SUMMARY
Synthetic monoclonal antibodies using phage display to bind and block the human growth hormone receptor, potentially offering a more potent and specific treatment for conditions like acromegaly by inhibiting receptor activation and downstream signaling.
The Unmet Need: Innovative approaches to develop fully-human, high-affinity inhibitors that can selectively block growth hormone receptor activation
- The field of endocrine therapy has long grappled with disorders caused by abnormal hormone signaling, such as acromegaly, where excessive levels of growth hormone lead to detrimental physiological effects. Traditional management of such conditions has relied on surgery, radiotherapy, and pharmacological agents that modulate hormone action. These treatments are rooted in decades of clinical practice, but they often fall short in delivering consistent, effective outcomes. There is a clear need for more refined approaches that can accurately target the molecular underpinnings of these disorders while minimizing collateral effects.
-
Current treatments, however, exhibit significant limitations that compromise patient care. Pharmaceutical interventions, for example, are frequently associated with low potency, requiring daily administrations that can burden patients and lead to diminished adherence. Moreover, these drugs can produce adverse side effects and lack the receptor specificity needed to fully suppress pathological signaling. Surgical and radiotherapeutic approaches, though sometimes effective, carry inherent risks, are invasive, and often incur high costs, further underscoring the pressing demand for improved therapeutic strategies.
The Proposed Solution: A synthetic approach employing iterative phage display mutagenesis to isolate high-affinity antibody fragments targeting the human growth hormone receptor
- The faculty inventor developed synthetic monoclonal antibodies generated by advanced phage display mutagenesis to selectively bind and antagonize the human growth hormone receptor (hGHR). These antibodies were engineered to inhibit hGH activation by targeting key receptor domains, including overlapping epitopes and the S2 region. Their binding kinetics and specificity were rigorously characterized by surface plasmon resonance and ELISA, while functional inhibition was confirmed through flow cytometry and STAT5 phosphorylation assays. Reformatted into full-length IgG expressed in mammalian systems, these antibodies demonstrate a promising framework for effectively modulating hGHR signaling.
-
These antibodies are distinct due to their fully human design and innovative selection strategy, which involved multiple rounds of phage display with decreasing antigen levels and strategic epitope masking. This approach not only improved binding affinity and selectivity but also minimized potential immunogenicity compared to traditional mouse- or rabbit-derived antibodies. Their methodical development process offers potential advantages in potency, dosing frequency, and production cost, positioning them as a unique alternative to current therapies for conditions like acromegaly and diseases linked to GHR dysregulation.
ADVANTAGES
ADVANTAGES
-
Enhanced binding affinity and selectivity for effective inhibition of hGHR signaling
-
Potential for longer half-life and less frequent dosing compared to existing treatments
-
Reduced immunogenicity by utilizing fully human monoclonal antibodies
-
Enhanced specificity
APPLICATIONS
- Rare disease- acromegaly
- Oncology
- Anti-aging therapeutics
- GHR diagnostic reagent kit
April 24, 2025
Proof of concept
Patent Pending
Licensing,Co-development
Anthony Kossiakoff