Opinion ID: 803481
Heading Depth: 2
Heading Rank: 2

Heading: Cheng In View of Timmins Raises a

Text: Substantial Question of Validity We conclude that Lupin’s obviousness arguments regarding Cheng and Timmins, considered in light of the 13 SCIELE PHARMA v. LUPIN LTD prosecution history and the correct standard of proof, raise a substantial question of invalidity. Lupin argues that the asserted claims are obvious over Cheng in view of Timmins. Cheng discloses all of the limitations of the asserted claims except for the Tmax range of 5.5 to 7.5 hours (Cheng discloses a Tmax of 8 to 12 hours). Lupin asserts that Timmins discloses a Tmax within the range recited in the asserted claims, and argues that the combination of Cheng and Timmins thus renders the claims obvious to one skilled in the art. As further evidence that the combination would be obvious to one of ordinary skill in the art, Lupin points to the applicant’s assertion during prosecution “that one skilled in the art would be able to manipulate the processes and formulations of the [prior art] by other methods to obtain the claimed pharmacokinetic parameters of the present invention by routine experimentation.” J.A. 2621. Lupin claims that this statement amounts to an admission of obviousness and further bolsters its obviousness claim. Shionogi argues that the Tmax range of the asserted claims is missing from Cheng, but does not dispute that Cheng discloses the other limitations of the asserted claims. Its primary distinction with respect to Timmins is that Timmins discloses a median Tmax and not the claimed mean Tmax. Shionogi further argues that, regardless of the Tmax disclosed in Timmins, there is no motivation to combine Cheng with Timmins. We agree with Lupin that it has raised a substantial question of validity with respect to the ’866 patent. Amazon.com, 239 F.3d at 1350. We conclude that the district court’s obviousness analysis was flawed. It failed to correctly apply KSR focusing on what it perceived was “a fundamental factual difference between this case and KSR,” namely that Cheng and Timmins were before the PTO during prosecution. Sciele, 2012 U.S. Dist. LEXIS 22782, at SCIELE PHARMA v. LUPIN LTD 14 -10; -20. The court incorrectly rejected Lupin’s substantive arguments regarding Timmins’s disclosure of a Tmax within the claimed range and the motivation to combine Cheng and Timmins. The ’866 patent admits that Cheng “discloses controlled release metformin formulations providing a Tmax from 8 to 12 hours.” ’866 patent col.2 ll.46-47. Although Timmins expressly discloses a median Tmax, it also provides the raw data from which one skilled in the art could compute the range of possible mean Tmax values. J.A. 2501-02. 2 Based on this data, one skilled in the art would understand that the mean Tmax in Timmins must fall between 4.67 and 6.33 hours. Counsel for Shionogi agreed that the only element missing from Cheng is the Tmax range, and that Timmins discloses a range of possible mean Tmax between 4.67 and 6.33 hours. See Oral Argument at 19:55-20:33, available at http://www.cafc.uscourts.gov/oral-argumentrecordings/2012-1228/all. Timmins thus teaches one skilled in the art to lower the Tmax of Cheng (8 hours). We also conclude that the district court clearly erred in its conclusion that there was no motivation to combine Cheng and Timmins. Timmins describes a controlled release formulation of metformin and explains that its formulation releases metformin in the portion of the gastrointestinal tract where better absorption of the drug can occur. J.A. 2470-73. The earlier release of the drug increases bioavailability and leads to a lower Tmax. Id. Timmins explains that “improved bioavailability from an extended release dosage form that releases metformin at a rate likely to provide the desired plasma levels of drug for 2 Timmins discloses that its study included 24 pa- tients and resulted in a median Tmax of 5 hours, with a minimum Tmax of 4 hours and a maximum Tmax of 8 hours. 15 SCIELE PHARMA v. LUPIN LTD an extended time period [could result] from a dosage form that has extended residence time in the upper gastrointestinal tract.” J.A. 2472-73. In other words, that earlier release, resulting in a lower Tmax, provides the benefit of “the desired plasma levels of drug for an extended time period.” Id. Timmins also identifies a number of benefits stemming from an earlier extended release, including “reduction in dosing frequency, providing patient convenience that would probably improve compliance” as well as “an extended time period over which therapeutically beneficial plasma levels of drug were maintained.” Id. These benefits would motivate one skilled in the art to modify Cheng to achieve a lower Tmax range. Cf. KSR, 550 U.S. at 424. Further motivation to pursue the approach in Timmins comes from the fact that lowering the Tmax allows one skilled in the art to approach the drug profile of Glucophage, the industry standard drug. J.A. 2469. In fact, Timmins expressly compares its extended release formulations to Glucophage with respect to various factors including Tmax. J.A. 2502. Timmins explains that, in light of this analogous kinetic profile and other identified benefits, the “formulations of the invention thus represent a useful advance in the administration of metformin hydrochloride to human[s] in the treatment of diabetes.” Id. Timmins thus articulates an explicit motivation to lower the Tmax in Cheng–to better match the Tmax profile of Glucophage while providing the convenience of an extended release. The applicant’s arguments during prosecution further buttress our belief that Lupin has raised a substantial question of validity with respect to the ’866 patent. During prosecution the applicant indicated “that one skilled in the art would be able to manipulate the processes and formulations of the [prior art] by other methods to obtain the claimed pharmacokinetic parameters of the present invenSCIELE PHARMA v. LUPIN LTD 16 tion by routine experimentation.” J.A. 2621. While Shionogi argued, and the district court seemed to accept, that this statement applies only to enablement, we are hard pressed to understand this distinction. Coupled with the motivation to lower the Tmax, as disclosed in Timmins, the applicant’s characterization of the predictability and skill in the art during prosecution provides further evidence that it would have been a routine and obvious design choice to make an extended release dosage form with a lower Tmax. After all, “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 550 U.S. at 417. Shionogi fails to effectively rebut Lupin’s argument that Timmins itself supplies a motivation to modify Cheng to lower the Tmax of a controlled release formulation to match that of an immediate release formulation. Likewise, Shionogi does not establish that Lupin’s arguments regarding the advantages of the lower Tmax disclosed in Timmins are unsound. We therefore believe the combination of Cheng and Timmins raises a substantial question as to the validity of the ’866 patent. Amazon.com, 239 F.3d at 1350.