Soluble ligands as drug targets


  • 1.

    Rask-Andersen, M., Masuram, S. & Schiöth, H. B. The druggable genome: evaluation of drug targets in clinical trials suggests major shifts in molecular class and indication. Annu. Rev. Pharmacol. Toxicol. 54, 9–26 (2014).

    CAS 
    PubMed 

    Google Scholar
     

  • 2.

    Attwood, M. M., Rask-Andersen, M. & Schiöth, H. B. Orphan drugs and their impact on pharmaceutical development. Trends Pharmacol. Sci. 39, 525–535 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 3.

    Hopkins, A. L. & Groom, C. R. The druggable genome. Nat. Rev. Drug Discov. 1, 727–730 (2002).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 4.

    Overington, J. P., Al-Lazikani, B. & Hopkins, A. L. How many drug targets are there? Nat. Rev. Drug Discov. 5, 993–996 (2006).

    CAS 
    PubMed 

    Google Scholar
     

  • 5.

    Santos, R. et al. A comprehensive map of molecular drug targets. Nat. Rev. Drug Discov. 16, 19–34 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 6.

    Kesik-Brodacka, M. Progress in biopharmaceutical development. Biotechnol. Appl. Biochem. 65, 306–322 (2017).

    PubMed 

    Google Scholar
     

  • 7.

    Urquhart, L. Top drugs and companies by sales in 2018. Nat. Rev. Drug Discov. 18, 245–245 (2019).


    Google Scholar
     

  • 8.

    Urquhart, L. Top companies and drugs by sales in 2019. Nat. Rev. Drug Discov. 19, 228–228 (2020).

    CAS 
    PubMed 

    Google Scholar
     

  • 9.

    Lu, R.-M. et al. Development of therapeutic antibodies for the treatment of diseases. J. Biomed. Sci. 27, 1 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 10.

    Sullivan, L. A. & Brekken, R. A. The VEGF family in cancer and antibody-based strategies for their inhibition. MAbs 2, 165–175 (2010).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 11.

    Shim, H. One target, different effects: a comparison of distinct therapeutic antibodies against the same targets. Exp. Mol. Med. 43, 539–549 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 12.

    Giacca, M. & Zacchigna, S. VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond. Gene Ther. 19, 622–629 (2012).

    CAS 
    PubMed 

    Google Scholar
     

  • 13.

    Suragani, R. N. V. S. et al. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat. Med. 20, 408–414 (2014).

    CAS 
    PubMed 

    Google Scholar
     

  • 14.

    Regula, J. T. et al. Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO Mol. Med. 8, 1265–1288 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 15.

    Ricklin, D., Mastellos, D. C., Reis, E. S. & Lambris, J. D. The renaissance of complement therapeutics. Nat. Rev. Nephrol. 14, 26–47 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 16.

    Monaco, C., Nanchahal, J., Taylor, P. & Feldmann, M. Anti-TNF therapy: past, present and future. Int. Immunol. 27, 55–62 (2015).

    CAS 
    PubMed 

    Google Scholar
     

  • 17.

    Apte, R. S., Chen, D. S. & Ferrara, N. VEGF in signaling and disease: beyond discovery and development. Cell 176, 1248–1264 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 18.

    Amadio, M., Govoni, S. & Pascale, A. Targeting VEGF in eye neovascularization: what’s new?: a comprehensive review on current therapies and oligonucleotide-based interventions under development. Pharmacol. Res. 103, 253–269 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 19.

    Bartlett, H. S. & Million, R. P. Targeting the IL-17–TH17 pathway. Nat. Rev. Drug Discov. 14, 11–12 (2015).

    CAS 
    PubMed 

    Google Scholar
     

  • 20.

    Hawkes, J. E., Yan, B. Y., Chan, T. C. & Krueger, J. G. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J. Immunol. 201, 1605–1613 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 21.

    FDA. FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture. http://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-osteoporosis-postmenopausal-women-high-risk-fracture (2019).

  • 22.

    Suen, P. K. & Qin, L. Sclerostin, an emerging therapeutic target for treating osteoporosis and osteoporotic fracture: a general review. J. Orthop. Translat. 4, 1–13 (2016).

    PubMed 

    Google Scholar
     

  • 23.

    Hoy, S. M. Fremanezumab: first global approval. Drugs 78, 1829–1834 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 24.

    Lamb, Y. N. Galcanezumab: first global approval. Drugs 78, 1769–1775 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 25.

    Dhillon, S. Eptinezumab: first approval. Drugs 80, 733–739 (2020).

    CAS 
    PubMed 

    Google Scholar
     

  • 26.

    Edvinsson, L. in Calcitonin Gene-Related Peptide (CGRP) Mechanisms: Focus on Migraine (eds Brain, S. D. & Geppetti, P.) 121–130 (Springer, 2019).

  • 27.

    Edvinsson, L. The CGRP pathway in migraine as a viable target for therapies. Headache J. Head Face Pain 58, 33–47 (2018).


    Google Scholar
     

  • 28.

    Goulet, D. R. & Atkins, W. M. Considerations for the design of antibody-based therapeutics. J. Pharm. Sci. 109, 74–103 (2019).

    PubMed 

    Google Scholar
     

  • 29.

    Igawa, T. et al. Engineering the variable region of therapeutic IgG antibodies. MAbs 3, 243–252 (2011).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 30.

    Pineda, C., Castañeda Hernández, G., Jacobs, I. A., Alvarez, D. F. & Carini, C. Assessing the immunogenicity of biopharmaceuticals. BioDrugs 30, 195–206 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 31.

    Chames, P., Regenmortel, M. V., Weiss, E. & Baty, D. Therapeutic antibodies: successes, limitations and hopes for the future. Br. J. Pharmacol. 157, 220–233 (2009).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 32.

    Brezski, R. J. & Georgiou, G. Immunoglobulin isotype knowledge and application to Fc engineering. Curr. Opin. Immunol. 40, 62–69 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 33.

    Sondermann, P. & Szymkowski, D. E. Harnessing Fc receptor biology in the design of therapeutic antibodies. Curr. Opin. Immunol. 40, 78–87 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 34.

    Tridandapani, S. et al. Regulated expression and inhibitory function of FcγRIIb in human monocytic cells. J. Biol. Chem. 277, 5082–5089 (2002).

    CAS 
    PubMed 

    Google Scholar
     

  • 35.

    Jiang, X.-R. et al. Advances in the assessment and control of the effector functions of therapeutic antibodies. Nat. Rev. Drug Discov. 10, 101–111 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • 36.

    Rother, R. P., Rollins, S. A., Mojcik, C. F., Brodsky, R. A. & Bell, L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat. Biotechnol. 25, 1256–1264 (2007).

    CAS 
    PubMed 

    Google Scholar
     

  • 37.

    Kennedy, P. J., Oliveira, C., Granja, P. L. & Sarmento, B. Monoclonal antibodies: technologies for early discovery and engineering. Crit. Rev. Biotechnol. 38, 394–408 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 38.

    Sheridan, D. et al. Design and preclinical characterization of ALXN1210: a novel anti-C5 antibody with extended duration of action. PLoS ONE 13, 0195909 (2018).


    Google Scholar
     

  • 39.

    Dubois, E. A., Rissmann, R. & Cohen, A. F. Rilonacept and canakinumab. Br. J. Clin. Pharmacol. 71, 639–641 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 40.

    Stewart, M. W. Aflibercept (VEGF Trap-eye): the newest anti-VEGF drug. Br. J. Ophthalmol. 96, 1157–1158 (2012).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 41.

    Perkins, S. L. & Cole, S. W. Ziv-aflibercept (Zaltrap) for the treatment of metastatic colorectal cancer. Ann. Pharmacother. 48, 93–98 (2014).

    PubMed 

    Google Scholar
     

  • 42.

    Shah, D. K. & Betts, A. M. Antibody biodistribution coefficients. MAbs 5, 297–305 (2013).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 43.

    Bates, A. & Power, C. A. David vs. Goliath: the structure, function, and clinical prospects of antibody fragments. Antibodies 8, 28 (2019).

    CAS 
    PubMed Central 

    Google Scholar
     

  • 44.

    Bannas, P., Hambach, J. & Koch-Nolte, F. Nanobodies and nanobody-based human heavy chain antibodies as antitumor therapeutics. Front Immunol 8, 1603 (2017).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 45.

    FDA. FDA approved caplacizumab-yhdp. http://www.fda.gov/drugs/resources-information-approved-drugs/fda-approved-caplacizumab-yhdp (2019).

  • 46.

    Haßel, S. K. & Mayer, G. Aptamers as therapeutic agents: has the initial euphoria subsided? Mol. Diagn. Ther. 23, 301–309 (2019).

    PubMed 

    Google Scholar
     

  • 47.

    Nimjee, S. M., White, R. R., Becker, R. C. & Sullenger, B. A. Aptamers as therapeutics. Annu. Rev. Pharmacol. Toxicol. 57, 61–79 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 48.

    Ali, M. H., Elsherbiny, M. E. & Emara, M. Updates on aptamer research. Int. J. Mol. Sci. 20, 2511 (2019).

    CAS 
    PubMed Central 

    Google Scholar
     

  • 49.

    Ng, E. W. M. et al. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat. Rev. Drug Discov. 5, 123–132 (2006).

    CAS 
    PubMed 

    Google Scholar
     

  • 50.

    Maier, K. E. & Levy, M. From selection hits to clinical leads: progress in aptamer discovery. Mol. Ther. Methods Clin. Dev. 5, 16014 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 51.

    Morita, Y., Leslie, M., Kameyama, H., Volk, D. E. & Tanaka, T. Aptamer therapeutics in cancer: current and future. Cancers 10, 80 (2018).

    PubMed Central 

    Google Scholar
     

  • 52.

    Yu, X., Yang, Y.-P., Dikici, E., Deo, S. K. & Daunert, S. Beyond antibodies as binding partners: the role of antibody mimetics in bioanalysis. Annu. Rev. Anal. Chem. 10, 293–320 (2017).

    CAS 

    Google Scholar
     

  • 53.

    Simeon, R. & Chen, Z. In vitro-engineered non-antibody protein therapeutics. Protein Cell 9, 3–14 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 54.

    Plückthun, A. Designed ankyrin repeat proteins (DARPins): binding proteins for research, diagnostics, and therapy. Annu. Rev. Pharmacol. Toxicol. 55, 489–511 (2015).

    PubMed 

    Google Scholar
     

  • 55.

    Stahl, A. et al. Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications. Angiogenesis 16, 101–111 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • 56.

    Frejd, F. Y. & Kim, K.-T. Affibody molecules as engineered protein drugs. Exp. Mol. Med. 49, e306 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 57.

    Goswami, R. et al. Gene therapy leaves a vicious cycle. Front. Oncol. 9, 297 (2019).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 58.

    Grishanin, R. et al. Preclinical evaluation of ADVM-022, a novel gene therapy approach to treating wet age-related macular degeneration. Mol. Ther. 27, 118–129 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • 59.

    Jiang, D. J., Xu, C. L. & Tsang, S. H. Revolution in gene medicine therapy and genome surgery. Genes 9, 575 (2018).

    PubMed Central 

    Google Scholar
     

  • 60.

    Guimaraes, T. A. C., de, Georgiou, M., Bainbridge, J. W. B. & Michaelides, M. Gene therapy for neovascular age-related macular degeneration: rationale, clinical trials and future directions. Br. J. Ophthalmol. https://doi.org/10.1136/bjophthalmol-2020-316195 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • 61.

    Anguela, X. M. & High, K. A. Entering the modern era of gene therapy. Annu. Rev. Med. 70, 273–288 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • 62.

    Hollingsworth, R. E. & Jansen, K. Turning the corner on therapeutic cancer vaccines. NPJ Vaccines 4, 1–10 (2019).


    Google Scholar
     

  • 63.

    Nakagami, H. & Morishita, R. Recent advances in therapeutic vaccines to treat hypertension. Hypertension 72, 1031–1036 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 64.

    Rosell, R. et al. Pathway targeted immunotherapy: rationale and evidence of durable clinical responses with a novel, EGF-directed agent for advanced NSCLC. J. Thorac. Oncol. 11, 1954–1961 (2016).


    Google Scholar
     

  • 65.

    Bennett, C. F., Baker, B. F., Pham, N., Swayze, E. & Geary, R. S. Pharmacology of antisense drugs. Annu. Rev. Pharmacol. Toxicol. 57, 81–105 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • 66.

    Setten, R. L., Rossi, J. J. & Han, S. The current state and future directions of RNAi-based therapeutics. Nat. Rev. Drug Discov. 18, 421–446 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 67.

    Rupaimoole, R. & Slack, F. J. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov. 16, 203–222 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • 68.

    Leavitt, B. et al. Discovery and early clinical development of ISIS-HTTRx, the first HTT-lowering drug to be tested in patients with Huntington’s disease (PL01.002). Neurology 86, PL01.002 (2016).


    Google Scholar
     

  • 69.

    Chakraborty, C., Sharma, A. R., Sharma, G., Doss, C. G. P. & Lee, S.-S. Therapeutic miRNA and siRNA: moving from bench to clinic as next generation medicine. Mol. Ther. Nucleic Acids 8, 132–143 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 70.

    Uijl, E. et al. A3941 long-lasting small interfering RNA targeting angiotensinogen induces a robust and durable antihypertensive effect. J. Hypertens. 36, e17 (2018).


    Google Scholar
     

  • 71.

    Neilsen, P. M. et al. Mutant p53 drives invasion in breast tumors through up-regulation of miR-155. Oncogene 32, 2992–3000 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • 72.

    Querfeld, C. et al. Preliminary results of a phase 1 trial evaluating MRG-106, a synthetic microRNA antagonist (LNA antimiR) of microRNA-155, in patients with CTCL. Blood 128, 1829–1829 (2016).


    Google Scholar
     

  • 73.

    Kim, J. W. & Cochran, J. R. Targeting ligand–receptor interactions for development of cancer therapeutics. Curr. Opin. Chem. Biol. 38, 62–69 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • 74.

    Sandercock, C. G. & Storz, U. Antibody specification beyond the target: claiming a later-generation therapeutic antibody by its target epitope. Nat. Biotechnol. 30, 615–618 (2012).

    CAS 
    PubMed 

    Google Scholar
     

  • 75.

    Nakayamada, S. & Tanaka, Y. BAFF- and APRIL-targeted therapy in systemic autoimmune diseases. Inflamm. Regen. 36, 6 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 76.

    Matsumoto, H. et al. Membrane-bound and soluble Fas ligands have opposite functions in photoreceptor cell death following separation from the retinal pigment epithelium. Cell Death Dis. 6, e1986 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 77.

    Genovese, M. C. et al. A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Arthritis Rheumatol. 66, 1693–1704 (2014).

    CAS 

    Google Scholar
     

  • 78.

    Martin, D. A. et al. A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis. Arthritis Res. Ther. 15, R164 (2013).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 79.

    Pavelka, K. et al. A study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with rheumatoid arthritis and an inadequate response to methotrexate. J. Rheumatol. 42, 912–919 (2015).

    CAS 
    PubMed 

    Google Scholar
     

  • 80.

    Beringer, A., Noack, M. & Miossec, P. IL-17 in chronic inflammation: from discovery to targeting. Trends Mol. Med. 22, 230–241 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 81.

    FDA. FDA approves novel preventive treatment for migraine. http://www.fda.gov/news-events/press-announcements/fda-approves-novel-preventive-treatment-migraine (2019).

  • 82.

    Przepiorka, D. et al. FDA approval: blinatumomab. Clin. Cancer Res. 21, 4035–4039 (2015).

    CAS 
    PubMed 

    Google Scholar
     

  • 83.

    Labrijn, A. F., Janmaat, M. L., Reichert, J. M. & Parren, P. W. H. I. Bispecific antibodies: a mechanistic review of the pipeline. Nat. Rev. Drug Discov. 18, 585–608 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • 84.

    Brinkmann, U. & Kontermann, R. E. The making of bispecific antibodies. MAbs 9, 182–212 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 85.

    Mullard, A. Bispecific antibody pipeline moves beyond oncology. Nat. Rev. Drug Discov. 16, 666–668 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • 86.

    Jimeno, A. et al. A first-in-human phase 1a study of the bispecific anti-DLL4/anti-VEGF antibody navicixizumab (OMP-305B83) in patients with previously treated solid tumors. Invest. New Drugs 37, 461–472 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • 87.

    Egan, T. J. et al. Novel multispecific heterodimeric antibody format allowing modular assembly of variable domain fragments. MAbs 9, 68–84 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 88.

    Levin, A. D., Wildenberg, M. E., Brink, V. D. & R, G. Mechanism of action of anti-TNF therapy in inflammatory bowel disease. J. Crohns Colitis 10, 989–997 (2016).

    PubMed 

    Google Scholar
     

  • 89.

    Sandborn, W. J. et al. Etanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology 121, 1088–1094 (2001).

    CAS 
    PubMed 

    Google Scholar
     

  • 90.

    Mitoma, H., Horiuchi, T., Tsukamoto, H. & Ueda, N. Molecular mechanisms of action of anti-TNF-α agents – comparison among therapeutic TNF-α antagonists. Cytokine 101, 56–63 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 91.

    Kirchner, S., Holler, E., Haffner, S., Andreesen, R. & Eissner, G. Effect of different tumor necrosis factor (TNF) reactive agents on reverse signaling of membrane integrated TNF in monocytes. Cytokine 28, 67–74 (2004).

    CAS 
    PubMed 

    Google Scholar
     

  • 92.

    Scallon, B. J., Moore, M. A., Trinh, H., Knight, D. M. & Ghrayeb, J. Chimeric anti-TNF-α monoclonal antibody cA2 binds recombinant transmembrane TNF-α and activates immune effector functions. Cytokine 7, 251–259 (1995).

    CAS 
    PubMed 

    Google Scholar
     

  • 93.

    Xin, L. et al. Dual regulation of soluble tumor necrosis factor-α induced activation of human monocytic cells via modulating transmembrane TNF-α-mediated ‘reverse signaling’. Int. J. Mol. Med. 18, 885–892 (2006).

    CAS 
    PubMed 

    Google Scholar
     

  • 94.

    Ringheanu, M. et al. Effects of infliximab on apoptosis and reverse signaling of monocytes from healthy individuals and patients with Crohn’s disease. Inflamm. Bowel Dis. 10, 801–810 (2004).

    PubMed 

    Google Scholar
     

  • 95.

    Toedter, G. et al. Genes associated with intestinal permeability in ulcerative colitis: changes in expression following infliximab therapy. Inflamm. Bowel Dis. 18, 1399–1410 (2012).

    PubMed 

    Google Scholar
     

  • 96.

    Vos, A. C. W. et al. Regulatory macrophages induced by infliximab are involved in healing in vivo and in vitro. Inflamm. Bowel Dis. 18, 401–408 (2012).

    PubMed 

    Google Scholar
     

  • 97.

    Olesen, C. M., Coskun, M., Peyrin-Biroulet, L. & Nielsen, O. H. Mechanisms behind efficacy of tumor necrosis factor inhibitors in inflammatory bowel diseases. Pharmacol. Ther. 159, 110–119 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 98.

    Yamazaki, H. et al. Certolizumab pegol for induction of remission in Crohn’s disease. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD012893.pub2 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • 99.

    Ueda, N. et al. The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor α. Inflamm. Bowel Dis. 19, 1224–1231 (2013).

    PubMed 

    Google Scholar
     

  • 100.

    Tracey, D., Klareskog, L., Sasso, E. H., Salfeld, J. G. & Tak, P. P. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol. Ther. 117, 244–279 (2008).

    CAS 
    PubMed 

    Google Scholar
     

  • 101.

    Guo, Q. et al. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 6, 15 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 102.

    Brennan, F. M. & McInnes, I. B. Evidence that cytokines play a role in rheumatoid arthritis. J. Clin. Invest. 118, 3537–3545 (2008).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 103.

    Calmon-Hamaty, F., Combe, B., Hahne, M. & Morel, J. Lymphotoxin α stimulates proliferation and pro-inflammatory cytokine secretion of rheumatoid arthritis synovial fibroblasts. Cytokine 53, 207–214 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • 104.

    Devine, E. B., Alfonso-Cristancho, R. & Sullivan, S. D. Effectiveness of biologic therapies for rheumatoid arthritis: an indirect comparisons approach. Pharmacotherapy 31, 39–51 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • 105.

    Gartlehner, G., Hansen, R. A., Jonas, B. L., Thieda, P. & Lohr, K. N. The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis: a systematic review and metaanalysis. J. Rheumatol. 33, 2398–2408 (2006).

    CAS 
    PubMed 

    Google Scholar
     

  • 106.

    Yang, S., Zhao, J. & Sun, X. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des. Devel. Ther. 10, 1857–1867 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 107.

    Gaudreault, J., Fei, D., Rusit, J., Suboc, P. & Shiu, V. Preclinical pharmacokinetics of ranibizumab (rhuFabV2) after a single intravitreal administration. Invest. Ophthalmol. Vis. Sci. 46, 726–733 (2005).

    PubMed 

    Google Scholar
     

  • 108.

    Gaudreault, J. et al. Preclinical pharmacology and safety of ESBA1008, a single-chain antibody fragment, investigated as potential treatment for age related macular degeneration. Invest. Ophthalmol. Vis. Sci. 53, 3025–3025 (2012).


    Google Scholar
     

  • 109.

    Schmid, M. K. et al. Efficacy and adverse events of aflibercept, ranibizumab and bevacizumab in age-related macular degeneration: a trade-off analysis. Br. J. Ophthalmol. 99, 141–146 (2015).

    PubMed 

    Google Scholar
     

  • 110.

    Zhang, Y., Chioreso, C., Schweizer, M. L. & Abràmoff, M. D. Effects of Aflibercept for neovascular age-related macular degeneration: a systematic review and meta-analysis of observational comparative studies. Invest. Ophthalmol. Vis. Sci. 58, 5616–5627 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 111.

    Sharma, A., Kumar, N., Kuppermann, B. D., Loewenstein, A. & Bandello, F. Brolucizumab: is extended VEGF suppression on the horizon? Eye 34, 424–426 (2020).

    PubMed 

    Google Scholar
     

  • 112.

    Dugel, P. U. et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 127, 72–84 (2020).

    PubMed 

    Google Scholar
     

  • 113.

    Bordet, T. & Behar-Cohen, F. Ocular gene therapies in clinical practice: viral vectors and nonviral alternatives. Drug Discov. Today https://doi.org/10.1016/j.drudis.2019.05.038 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • 114.

    Carter, P. J. & Lazar, G. A. Next generation antibody drugs: pursuit of the ‘high-hanging fruit’. Nat. Rev. Drug Discov. 17, 197–223 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 115.

    Neves, V., Aires-da-Silva, F., Corte-Real, S. & Castanho, M. A. R. B. Antibody approaches to treat brain diseases. Trends Biotechnol. 34, 36–48 (2016).

    CAS 

    Google Scholar
     

  • 116.

    Erdő, F., Bors, L. A., Farkas, D., Bajza, Á. & Gizurarson, S. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res. Bull. 143, 155–170 (2018).

    PubMed 

    Google Scholar
     

  • 117.

    Crowe, J. S. et al. Preclinical development of a novel, orally-administered anti-tumour necrosis factor domain antibody for the treatment of inflammatory bowel disease. Sci. Rep. 8, 4941 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 118.

    Burgess, G. et al. Randomized study of the safety and pharmacodynamics of inhaled interleukin-13 monoclonal antibody fragment VR942. EBioMedicine 35, 67–75 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 119.

    Miller, A. H. & Raison, C. L. Are anti-inflammatory therapies viable treatments for psychiatric disorders?: Where the rubber meets the road. JAMA Psychiatry 72, 527–528 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 120.

    Goldsmith, D., Rapaport, M. & Miller, B. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol. Psychiatry 21, 1696–1709 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 121.

    Wittenberg, G. M. et al. Effects of immunomodulatory drugs on depressive symptoms: a mega-analysis of randomized, placebo-controlled clinical trials in inflammatory disorders. Mol. Psychiatry 25, 1275–1285 (2020).

    CAS 
    PubMed 

    Google Scholar
     

  • 122.

    Vabret, N. et al. Immunology of COVID-19: current state of the science. Immunity https://doi.org/10.1016/j.immuni.2020.05.002 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 123.

    Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 124.

    McGrath, N. A., Brichacek, M. & Njardarson, J. T. A graphical journey of innovative organic architectures that have improved our lives. J. Chem. Educ. 87, 1348–1349 (2010).

    CAS 

    Google Scholar
     

  • 125.

    Oprea, T. I. et al. Unexplored therapeutic opportunities in the human genome. Nat. Rev. Drug Discov. 17, 317–332 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 126.

    Malik, A. & Urquhart, L. EvaluatePharma World Preview 2018, outlook to 2024. http://info.evaluategroup.com/WP2018-EPV.html (2018).

  • 127.

    Urquhart, L. FDA new drug approvals in Q2 2019. Nat. Rev. Drug Discov. 18, 575–575 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • 128.

    Harding, S. D. et al. The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY. Nucleic Acids Res. 46, D1091–D1106 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 129.

    Igawa, T., Haraya, K. & Hattori, K. Sweeping antibody as a novel therapeutic antibody modality capable of eliminating soluble antigens from circulation. Immunol. Rev. 270, 132–151 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 130.

    Rask-Andersen, M., Almén, M. S. & Schiöth, H. B. Trends in the exploitation of novel drug targets. Nat. Rev. Drug Discov. 10, 579–590 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • 131.

    Wishart, D. S. et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 46, D1074–D1082 (2018).

    CAS 
    PubMed 

    Google Scholar
     



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