ProtExtent Biosolutions Pvt. Ltd. (PBPL) is a biotech startup incubated with the ILS-Bioincubation Centre, Bhubaneswar, Odisha.

PBPL is working towards ensuring affordable healthcare for all through cost-effective production of recombinant protein based vaccines and biotherapeutics.

What is the problem PBPL is solving?
PBPL has the expertiseto produce cost-effective recombinant protein based vaccines and biotherapeutics.

As a flagship in-house R&D program, PBPL is developing a novel and versatile Virus-Like Particle (VLP) based platform amenable tohighly efficient bioconjugation (essentially in a ‘plug-n-display’ approach) with antigens of choice for improving their immunogenicity. This VLP-platform being developed by PBPL would have several advantages over traditional approaches of generating chimeric VLP-backbones (consisting of in-frame insertions with antigens of interest). The novel VLP-platform would be versatile and easily amenable to highly efficient bioconjugation with antigens of choice with minimal amino acid sequence carry-over from the conjugation technique itself thus, accelerating VLP-based vaccine research with potential application in a variety of infectious and non-infectious diseases. A schematic representation of the VLP-platform being developed by PBPL is shown below.

Additionally, PBPL aims to produce cost-effective recombinant biotherapeutics and enzymes. Despite advantages of higher specificity and fewer off-target effects, biotherapeutics are expensive due to the associated high cost of their production, and even introduction of biogenerics have so far resulted only in modest price benefit (at best around 30%) to the end users. In comparison ‘generic versions’ for several small molecule therapeutics have resultedin an impressive reduction in the prices (overall estimated to be >90%) for these drugs. PBPL aims to achieve production of cost-effective recombinant biotherapeutics and enzymes, thereby making it highly affordable for the end users.

Several factors and critical go/no-go decisions are involved in the entire process of production of recombinant biotherapeutics, starting right from the step of design of the target gene encoding the protein of interest (carefully engineered with a foresight about the choice of expression platform and downstream purification strategies), the steps actually involved in the upstream (fermentation / protein expression) as well as the downstream (purification of the protein of interest), and the final formulation along with the choice of the delivery method, all collectively contribute to the market cost of the given biotherapeutic.

PBPL has optimized solutions for each of these steps involved towards achieving maximum cost-effectiveness. These involves careful deliberations about the choice of protein expression platform, the optimal engineering of the gene not only to produce the highest possible yield of the ‘protein of interest (retaining the desired biological activity)’, but also with a foresight of reducing costs involved in upstream and downstream processes. Applying these strategies PBPLhas the expertise for more efficient and cost-effective production of the biotherapeutics / other commercially valuable recombinant proteins of choice.

How does PBPL propose to solve the problem(s)?
PBPL has the expertise to produce cost-effective industrial recombinant proteins / enzymes with wide applications in food, drug (vaccines and biotherapeutics) and other industrially valuable enzymes. PBPL would capitalize on its competence with different recombinant protein expression platforms, which includes bacterial, yeast and higher eukaryotic (insect-based) protein expression platforms. This includes making the requisite judgement about the choice of the protein expression platforms through analysis of the primary sequence (and the predicted secondary and tertiary structure) of the recombinant protein of interest, as well as taking into consideration its marketing value. For those recombinant proteins suited for bacterial protein expression platform, optimization for cost effectiveness in both Gram-negative (E. coli, a standard protein expression platform widely used) and Gram-positive (Lactococcus lactis, a specialized recombinant protein expression platform for obtaining soluble recombinant proteins) would be conducted.

Additionally, L. lactis is also a GRAS (Generally Regarded As Safe) organism, with added advantages for the production of recombinant proteins of value to the healthcare and food industry. For those recombinant proteins suited for eukaryotic expression, optimization for the cost effectiveness using the yeast protein expression platform of either Pichia pastoris or Kluveromyces lactis (where K. lactis is again a GRAS organism with the advantages of producing safe and effective recombinant proteins with application in the food and drug industry) would be carried out. Subsequently, for mass production of desired recombinant proteins (of commercial value) for achieving higher competitive cost-effectiveness, we useinsect cell based (a higher eukaryotic platform) for the production of desired recombinant proteins. Apart from the choice of the protein expression platform, PBPL has the expertise to engineer the gene encoding the protein of interest to facilitate cost-effective purification, thereby further bringing down the production cost.

What is the uniqueness of the solution offered by PBPL?
ProtExtent Biosolutions Pvt. Ltd. (PBPL) focuses on developing a combination of efficient processes for recombinant protein expression and purification with the aim of producing cost-effective recombinant proteins with application in the drug and food industry and in other industrial applications (such as recombinant enzymes).

The core team at PBPL has advanced research experience in complementary disciplines of protein research from some of the most prestigious research organizations around the world. Briefly, we collectively specialize in molecular biology, protein chemistry, recombinant protein technology and vaccine research, and a proven track-record of recombinant protein scale-up, cGMP production and technology transfer for commercial production.PBPL thus, has the requisite experience of working at the techno-commercial interface, which is one of the essential ingredients required for succeeding in a biotech venture. Additionally, PBPL capitalizes on its expertise and choicefrom a wide range of recombinant protein expression platforms (bacterial, yeast or higher eukaryotes) for cost-effective production of recombinant proteins. PBPL uses a unique combination of protein expression and purification strategies ensuring high yield and purity of functional recombinant proteins optimized through highly cost-effective process development, thus achieving high level of market competitiveness.

PBPL is also developing a novel and versatile VLP-based platform (our flagship in-house R&D program) amenable to high efficiency bioconjugation with different antigens of choice for improving their immunogenicity. The VLP-based antigen delivery strategy has been found to be highly effective for improving immunogenicity of several vaccines such as Hepatitis B, Human Papilloma Virus, and the malaria vaccine RTS,S (Mosquirix, GSK). The novel VLP-platform being developed by PBPL would be designed based on a unique protein engineering approach to ensure high efficiency bioconjugation resulting in high and uniform display of the antigenic domains / antigen of choice (essentially in a ‘plug-n-play’ approach) on the surface of the VLP, thereby potentiating the immune response against the antigen of choice. This novel VLP platform being developed by the PBPL would circumvent the necessity for optimizing assembly of chimeric-VLP backbones with in-frame insertion of antigenic domains, a major hurdle so far for deploying wide usage of VLP-based immunopotentiating approaches, and would find wide application for improving immunogenicity of antigens from various infectious / non-infectious disease targets.

How does PBPL generate revenue?
PBPL has chalked out a clear roadmap for revenue generation. This includes phase wise initiation of the following activities:

1. Contract Research Services:
PBPL would capitalize on its expertise in recombinant protein technology to cater to various other public/private national / international groups to develop process for custom production of recombinant proteins of their interest. PBPL has been contractedby Vac4All, Paris, France, a company dedicated to malaria vaccine research, for process development for the production of their lead asexual blood and liver stage malaria vaccine candidates. Similarly, PBPL has also partnered with the Staten Serum Institute, Copenhagen, Denmark, for pre-clinical development of several recombinant antigens.

2. Developing recombinant biotherapeutics and enzymes:
PBPL is developing in-house processes for cost-effective production of peptide therapeutics and other biogenerics, for which the innovator patent has expired. Once again for this, PBPL capitalizes on its inherent strength of designing cost-effective processes for production of recombinant proteins. Cost-effective generic recombinant biotherapeutics produced by PBPL would be commercialized through B2B mode.

3. Developing novel VLP-conjugate vaccines:
PBPL is developing a noveland versatile VLP-based vaccinedelivery platform, as its flagship in-house R&D activity, which will be amenableto highly efficientbioconjugation with various antigens of choice, facilitating their uniform display on the VLP surface (with minimal carry-over from the conjugation process itself). This novel-VLP platform would thus serve to potentiate immunogenicity of a wide range of antigens of choice (essentially in a ‘plug-n-display’ approach), circumventing the need to generate time consuming optimization of chimeric VLP-backbones with in-frame insertion with each antigen of choice one at a time.