Therapeutic compositions and uses of alpha1-antitrypsin: a patent review (2012 – 2015)

ABSTRACT

Introduction: Identified as a circulating serine-protease inhibitor, the genetic deficiency of which predisposes to the development of lung emphysema, alpha1-antitrypsin (AAT) has recently been found to possess various anti-inflammatory and immunomodulatory activities outside the biochemical inhibition of serine-proteases. AAT is presently extracted from human plasma to supply life-long infusions to patients with genetic AAT deficiency. However, its newly appreciated functions point to extended therapeutic uses; these, alongside modified production attempts, represent a novel and dynamic niche of drug repurposing, set apart from addressing lung emphysema in AAT-deficient individuals.

Areas Covered: The review provides a comprehensive summary of patent-protected inventions in the field of novel clinical indications for AAT and innovations in AAT production.

Expert Opinion: A molecule no longer patentable per se, presents with novel clinical applications; its mechanism still unfolding. While modified protein sequences are patentable and potentially superior, they are burdened by regulatory setbacks. Thus, recent approaches in the context of AAT appear in patents that describe combinations with other drugs, redefined clinical subclasses, and unique recombinant entities, carefully skirting saturated areas of AAT patentology. It will be fascinating to follow technologies and creative patenting as AAT navigates the trying trades of pharmaceutical industry towards an increasing lineup of unmet clinical needs.

KEYWORDS:

• Acute myocardial infarction
• allograft rejection
• alpha1 proteinase inhibitor
• diabetes
• graft versus host disease
• immunomodulation
• inflammation
• SERPINA1
• xenoimmune response

Article highlights

• Alpha1-antitrypsin (AAT) is a serine–protease inhibitor glycoprotein housing a multitude of immunoregulatory and immunomodulatory activities.

• To date AAT is purified from pooled human plasma, a process still being perfects by recent patents.

• Currently, the sole clinical indication for AAT transfusion remains AAT deficiency, a one gene disease usually characterized by early onset emphysema and liver disease.

• Patents published in recent years depict the clinical use of AAT in conditions varying from treatment of diabetes, Graft vs Host disease, graft protection, bacterial infections and even ameliorating radiation exposure adverse effects.

• The need for increased production rates has raised attention to recombinant production of AAT, alongside the modification options this method harbors.

This box summarizes the key points contained in the article.

Declaration of interest

EC Lewis is a scientific advisor to Kamada Ltd., Israel. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.