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US 2026/0217800 A1Published application
Compositions and methods for making pan-variant antibodies
OwnerMichael P. Weinerinventor
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Abstract
The present disclosure provides a method of examining antigen-binding region, such as antibody, specificity and/or affinity and making pan-variant specific antigen-binding regions, such as antibodies.
Claims39
A method of screening or examining specificity, avidity, and/or affinity of an antigen-binding region for a protein or peptide of interest, the method comprising:
- providing a set of fusion proteins that comprises two or more fusion proteins, wherein:
- each fusion protein includes a maltose-binding protein, or amylose-binding derivative thereof, fused directly to or via a linker to a target sequence of about 8 amino acids to 18 amino acids from the protein or peptide of interest;
- and
- each target sequence of the set of fusion proteins has a different proteinogenic amino acid at a site of interest in the target sequence, including (i) one that has the native amino acid of the target sequence or (ii) one or more has a native amino acid when the site of interest is a variant site;
- and
- examining or detecting which of the fusion proteins that the antigen-binding region binds.
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The method of claim 12, wherein at least one of:
- detecting is performed via an enzyme-linked immunosorbent assay, and each fusion protein is a different antigen of the enzyme-linked immunosorbent assay;
- the maltose-binding protein derivative has been engineered/modified to provide tighter or enhanced binding to amylose resin;
- the linker is a protein linker;
- the linker is a protein linker, wherein the protein linker includes or consists of about 1 to about 10 amino acids;
- the target sequence is linked to the C-terminus of the maltose-binding protein;
- or
- a combination thereof.
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A method of producing a variant or a pan-variant specific binding agent to a protein or peptide of interest having a defined variant site, the method comprising:
- a. providing a modified peptide having an amino acid sequence of about 10 to about 20 amino acids identical to an amino acid sequence of the protein or peptide of interest and includes the amino acids of the target sequence, except wherein the wild-type amino acid at the defined variant site has been substituted with a non-native amino acid (nnAA);
- and
- b. screening the modified peptides against a library;
- c. isolating one or more binding agents that bind to the modified peptide;
- d. generating a library of clonotypes of the one or more binding agents isolated in step (c);
- e. screening the library of clonotypes against:
- i. the modified peptide of step (a);
- and
- ii. a first unmodified peptide comprising a core amino acid sequence identical to the modified peptide of step (a), except wherein the non-native amino acid (nnAA) has been substituted with the wild-type amino acid (nAA) and comprising a first N-terminal amino acid sequence that is not native to the protein or peptide of interest and a first C-terminal amino acid sequence that is not native to the protein or peptide of interest;
- f. isolating a binding agent that bind to both the first unmodified peptide and the modified peptide;
- g. generating a library of clonotypes of the binding agent isolated in step (f);
- h. screening the library of clonotypes of step (g) against:
- i. the modified peptide;
- ii. the first unmodified peptide;
- and
- iii. a second unmodified peptide comprising a core amino acid sequence that is identical to the first unmodified peptide, except wherein the wild-type amino acid (nAA) has been substituted with an amino acid corresponding to a variant and comprising a second N-terminal amino acid sequence that is not native to the protein or peptide of interest and a second C-terminal amino acid sequence that is not native to the protein or peptide of interest;
- and
- i. isolating a binding agent that binds to the second unmodified peptide and does not bind the first modified peptide.
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Dependencies are inferred from the claim text.