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false;" target="_blank" rel="nofollow" class="nolightbox essb-s-bg-flipboard essb-s-bgh-flipboard essb-s-c-light essb-s-hover-effect essb-s-bg-network essb-s-bgh-network" ><span class="essb_icon essb_icon_flipboard"></span><span class="essb_network_name">Flipboard</span></a></li></ul></div></div></div> <div class="essb_morepopup_shadow essb_morepopup_shadow_636335496" onclick="essb.toggle_less_popup('636335496'); return false;"></div></div> <div id="meta2"><p>Posted: 5 November 2024 | <a href="https://www.drugtargetreview.com/content_author/john-cardone-bio-rad-laboratories/" rel="tag">John Cardone (Bio-Rad Laboratories)</a> | <a href="https://www.drugtargetreview.com/article/152235/the-essential-role-of-recombinant-phage-display-antibody-libraries/#respond" class="comments-link" >No comments yet</a></p> </div> <div class="excerpt"><p>The emergence of new antibody-based therapeutics, such as antibody-drug conjugates, alongside a continued drive towards alternatives to animal testing approaches, highlights the need for precise and sensitive tools enabling the identification and characterisation of the best drug candidates for clinical progression. Capable of keeping up with the evolving drug development field, recombinant antibody phage display libraries provide flexibility to support new technologies and complex drug modalities in preclinical research.</p> </div> <div class="articleImage"> <img data-lazyloaded="1" src="data:image/gif;base64,R0lGODdhAQABAPAAAMPDwwAAACwAAAAAAQABAAACAkQBADs=" width="750" height="500" data-src="https://www.drugtargetreview.com/wp-content/uploads/shutterstock_2181578479-750x500.jpg" class="attachment-large-rectangle size-large-rectangle wp-post-image" alt="antibodies" decoding="async" fetchpriority="high" data-srcset="https://www.drugtargetreview.com/wp-content/uploads/shutterstock_2181578479-750x500.jpg 750w, https://www.drugtargetreview.com/wp-content/uploads/shutterstock_2181578479-375x250.jpg 375w, https://www.drugtargetreview.com/wp-content/uploads/shutterstock_2181578479-200x134.jpg 200w" data-sizes="(max-width: 750px) 100vw, 750px" /><noscript><img width="750" height="500" src="https://www.drugtargetreview.com/wp-content/uploads/shutterstock_2181578479-750x500.jpg" class="attachment-large-rectangle size-large-rectangle wp-post-image" alt="antibodies" decoding="async" fetchpriority="high" srcset="https://www.drugtargetreview.com/wp-content/uploads/shutterstock_2181578479-750x500.jpg 750w, https://www.drugtargetreview.com/wp-content/uploads/shutterstock_2181578479-375x250.jpg 375w, https://www.drugtargetreview.com/wp-content/uploads/shutterstock_2181578479-200x134.jpg 200w" sizes="(max-width: 750px) 100vw, 750px" /></noscript></div>   <p>Since the 1970s, when hybridoma technology enabling the generation of monoclonal antibodies (mAbs) was first developed,<sup>1</sup> antibody-based therapeutics have become one of the most rapidly growing drug categories, with applications across cancer indications, immune disorders and infections. In 2024 alone, almost 50 antibody drug candidates are anticipated to enter regulatory review, the majority of which are mAbs.<sup>2</sup> The industry has also started to embrace novel innovative antibody-based drug modalities, with the inclusion of numerous bispecific antibodies and antibody-drug conjugates (ADCs), for lung and breast cancer respectively, as well as a mixture of two immunocytokines for skin cancer.</p> <p>Aside from the advent of complex antibody-based drugs, the industry is facing some additional changes which are shaping drug development. Recently, the FDA announced that new medicines need not be tested in animals to receive regulatory approval.<sup>3</sup> This change signals a major shift away from animal use in drug safety regulation and encourages the use of alternative methods like organ-on-chip or other animal-free technologies.</p> <p>In light of these key developments, the need for flexible yet highly specific and sensitive tools that provide vital information on a drug’s safety and efficacy are essential to help determine the best drug candidates for preclinical and clinical progression.</p><div class="drugt-c1b85c1c4b187aa472466f00664f85f5 drugt-content" id="drugt-c1b85c1c4b187aa472466f00664f85f5"></div> <h2>Overcoming traditional antibody generation limitations with recombinant technologies</h2> <p>Antibodies remain essential tools in this ever-changing field for preclinical bioanalysis and drug monitoring through ligand-binding assays (LBAs). These assays may include pharmacokinetic (PK) assays, which provide information on the drug’s properties, and immunogenicity assays for the detection of anti-drug antibodies (ADA), which can lead to adverse events and reduced efficacy. When the drug is a human or humanised monoclonal antibody, developing drug monitoring assays presents specific challenges due to the abundance of human antibodies in patient serum. Therefore, PK assays require highly specific detection reagents that can bind to the drug without interacting with similar immunoglobulin molecules. Additionally, a well-designed ADA assay needs a highly specific reference antibody to measure the anti-drug response accurately.</p> <p>While polyclonal antibodies are cost-effective, their batch-to-batch variability leads to inconsistent results.<sup>4</sup> mAbs offer better consistency, but a study found that nearly a third of hybridoma cell lines contained extra heavy or light chains, compromising their reliability.<sup>5</sup> Additionally, genetic drift in hybridoma cell lines can lead to loss of antibody binding or expression over time. Anti-idiotypic antibodies (which specifically target the idiotope of another antibody) are considered optimal for PK assays and as surrogate positive controls or reference standards in ADA assays.<sup>6</sup> However, traditional sources like rodent monoclonal anti-idiotypic antibodies and primate polyclonal serum pose several challenges. Identifying rare specificities for drug-target complex-specific antibodies and determining the affinities of immunoglobulin G (IgG) antibodies generated through immunisation is particularly difficult. Moreover, ethical considerations regarding the use of laboratory animals further complicate the use of primate polyclonal serum, and successful immunisation is not always guaranteed.</p> <p>The creation of sophisticated human antibody libraries covering a vast immune repertoire through <em>de novo</em> synthesis, such as HuCAL (human combinatorial antibody library),<sup>7</sup> combined with phage display technology and optimised for <em>in vitro</em> expression, have revolutionised the development of recombinant monoclonal anti-idiotypic antibodies.<sup>8</sup> These libraries enable the generation of antibodies enhancing biotherapeutic analysis during preclinical and clinical development and routine drug monitoring, while also addressing common antibody production challenges. Generated using entirely <em>in vitro</em> processes, recombinant anti-idiotypic antibodies offer greater predictability, flexibility and optimisation potential, ensuring a long-term supply of sequence-defined, fully human antibodies without the use of animal-derived components or laboratory animals.<sup>8</sup> <em>In vitro</em> selection methods also enable the isolation of antibodies targeting specific epitopes, including phosphorylated residues or point mutations, for precise detection or inhibition of target molecules, and address ethical concerns relating to animal immunisation with toxins in ADC development.</p> <h2>Innovations in anti-idiotypic antibody development and diverse applications</h2> <p>Phage display libraries and guided selection strategies have successfully generated anti-idiotypic antibodies with varying affinities and different binding modes specific to different forms of antibody drugs (eg, free, target-bound) (Figure 1).<sup>8</sup> Selection in the presence of isotype subclass-matched antibodies produces paratope-specific (ie, antigen-binding site-specific) anti-idiotypic antibodies, termed Type 1, which inhibit drug-target binding and are useful for measuring free drug concentrations and as positive controls in ADA assays. Alternatively, non-inhibitory anti-idiotypic antibodies, termed Type 2, are selected for idiotope specificity outside the antigen-binding site, detecting total drug-free, partially bound and fully bound. Through refined guided selection strategies, drug-target complex-specific antibodies, termed Type 3, can be selected by using the drug-target-bound antibody as bait and blocking the library with individual complex components. Finally, Type 4 antibodies bind to a complex between a drug antibody and a Type 1 antibody.</p> <div class="wp-block-image"><img data-lazyloaded="1" src="data:image/gif;base64,R0lGODdhAQABAPAAAMPDwwAAACwAAAAAAQABAAACAkQBADs=" decoding="async" class="wpa-warning wpa-image-missing-alt aligncenter wp-image-152237 size-full" data-src="https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1.png" alt="lternative binding modes of anti-idiotypic antibodies generated using an antibody phage display library in combination with guided in vitro selection. Adapted from Harth S et al. (8) under a CC BY-NC-ND 4.0." width="2885" height="1287" data-warning="Missing alt text" data-srcset="https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1.png 2885w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-375x167.png 375w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-750x335.png 750w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-768x343.png 768w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-1536x685.png 1536w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-2048x914.png 2048w" data-sizes="(max-width: 2885px) 100vw, 2885px" /><noscript><img decoding="async" class="wpa-warning wpa-image-missing-alt aligncenter wp-image-152237 size-full" src="https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1.png" alt="lternative binding modes of anti-idiotypic antibodies generated using an antibody phage display library in combination with guided in vitro selection. Adapted from Harth S et al. (8) under a CC BY-NC-ND 4.0." width="2885" height="1287" data-warning="Missing alt text" srcset="https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1.png 2885w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-375x167.png 375w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-750x335.png 750w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-768x343.png 768w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-1536x685.png 1536w, https://www.drugtargetreview.com/wp-content/uploads/Bio-Rad_DTR_Figure-1-2048x914.png 2048w" sizes="(max-width: 2885px) 100vw, 2885px" /></noscript></div> <p><strong>Figure 1.</strong> Alternative binding modes of anti-idiotypic antibodies generated using an antibody phage display library in combination with guided <em>in vitro</em> selection. Adapted from Harth S <em>et al</em>. (8) under a CC BY-NC-ND 4.0.</p> <p>This comprehensive toolbox of Type 1, Type 2, Type 3 and Type 4 anti-idiotypic antibodies provides PK and ADA assay developers with enhanced flexibility for a thorough analysis of antibody candidates. For example, Type 3 antibodies with antigen-capture ELISA enable detection of monovalent Fab fragments, such as ranibizumab, which is otherwise undetectable using Type 1 antibodies in an ELISA bridging format due to its single binding domain.<sup>8</sup></p> <h2>Keeping up with evolving strategies in preclinical bioanalysis</h2> <p>Recombinant anti-idiotypic antibodies, generated <em>in vitro</em> through sophisticated antibody libraries in combination with phage display technology, provide a reproducible, long-term supply of highly sensitive and specific detection reagents and controls needed for preclinical assays. These antibodies ensure predictability, flexibility and optimisation potential, addressing common production challenges, while eliminating the need for animal-derived components.</p> <h2>References</h2> <ol> <li>Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. <em>Nature</em>. 1975 Aug;256(5517):495–7.</li> <li>Crescioli S, Kaplon H, Chenoweth A, <em>et al</em>. Antibodies to watch in 2024. <em>mAbs</em>. 2024 Jan 5;16(1).</li> <li>‌Wadman M. FDA no longer needs to require animal tests before human drug trials [Internet]. www.science.org. 2023. Available from: https://www.science.org/content/article/fda-no-longer-needs-require-animal-tests-human-drug-trials</li> <li>‌Baker M. Reproducibility crisis: Blame it on the antibodies. <em>Nature</em>. 2015 May;521(7552):274–6.</li> <li>‌Bradbury ARM, Trinklein ND, Thie H, <em>et al</em>. When monoclonal antibodies are not monospecific: Hybridomas frequently express additional functional variable regions. <em>mAbs</em>. 2018;10(4):539–46.</li> <li>‌Harth S, Frisch C. Recombinant Anti-idiotypic Antibodies in Ligand Binding Assays for Antibody Drug Development. <em>Methods in Molecular Biology</em>. 2021;291–306.</li> <li>Prassler J, Thiel S, Pracht C, <em>et al</em>. HuCAL PLATINUM, a Synthetic Fab Library Optimized for Sequence Diversity and Superior Performance in Mammalian Expression Systems. <em>Journal of Molecular Biology</em>. 2011 Oct 1;413(1):261–78.</li> <li>‌‌Harth S, Ten Haaf A, Loew C, <em>et al</em>. Generation by phage display and characterization of drug-target complex-specific antibodies for pharmacokinetic analysis of biotherapeutics. <em>mAbs</em>. 2018 Dec 5;11(1):178–90.</li> </ol> <div class="box"> <p><strong>About the author</strong></p> <p><strong>John Cardone, PhD, Marketing Manager – Custom Antibodies at Bio-Rad Laboratories</strong></p> <p>John Cardone is the Marketing Manager for Bio-Rad’s Custom Antibody Services. He manages the Pioneer™ Antibody Discovery Platform for biotherapeutic lead generation and the HuCAL® service for bioanalytical antibodies. Prior to this, he worked at an <em>in vitro</em> immuno-diagnostic company as Strategic Marketing Manager. John holds a PhD in immunology from Kings College London and an MBA from Warwick Business School, both in the UK.</p> </div> <div id="taxos2"> <div class="terms"><p>Related topics<br /><a href="https://www.drugtargetreview.com/topic/antibodies/" rel="tag">Antibodies</a>, <a href="https://www.drugtargetreview.com/topic/assays/" rel="tag">Assays</a>, <a href="https://www.drugtargetreview.com/topic/drug-development/" rel="tag">Drug Development</a>, <a href="https://www.drugtargetreview.com/topic/in-vitro/" rel="tag">In Vitro</a></p></div> <div class="terms"><p>Related organisations<br /><a href="https://www.drugtargetreview.com/organisations/bio-rad-laboratories/" rel="tag">Bio-Rad Laboratories</a></p></div> <div class="terms"><p>Related people<br /><a href="https://www.drugtargetreview.com/people/john-cardone-bio-rad-laboratories/" rel="tag">John Cardone (Bio-Rad Laboratories)</a></p></div></div> </article>    <div id="sidebarFallback1" class="bodyMpu"> <div id="group3"> <div class="randomordercontent group3">  <div id="ad20"></div> <script data-cfasync="false" src="/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js"></script><script type="text/javascript"> jQuery(document).ready(function() { var cur_width = jQuery(document).width(); 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View our <a href="/cookie-policy/">Cookie Policy</a> page.</p></div> </div> <a id="wt-cli-privacy-readmore" tabindex="0" role="button" class="cli-privacy-readmore" data-readmore-text="Show more" data-readless-text="Show less"></a> </div> </div> <div class="cli-col-12 cli-align-items-stretch cli-px-0 cli-tab-section-container" role="tablist"> <div class="cli-tab-section"> <div class="cli-tab-header"> <a id="wt-cli-tab-link-necessary" tabindex="0" role="tab" aria-expanded="false" aria-describedby="wt-cli-tab-necessary" aria-controls="wt-cli-tab-necessary" class="cli-nav-link cli-settings-mobile" data-target="necessary" data-toggle="cli-toggle-tab"> Necessary </a> <div class="wt-cli-necessary-checkbox"> <input type="checkbox" class="cli-user-preference-checkbox" id="wt-cli-checkbox-necessary" aria-label="Necessary" data-id="checkbox-necessary" checked="checked" /> <label class="form-check-label" for="wt-cli-checkbox-necessary"> Necessary </label> </div> <span class="cli-necessary-caption"> Always Enabled </span> </div> <div class="cli-tab-content"> <div id="wt-cli-tab-necessary" tabindex="0" role="tabpanel" aria-labelledby="wt-cli-tab-link-necessary" class="cli-tab-pane cli-fade" data-id="necessary"> <div class="wt-cli-cookie-description"><p>Necessary cookies enable the core functionality of the website, including security, network management and accessibility. These cookies do not store any personal information. You may disable these by changing your browser settings, but this may affect how the website functions.</p> <p><table class="wt-cli-element cookielawinfo-row-cat-table cookielawinfo-winter"><thead><tr><th scope="col" class="cookielawinfo-column-1">Cookie</th><th scope="col" class="cookielawinfo-column-2">Type</th><th scope="col" class="cookielawinfo-column-3">Duration</th><th scope="col" class="cookielawinfo-column-4">Description</th></tr></thead><tbody><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">cookielawinfo-checkbox-advertising-targeting</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Advertising & Targeting".</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">cookielawinfo-checkbox-analytics</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">This cookie is set by GDPR Cookie Consent WordPress Plugin. The cookie is used to remember the user consent for the cookies under the category "Analytics".</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">cookielawinfo-checkbox-necessary</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Necessary".</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">cookielawinfo-checkbox-performance</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">This cookie is set by GDPR Cookie Consent WordPress Plugin. The cookie is used to remember the user consent for the cookies under the category "Performance".</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">PHPSESSID</td><td class="cookielawinfo-column-2">session</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">This cookie is native to PHP applications. The cookie is used to store and identify a users' unique session ID for the purpose of managing user session on the website. The cookie is a session cookies and is deleted when all the browser windows are closed.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">viewed_cookie_policy</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">The cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. It does not store any personal data.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">zmember_logged</td><td class="cookielawinfo-column-2">session</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">This session cookie is served by our membership/subscription system and controls whether you are able to see content which is only available to logged in users.</td></tr></tbody></table></p></div> </div> </div> </div> <div class="cli-tab-section"> <div class="cli-tab-header"> <a id="wt-cli-tab-link-advertising-targeting" tabindex="0" role="tab" aria-expanded="false" aria-describedby="wt-cli-tab-advertising-targeting" aria-controls="wt-cli-tab-advertising-targeting" class="cli-nav-link cli-settings-mobile" data-target="advertising-targeting" data-toggle="cli-toggle-tab"> Advertising & Targeting </a> <div class="cli-switch"> <input type="checkbox" class="cli-user-preference-checkbox" id="wt-cli-checkbox-advertising-targeting" aria-label="advertising-targeting" data-id="checkbox-advertising-targeting" role="switch" aria-controls="wt-cli-tab-link-advertising-targeting" aria-labelledby="wt-cli-tab-link-advertising-targeting" checked='checked' /> <label for="wt-cli-checkbox-advertising-targeting" class="cli-slider" data-cli-enable="Enabled" data-cli-disable="Disabled"><span class="wt-cli-sr-only">advertising-targeting</span></label> </div> </div> <div class="cli-tab-content"> <div id="wt-cli-tab-advertising-targeting" tabindex="0" role="tabpanel" aria-labelledby="wt-cli-tab-link-advertising-targeting" class="cli-tab-pane cli-fade" data-id="advertising-targeting"> <div class="wt-cli-cookie-description"><p>Advertising and targeting cookies help us provide our visitors with relevant ads and marketing campaigns.</p> <p><table class="wt-cli-element cookielawinfo-row-cat-table cookielawinfo-winter"><thead><tr><th scope="col" class="cookielawinfo-column-1">Cookie</th><th scope="col" class="cookielawinfo-column-2">Type</th><th scope="col" class="cookielawinfo-column-3">Duration</th><th scope="col" class="cookielawinfo-column-4">Description</th></tr></thead><tbody><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">advanced_ads_browser_width</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 month</td><td class="cookielawinfo-column-4">This cookie is set by Advanced Ads and measures the browser width.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">advanced_ads_page_impressions</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">2 years</td><td class="cookielawinfo-column-4">This cookie is set by Advanced Ads and measures the number of previous page impressions.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">advanced_ads_pro_server_info</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 month</td><td class="cookielawinfo-column-4">This cookie is set by Advanced Ads and sets geo-location, user role and user capabilities. It is used by cache busting in Advanced Ads Pro when the appropriate visitor conditions are used.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">advanced_ads_pro_visitor_referrer</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">This cookie is set by Advanced Ads and sets the referrer URL.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">bscookie</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">2 years</td><td class="cookielawinfo-column-4">This cookie is a browser ID cookie set by LinkedIn share Buttons and ad tags.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">IDE</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">2 years</td><td class="cookielawinfo-column-4">This cookie is set by Google DoubleClick and stores information about how the user uses the website and any other advertisement before visiting the website. This is used to present users with ads that are relevant to them according to the user profile.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">li_sugr</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">3 months</td><td class="cookielawinfo-column-4">This cookie is set by LinkedIn and is used for tracking.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">UserMatchHistory</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 month</td><td class="cookielawinfo-column-4">This cookie is set by Linkedin and is used to track visitors on multiple websites, in order to present relevant advertisement based on the visitor's preferences.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">VISITOR_INFO1_LIVE</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">5 months</td><td class="cookielawinfo-column-4">This cookie is set by YouTube. Used to track the information of the embedded YouTube videos on a website.</td></tr></tbody></table></p></div> </div> </div> </div> <div class="cli-tab-section"> <div class="cli-tab-header"> <a id="wt-cli-tab-link-analytics" tabindex="0" role="tab" aria-expanded="false" aria-describedby="wt-cli-tab-analytics" aria-controls="wt-cli-tab-analytics" class="cli-nav-link cli-settings-mobile" data-target="analytics" data-toggle="cli-toggle-tab"> Analytics </a> <div class="cli-switch"> <input type="checkbox" class="cli-user-preference-checkbox" id="wt-cli-checkbox-analytics" aria-label="analytics" data-id="checkbox-analytics" role="switch" aria-controls="wt-cli-tab-link-analytics" aria-labelledby="wt-cli-tab-link-analytics" checked='checked' /> <label for="wt-cli-checkbox-analytics" class="cli-slider" data-cli-enable="Enabled" data-cli-disable="Disabled"><span class="wt-cli-sr-only">analytics</span></label> </div> </div> <div class="cli-tab-content"> <div id="wt-cli-tab-analytics" tabindex="0" role="tabpanel" aria-labelledby="wt-cli-tab-link-analytics" class="cli-tab-pane cli-fade" data-id="analytics"> <div class="wt-cli-cookie-description"><p>Analytics cookies collect information about your use of the content, and in combination with previously collected information, are used to measure, understand, and report on your usage of this website.</p> <p><table class="wt-cli-element cookielawinfo-row-cat-table cookielawinfo-winter"><thead><tr><th scope="col" class="cookielawinfo-column-1">Cookie</th><th scope="col" class="cookielawinfo-column-2">Type</th><th scope="col" class="cookielawinfo-column-3">Duration</th><th scope="col" class="cookielawinfo-column-4">Description</th></tr></thead><tbody><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">bcookie</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">2 years</td><td class="cookielawinfo-column-4">This cookie is set by LinkedIn. The purpose of the cookie is to enable LinkedIn functionalities on the page.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">GPS</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">30 minutes</td><td class="cookielawinfo-column-4">This cookie is set by YouTube and registers a unique ID for tracking users based on their geographical location</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">lang</td><td class="cookielawinfo-column-2">session</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">This cookie is set by LinkedIn and is used to store the language preferences of a user to serve up content in that stored language the next time user visit the website.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">lidc</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 day</td><td class="cookielawinfo-column-4">This cookie is set by LinkedIn and used for routing.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">lissc</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">11 months</td><td class="cookielawinfo-column-4">This cookie is set by LinkedIn share Buttons and ad tags.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">vuid</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">2 years</td><td class="cookielawinfo-column-4">We embed videos from our official Vimeo channel. When you press play, Vimeo will drop third party cookies to enable the video to play and to see how long a viewer has watched the video. This cookie does not track individuals.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">wow.anonymousId</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">2 years</td><td class="cookielawinfo-column-4">This cookie is set by Spotler and tracks an anonymous visitor ID.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">wow.schedule</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">20 minutes</td><td class="cookielawinfo-column-4">This cookie is set by Spotler and enables it to track the Load Balance Session Queue.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">wow.session</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">20 minutes</td><td class="cookielawinfo-column-4">This cookie is set by Spotler to track the Internet Information Services (IIS) session state.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">wow.utmvalues</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">20 minutes</td><td class="cookielawinfo-column-4">This cookie is set by Spotler and stores the UTM values for the session. UTM values are specific text strings that are appended to URLs that allow Communigator to track the URLs and the UTM values when they get clicked on.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">_ga</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">2 years</td><td class="cookielawinfo-column-4">This cookie is set by Google Analytics and is used to calculate visitor, session, campaign data and keep track of site usage for the site's analytics report. It stores information anonymously and assign a randomly generated number to identify unique visitors.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">_gat</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 minute</td><td class="cookielawinfo-column-4">This cookies is set by Google Universal Analytics to throttle the request rate to limit the collection of data on high traffic sites.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">_gid</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 day</td><td class="cookielawinfo-column-4">This cookie is set by Google Analytics and is used to store information of how visitors use a website and helps in creating an analytics report of how the website is doing. The data collected including the number visitors, the source where they have come from, and the pages visited in an anonymous form.</td></tr></tbody></table></p></div> </div> </div> </div> <div class="cli-tab-section"> <div class="cli-tab-header"> <a id="wt-cli-tab-link-performance" tabindex="0" role="tab" aria-expanded="false" aria-describedby="wt-cli-tab-performance" aria-controls="wt-cli-tab-performance" class="cli-nav-link cli-settings-mobile" data-target="performance" data-toggle="cli-toggle-tab"> Performance </a> <div class="cli-switch"> <input type="checkbox" class="cli-user-preference-checkbox" id="wt-cli-checkbox-performance" aria-label="performance" data-id="checkbox-performance" role="switch" aria-controls="wt-cli-tab-link-performance" aria-labelledby="wt-cli-tab-link-performance" checked='checked' /> <label for="wt-cli-checkbox-performance" class="cli-slider" data-cli-enable="Enabled" data-cli-disable="Disabled"><span class="wt-cli-sr-only">performance</span></label> </div> </div> <div class="cli-tab-content"> <div id="wt-cli-tab-performance" tabindex="0" role="tabpanel" aria-labelledby="wt-cli-tab-link-performance" class="cli-tab-pane cli-fade" data-id="performance"> <div class="wt-cli-cookie-description"><p>Performance cookies include cookies that deliver enhanced functionalities of the website, such as caching. These cookies do not store any personal information.</p> <p><table class="wt-cli-element cookielawinfo-row-cat-table cookielawinfo-winter"><thead><tr><th scope="col" class="cookielawinfo-column-1">Cookie</th><th scope="col" class="cookielawinfo-column-2">Type</th><th scope="col" class="cookielawinfo-column-3">Duration</th><th scope="col" class="cookielawinfo-column-4">Description</th></tr></thead><tbody><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">cf_ob_info</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 minute</td><td class="cookielawinfo-column-4">This cookie is set by Cloudflare content delivery network and, in conjunction with the cookie 'cf_use_ob', is used to determine whether it should continue serving “Always Online” until the cookie expires.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">cf_use_ob</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 minute</td><td class="cookielawinfo-column-4">This cookie is set by Cloudflare content delivery network and is used to determine whether it should continue serving “Always Online” until the cookie expires.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">free_subscription_only</td><td class="cookielawinfo-column-2">session</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">This session cookie is served by our membership/subscription system and controls which types of content you are able to access.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">ls_smartpush</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">1 month</td><td class="cookielawinfo-column-4">This cookie is set by Litespeed Server and allows the server to store settings to help improve performance of the site.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">one_signal_sdk_db</td><td class="cookielawinfo-column-2">persistent</td><td class="cookielawinfo-column-3">Until cleared</td><td class="cookielawinfo-column-4">This cookie is set by OneSignal push notifications and is used for storing user preferences in connection with their notification permission status.</td></tr><tr class="cookielawinfo-row"><td class="cookielawinfo-column-1">YSC</td><td class="cookielawinfo-column-2">session</td><td class="cookielawinfo-column-3">1 year</td><td class="cookielawinfo-column-4">This cookie is set by Youtube and is used to track the views of embedded videos.</td></tr></tbody></table></p></div> </div> </div> </div> </div> </div> </div> </div> <div class="cli-modal-footer"> <div class="wt-cli-element cli-container-fluid cli-tab-container"> <div class="cli-row"> <div class="cli-col-12 cli-align-items-stretch cli-px-0"> <div class="cli-tab-footer wt-cli-privacy-overview-actions"> <a id="wt-cli-privacy-save-btn" role="button" tabindex="0" data-cli-action="accept" class="wt-cli-privacy-btn cli_setting_save_button wt-cli-privacy-accept-btn cli-btn">Save & Accept</a> </div> </div> </div> </div> </div> </div> </div> </div> <div class="cli-modal-backdrop cli-fade cli-settings-overlay"></div> <div class="cli-modal-backdrop cli-fade cli-popupbar-overlay"></div> </div> <script type="text/javascript"> /* <![CDATA[ */ cli_cookiebar_settings='{"animate_speed_hide":"500","animate_speed_show":"500","background":"rgb(255, 255, 255)","border":"#3c3c3b","border_on":false,"button_1_button_colour":"rgb(135, 31, 128)","button_1_button_hover":"rgb(135, 31, 128)","button_1_link_colour":"#fff","button_1_as_button":true,"button_1_new_win":false,"button_2_button_colour":"rgb(51, 51, 51)","button_2_button_hover":"rgb(51, 51, 51)","button_2_link_colour":"#871f80","button_2_as_button":false,"button_2_hidebar":false,"button_2_nofollow":true,"button_3_button_colour":"rgb(0, 0, 0)","button_3_button_hover":"rgb(0, 0, 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