Lysine conjugated immunoglobulins
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Publication Number
US-10941431-B2
Publication Date
2021-03-09
Expiration Date
Abstract
Provided herein are conjugated immunoglobulins and methods for generating conjugated immunoglobulins using a microbial transglutaminase.
Core Innovation
The disclosure relates to a conjugated immunoglobulin, or antigen-binding portion thereof, that includes an engineered lysine residue. The engineered lysine residue is a natural amino acid residue mutated to a lysine residue at specified heavy chain, kappa light chain, and lambda light chain positions numbered according to the EU numbering system, and the immunoglobulin further comprises an acyl donor substrate to which the engineered lysine residue is conjugated via a glutamine residue.
The acyl donor substrate includes a glutamine residue and a reactive group, and is defined by one of Formulae (III) or (IV). In these formulae, Z is a carboxylbenzyloxy (CBZ) group or an amino acid residue, Gln is a glutamine amino acid residue, each L is independently a straight or branched linker from 1 to 20 carbon atoms, and X is a reactive group.
A method is also disclosed for generating the conjugated immunoglobulin using a microbial transglutaminase and the acyl donor substrate. The method includes contacting an immunoglobulin, or antigen-binding portion thereof, comprising the engineered lysine residue with the microbial transglutaminase and the acyl donor substrate, and the enzyme conjugates the engineered lysine residue to the glutamine residue of the acyl donor substrate.
Claims Coverage
The document contains two independent claims, each covering a distinct aspect: the conjugated immunoglobulin composition and the method for generating it. Across these independent claims, the inventive coverage centers on engineered lysine residues conjugated to a glutamine-containing acyl donor substrate defined by Formulae (III) or (IV), with a reactive group for attachment of a functional agent.
Conjugated immunoglobulin with engineered lysine conjugated via glutamine acyl donor
An immunoglobulin, or antigen-binding portion thereof, comprising an engineered lysine residue at specified heavy chain, kappa light chain, and lambda light chain positions numbered according to the EU numbering system, wherein the engineered lysine residue is conjugated to a glutamine residue on an acyl donor substrate defined by Formulae (III) or (IV), with Z, L, and reactive group X.
Method for generating conjugated immunoglobulin using microbial transglutaminase and glutamine acyl donor substrate
A method for generating a conjugated immunoglobulin comprising contacting an immunoglobulin, or antigen-binding portion thereof, comprising engineered lysine residue with a microbial transglutaminase and an acyl donor substrate defined by Formulae (III) or (IV), wherein the enzyme conjugates the engineered lysine residue to the glutamine residue.
Together, the independent claims require engineered lysine residues at specified EU-numbered antibody positions and enzymatic conjugation to a glutamine residue on an acyl donor substrate defined by Formulae (III) or (IV).
Stated Advantages
Documented Applications
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