GlaxoSmithKline PLC v. Hikma Pharm. Co. Ltd.

Finding that the ANDA product did not infringe the asserted claims (literally or under the doctrine of equivalents) since propylene glycol is not a saccharide; the claims were sufficiently enabled.

October 16, 2012

GENERICally Speaking

Case Name: GlaxoSmithKline PLC v. Hikma Pharm. Co. Ltd., Civ. No. 12-1965 (FLW), 2012 U.S. Dist. LEXIS 115736 (D.N.J. August 16, 2012) (Wolfson, J.)

Drug Product and Patent(s)-in-Suit: Argatroban® (argipidine/arginineamide); U.S. Pat. No. 5,214,052 (“the ’052 patent”)

Nature of the Case and Issue(s) Presented:  Hikma filed an ANDA seeking to market a generic version of Argatroban before the expiration of the ’052 patent.  GSK initially sought to preliminarily enjoin Hikma from introducing its generic product; however, because of the limited issues, the parties agreed to resolve the dispute in an expedited hearing.  The first issue presented was whether propylene glycol is a “saccharide” as understood by the ’052 patent.  The claims of the ’052 patent are directed to a method and a pharmaceutical injection containing argatroban and a solvent system containing ethanol, water, and a saccharide (the “three solvent system”).  The court defined “saccharide” as “monosaccharide, oligosaccharides, polysaccharides, and their reduced derivatives (for example sugar alcohol) which are soluble in water.”  Hikma’s proposed generic product contained propylene glycol.  There was no dispute between the parties that propylene glycol is not a monosaccharide, an oligosaccharide, or a polysaccharide.  GSK argued that propylene glycol can be derived from a saccharide, which requires, at a minimum, two reduction reactions.  Thus, the question before the court was whether propylene glycol could be a “reduced derivative.”  The parties framed the question as whether “reduced derivatives” allows for “doubly-reduced” derivate compounds or “directly-reduced” derivative compounds.  The court determined that the phrase, “reduced derivatives” are compounds that must result from a single reduction reaction of the base saccharide compound. Relying on the intrinsic evidence, the court found that propylene glycol did not meet the saccharide limitation and Hikma’s formulation did not literally infringe the ’052 patent.  The court also found that the Hikma formulation did not infringe under the doctrine of equivalents since propylene glycol does not perform in substantially the same way and does not produce substantially the same results as saccharide.  Yet the court explicitly did not make a finding that the prosecution history estoppel applied.

The second issue presented is whether the patent was sufficiently enabled.  Hikma framed the issue as if the term “saccharide” is so expansive as to include compounds such as propylene glycol, then a person of ordinary skill in the art could not practice the patent without undue experimentation.  First, the Court noted that the issue of whether the ’052 patent was enabled had been discussed in detail by the Southern District of New York and the Federal Circuit. Both found the patent to be enabled, although they were considering different legal arguments. Relying on the construction of saccharide and those previous court decisions, the Court found the patent to be sufficiently enabled.

Why Hikma Prevailed:  Hikma prevailed because the patent term “saccharide” could not be expanded to cover propylene glycol. Relying heavily on statements made in the patent specification and the prosecution history, the court found that GSK could not expand saccharide to encompass propylene glycol.  During the prosecution of the ’052 patent application, the patentee cancelled all pending claims not containing the three solvent system - ethanol, water, and a saccharide.  In addition, the examiner rejected the pending claims based on prior art teaching that the drug solubility in water can be increased with the addition of co-solvents such as an alcohol, propylene glycol, polyethylene glycol, and the like.  Throughout the ’052 patent application prosecution, the patentee made statements distinguishing prior art that discussed propylene glycol from the claimed invention.  The prior art contained a four solvent system - water, ethanol, propylene glycol, and sorbitol.  While the patentee did not explicitly state that propylene glycol is not a saccharide, the patentee discussed only one of the four compounds – sorbitol.  The court found this to be a clear and unmistakable statement to one of ordinary skill in the art that the patentee did not consider propylene glycol to be a saccharide.  The court was also not persuaded by GSK’s argument that “doubly-reduced” compounds could fall within the meaning of the term “saccharide.” The court determined that GSK’s argument, followed to its logical conclusion, could bring limitless numbers of compounds within the definition of “saccharide.” 

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