Libraries and methods for isolating antibodies
AssigneeDyax Corp.
InventorsRene Hoet, Sonia Schoonbroodt, Robert Ladner
Life of this patent
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Abstract
The disclosure features methods for identifying antibodies that bind to a carbohydrate moiety. Libraries coding for antibodies that bind to a carbohydrate moiety are provided. The libraries can be provided by modifying a pre-existing nucleic acid library. Antibodies that bind to a carbohydrate moiety are described.
Claims35
A method for identifying an antibody that binds to a negatively charged carbohydrate or polypeptide moiety, the method comprising:
- providing a protein library that comprises a plurality of diverse antibodies, each antibody comprising a heavy chain variable domain sequence and a light chain variable domain sequence, wherein the heavy chain variable domain sequence comprises diversity in HC CDR3, and the HC CDR3 comprises (GIS)-X-(K/R)-X-(K/R)-X (SEQ ID NO:
- 3), wherein X is any amino acid;
- contacting members of the protein library to a target molecule that includes a negatively charged carbohydrate or polypeptide moiety;
- and
- identifying one or more members that interact with the target molecule.
A method for providing an antibody coding library, the method comprising:
- providing an antibody coding library that includes a plurality of members, each member comprising a sequence encoding a heavy chain variable domain sequence, wherein the HC variable domain coding sequences are diverse among members of the plurality;
- providing nucleic acids that encode a diverse population of HC CDR3 sequences but such that at least one amino acid position in CDR3 is restricted to a basic amino acid, or complements of such nucleic acids;
- and
- modifying the HC variable domain coding sequences to include the HC CDR3 coding sequence.
A protein library comprising a plurality of diverse antibodies, each antibody comprising a heavy chain variable domain sequence and a light chain variable domain sequence, wherein the heavy chain variable domain sequence comprises diversity in CDR3, and at least one amino acid is restricted to a basic amino acid.
A pool of oligonucleotides comprising a plurality of different oligonucleotides, wherein each oligonucleotide of the plurality comprises a sequence with a CDR3-coding sequence that encodes the amino acid sequence (G/S)-X-(K/R)-X-(K/R)-X (SEQ ID NO:3), wherein X can be any amino acid, (K/R) can be either lysine or arginine, and (G/S) can be either glycine or serine.
A pool of oligonucleotides comprising a plurality of different oligonucleotides, wherein each oligonucleotide of the plurality comprises a sequence with a CDR3-coding sequence RGTNNKARGNNKARGNNK (SEQ ID NO:8), or the complement thereof.
An antibody which binds to at least one antigen selected from the group consisting of heparan sulfate (HS) and chemically desulfated N-sulfated heparin (CDSNS), said antibody comprising a sequence selected from the group consisting of:
- (a) a heavy chain (HC) immunoglobulin variable domain sequence comprising at least one CDR that is at least 85% identical to a CDR of a HC variable domain of an antibody selected from the group consisting of 1HS, 2HS, and 3HS;
- (b) a light chain (LC) immunoglobulin variable domain sequence comprising at least one CDR that is at least 85% identical to a CDR of a LC variable domain of an antibody selected from the group consisting of 1HS, 2HS, and 3HS;
- (c) a LC immunoglobulin variable domain sequence is at least 85% identical to a LC variable domain of an antibody selected from the group consisting of 1HS, 2HS, and 3HS;
- and
- (d) a HC immunoglobulin variable domain sequence is at least 85% identical to a HC variable domain of an antibody selected from the group consisting of 1HS, 2HS, and 3HS.
An antibody which binds to sulfocore 6, said antibody comprising a sequence selected from the group consisting of:
- (a) a heavy chain (HC) immunoglobulin variable domain sequence comprising at least one CDR that is at least 85% identical to a CDR of a HC variable domain of an antibody selected from the group consisting of 1SC6, 2SC6, 3SC6, and 4SC6;
- (b) a light chain (LC) immunoglobulin variable domain sequence comprising at least one CDR that is at least 85% identical to a CDR of a LC variable domain of an antibody selected from the group consisting of 1 SC6, 2SC6, 3SC6, and 4SC6;
- (c) a LC immunoglobulin variable domain sequence is at least 85% identical to a LC variable domain of an antibody selected from the group consisting of 1 SC6, 2SC6, 3SC6, and 4SC6;
- and
- (d) a HC immunoglobulin variable domain sequence is at least 85% identical to a HC variable domain of an antibody selected from the group consisting of 1SC6, 2SC6, 3SC6, and 4SC6.
Dependencies are inferred from the claim text.