The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Biophysical properties of the clinical-stage antibody landscape
Open accessAbstract
Significance: In addition to binding to a desired target molecule, all antibody drugs must also meet a set of criteria regarding the feasibility of their manufacture, stability in storage, and absence of off-target stickiness. This suite of characteristics is often termed “developability.” We present here a comprehensive analysis of these properties for essentially the full set of antibody drugs that have been tested in phase-2 or -3 clinical trials, or are approved by the FDA. Surprisingly, many of the drugs or candidates in this set exhibit properties that indicate significant developability risks; however, the number of such red warning flags decreases with advancement toward approval. This reference dataset should help prioritize future drug candidates for development.
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“The increasing number of structural [16], sequence [17] and experimental data [18–21] on antibodies being deposited in the public domain provides the necessary foundation for improving such data-driven methods.”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [21]
In the citing paper
“and Jain et al. demonstrated the feasibility of using multiple biophysical metrics to characterize mAbs for drug‐like behavior.58”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [58]
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Citations
Cites
1 retracted
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Developability Index: A Rapid In Silico Tool for the Screening of Antibody Aggregation Propensity
Lauer, T. M., Agrawal, N. J., Chennamsetty, N., Egodage, K. L., Helk, B., & Trout, B. L. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22758 · Cited by 206
Cited by
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Items 601–630 of 630
Weiner, J. A., BANKS, L. A., Natarajan, H., Lin, S., Sami, S., Kovacikova, G., Carpenter, M. C., & Ackerman, M. E. (2026) · Bioanalysis · doi:10.1080/17576180.2026.2698615 · Cited by 1
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“The Jain et al. dataset remains a widely used benchmark because it reports 12 biophysical measurements for 137 clinical-stage antibodies, including expression titer, purity, thermal stability, aggregation, hydrophobicity, self-association, and polyreactiv-ity [ 31].”
Physicochemical developability insights into human Fab fragments with extended hypervariable loops
Passon, M., Bandera, G., Mayerhöfer, L., Smedt, S. C. D., & Svilenov, H. L. (2026) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2026.104447
Liu, F. C., Mayberry, K. A., Lee, J., Bleiholder, C., & Gunawardena, H. P. (2026) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.6c00316
陈文青, Tu, Y., Wang, K., Xie, R., Yang, P., Gao, Y., & Huang, W. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48080791
Wang, B., Cai, B., Chen, H., Xia, H., Wang, B., Liu, J., Han, L., & Wang, R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.05.742939
Aligning protein-generative models to experimental fitness with ProteinDPO
Widatalla, T., Borah, A. A., King, S. B., Driscoll, C. L., Rafailov, R., & Hie, B. (2026) · Nature Methods · doi:10.1038/s41592-026-03137-3 · Cited by 49
“To this end, we evaluate on a dataset of thermal melting points ( T m ) of 483 clinical and human-derived antibodies from Jain et al. and Shehata et al. 33,34 (Fig.”
Exploring the relationship between natural and cryptic polyreactivity in human antibodies
Lacombe, R. V., Lecerf, M., & Dimitrov, J. D. (2026) · Molecular Immunology · doi:10.1016/j.molimm.2026.08.010
Montefusco-Pereira, C. V. (2026) · Entropic and Disordered Matter · doi:10.3390/edm1010003
“The model should not force a correlation that is absent in the data [24,43,44].”
Erasmus, M. F., Bedinger, D., Hopkins, E., Ferguson, G., Strickler, J., Graff, C. P., Summers, S. R., Capehart, S. L., Slocum, J. D., Richardson, C., et al. (2026) · Nature Biotechnology · doi:10.1038/s41587-026-03238-6 · Cited by 5
Schneider, N., Frank, T., Müller, A., & Meier, C. (2025) · International Journal Of Pharmaceutical Research And Allied Sciences · doi:10.51847/zjqeltofid
Walker, J., Harris, O., & Wilson, G. (2026) · International Journal Of Pharmaceutical Research And Allied Sciences · doi:10.51847/5gtariiafd
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Quantifying molecular specificity in excipient-driven antibody solubilization
Han, Z., Erkamp, N. A., Scrutton, R. M., Licari, G., Predeina, O., Evers, A., Sormanni, P., & Knowles, T. P. J. (2026) · mAbs · doi:10.1080/19420862.2026.2722444
“We first computationally examined a total of 65 clinically relevant mAbs, with substantial overlap with those reported by Jain et al ., 2 including the 14 investigated experimentally in this work.”
Shi, Z., Xu, X., Zhang, H., Ren, S., & Wang, H. (2026) · Swarm and Evolutionary Computation · doi:10.1016/j.swevo.2026.102526
Jiang, S., Ige, M. A., Kan, H. W., Wan, X., Li, J., Zhang, J. Z. H., Zheng, Z., & Zhang, H. (2026) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.6c02385
Predicting non-specific binding of VHHs using machine learning models with cluster-aware validation
Stanev, V., Devalle, F., Boroumand, M., Pouryahya, M., Sermadiras, I., Caldwell, J. G., Chen, K.-L., Jo, J. H., Jain, R., Amofah, B., et al. (2026) · mAbs · doi:10.1080/19420862.2026.2732787
“7 Given the enormous time and resource investment needed to produce material and collect clinical and non-clinical data, there is a clear need to accelerate the process by quickly and efficiently filtering out sequences with undesirable developability profiles.”
Strategy for modular assembly of tetravalent, multispecific antibodies
Mallette, E., Blazer, L. L., Hokanson, C. A., Chen, C., Perez, J. G., Pavlenco, A., Ploder, L., Singer, A. U., Suits, M. D. L., Bhakta, S., et al. (2026) · Protein Science · doi:10.1002/pro.70797
Anew Labs Team, & Liu, K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.20.752967
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“Using five early-stage developability assays curated from historical clinical candidates [23, 29]: accelerated stability under stress (AS; SEC slope), PSR, AC-SINS, an ELISA-based nonspecific-binding readout, and BVP (supplementary table S1), we trained ACeT to classify antibody programs that had…”
InfluentialТрофимова, Е., Shaburova, E. V., Антонец, Д., & Ramensky, V. E. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.09.750540
Hu, R.-S., Ehsan, M., Luo, W., Zhou, J., Xiao, Y., Wang, H.-X., Li, C.-Y., & Gu, K. (2026) · Biomolecules · doi:10.3390/biom16101479
“A high-affinity VHH may still suffer from poor solubility, aggregation, low thermal stability, or inefficient recombinant expression, restricting formulation and scalable production [2,154].”
Schlegel, T. U., de Riz, J. V. B., Riccabona, J. R., Dietzmeyer, F., Leman, J. K., Meiler, J., Schoeder, C. T., & Schiffner, T. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1958625
“Selecting structurally compatible, naturally occurring scaffolds for this process provides a robust starting point for rational engineering, mitigating the risk of instability and reduced therapeutic ef fi cacy associated with entirely arbitrary feature combinations (19, 63 – 69, 112, 113).”
Sakurai, R., Hashimoto, N., Uno, N., Hotta, A., Kazuki, Y., & Tomizuka, K. (2026) · Antibodies · doi:10.3390/antib15060099
Qiu, M., Wang, Z., Liu, X., Wang, H., 华权高, Shu, Q., Luo, S., Niu, M., Ma, F., Huang, F. F., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-78533-6
“In clinical drug development, therapeutic antibody design necessitates ful fi lling multiple biophysical properties 4 .”
Design of full-length agonist and antagonist antibodies for hard targetsPreprint
Aglietti, R. A., Ansari, R., Bowers, P. M., Buelles, T.-H., Chauvin, H., Duplay, T. M., Hibouri, M. E., Jorda, J., Laniado, J., Malago, M. M. A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.21.760573
“Antibodies identified through phage display, for example, can exhibit polyspecificity, self-interaction, and other unfavorable biophysical characteristics [8].”
FAIRsharing record for: ABCD database
FAIRsharing Team (2018) · FAIRsharing.org · doi:10.25504/fairsharing.z8oki5
BindingDB Entry 50019630: The medicinal chemistry evolution of antibody-drug conjugates.
BindingDB (2024) · UC San Diego · doi:10.7270/q2sq94sc
Integrating computational and experimental approaches to identify antigen–specific antibodies
Abbate, M. F., Pereira, P., Toxe, P., Maestrali, N., Gagnaire, M., Vigne, E., Shahsavarian, M. A., Mora, T., & Walczak, A. M. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1951538
“Antibodies derived from both in vitro and in vivo approaches often require optimization to achieve desired binding and functional properties, as well as to address developability liabilities (27 – 30).”
Metadata
- Authors
- Jain, T., Sun, T., Durand, S., Hall, A., Houston, N. R., Nett, J. H., Sharkey, B., Bobrowicz, B., Caffry, I., Yu, Y., Cao, Y., Lynaugh, H., Brown, M., Baruah, H., Gray, L. T., Krauland, E. M., Xu, Y., Vásquez, M., & Wittrup, K. D.
- Affiliations
- Adimab (United States) (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-01-17
- Volume
- 114
- Issue
- 5
- Pages
- 944-949
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5293111
- OpenAlex
- W2578029714
- Cited by
- 629
- References
- 33
- Citations by year
- 2026: 84 · 2025: 75 · 2024: 75 · 2023: 83 · 2022: 80 · 2021: 71 · 2020: 52 · 2019: 58 · 2018: 35 · 2017: 15
- FWCI
- 33.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- therapeutic antibodies, antibody developability, biophysical properties, IgG1 antibodies, antibody engineering, drug-likeness
- MeSH terms
- Amino Acid Sequence, Antibodies, Monoclonal, Humans, Immunoglobulin G, Drug Approval, Biophysical Phenomena, Drug Discovery, HEK293 Cells
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