Structure-Based Design & Bioprocess Technology
3D-VAXLOCK® PROTEIN ENGINEERING
CONFORMATION-LOCKED PROTEINS & AMINO ACID CROSS-LINKING
Calder’s proprietary 3D-Vaxlock® protein engineering technology targets dityrosine crosslinks to lock proteins in their desired conformations. Dityrosine bonds are targeted within protein structures by (i) introducing tyrosine substitutions at positions that are in structural proximity, and (ii) introducing covalent crosslinks between these tyrosine sidechain pairs, using a reaction that otherwise maintains the structural integrity of the protein. The technology combines structure-based design and a bio-manufacturing process and thereby supports novel composition of matter IP each time the technology is applied.
We apply Calder's 3D-Vaxlock® technology to lock the most potent conformations of spring-loaded and metastable viral surface proteins (e.g., fusion proteins), and engineer novel vaccine immunogens that elicit the most potently protective antibody responses.
3D-Vaxlock® dityrosine bonds are introduced after the protein is fully folded, and they create zero-length carbon-carbon bonds.
Zero-length carbon-carbon bonds lock the protein in its desired conformation, without altering the rest of the molecule.
Lower cost of goods & lower cold-chain requirements. Technology enhances vaccine stability, which translates into greater potency and improved safety – and reduced costs
Sophisticated, nano-scale bioprocess-technology leverages natural enzymatic reaction:
- Locks vaccines in 3D shapes that maximize efficacy and prolong shelf life, reducing cold-chain requirements
- Economic engineering minimizes risks
Compatible with standard biologics manufacturing & substantial synergies between programs
Applying technology generates NCEs and supports novel composition of matter patents to enhance broad IP protection
Targeted approach, focused responses
Substantially reduced risk vis-à-vis other modalities
Successful recombinant subunit vaccines elicit the highest Ab responses:
- Shingrix vs. Zostavax
- HBsAg (Recombivax, Engerix, Heplisav)
- HAV (Vaqta, Havrix)
Antibodies recognize 3-D shapes/surfaces
- Vaccines need to present surface proteins in the same 3-D shape as present on the surface of the pathogen
- Calder’s focus: spring-loaded and metastable viral fusion proteins: best viral vaccine targets. - Conformational stabilization needed
Sophisticated, nano-scale technology combines structure based design with in-process modification of recombinant subunit immunogens to improve protection
Maximizes efficacy and prolongs shelf life, while reducing cold-chain requirements
Generates new chemical entities, supports novel composition of matter patents
Calder’s focus: spring-loaded and metastable viral fusion proteins: best viral vaccine targets
Conformational stabilization needed
3D-Vaxlock® Technology enhances RSV vaccine potency 10-fold ...
Calder’s Unique Platform Conformationally Locks Vaccine Immunogens
Technology can be applied to 40+ human viruses, including EBV, CMV, rabies, etc.
Differentiation: RSV DT-preF Elicits Stronger Immune Response Via Multiple Mechanisms
The 3D-Vaxlock® platform generates vaccines with consideration of the transfer of technology to manufacturing.
3D-Vaxlock® is a scalable and affordable means to create the quantities needed to protect during global pandemics and against new viral pathogens.
Portability of bio process to maufacturing
Compatibility with existing supply chains
Patent enforced to 2040
3D-VAXLOCK® ADVANTAGES: TARGETED MOLECULAR CROSS-LINKING
The 3D-Vaxlock® cross-linking reaction is highly specific to tyrosine residues; and it only results between two tyrosine residues that are in close proximity (<3Å).
Mild cross-linking reaction conditions result in little non-specific side-chain modifications. We are able to introduce only the desired, targeted crosslinks while leaving the rest of the protein essentially unchanged. The 3D-Vaxlock® minimally modifying approach retains the target protein’s structural integrity.
3D-Vaxlock® cross-links are introduced after the protein is fully folded, and create zero-length (C-C) covalent bonds that simply lock in the protein’s native structure without distorting it. In contrast to disulfide bonds, dityrosine bonds form readily, are stable under virtually any physiological conditions, and do not result in aggregate formation.
Dityrosine bonds are fluorescent with highly specific excitation and emission wavelengths, allowing dityrosine bond formation to be measured with great sensitivity, in real-time - enabling attribute-based controls in clinical manufacturing.
Our patented 3D-Vaxlock® technology enables us to develop novel, vaccines with optimized potency, safety and efficacy. Enhanced stability reduces cost of goods and distribution requirements.
What is Dityrosine?
Dityrosine is a biphenyl compound comprising two tyrosine residues linked at carbon-3 of their benzene rings. It is a member of biphenyls, and a tyrosine derivative. Calder's proprietary protein engineering technology targets DT crosslinks within protein structures to stabilize desired conformations of our subunit vaccine immunogens.
Patents US7037894, US7445912, US9393297, US10125172, US10155023, EP1282722