Galderma Labs., L.P., v. Tolmar, Inc.

Because prior art shows that increased drug concentration caused irritation, it taught away from claimed invention that disclosed tripling prior art ranges, and therefore asserted claims were not obvious; no inequitable conduct; not invalid for lack of written description; no standing to sue as to non-exclusive licensee.

October 16, 2012

GENERICally Speaking

Case Name: Galderma Labs., L.P., v. Tolmar, Inc., Civ. No. 10-45-LPS, 2012 U.S. Dist. LEXIS 139524 (D. Del. Sept. 11, 2012) (Stark, J.)

Drug Product and Patent(s)-in-Suit: Differin® (0.3% adapalene); U.S. Pat. Nos. 7,737,181 (“the ‘181 patent”), 7,838,558 (“the ‘558 patent”), 7,834,060 (“the ‘060 patent”), and 7,868,044 (“the ‘044 patent”)

Nature of the Case and Issue(s) Presented: The active ingredient in Galderma’s Differin® is a 0.3% adapalene in topical gel solution. On September 14, 2009, Tolmar filed an ANDA, including a Paragraph IV certification, seeking approval to market a generic version of the 0.3% adapalene topical gel. Galderma filed suit. A bench trial was held from March 5 to March 14, 2012. Various issues were presented at trial: (i) were the asserted claims invalid on the basis of anticipation and/or obviousness; (ii) had Galderma engaged in inequitable conduct; (iii) were certain asserted claims invalid for lack of written description; and (iv) did plaintiffs have standing to assert the patents covering Differin.

Why Galderma Prevailed:  The court first considered Tolmar’s allegations that the claims of the asserted patents were obvious in view of a number of prior art references.  The first prior art reference was identified as the Shroot Patents. Those patents disclosed various benzophthalene derivatives (including adapalene) and claimed concentrations of those derivatives in a range between 0.01% to 1.0% by weight. The court noted that although the 0.3% concentration at issue fell within that prior art range, there was an enormous number of compounds and concentrations identified in the references, and there was no specific teaching that would direct a skilled artisan to select 0.3% adapalene to treat acne. Tolmar also introduced a data sheet that included Differin (at 0.1% concentration) and claimed that the excipients identified in the data sheet were the same as the excipients identified in the 0.3% patented formulation. The court disagreed that this reference was significant, because while the data sheet identified an identical excipient gel, it did not identify the use of a 0.3% adapalene formulation. The court next considered a prior art Phase I clinical study (“Vershoore”) conducted in 1997 where a 0.3% adapalene solution was applied to the backs and forearms of healthy patients. The court agreed with Galderma that the fact that the 0.3% solution did not result in significantly higher side effects during the clinical trial than the 0.1% solution would not have been obvious to one skilled in the art because the test subjects and area of treatment (back vs. face) were different from the population and disorder treated with Differin. Similar to the Vershoore study, Tolmar also introduced an abstract that referenced a Goldfarb reference. Goldfarb described a study where 0.1% and 0.3% adapalene formulas were used to treat actinic keratosis in a population of patients in their mid-60s with heavily sun-damaged skin. The court again determined that this reference would not have made it obvious for a skilled artisan to use a 0.3% adapalene formulation to treat acne in teen-aged patients because the disease at issue in the abstract (actinic keratosis) was different than acne, and the patient population was much more advanced in age, and typically had skin that was thicker and more resilient than the skin found on the face of teenaged patients who were the target population for Differin. Finally, Tolmar introduced two additional references (Euvrard and Czernielewski) that the court again discounted because the references addressed disorders other than acne or target populations that differed substantially from the target population for Differin. The court found that the prior art references taught away from increasing the concentration of adapalene from 0.1% to the claimed 0.3% formulation. Specifically, the court identified studies where an increased irritation was observed when adapalene concentrations were increased from 0.03% to 0.1%. The available prior art references in combination seemed to indicate that tripling the then-accepted 0.1% concentration adapalene formulation would have resulted in a substantial increase in irritation. Coupling the aforementioned findings with two secondary considerations of non-obvious—unexpected results and commercial success—that the court found to be well supported, the court held that the asserted claims were not obvious.

The court next analyzed Tolmar’s allegation that the asserted claims of the ‘558 and ‘044 patents were invalid for lack of written description under 35 U.S.C. § 112. Tolmar’s argument was that the claims at issue failed to provide adequate written support for the treatment of severe forms of acne. The court rejected this defense, finding that Galderma had presented persuasive evidence at trial that it was well-known in the art that topical retinoids could be used in combination with other agents as part of a treatment algorithm to treat severe acne.

Tolmar’s inequitable conduct allegations were likewise rejected. Tolmar alleged that the inventors withheld from the USPTO three material prior art references. Specifically, the three references disclosed that adapalene was known to be well-tolerated. The court found that the three references failed to meet the “but for” materiality standard required by the Federal Circuit in Therasense. According to the court, the references were cumulative of other prior art that was already before the USPTO. Additionally, the court found that Tolmar failed to provide any evidence that Galderma had engaged in affirmative acts of egregious misconduct, nor had it manifested an intent to deceive the USPTO in its omission of the prior art references.

At trial, Tolmar stipulated to infringement of all asserted claims with the exception of claim 27 of the ‘060 patent. Tolmar’s non-infringement argument was based on the fact that its proposed generic formulation used a different wetting/dispersing agent (poloxamer 182) than the compound claimed in claim 27 (poloxamer 124). The court rejected Tolmar’s argument and found that the generic formulation still infringed under the doctrine of equivalents. The court concluded that poloxamer 124 and 182 performed substantially the same function, in substantially the same way to achieve substantially the same result.

Last, the court considered Tolmar’s argument that Galderma R&D was the only named plaintiff that had standing to assert the patents-in-suit. Before the court were three agreements between the co-plaintiffs executed in 1995, 1998 and 2004. After reviewing the provisions of each agreement, the court concluded that co-plaintiff Galderma Laboratories, L.P. was a non-exclusive licensee. Its conclusion was based on the fact that at the time the 1998 sub-license agreement between Galderma S.A. and Galderma Labs was executed, Galderma S.A. only possessed non-exclusive rights to adapalene, and therefore could not confer exclusive rights to Galderma Labs. Accordingly, the court dismissed co-plaintiff Galderma Labs from the suit for lack of subject matter jurisdiction, leaving Galderma R&D as plaintiff.

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