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Heptares Highlights Potential Of StaRA® Proteins As Antigens For GPCR-Targeted Antibody Discovery In New Scientific Publication

LONDON and BOSTON, December 16, 2013 /PRNewswire/ --

Biased Agonist Antibodies Generated To G Protein-Coupled Receptor

Heptares Therapeutics, the leading GPCR structure-guided drug discovery and development company, announces the publication of a new scientific paper describing the use of StaR® proteins (thermostabilised G protein-coupled receptors, GPCRs) as antigens for antibody drug discovery. StaR proteins based on the β 1-adrenergic (β 1AR) receptor were designed and used as antigens for in vivo immunization leading to the generation of functional anti-β 1AR agonistic monoclonal antibodies (mAbs). These mAbs signalled through G proteins but did not recruit -arrestin, indicating the potential for StaR proteins to elicit antibodies with highly selective pharmacology. The paper has been published in the peer-reviewed journal mAbs (Ref. 1).

Fiona Marshall, Heptares' Chief Scientific Officer, commented: "Our StaR technology offers a breakthrough solution to the central challenge of reliably making pharmacologically active antibodies against GPCRs: namely producing purified, properly folded and functional protein when removed from the cell membrane for use as an antigen. This publication provides important validation of this solution and further demonstrates that StaR antigens preserve biologically relevant epitopes, thereby enabling generation of diverse panels of functional antibodies."

By the end of 2012, 37 therapeutic antibodies had been approved and are being marketed in countries around the world, generating sales of $64.5 billion in 2012 (Ref. 2). Of the ten best-selling drugs in 2012, six were monoclonal antibody drugs, each with annual sales exceeding $5 billion. However, only one GPCR-targeting antibody has been approved (Poteligeo mogamulizumab, an anti-CCR4 antibody approved in Japan), which reflects the central technical challenge of accessing reliable high-quality GPCR antigen. Heptares has determined that approximately 100 GPCR targets across a range of diseases (cancer, fibrosis, inflammation, respiratory, pain) are suitable and commercially compelling as antibody targets. Heptares is now leveraging its StaR platform to generate antigens for GPCR antibody drug discovery via partnerships with MorphoSys, MedImmune and with an undisclosed major US pharmaceutical company.

Reference

  1. Hutchings, C.J. et al Monoclonal anti-β1-adrenergic receptor antibodies activate G protein signaling in the absence of β-arrestin recruitment (2013) mAbs 6:1, 1-16 (dx.doi.org/10.4161/mabs.27226)
  2. La Merie Business Intelligence. Blockbuster Biologics 2012.

About Heptares Therapeutics

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