Scope
| In scope | Out of scope |
|---|---|
>Molecules: standard and non-standard mAbs (i.e. bi-/multi-specific's, ADCs, IgG/Fc fusions). >Data: Chemical & structural stability, Aggregation, Toxicity, PK and Immunogenicity. >Assays: early selection (high-throughput), detailed profiling (bespoke, low-throughput) and endpoint (pre-candidate nomination). | >Data: Manufacturability (expression yields). |
Basecase scenario
This table captures the minimum information required to meet some of our objectives (see 'objectives') and for the database to be of value (see 'value proposition')
Colour coding: Jain et el (2017), Abvance Biotech, GSK, Lilly, MedImmune, Novartis
DEVELOPABILITY ASSESSMENT | ||||||
|---|---|---|---|---|---|---|
| EARLY SELECTION | FINAL PROFILING | ENDPOINT DATA | ||||
MOLECULES From patented, published or 'dead' discovery campaigns. Need molecules with 'interesting' or 'poor' properties | ||||||
Typical throughput number x (# organisations), x (# projects) | ~50 | ~5 | ~1+1 | |||
| Type | <standard mAbs, bi-multi specifics, ADC's, IgG/Fc fusions> | <standard mAbs, bi-multi specifics, ADC's, IgG/Fc fusions> | <standard mAbs, bi-multi specifics, ADC's, IgG/Fc fusions> | |||
| Sequence | <Yes/No> | <Yes/No> | <Yes/No> | |||
| 3D structure | <Yes/No (homology model)> | <Yes/No (homology model)> | <Yes/No (homology model)> | |||
| Structure descriptors | How are we going to quantify this? | <list which> | <list which> | |||
Select assays based on: whether a peer-reviewed publication exists of its use for Ab characterisation, amenable to characterising 100s of Abs, consumes <1mg material, provides decision-making data for the below developability risk factors (ideally part of TPP at Lead Identification) | ||||||
Chemical stability <definition> | cIEF e.g. NanoPro in silico predictions
| Antigen binding by biacore (active concentration & kinetics) - pre/post stress cIEF LC-MS CE-SDS
| Mass spec (glycan analysis, intact mass, peptide mapping) cIEF CGE (capillary gel electrophoresis) reverse phase HPLC Antigen binding by biacore (active concentration & kinetics) (ad hoc testing as needed includes CD, DSC, bioanalyser NGHC, ion exchange chromatography)
Antigen binding by biacore - pre/post serum incubation | |||
Structural stability <definition> | Tm, SEC (AS) DSF, HP-SEC (post-stress) DSF, aSEC DSF, aSEC DSF, aSEC, MALLS | aSEC, DLS, AUC DSC AUC DSC, aSEC aSEC, DLS, AUC | aSEC
| |||
(self) Aggregation <definition> | AC-SINS, CSI-BLI, PSR binding, BVP, CIC, ELISA, SGAC-SINS, HIC, SMAC AC-SINS, HP-SEC column interaction | |||||
...
Toxicity
...
HIC, aSEC HIC, aSEC, MALLS HIC, aSEC | PEG-induced precipitation K-Diff K-Diff by DLS, aSEC |
| ||
Immunogenicity <definition> | in silico predictions | (MAPPS assay) | (MAPPS assay) | |
Cyno PK (non-specific Clearance) <definition> | Baculovirus particles, HEK or CHO cells, yeast extracts, Heparin, etc. HepSO4 chromatogaphy, | FcRN interaction (chromatography or SPR) |
| |
Human PK (non-specific Clearance) <definition> | As above | FcRN interaction (chromatography or SPR) |
|