An overview of pharmaceutical cocrystals as intellectual property.

This review article focuses on the interaction among certain scientific, legal, and regulatory aspects of pharmaceutical crystal forms. The article offers an analysis of pharmaceutical cocrystals as patentable inventions by drawing upon recent scientific developments in the field. Several potential commercial advantages of pharmaceutical cocrystals are highlighted, and a number of recent court decisions involving salient issues are summarized. The article provides an outlook on how the developing field of cocrystallization may impact the pharmaceutical intellectual property landscape.

[1]  Peddy Vishweshwar,et al.  Pharmaceutical co-crystals. , 2006, Journal of pharmaceutical sciences.

[2]  G. Desiraju,et al.  On the polymorphism of aspirin: crystalline aspirin as intergrowths of two "polymorphic" domains. , 2007, Angewandte Chemie.

[3]  Gautam R. Desiraju,et al.  Cryptic crystallography , 2002, Nature materials.

[4]  Peddy Vishweshwar,et al.  The predictably elusive form II of aspirin. , 2005, Journal of the American Chemical Society.

[5]  Jeanette T. Dunlap,et al.  Crystal engineering approach to forming cocrystals of amine hydrochlorides with organic acids. Molecular complexes of fluoxetine hydrochloride with benzoic, succinic, and fumaric acids. , 2004, Journal of the American Chemical Society.

[6]  M. Caira,et al.  Selective formation of hydrogen bonded cocrystals between a sulfonamide and aromatic carboxylic acids in the solid state , 1995 .

[7]  Michael J Cima,et al.  High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids. , 2004, Advanced drug delivery reviews.

[8]  J. Chisholm A third blind test of crystal structure prediction , 2004 .

[9]  J. Maddox Crystals from first principles , 1988, Nature.

[10]  Christer B. Aakeröy,et al.  Crystal engineering : Strategies and architectures , 1997 .

[11]  W. D. Sam Motherwell,et al.  An Experiment in Crystal Structure Prediction by Popular Vote , 2006 .

[12]  Aeri Park,et al.  Use of a Glutaric Acid Cocrystal to Improve Oral Bioavailability of a Low Solubility API , 2006, Pharmaceutical Research.

[13]  D. Allan,et al.  The formation of paracetamol (acetaminophen) adducts with hydrogen-bond acceptors. , 2002, Acta crystallographica. Section B, Structural science.

[14]  S. Chemburkar,et al.  Dealing with the Impact of Ritonavir Polymorphs on the Late Stages of Bulk Drug Process Development , 2000 .

[15]  F. Allen The Cambridge Structural Database: a quarter of a million crystal structures and rising. , 2002, Acta crystallographica. Section B, Structural science.

[16]  A. Matzger,et al.  General Principles of Pharmaceutical Solid Polymorphism. A Supramolecular Perspective , 2004 .

[17]  Narayan Variankaval,et al.  Preparation and Solid-State Characterization of Nonstoichiometric Cocrystals of a Phosphodiesterase-IV Inhibitor and l-Tartaric Acid , 2006 .

[18]  Dan Boström,et al.  Pharmaceutical Cocrystal and Salts of Norfloxacin , 2006 .

[19]  A. Medek,et al.  Solid-state acid-base interactions in complexes of heterocyclic bases with dicarboxylic acids: crystallography, hydrogen bond analysis, and 15N NMR spectroscopy. , 2006, Journal of the American Chemical Society.

[20]  Orn Almarsson,et al.  Crystal engineering of novel cocrystals of a triazole drug with 1,4-dicarboxylic acids. , 2003, Journal of the American Chemical Society.

[21]  Sharmistha Datta,et al.  Crystal structures of drugs: advances in determination, prediction and engineering , 2004, Nature reviews. Drug discovery.

[22]  William Jones,et al.  Prediction and observation of isostructurality induced by solvent incorporation in multicomponent crystals. , 2006, Journal of the American Chemical Society.

[23]  L. Reddy,et al.  Carboxamide-pyridine N-oxide heterosynthon for crystal engineering and pharmaceutical cocrystals. , 2006, Chemical communications.

[24]  William Jones,et al.  Pharmaceutical Cocrystals: An Emerging Approach to Physical Property Enhancement , 2006 .

[25]  Alex M. Chen,et al.  Development of a pharmaceutical cocrystal of a monophosphate salt with phosphoric acid. , 2007, Chemical communications.

[26]  L Yu,et al.  Amorphous pharmaceutical solids: preparation, characterization and stabilization. , 2001, Advanced drug delivery reviews.

[27]  A. Beatty,et al.  "Total Synthesis" Supramolecular Style: Design and Hydrogen-Bond-Directed Assembly of Ternary Supermolecules. , 2001, Angewandte Chemie.

[28]  Naír Rodríguez-Hornedo,et al.  Cocrystal Formation during Cogrinding and Storage is Mediated by Amorphous Phase , 2006, Pharmaceutical Research.

[29]  J. McMahon,et al.  Crystal engineering of the composition of pharmaceutical phases. , 2003, Chemical communications.

[30]  T. Friščić,et al.  Screening for inclusion compounds and systematic construction of three-component solids by liquid-assisted grinding. , 2006, Angewandte Chemie.

[31]  W. Motherwell,et al.  Physical stability enhancement of theophylline via cocrystallization. , 2006, International journal of pharmaceutics.

[32]  G. Day,et al.  Investigating the latent polymorphism of maleic acid. , 2006, Chemical communications.

[33]  Michael J. Zaworotko,et al.  Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? , 2003, Chemical communications.