Data mining patented antibody sequences

Abstract

The patent literature should reflect the past 30 years of engineering efforts directed toward developing monoclonal antibody therapeutics. Such information is potentially valuable for rational antibody design. Patents, however, are designed not to convey scientific knowledge, but to provide legal protection. It is not obvious whether antibody information from patent documents, such as antibody sequences, is useful in conveying engineering know-how, rather than as a legal reference only. To assess the utility of patent data for therapeutic antibody engineering, we quantified the amount of antibody sequences in patents destined for medicinal purposes and how well they reflect the primary sequences of therapeutic antibodies in clinical use. We identified 16,526 patent families covering major jurisdictions (e.g., US Patent and Trademark Office (USPTO) and World Intellectual Property Organization) that contained antibody sequences. These families held 245,109 unique antibody chains (135,397 heavy chains and 109,712 light chains) that we compiled in our Patented Antibody Database (PAD, http://naturalantibody.com/pad). We find that antibodies make up a non-trivial proportion of all patent amino acid sequence depositions (e.g., 11% of USPTO Full Text database). Our analysis of the 16,526 families demonstrates that the volume of patent documents with antibody sequences is growing, with the majority of documents classified as containing antibodies for medicinal purposes. We further studied the 245,109 antibody chains from patent literature to reveal that they very well reflect the primary sequences of antibody therapeutics in clinical use. This suggests that the patent literature could serve as a reference for previous engineering efforts to improve rational antibody design.

INDI – Integrated Nanobody Database for Immunoinformatics

“…In total 16,271,610 entries matched these criteria. Antibody sequences were identified employing our adapted version of antibody numbering software (8,24).…”

“…The copyright holder for this preprint this version posted August 9, 2021. ; https://doi.org/10.1101/2021.08.04.21261581 doi: medRxiv preprint We identified five major sources of biological sequence information: NCBI GenBank (20), Protein Data Bank (21), patents (8), next-generation sequencing (NGS) repositories (22,23) and scientific publications. These sources provide a good coverage associated with systematic repositories collecting protein information from scientific literature and patent documents.…”

“…In total 16,271,610 entries matched these criteria. Antibody sequences were identified employing our adapted version of antibody numbering software (8,24). Individual GenBank entries were identified as containing nanobodies if their textual description contained a set of nanobody-specific keywords (19,26) and if the declared organism matched one of: 'Lama glama', 'Camelus dromedarius', 'Vicugna pacos', 'synthetic construct', 'Camelus bactrianus', 'Camelidae' or .…”

“…We extracted patent nanobody sequences from our Patented Antibody Database (8) This resulted in a total of 13,950 unique variable region sequences from 659 patent families.…”

AbDiver – A tool to explore the natural antibody landscape to aid therapeutic design

“…We envisage updates to the services as more datasets become available. For benchmarking, we employed a set of 742 therapeutic antibodies, discontinued, in clinical trials or approved in USA and the EU extending a set from our previous study (Krawczyk et al, 2021). Certain therapeutics were multi-specific or contained chain duplicates resulting in 738 unique heavy chains, 707 unique light chains, 686 unique CDRH3s and 573 unique CDRL3s.…”