Scope

Owned by Richard Norman (Unlicensed)
Last updated: Sept 12, 2018

Scope

In scopeOut 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
Candidate Screening (post-Target Validation) to Lead Candidate Selection (pre-Pre Clinical)


EARLY SELECTIONFINAL PROFILINGENDPOINT 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 descriptorsHow are we going to quantify this? <list which><list which>




ASSAYS

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

in silico predictions

Antigen binding by biacore (active concentration & kinetics) - pre/post stress

cIEF

LC-MS

CE-SDS

LC-MS, CZE, 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)

LC-MS, CZE, CE-SDS - pre/post stress

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

aSEC, turbidity – pre/post incubation in different formulations

(self) Aggregation

<definition>

AC-SINS, CSI-BLI, PSR binding, BVP, CIC, ELISA, SGAC-SINS, HIC, SMAC

AC-SINS, HP-SEC column interaction

HIC, aSEC

HIC, aSEC, MALLS

HIC, aSEC

PEG-induced precipitation

K-Diff

K-Diff by DLS, aSEC


aSEC, turbidity – pre/post incubation in different formulations (rheometry)

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)

FcRN interaction by SPR

ProteinChip to evaluate potential for unspecific interactions

Human PK (non-specific Clearance)

<definition>

As aboveFcRN interaction (chromatography or SPR)

FcRN interaction by SPR