Development of an Imperacer (Immuno-PCR) assay combining broad assay range and excellent sensitivity to support development of an immuno modulator antibody drug
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1
Merck Research Labs, Bioanalytical Development, Biologics, United States
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2
Chimera Biotec, Project Management, Germany
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3
Chimera Biotec, Assay Development, Germany
Purpose: Biologics such as therapeutic antibody drugs are often administered in wide concentration ranges for dose-response
evaluation. Safety and potency considerations demand low dosing in clinical trials. In contrast, higher dosing is applied in preclinical
safety assessment for fast cleared drugs. Thus, sensitive pharmacokinetic analysis with broad quantification range is
required.
Method: An Imperacer assay for quantification of a therapeutic antibody for cancer treatment was developed. The assay applies
tailored antibody-DNA conjugates for target detection and subsequent exponential DNA amplification for signal generation.
Results: A quantification range of 2 – 32,768 pg/ml target antibody was demonstrated with accuracy and precision <25%.
Selectivity at spiked 6 - 10 pg/ml was challenged with 10 healthy human serum samples. Dilution linearity confirmed that
concentrations >5 μg/ml can be diluted into the assay range with acceptable recovery despite Prozone (hook) effect starting at
approx. 1 μg/ml.
Conclusions: Exponential signal amplification provides a combination of excellent sensitivity and broad assay range for the
Imperacer platform. As only one assay is required for >5 orders of magnitude target concentration, the need for multiple
quantification windows in different technologies is circumvented. This significantly reduces bioanalytical sample testing time
and effort during all phases in the development of Biologics. Assay optimization is still in progress and will be adapted towards
further study requirements prior to method validation.
Keywords:
pharmacokinetic,
pk,
Clinical support,
immuno-PCR,
IPCR,
ultra sensitive immunoassays
Conference:
EUFEMED 2017, London, United Kingdom, 17 May - 19 May, 2017.
Presentation Type:
Poster
Topic:
EUFEMED 2017 CONFERENCE
Citation:
Shi
S,
Spengler
M,
Punnamoottil
B,
Adler
M and
Lee
D
(2019). Development of an Imperacer (Immuno-PCR) assay combining broad assay range and excellent sensitivity to support development of an immuno modulator antibody drug.
Front. Pharmacol.
Conference Abstract:
EUFEMED 2017.
doi: 10.3389/conf.fphar.2017.62.00007
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Received:
29 Aug 2017;
Published Online:
25 Jan 2019.
*
Correspondence:
Dr. Mark Spengler, Chimera Biotec, Project Management, Bremen, Germany, spengler@chimera-biotec.com