Glycan-based antibody-drug conjugates

1. An engineered IgG antibody or heavy chain constant domain fragment comprising

an S134N mutation in the heavy chain constant domain, which forms a non-native N-glycosylation site having the amino acid sequence NTS over positions 134-136 of the heavy chain constant domain, said non-native N-glycosylation site having an N-glycan attached to the N at position 134, wherein the N-glycan has a Gal 2 GlcNAc 2 Man 3 GlcNAc 2 glycoform in which the terminal galactose residues have been oxidized to a C-6 aldehyde group, which is conjugated to a reactive amine group of a derivatized drug by an oxime bond, and wherein the amino acid positions of the heavy chain constant domain are according to Eu numbering.

2. The engineered antibody or heavy chain constant domain fragment of claim 1 , wherein the antibody or heavy chain constant domain fragment further comprises a G161T mutation, which forms a second non-native N-glycosylation site in the heavy chain constant domain having the amino acid sequence NST over positions 159-161 of the heavy chain constant domain, said second non-native N-glycosylation site having an N-glycan attached to the N at position 159, wherein the N-glycan has a Gal 2 GlcNAc 2 Man 3 GlcNAc 2 glycoform in which the terminal galactose residues have been oxidized to have a C-6 aldehyde group, which is conjugated to a reactive amine group of a derivatized drug by an oxime bond, and wherein the amino acid positions of the heavy chain constant domain are according to Eu numbering.

3. The engineered IgG antibody or constant domain fragment of claim 1 , wherein the IgG antibody is selected from the group consisting of anti-Her2, anti-Her2/neu, anti-glycoprotein IIb/IIIa, anti-TNF-α, anti-CD52, anti-CD25, anti-BAFF, anti-Vascular endothelial growth factor, anti-CD30, anti-IL-1β, anti-epidermal growth factor receptor, anti-RANK Ligand, anti-Complement C5, anti-CD11a, anti-CD33, anti-CD20, anti-CTLA-4, anti-T cell CD3 Receptor, anti-α-4 (α4) integrin, anti-Immunoglobulin E, anti-RSV F protein, anti-epidermal growth factor receptor, anti-VEGF-A, anti-ErbB2, anti-IL-12/IL-23, anti-integrin α4β7, anti-CD274, anti-3-amyloid, anti-4-1BB, anti-SAC, anti-5T4, anti-ACVR2B, anti-adenocarcinomaantigen, anti-AGS-22M6, anti-α-fetoprotein, anti-angiopoietin 2, anti-angiopoietin 3, anti-anthrax toxin, anti-AOC3, anti-B7-H3, anti- Bacillus anthracia , anti-β amyloid, anti-B-lymphoma cell, anti-C242 antigen, anti-05, anti-CA-125, anti-carbonic anhydrase 9, anti-cardiac myosin, anti-CCL11, anti-CCR4, anti-CCR5, anti-CD11/CD18, anti-CD125, anti-CD140a, anti-CD147, anti-CD15, anti-CD152, anti-CD154, anti-CD19, anti-CD2, anti-CD200, anti-CD22, anti-CD221, anti-CD23, anti-CD27, anti-CD28, anti-CD3, anti-CD3 epsilon, anti-CD30, anti-CD37, anti-CD38, anti-CD4, anti-CD40, anti-CD41, anti-CD44, anti-CD5, anti-CD51, anti-CD52, anti-CD56, anti-CD6, anti-CD70, anti-CD74, anti-CD79B, anti-CD80, anti-CEA, anti-CFD, anti-ch4D5, anti-CLDN18.2, anti- C. difficile , anti-clumping factor A, anti-CSF2, anti-cytomegalovirus, anti-CMV gp B, anti-DLL4, anti-DRS, anti- E. coli shiga toxin type-1 or 2, anti-EGFL7, anti-endotoxin, anti-EpCAM, anti-EpCAM/CD3, anti-episialin, anti-ERBB3, anti- Escherichia coli , anti-F protein, anti-FAP, anti-fibrin II, anti-β chain, anti-fibronectin extra domain-B, anti-folate receptor 1, anti-Frizzled receptor, anti-GD2 ganglioside, anti-GD3 ganglioside, anti-GMCSF receptor α-chain, anti-GPNMB, anti-Influenza, anti-Influenza hemagglutinin, anti-hepatitis B, anti-surface antigen, anti-HER1, anti-HER3, anti-HGF, anti-HHGFR, anti-HIV-1, anti-HLA-DR, anti-HNGF, anti-Hsp90, anti-human scatter factor receptor kinase, anti-human TNF, anti-human β-amyloid, anti-CD54, anti-IFN-α, anti-IFN-γ, anti-IgE Fc region, anti-IGF-1 receptor, anti-IGF-I, anti-IgG4, anti-IGHE, anti-IL-13, anti-IL-17, anti-IL-17A, anti-IL-10, anti-IL-22, anti-IL-23, anti-IL-4, anti-IL-5, anti-IL-6, anti-IL-6 receptor, anti-IL9, anti-ILGF2, anti-insulin-like growth factor I receptor anti-integrin α4, anti-integrin α5β1, anti-integrin α7β7, anti-integrin αIIbβ3, anti-integrin αvβ3, anti-interferon receptor, anti-interferon α/β receptor, anti-interferon γ-induced protein, anti-ITGA2, anti-KIR2D, anti-Lewis-Y antigen, anti-lipoteichoic acid, anti-LOXL2, anti-L-selectin (CD62L), anti-LTA, anti-MCP-1, anti-mesothelin, anti-MS4A1, anti-MUC1, anti-mucin CanAg, anti-myostatin, anti-NARP-1, anti-NCA-90, anti-NGF, anti-N-glycolylneuraminic acid, anti-NOGO-A, anti-Notch receptor, anti-NRP1, anti- Oryctolagus cuniculus , anti-OX-40, anti-oxLDL, anti-PCSK9, anti-PD-1, anti-PDCD1, anti-PDGF-R α, anti-phosphate-sodium co-transporter, anti-phosphatidylserine, anti-prostatic carcinoma cells, anti- Pseudomonas aeruginosa , anti-rabies virus, anti-rabies virus glycoprotein, anti-respiratory syncytial virus, anti-RHD, anti-Rhesus factor, anti-RON, anti-RTN4, anti-sclerostin, anti-SDC1, anti-selectin P, anti-SLAMF7, anti-SOST, anti-sphingosine-1-phosphate, anti-TAG-72, anti-T-cell receptor, anti-TEM1, anti-tenascin C, anti-TFPI, anti-TGFβ1, anti-TGFβ2, anti-TGF-β, anti-TRAIL-R1, anti-TRAIL-R2, anti-tumor antigen CTAA16.88, anti-TWEAK receptor, anti-TYRP1, anti-VEGF-A, anti-VEGFR-1, anti-VEGFR2, anti-vimentin, anti-VWF, anti-IL-1, anti-IL-2, anti-IL-5, anti-IL-8, anti-IL-12, anti-IL-15, anti-IL-18, anti-IL-20, anti-IL-21, anti-IL-23R, anti-IL-25, anti-IL-27, anti-IL-33, anti-CD14, anti-CD18, anti-CD64, anti-CD200, anti-CD200R, anti-TSLP, anti-TSLPR, anti-PDL1, anti-VLA-4, anti-E-selectin, anti-Fact II, anti-ICAM-3, anti-β2-integrin, anti-CBL, anti-LCAT, anti-CR3, anti-MDL-1, anti-GITR, anti-CGRP, anti-TRKA, anti-IGF1R, and anti-GTC.

4. The engineered IgG antibody or constant domain fragment of claim 1 , wherein the IgG antibody is selected from the group consisting of abciximab, adalimumab, certolizumab pegol, golimumab, infliximab, alemtuzumab, basiliximab, belimumab, bevacizumab, brentuximab vedotin, canakinumab, cetuximab, daclizumab, denosumab, eculizumab, efalizumab, gemtuzumab, ibritumomab tiuxetan, ipilimumab, muromonab-cd3, natalizumab, ofatumumab, omalizumab, palivizumab, panitumumab, ranibizumab, rituximab, tocilizumab, atlizumab, tositumomab, trastuzumab, ustekinumab, and vedolizumab.