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September 4, 2010

Bone Loss

Eli Lilly got 6,458,811 and 6,894,064 (the "Particle Size Patents") for processing "raloxifene particles until their size falls 'within a specified narrow range.'" Raloxifene, an antiestrogen, aims at treating osteoporosis in women by mimicking estrogen, without inciting increased incidence of breast cancer. 6,906,086; RE39,049; and RE38,968 (the "Bone Loss Patents") aim more specifically at preventing bone loss. RE39,050 was called by the court "the Low Dose Patent." Generic drug manufacturer Teva embroiled itself into a patent fight with Lily by filing an ANDA with the FDA to make generic versions. Lilly prevailed on all but the Particle Size Patents - not invalidated by prior art, but by failing the written description requirement of §112.

Eli Lilly v. Teva Pharmaceuticals USA (CAFC 2010-1005, 1033) precedential

Teva argued the Bone Loss Patents and Low Dose Patent were obvious.

Under 35 U.S.C. § 103, a patent claim is invalid "if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art." An accused infringer must prove invalidity by clear and convincing evidence. Robotic Vision Sys., Inc. v. View Eng'g, Inc., 189 F.3d 1370, 1377 (Fed. Cir. 1999). "On appeal from a bench trial, the ultimate determination of whether an invention would have been obvious under 35 U.S.C. § 103 is a legal conclusion that we review de novo." Id. at 1376. An obviousness determination, however, is based on underlying factual inquiries including: (1) the scope and content of the prior art; (2) the level of ordinary skill in the art; (3) the differences between the claimed invention and the prior art; and (4) objective evidence of nonobviousness. Id.; see KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 405 (2007).

The district court concluded that the widely reported bioavailability concerns would have precluded a person of ordinary skill in the art from reasonably expecting to successfully treat postmenopausal osteoporosis with raloxifene.

Teva pointed to prior art, but...

Teva points to no evidence from before the time of invention that would teach, suggest, or motivate or supply any common sense reason for a person of ordinary skill in the art to reject the bioavailability concerns and routinely, simply, or easily arrive at the inventive result.

Teva came up with a new invalidity argument on appeal, not raised in district court: nonstatutory double patenting: "that if the Bone Loss Patents are valid, then the Low Dose Patent claims are invalid for nonstatutory double patenting."

Nonstatutory double patenting was borne out of 35 U.S.C. § 101, not § 103. Specifically, § 101 precludes more than one patent on the same invention. This court's predecessor, concerned that applicants could evade that § 101 requirement by drafting claims that "vary slightly from the earlier patent," fashioned the doctrine of nonstatutory double patenting "to prevent issuance of a patent on claims that are nearly identical to claims in an earlier patent." Geneva Pharm., Inc. v. Glaxosmithkline PLC, 349 F.3d 1373, 1377-78 (Fed. Cir. 2003). The primary inquiry in double patenting cases is therefore whether the claims in the latter patent are more than a "slight variant" from the claims in the earlier patent. Id. (citing In re Lonardo, 119 F.3d 960, 965 (Fed. Cir. 1997)). Nonetheless, nonstatutory double patenting is sometimes referred to as "obviousness-type" double patenting, id. at 967, and "prevents the extension of the term of the original patent via the patenting of an obvious variation." Georgia-Pacific Corp. v. U.S. Gypsum Co., 195 F.3d 1322, 1326 (Fed. Cir. 1999).

The CAFC waived Teva away on that, as "the record is insufficiently clear for it to conclude that the proper resolution is beyond any doubt."

Next, enablement on the Bone Loss Patents and Low Dose Patent.

Section 112, first paragraph, requires a patent specification to enable a person of skill in the art to make and use the claimed invention. The enablement requirement "incorporates as a matter of law the requirement of 35 U.S.C. § 101 that the specification disclose as a matter of fact a practical utility for the invention." Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1323 (Fed. Cir. 2005) (internal quotation marks omitted). "In the context of determining whether sufficient utility as a drug, medicant, and the like in human therapy has been alleged, it is proper for the examiner to ask for substantiating evidence unless one with ordinary skill in the art would accept the allegations as obviously correct." Id. (internal quotation marks omitted).

Teva argues that if the Jordan Reference did not render the Bone Loss Patents obvious due to concerns about raloxifene's bioavailability, then the disclosure in the Bone Loss Patents and the Low Dose Patent could not have been enabling because of the prevailing view that raloxifene would not work in humans. This contention fails on this record because the Bone Loss Patents disclose two sets of information not found in the prior art.

The problem with Teva's argument is that it once again treats all bioavailability issues the same. As the party with the burden both in the district court and in this court, Teva must do more.

Teva had lumped together studies related to breast cancer with that focused on bone loss.

Second, the Bone Loss Patents describe the details of a human clinical study, which was ongoing at the time the application was filed. As the district court acknowledged, the Manual of Patent Examining Procedure (MPEP) explains that the initiation of a clinical trial has a significant impact on the PTO's utility inquiry:

Before a drug can enter human clinical trials, the sponsor, often the applicant, must provide a convincing rationale to those especially skilled in the art (e.g., the Food and Drug Administration) that the investigation may be successful. Such a rational would provide a basis for the sponsor's expectation that the investigation may be successful. In order to determine a protocol for phase I testing, the first phase of the clinical investigation, some credible rationale of how the drug might be effective or could be effective would be necessary. Thus, as a general rule, if an applicant has initiated human clinical trials for a therapeutic product or process, Office personnel should presume that the applicant has established that the subject matter of that trial is reasonably predictive of having the asserted therapeutic utility.

MPEP (2008) § 2107.03 at IV (emphasis added).

By that, the CAFC affirmed that the patents were enabled.

Finally, the Particle Size Patents lost their backbone for failing to disclose how to accomplish what was claimed.

[T]he district court determined that the question of infringement turned on an issue of claim construction, namely, "whether the particle size patents claim only size measurements made on bulk raloxifene before it is formulated or, by contrast, whether the patents also claim the particle size of raloxifene within a formulated tablet, as measured after extraction from the tablet." Eli Lilly, 657 F. Supp. 2d at 1021. The district court concluded that the limitation "in particulate form" as used in the Particle Size Patents should be construed broadly to include raloxifene particles both before and after formulation.

Even though Lilly won on claim construction, the district court ruled that the breadth of the limitation rendered the Particle Size Patents invalid for failure to comply with the written description requirement of 35 U.S.C. § 112, first paragraph. The district court noted that the Particle Size Patents did not disclose the idea of measuring the particle size of raloxifene extracted from a tablet, nor did the inventors perform any tests to determine how the granulation or tableting process could affect particle size. Moreover, the district court concluded,

after reading the patent, a person of ordinary skill in the art would not understand how to extract raloxifene particles from a formulation in order to determine whether they fall within the claimed particle size range and, in fact, would have no indication that size measurements on anything other than unformulated raloxifene would bear any relevance to the invention.

Id. at 1027.

Lilly countered with a two-pronged attack. First, that Teva's argument was belated: after invalidity contentions. The district court held that Lilly had sufficient notice. The CAFC ruled that Lily failed to establish district court abuse of discretion.

Second, Lilly argues that the district court applied an improper test in determining whether the Particle Size Patents comply with the written description requirement of § 112, first paragraph. As this court recently confirmed, the test for written description is "whether the disclosure of the application . . . reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). The district court's decision, which was issued before this court's en banc decision in Ariad, appears in some places to have been premised on a misunderstanding of that test. Certain statements indicate that the district court may have been focused on whether "a person of ordinary skill in the art would . . . understand how to extract raloxifene particles from formulation in order to determine whether they fall within the claimed particle size range." Eli Lilly, 657 F. Supp. 2d at 1027. The test for written description, however, has never been whether the patent includes a description of the steps that may be used to prove infringement.

Nonetheless, the written description requirement is a question of fact, Ariad, 598 F.3d at 1351, which this court reviews for clear error, Ralston Purina Co. v. Far-Mar-Co, Inc., 772 F.2d 1570, 1575 (Fed. Cir. 1985). The district court here concluded that "a person of skill in the art would not understand the inventors of the particle size patents to have invented anything other than 'a control strategy for . . . the particle size distribution . . . of the bulk drug substance,' as expressly provided in the specification." Eli Lilly, 657 F. Supp. 2d at 1027 (quoting the '811 patent, col.25 ll.60-61).

This court cannot characterize that finding as clearly erroneous. The patent specification only discloses measurements of bulk raloxifene. The record then features conflicting evidence about the reading a person of ordinary skill in the art would give to the passages to determine that the inventor possessed the invention of formulated raloxifene falling within the claimed size range. Lilly's own expert conceded that "[o]ne reading the [Particle Size Patent] in 1996 would not know whether the particle size was being increased or decreased [or remain the same] in the formulation." J.A. 3362 at 1434:1-10. With that concession, Lilly cannot establish that the district court made a clearly erroneous factual finding. Thus, this court affirms the district court's judgment invalidating the asserted claims of the Particle Size Patents.


Posted by Patent Hawk at September 4, 2010 7:29 PM | § 112


Nice case Hawk. I'm looking forward to reading it myself. I have a feeling there is a comparison to be made here, with a well-known "subject matter added during prosecution" case in Europe, DSS v. ECB, still running, in which the EPO issued to a lone inventor a patent with claims covering every banknote in Euro-land. The Examining Division was adamant, that his patent application contained nothing patentable, so the inventor had to go and see the Appeal Board. During the Hearing, his attorney slipped in a claim amendment, to wriggle the application through to issue.

The inventor found an investor, who then brought proceedings against the European Central Bank (ECB). The duly issued claims had the accused product well covered, and the patent turned out to be valid on all the usual heads. ECB's remaining hope lay in Europe's equivalent of the "written description" provision.

In Germany, the (specialist and expert) Federal Patents Court was having none of it. It took a trip to the German Supreme Court to get a reversal of that decision.

The interesting thing in Europe (and perhaps also now in the USA following Ariad) is whether such cases increase the difficulties an Applicant fces, in getting through to issue claims that have been amended during prosecution. Americans have always complained bitterly, how mean the EPO is about admitting prosecution amendments to the claims, but I doubt it is going to get any easier for them, any time soon.

Posted by: MaxDrei at September 5, 2010 12:59 AM