The rise of the Polyclonal Antibody.

Human polyclonal antibodies (hpAbs) have been studied for decades, but medical science turned its focus to monoclonal antibodies (mAbs), because of their scarcity as traditionally they could be sourced only from humans, and lack of consistent performance because hpABs were derived from humans and every human is different.  For decades, the only way to produce human antibody treatment that has consistent batch to batch performance was through monoclonal platforms.  Mab treatments have precision and ability to target a specific antigen, but they target only a specific epitope of a single antigen. While numerous effective mAb therapies have been launched in recent years and have provided effective treatments for a host of serious illnesses, mAbs haven’t been as effective in treating certain kinds of diseases. 

The specificity, precision and targeting of mAbs – the very reason these antibodies were preferred in biotech development – actually make mAb’s less effective in diseases caused by complex and rapidly mutating pathogens. Indeed, this is what happened with the COVID-19 pandemic when many mAb treatments became ineffective as soon as a new COVID variant emerged. The mAbs were specific to the single epitope on earlier variants, and once SARs-CoV2 virus mutated, they were unable to attach to the virus to neutralize it. Monoclonal antibodies are only one mutation away from becoming ineffective.

This is what has led to the medical community’s renewed interest in human Polyclonal Antibodies, as they mimic the body’s natural response to treating disease. As such, target-specific yet broadly neutralizing human pAbs may be the answer to treating complex diseases that continually mutate or have multiple antigens. The polyclonal nature of the antibodies allow them to attack a pathogen from multiple epitopes, thus maintaining hpAb’s neutralizing activity even when a pathogen mutates.  

There is only one company that has emerged as a global leader in producing large quantities of fully-human polyclonal antibodies without the need for human donors to target these complex diseases. Meet SAB Biotherapeutics, whose dedicated team has spent the past two decades perfecting their novel technology, and their transchromosomic miraculous cows. Yes—cows. But more on that in a moment.

Monoclonals vs. Polyclonals

Monoclonal Approach

• Highly-targeted with specific activity
• Iterative Ab identification and selection process
• Selected and cloned in vitro
• May promote escape mutants via selective pressure
• Resistance may develop as pathogen/target mutates
• Current cocktail trend to address resistance

Polyclonal Approach

• Diversity of antibodies with multiple modalities
• Naturally selected and produced in vivo
• Effective against escape mutants
• Reduced possibility of resistance
• Activates cellular immunity
• Synergistic properties not duplicated by mono- or oligoclonals

The Power of the DiversitAb™ platform and the next generation of human polyclonal antibodies.

Harnessing the natural human antibody immune response, SAB’s innovative DiversitAb™ platform enables—for the first time—scalable and sustainable  production of highly-potent fully-human polyclonal antibody therapies that can address the emergence, mutation, and diversity of modern health challenges including Clostridioides difficile (C. diff), pan-influenza, Type 1 diabetes, COVID-19, and cancers. 

SAB’s technology platform leverages the natural human immune response to develop next-generation, fully-human polyclonal antibody therapeutics with a consistent infinite supply of human pABs with remarkable batch to batch consistency. DiversitAb™ fully-human polyclonal antibodies are a natural mix of antibodies all humans produce that target many epitopes of a given antigen, providing highly effective broad protection against pathogens including mutations or strain changes. SAB’s polyclonal antibodies can also target multiple antigens in a single treatment creating promising therapeutics for complex chronic immunological disorders.  DiversitAb™ fully-human polyclonal antibodies are naturally designed to engage and activate the human immune system in a supercharged way that supports human health and healing.

A novel approach using nature’s genius to fight disease.

SAB’s DiversitAb™ immunotherapy platform enables a scalable and sustainable production of targeted, higher-potency neutralizing antibody products than has been previously possible. Our platform can consistently and reliably produce an infinite supply of fully-human polyclonal antibodies without the need for convalescent plasma from human donors. SAB’s founding scientists have optimized and advanced genetic engineering and antibody science to develop Transchromosomic cows (Tc Bovine™) that produce fully-human, highly-efficacious, specific to their target yet broadly neutralizing polyclonal antibodies. 

SAB’s Tc Bovine™ are a unique and proprietary component of SAB’s novel platform that create an exponentially higher rate of successful fully-human antibody treatments compared to animal-derived or synthetic human monoclonal immunotherapies. Our genetically engineered cows mount the same immune response as humans, only with a much higher concentration of targeted, broadly neutralizing fully-human antibodies. Our novel approach opens the door to medicines that are potentially more effective, potent, safer, and longer-lasting than current monoclonal antibody platforms.

SAB’s proprietary streamlined antibody generation process eliminates the step needed to select the most potent antibody candidates. Rather, a specifically designed immunization for genetically engineered cows activates the entire disease-fighting force of fully-human antibodies. This vertical integration allows R&D process that is significantly faster and has higher probability of technical and regulatory success. Hyperimmunization of these cows results in diverse, high-titer, high-avidity fully-human polyclonal antibodies that are then captured in large amounts of plasma resulting in a high-potency therapy.

Tc Bovine™-produced fully-human polyclonal antibodies have demonstrated to behave identically to those produced in humans. As such, our therapeutics work with a patient’s own immune system to both neutralize a virus and activate other components of the immune system that are important in helping the body fight disease. Data from across SAB’s clinical platform has shown that our antibodies are effective – even when antivirals or monoclonal antibodies have become ineffective due to pathogen mutation.

This is one of the compelling reasons why our novel fully-human broadly neutralizing polyclonal antibodies have the potential to serve as the primary line of defense against mutating viral targets, such as SARs-CoV-2, seasonal and pandemic influenza and other infectious, autoimmune and immunological diseases, including cancer, that have a significant mortality and health impact on immunocompromised patients. Respiratory, gastroenterology, oncology, and anti-infectives are the key therapeutic areas where DiversitAb™ platform is revolutionizing the approach to biologic modalities.

Treating Human Disease May Never Be The Same

Meet SAB’s Miraculous Cows. 

Cows are ruminant animals and inherently have a more robust immune response than humans. This response is stimulated when an immunogen specific and exclusive to a target is introduced to our special Tc Bovine^TM. We further boost the response with a specialized vaccine formulation and strategy that maintains a high level of antibody production over an extended period of time, targeting plasma collection at the highest levels.  

What is unique and proprietary about our polyclonal science that sets us apart from other mAbs and hpAbs is the introduction of Human Artificial Chromosomes (HAC) into our cows, which ultimately make them identical clones, allowing their immune system to produce fully-human polyclonal antibodies and enable large batch to batch consistency of hpABs.

These optimized technologies result in large amounts of diverse, high-titer, high-avidity fully-human polyclonal antibodies, which lead to a high-potency therapy, with a nearly endless supply.

Large Scale.

As a large animal production system, greater volumes of neutralizing antibodies are generated and can be collected up to three times per month per animal. Production can be ramped up by simply continuing to immunize and collect plasma, or by adding more animal donors.

Safety and Consistency.

Unlike human plasma donors, who may have previous exposures to many pathogens and varying genetic backgrounds, SAB’s platform offers a large-scale, consistently managed donor pool, genetically representing a single human donor. In addition, because our Tc Bovine™ are inoculated with a non-infectious antigen, they produce antibodies to the immunogen without becoming infected or ill. Miraculous cows, indeed.