Computational Antibody Papers

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2025
TitleKey points

  • 2025-09-30

    Advancing large-molecule discovery with a unified digital platform for data analysis and workflow management

    • experimental techniques
    • ngs
    • annotation/numbering
    • server/webapp
    • Review of currently available large scale software for antibody analysis.
    • Today’s biologics R&D is slowed by fragmented tools and manual data wrangling; the paper proposes a unified, open-architecture platform that spans registration, tracking, analysis, and decisions from discovery through developability.
    • Key components are end-to-end registration of molecules/materials/assays; a harmonized data schema with normalized outputs; automated analytics with consistent QC; complete metadata capture and “data integrity by design.”
    • The platform should natively interface with AI, enable multimodal foundation models and continuous “lab-in-the-loop” learning, and support federated approaches to counter data scarcity while preserving privacy.
    • Dotmatics, Genedata, and Schrödinger each cover pieces (e.g., LiveDesign lacks end-to-end registration), and the authors stress regulatory-ready features.

  • 2025-09-30

    mBER: Controllable de novo antibody design with million-scale experimental screening

    • binding prediction
    • generative methods
    • protein design
    • experimental techniques
    • Novel de novo antibody design method with massive experimental testing.
    • The computational method involves integration, not retraining, of existing tools. It combines AlphaFold-Multimer, protein language models (ESM2/AbLang2), and NanoBodyBuilder2 with templating/sequence priors to design/filter antibody-format binders.
    • They perform massive testing. >1.1 million VHH binders designed across 436 targets (145 tested); ~330k experimentally screened.
    • Hit rates look low per binder (~0.5–1%) but that’s ~50× above random libraries, and still yields thousands of validated binders.
    • Target-level success is 45%, for how many targets we got binders; some epitopes reached 30–38% hit rates after filtering.
    • The big caveat is the specificity of epitopes- it really makes a difference, with some epitopes producing nought.

  • 2025-07-03

    Developing drug-like single-domain antibodies (VHH) from in vitro libraries

    • experimental techniques
    • ngs
    • Novel library design technique for VHHs that produces developable and humanized antibodies without the need for further optimization.
    • The authors built a humanized VHH phage display library using four therapeutic VHH scaffolds, incorporating CDR1 and CDR2 sequences from human VH3 germline genes (filtered for sequence liabilities) and highly diverse CDR3s from CD19⁺ IgM⁺ human B cells.
    • CDR1 and CDR2 libraries were filtered via yeast display for proper folding and protein A binding, while CDR3s were refined to remove poly-tyrosine stretches to reduce polyreactivity.
    • An improved library version incorporated CDR1/2 variants selected for heat tolerance and further depleted CDR3s with poly-tyrosine motifs, increasing stability and developability.
    • VHHs were tested for expression, thermal stability, aggregation, hydrophobicity, and polyreactivity, showing that the V2 library yielded a higher proportion of drug-like antibodies with favorable biophysical properties.

  • 2025-03-11

    Redefining antibody patent protection using paratope mapping and CDR-scanning

    • paratope prediction
    • experimental techniques
    • Proposal how to make antibody patents reasonable via mutational scanning.
    • If you develop a therapeutic antibody you want to claim a space around it so that no-one piggy backs off your effort by doing one substitution.
    • If you claim a ’homology space around your mabs’, then even a small amount of substitutions can circumvent 90-95% sequence identity of either CDRs or variable region.
    • Claiming that you own all antibodies that bind some protein (e.g. like Amgen did with pcks9) is too broad. That goes back to the ‘enablement’ of patents, as it needs to allow a skilled person to reproduce it. If you claim a handful of abs against pcks9, you do not exactly give a way to make ‘all others’.
    • Authors propose to make broader claims by point mutations in the CDRs in strategic paratope positions and characterizing binders. For a single lead you are looking at a ballpark 1,000 mutants, which is experimentally feasible. This would give hard data for a broad spectrum of binders around your candidates, giving wider protection.