In the field of ophthalmology, numerous diseases are closely associated with vascular abnormalities. For instance, diabetic retinopathy (DR) and age-related macular degeneration (AMD), which stand as major causes of visual impairment, stem from aberrant neovascularization within the retinal or choroidal regions, respectively. The foundation of therapeutic approaches in ophthalmology often involves interference with receptor signaling pathways. A widely adopted strategy entails the inhibition of signaling pathways that play a pivotal role in angiogenesis or vasculogenesis within the eyes. BsAbs offer a compelling solution, as they have the capability to simultaneously target two distinct pathways or intervene at two distinct points within the same pathway. Consequently, BsAbs stand as a formidable class of therapeutic agents, poised to lead the next generation of pharmaceutical innovations in the treatment of ocular diseases.
Fig.1 Spectral-domain OCT images: baseline vs 1-month post-last BsAb dose in three patients.1
| Paper Title | Design and Pharmacokinetic Characterization of Novel Antibody Formats for Ocular Therapeutics |
| Journal | Investigative Ophthalmology & Visual Science |
| Published | 2015 |
| Abstract | To facilitate our investigations, scientists devised a groundbreaking mathematical model to quantify the intricate structure-PK relationships. The F(ab')2 format emerged as the optimal choice for ocular therapeutic applications, boasting a vitreal half-life comparable to full-length antibodies while minimizing systemic exposure. Concurrently, the concordance between our mathematical model predictions and the observed data served to validate the model for prospective PK forecasting. Additionally, scientists introduced a novel approach for the development of bispecific antibodies, demonstrating their efficacy in targeting multiple angiogenesis pathways. |
| Result |
Scientists have shown that protein molecular weight and the Fc region do not exert a pivotal influence on ocular pharmacokinetics, in contrast to their systemic effects. Furthermore, the mathematical model substantiates the capability of selecting the 'optimal therapeutic' by forecasting the ocular and systemic pharmacokinetics of any antibody format, under any dosing regimen. These discoveries carry significant implications in the design and selection of ocular therapeutics, offering the potential to tailor treatments to specific requirements, including the enhancement of ocular half-life and the reduction of systemic exposure.
Fig. 2 Generation of bispecific F(ab')2 antibodies with Mono-or Di-sulfide bond interlinkages between two Fab' fragments.2 |
| Paper Title | Bispecific therapeutics for ophthalmic indications: target selection and the optimal molecular format |
| Journal | Expert Review of Ophthalmology |
| Published | 2014 |
| Abstract | The authors delve into the examination of technologies devised to engineer dual targeting mechanisms within protein-based therapeutics designated for intravitreal delivery. An additional objective is the reduction of systemic exposure subsequent to intraocular injection. Within the summarization, the authors underscore the significance of two such technologies, known as DAPRin and Fab'2, emphasizing their pivotal role in the vigilance of bispecifics for the advancement of ocular therapy. |
| Result |
Fig. 3 BsAbs designed for ocular disease treatment.3 |
Creative Biolabs provides our customers with top-tier BsAbs developed on the basis of our cutting-edge and innovative technology platforms. Our accomplished team of researchers is well-versed in BsAbs design, and equipped to formulate tailored BsAbs and innovative strategies to elevate the caliber of your scientific and clinical endeavors within the realm of ophthalmology. Please feel free to reach out to us for further information or inquiries.
References
1. Chakravarthy, Usha, et al. "Phase I trial of anti-vascular endothelial growth factor/anti-angiopoietin 2 bispecific antibody RG7716 for neovascular age-related macular degeneration." Ophthalmology Retina 1.6 (2017): 474-485.
2. Gadkar, Kapil, et al. "Design and pharmacokinetic characterization of novel antibody formats for ocular therapeutics." Investigative Ophthalmology & Visual Science 56.9 (2015): 5390-5400.
3. Le Couter, Jennifer, and Justin M. Scheer. "Bispecific therapeutics for ophthalmic indications: target selection and the optimal molecular format." Expert Review of Ophthalmology 9.3 (2014): 217-225.
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