The patent relates to a method of generating CAB proteins from ordinary proteins, but in particular therapeutic proteins, which are inactivated under normal physiological conditions.
CABs are proteins, such as antibodies or enzymes, activated by specific microenvironments within the body; they might turn on when in a cancerous tumour environment, for example.
BioAtla’s patent is method-independent, meaning that it covers methods of designing CABs as well as developing CABs through selection. An example of one method is to make changes in the gene that encodes the protein, which results in variants in the protein’s amino acid sequence. These are screened to spot variants that will respond to conditions matching those in a targeted microenvironment.
The company said that the technology increases the number of tumour targets, improves selectivity of existing targets, improves therapeutic safety and allows for increased potency of antibody therapeutics. “This technology is aimed at the core of what is needed in the marketplace – greater efficacy and safety for the patient,” said Richard Waldron, Chief Financial Officer at BioAtla.
“Our first CAB development partnership is with a commercial stage biotechnology company and the antibody and potential indicators are undisclosed,” he told Biopharma-Reporter.com. This is an anti-tumour compound that targets colorectal, pancreatic and non-small cell lung cancers.
Studies have shown that cancerous tumours generate highly specific conditions that are different from normal tissue. This can be used to lock CABs to a tumour target, as the proteins can be evolved or optimized to become active at certain temperatures, pH, osmotic pressure or electrolyte concentrations.
Opening doors for Biobetters
In a statement, BioAta’s president, Jay M. Short, said its CAB discovery platform “promises several novel product candidates and unprecedented biobetter antibodies as our strategic direction expands to include developing highly differentiated compounds for our internal pipeline, as well as for our partners.”
Biobetters are therapeutic antibodies that target the same validated targets as a marketed antibody, but they are engineered to have properties such as improved specificity to target cells, longer serum half life, improved manufacturability or enhancements in initiating and directing a desired immune response.
“The greater the improvement in key properties, the greater the demand for the biobetter. The CAB technology allows for biobetters with potentially all of those attributes while lowering the toxicity to normal tissue,” Waldron said.
“We expect an even greater impact of CAB technology will be through the development of antibodies for novel targets such as those receptor sites that are considered too concentrated in normal tissues to be useful as targets for immunotherapies,” he added. An antibody active only in a distinct tumour environment gets around this problem.
BioAtla expressed confidence that the broad potential and applicability of CAB technology should present several partnering opportunities in the field of oncology, and in other therapeutic areas.