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Breaking the barrier

Companies are finally finding ways to develop cell-penetrating biologics

A three-way deal between Amgen Inc., Feldan Therapeutics Inc. and Elasmogen Ltd. is the latest cause for optimism that technologies are finally converging to enable the generation of cell-penetrating biologics.

The biotechs join a small but growing cohort of companies creating protein-based therapeutics that can cross the plasma membrane to reach intracellular targets - a challenge that has plagued the field almost since the dawn of the industry.

Last month, the partners signed a deal to combine Feldan’s intracellular delivery platform, dubbed Shuttle, with target-binding small proteins from Elasmogen, a 2016 spinout from the University of Aberdeen. Amgen is selecting two undisclosed targets. Financial terms have not been disclosed.

While small molecules can easily penetrate cell membranes to hit intracellular targets, they require a defined, hydrophobic binding pocket, leaving many intracellular targets undruggable. Small molecules also often lack specificity, in particular when multiple targets have similar binding pockets.

Antibodies can solve the specificity problem, but because they cannot cross the lipid bilayer they have been largely restricted to extracellular targets.

“The goal for years has been to develop a method combining the targeting power of biologics with the cell penetrating abilities of small molecules,” said Heehyoung Lee, senior director of target discovery and validation of LA Cell at Sorrento Therapeutics Inc. LA Cell is a 2015 JV formed between Sorrento and City of Hope to develop antibodies and peptides against intracellular targets.

Now, activity in the field is showing a palpable rise. Patents on cell-penetrating peptides or antibodies increased in the last decade, and rose sharply in the last three years, with about twice the number published in 2014 over 2013 (see “Patents on Cell-penetrating Biologics”).


Figure: patents on cell-penetrating biologics

The number of published patents involving cell-penetrating peptides surged in the last three years, more than doubling from 47 in 2013 to

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