Argentum Pharmaceuticals LLC v. Research Corp Technologies Inc

1. Case Identification

• Case #: IPR2016-00204
• Patent #: RE38,551
• Filed: November 23, 2015
• Petitioner(s): Argentum Pharmaceuticals LLC
• Patent Owner(s): Research Corporation Technologies, Inc.
• Challenged Claims: 1-13

2. Patent Overview

• Title: Anticonvulsant Enantiomeric Amino Acid Derivatives
• Brief Description: The ’551 patent relates to specific enantiomers of functionalized amino acid derivatives, particularly (R)-N-Benzyl 2-Acetamido-3-methoxypropion-amide, known as lacosamide. The claims cover the compound itself (claim 1), therapeutic compositions containing it (claim 10), and methods for treating central nervous system disorders (claims 11-13).

3. Grounds for Unpatentability

Ground 1: Anticipation and Obviousness over LeGall and the ’729 Patent - Claims 1-13 are anticipated by LeGall or obvious over LeGall in view of the ’729 patent.

• Prior Art Relied Upon: LeGall (a 1987 master's thesis) and Patent 5,378,729 (’729 patent).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued LeGall, which Patent Owner had recently admitted qualifies as a prior art "printed publication," explicitly discloses racemic lacosamide (compound 107e). Because a racemic mixture is composed of both R- and S-isomers, Petitioner asserted this disclosure inherently anticipates claim 1 (which covers mixtures containing the R-isomer) and its dependent compound claims 3-8. For claims requiring substantial enantiopurity (claims 2 and 9) and for the composition and method claims (10-13), Petitioner argued the combination of LeGall and the ’729 patent rendered them obvious.
  • Motivation to Combine: A POSITA would be motivated to isolate the R-enantiomer from LeGall’s racemic mixture because both LeGall and the ’729 patent taught that the R-isomer was the biologically active form, being significantly more potent and less toxic than the corresponding S-isomer or racemate. The ’729 patent further provided the motivation to combine the active compound with a pharmaceutically acceptable carrier to create a therapeutic composition for treating CNS disorders like epilepsy.
  • Expectation of Success: A POSITA would have a high expectation of success in isolating the R-isomer using standard techniques like chiral chromatography, which were well-known in the art and acknowledged as routine in both the ’729 patent and the challenged ’551 patent itself.

Ground 2: Obviousness over Choi and Kohn 1991 - Claims 1-9 are obvious over Choi in view of Kohn 1991.

• Prior Art Relied Upon: Choi (a 1995 journal article) and Kohn 1991 (a 1991 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted a "lead compound" modification theory. Choi disclosed a hydroxymethyl compound (2d) as a useful synthetic intermediate for preparing new anticonvulsants. Kohn 1991 established a key structure-activity relationship (SAR) for this class of compounds, teaching that the "most potent" analogs were achieved when "a functionalized oxygen atom existed two atoms removed from the α-carbon atom" and demonstrated a significant (~16-fold) increase in potency when a hydroxyl group was converted to a methoxy group.
  • Motivation to Combine: A POSITA would select Choi's hydroxymethyl compound as a lead compound due to its disclosed synthetic utility and close structural similarity to other known anticonvulsants. Guided by the clear SAR teachings in Kohn 1991, a POSITA would be motivated to modify the hydroxyl group of Choi's compound to a methoxy group to achieve the predicted substantial increase in anticonvulsant activity. This single, routine modification yields lacosamide.
  • Expectation of Success: Converting a hydroxyl to a methoxy group via Williamson ether synthesis is a routine and predictable chemical procedure, giving a POSITA a very high expectation of success in synthesizing lacosamide.

Ground 3: Obviousness over Kohn 1991 and Silverman - Claims 1-9 are obvious over Kohn 1991 in view of Silverman.

• Prior Art Relied Upon: Kohn 1991 (a 1991 journal article) and Silverman (a 1992 textbook on drug design).

• Core Argument for this Ground:

  • Prior Art Mapping: Petitioner presented a bioisosterism argument starting from a different lead compound. Kohn 1991 identified the methoxyamino compound (3l) as the most potent analog disclosed, making it an attractive starting point for optimization. Silverman, a standard textbook, taught the well-known principle of bioisosterism, identifying the methylene group (-CH2-) as a classic bioisosteric replacement for a secondary amino group (-NH-).
  • Motivation to Combine: A POSITA would select the highly potent methoxyamino compound from Kohn 1991 as a lead compound. Recognizing that the methoxyamino moiety is uncommon in pharmaceuticals and could present stability or synthetic issues, a POSITA would be motivated to apply the established principle of bioisosteric replacement. Substituting the -NH- group of the methoxyamino moiety with a -CH2- group, as taught by Silverman, directly results in the methoxymethyl group of lacosamide, a more common and stable moiety.
  • Expectation of Success: Given that bioisosteric replacement was a common and well-understood strategy in drug design to improve properties while retaining activity, a POSITA would have a reasonable expectation that the resulting compound (lacosamide) would retain the high potency of the lead compound.

• Additional Grounds: Petitioner asserted additional obviousness challenges based on Cortes and Kohn 1991, which relied on a similar lead compound modification theory starting from the known "methyl compound" (AAB).

4. Key Claim Construction Positions

• "Therapeutic Composition" (in claim 10): Petitioner argued this preamble term is non-limiting and merely states an intended purpose. Under the Broadest Reasonable Interpretation (BRI), the claim only required an anticonvulsant effective amount of a claimed compound and a pharmaceutical carrier, contrary to a more limiting construction adopted in a related district court case.
• "A Compound in the R Configuration" (in claim 1): Petitioner argued the BRI covers any compound containing the R-isomer, whether it is substantially pure or part of a mixture (such as a racemate), so long as it is not the pure S-isomer. This construction was critical to the anticipation argument, as it would cause LeGall’s disclosure of racemic lacosamide to read on claim 1.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) would be inappropriate. The petition asserted that its primary reference, LeGall, was never considered on its substantive merits in any prior proceeding, as a previous IPR was denied institution based on a now-conceded argument that LeGall was not a "printed publication." Furthermore, Petitioner argued that Grounds 2, 3, and 4 were entirely new and had never been presented to the Patent Office.

6. Relief Requested

• Petitioner requests institution of an IPR and cancellation of claims 1-13 of Patent RE38,551 as unpatentable.