The Importance of Antibody Pharmacokinetic Improvement
Therapeutic antibodies have been instrumental in revolutionizing the way various diseases, such as autoimmune disorders and cancer, are treated. However, their effectiveness is limited by poor pharmacokinetics, which can necessitate higher doses and drive up costs for patients. Therefore, optimizing pharmacokinetics is a crucial factor in the developability profile of therapeutic antibodies to enhance their efficacy and reduce the likelihood of setbacks during further development stages.
Fig. 1 Possible causes of anti-drug antibody formation.1,2
Our Antibody Pharmacokinetic Improvement Service
Leveraging our wealth in antibody engineering, Creative Biolabs offers an antibody pharmacokinetic improvement service to help our clients transform their research into life-saving treatments. Initially, we take advantage of computer-aided structure design to achieve the optimal antibody sequence and structures, which is crucial for the precise distribution of antibodies. In addition, we also provide model-dependent or independent assays to predict and select the appropriate therapeutic delivery approaches and, at the same time evaluate the pharmacokinetics of improved therapeutic antibodies. At Creative Biolabs, we strive to bring out each of you with desirable antibodies in a timely manner.
Fig. 2 Workflow of our antibody pharmacokinetic improvement service.
Technologies & Strategies for Antibody Pharmacokinetic Improvement
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Antibody Nonspecific Clearance Reduction Technology
Nonspecific clearance of antibodies involves their uptake by cells through pinocytosis or proteolysis, leading to their removal from circulation without specifically targeting the desired therapeutic site. This mechanism plays a crucial role in eliminating therapeutic antibodies from the body. By modifying the isoelectric point of antibodies, we are capable of reducing their non-specific clearance and improving their therapeutic efficacy.
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Antibody-Antigen Binding-mediated Clearance Technology
Antigen-binding-mediated clearance is another crucial pathway to clear therapeutic antibodies from the body. We deliver distinctive antigen-eliminating (Mouse & Primate/Human) involving a variety of technologies as follows:
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Mouse Antigen Eliminating
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Antibody Variable Region Engineering Technology
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By applying recycling technology, we modify the variable region of the antibody to develop an antibody that binds to the antigen in a pH-dependent manner to achieve long-lasting neutralization of the antigen.
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Antibody Constant Region Engineering Technology
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We modify the constant region of the antibody to improve its interaction with FcRn at neutral pH. This alteration enhances the uptake of the antibody-antigen complex by FcRn into the endosome. In this acidic environment, the antibody-antigen bond is disrupted, enabling the antibody to evade degradation.
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Primate/Human Antigen Eliminating
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FcγRIIb Binding Enhancing
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Antibodies that are engineered to enhance their binding to FcγRIIb play a crucial role in eliminating soluble antigens from the bloodstream. This enhanced binding leads to increased uptake of immune complexes by cells, ultimately resulting in the degradation of the antigens within the endosome.
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Positive Charge Enhancing
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Antibodies engineered with increased positive charge show improved binding to cell surfaces and enhanced cellular uptake, especially in antigen-negative cells.
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For more details about our antibody pharmacokinetic improvement service, please get in touch with us with your projects.
References
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Vaisman-Mentesh, Anna, et al. "The molecular mechanisms that underlie the immune biology of anti-drug antibody formation following treatment with monoclonal antibodies." Frontiers in Immunology 11 (2020): 540270.
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All products and services are for Research Use Only. Do Not use in humans.
