-L3 as defined in SEQ ID NO:
40 [anti-PA(S) MAb 1.1];
or
is an antibody or an antigen-binding fragment thereof binding to the same epitope as an antibody comprising any one or more of the CDRs of (a);
b) an antibody or an antigen-binding fragment thereof, comprising
a variable heavy (VH) chain comprising
the CDR-H1 as defined in SEQ ID NO:
41 [anti-PA(S) MAb 1.2],
the CDR-H2 as defined in SEQ ID NO:
42 [anti-PA(S) MAb 1.2], and
the CDR-H3 as defined in SEQ ID NO:
43 [anti-PA(S) MAb 1.2];
and/or
a variable light (VL) chain comprising
the CDR-L1 as defined in SEQ ID NO:
44 [anti-PA(S) MAb 1.2],
the CDR-L2 as defined in SEQ ID NO:
45 [anti-PA(S) MAb 1.2], and
the CDR-L3 as defined in SEQ ID NO:
46 [anti-PA(S) MAb 1.2];
or
is an antibody or an antigen-binding fragment thereof binding to the same epitope as an antibody comprising any one or more of the CDRs of (b);
c) an antibody or an antigen-binding fragment thereof, comprising
a variable heavy (VH) chain comprising
the CDR-H1 as defined in SEQ ID NO:
47 [anti-PA(S) MAb 2.1],
the CDR-H2 as defined in SEQ ID NO:
48 [anti-PA(S) MAb 2.1], and
the CDR-H3 as defined in SEQ ID NO:
49 [anti-PA(S) MAb 2.1];
and/or
a variable light (VL) chain comprising
the CDR-L1 as defined in SEQ ID NO:
50 [anti-PA(S) MAb 2.1],
the CDR-L2 as defined in SEQ ID NO:
51 [anti-PA(S) MAb 2.1], and
the CDR-L3 as defined in SEQ ID NO:
52 [anti-PA(S) MAb 2.1];
or
is an antibody or an antigen-binding fragment thereof binding to the same epitope as an antibody comprising any one or more of the CDRs of (c);
d) an antibody or an antigen-binding fragment thereof, comprising
a variable heavy (VH) chain comprising
the CDR-H1 as defined in SEQ ID NO:
53 [anti-PA(S) MAb 2.2],
the CDR-H2 as defined in SEQ ID NO:
54 [anti-PA(S) MAb 2.2], and
the CDR-H3 as defined in SEQ ID NO:
55 [anti-PA(S) MAb 2.2];
and/or
a variable light (VL) chain comprising
the CDR-L1 as defined in SEQ ID NO:
56 [anti-PA(S) MAb 2.2],
the CDR-L2 as defined in SEQ ID NO:
57 [anti-PA(S) MAb 2.2], and
the CDR-L3 as defined in SEQ ID NO:
58 [anti-PA(S) MAb 2.2];
or
is an antibody or an antigen-binding fragment thereof binding to the same epitope as an antibody comprising any one or more of the CDRs of (d);
e) an antibody or an antigen-binding fragment thereof, comprising
a variable heavy (VH) chain comprising
the CDR-H1 as defined in SEQ ID NO:
59 [anti-PA(S) MAb 3.1],
the CDR-H2 as defined in SEQ ID NO:
60 [anti-PA(S) MAb 3.1], and
the CDR-H3 comprising or consisting of the amino acid sequence Trp-Gly-Arg [anti-PA(S) MAb 3.1];
and/or
a variable light (VL) chain comprising
the CDR1-L as defined in SEQ ID NO:
62 [anti-PA(S) MAb 3.1],
the CDR2-L as defined in SEQ ID NO:
63 [anti-PA(S) MAb 3.1], and
the CDR3-L as defined in SEQ ID NO:
64 [anti-PA(S) MAb 3.1];
or
is an antibody or an antigen-binding fragment thereof binding to the same epitope as an antibody comprising any one or more of the CDRs of (e);
and
f) an antibody or an antigen-binding fragment thereof, comprising
a variable heavy (VH) chain comprising
the CDR-H1 as defined in SEQ ID NO:
65 [anti-PA(S) MAb 3.2],
the CDR-H2 as defined in SEQ ID NO:
66 [anti-PA(S) MAb 3.2], and
the CDR-H3 as defined in SEQ ID NO:
67 [anti-PA(S) MAb 3.2];
and/or
a variable light (VL) chain comprising
the CDR-L1 as defined in SEQ ID NO:
68 [anti-PA(S) MAb 3.2],
the CDR-L2 as defined in SEQ ID NO:
69 [anti-PA(S) MAb 3.2], and
the CDR-L3 as defined in SEQ ID NO:
70 [anti-PA(S) MAb 3.2];
or
is an antibody or an antigen-binding fragment thereof binding to the same epitope as an antibody comprising any one or more of the CDRs of (f)

105 more elements

Dependencies are inferred from the claim text.

Antibodies specific for structurally disordered sequences

Life of this patent

Antibodies specific for structurally disordered sequences

Life of this patent

Abstract

Claims23