Evidence map›Paper›PMID 25759214›Full record

ArticlemAbs2015

Boosting antibody developability through rational sequence optimization.

Daniel Seeliger, Patrick Schulz, Tobias Litzenburger, Julia Spitz, Stefan Hoerer, Michaela Blech, Barbara Enenkel, Joey M Studts, Patrick Garidel, Anne R Karow

Abstract read
In one paragraph

Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Daniel Seeligera Division Research Germany; Boehringer Ingelheim Pharma GmbH & Co. KG ; Biberach/Riss , Germany.
Patrick Schulz
Tobias Litzenburger
Julia Spitz
Stefan Hoerer
Michaela Blech
Barbara Enenkel
Joey M Studts
Patrick Garidel
Anne R Karow

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The application of monoclonal antibodies as commercial therapeutics poses substantial demands on stability and properties of an antibody. Therapeutic molecules that exhibit favorable properties increase the success rate in development. However, it is not yet fully understood how the protein sequences of an antibody translates into favorable in vitro molecule properties. In this work, computational design strategies based on heuristic sequence analysis were used to systematically modify an antibody that exhibited a tendency to precipitation in vitro. The resulting series of closely related antibodies showed improved stability as assessed by biophysical methods and long-term stability experiments. As a notable observation, expression levels also improved in comparison with the wild-type candidate. The methods employed to optimize the protein sequences, as well as the biophysical data used to determine the effect on stability under conditions commonly used in the formulation of therapeutic proteins, are described. Together, the experimental and computational data led to consistent conclusions regarding the effect of the introduced mutations. Our approach exemplifies how computational methods can be used to guide antibody optimization for increased stability.

Indexed as

Amino Acid SequenceAntibodies, MonoclonalHumansProtein EngineeringProtein StabilityAntibodies, MonoclonalbiopharmaceuticalsCMC, chemistry, manufacturing and controldesigndevelopabilityDSC, differential scanning calorimetryHC, heavy chainLC, light chainmAb, monoclonal antibodymonoclonal antibodiesPK, pharmacokineticspredictionprotein engineeringRALS, right angle light scatteringstabilitythermal stabilityWT, wild-type

Identifiers

PMID25759214
PMCPMC4622947

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.