Cubist Pharms., Inc. v. Hospira, Inc.

Case Name:  Cubist Pharms., Inc. v. Hospira, Inc., No. 12-367-GMS, 2014 U.S. Dist. LEXIS 169679 (D. Del. Dec. 8, 2014) (Sleet, J.) (Valid certificate of correction results in finding of infringement and validity; remaining patents-in-suit are invalid as anticipated and/or obvious.)

Drug Product and Patent(s)-in-Suit: Cubicin® (daptomycin); U.S. Pats. Nos. 6,468,967 (“the ’967 patent”), 6,852,689 (“the ’689 patent”), 8,058,238 (“the ’238 patent”), 8,129,342 (“the ’342 patent”), RE39,071 (“the ’071 patent”)

Nature of the Case and Issue(s) Presented: Cubist alleged that Hospira’s ANDA products infringe the asserted claims of the patents-in-suit. The court held a five-day bench trial. The court found that Hospira infringed all of the elements of the asserted claims, but that all of those claims, except for the ones in the ’071 patent, were invalid. The claims of the ’071 patent were not invalid.

Why Cubist Prevailed:  The court began with analyzing the ’071 patent, and the Certificate of Correction (“Certificate”) included therewith. Hospira argued that the Certificate filed in 2007 was invalid because it did not correct a mistake of “minor character.” The claims of the ’071 patent only cover compounds of “Formula 3” as it was originally identified, prior to correction, having an L-asparagine amino acid in the tail portion of the chemical structure. Because its ANDA product possesses D-asparagine instead, Hospira argues that it does not infringe the ’071 patent. Although the Court found that “Hospira is certainly correct that Formula 3 in the corrected [’071] patent is different from the pre-correction Formula 3,” a Formula 2 compound is not defined just by its chemical structure but by additional language in the specification. Relying on language from the specification, the Court found that D-asparagine daptomycin was covered both before and after issuance of the Certificate. The patent was therefore valid and Hospira infringes.

Hospira next argued that if the Certificate is valid, then the ’071 patent is invalid for failing to meet the written description requirement. This argument too rested on the flawed premise that one would have looked solely at the chemical structure in the claim. Rather, the court found that a skilled artisan would have understood that the inventors possessed and were working with the naturally occurring daptomycin molecule and its fermentation by-product.

Next, Hospira contended that the ’071 patent is invalid because the patentee cancelled claim 24 during prosecution which claimed a composition of “substantially pure” daptomycin, and tried to recapture this surrendered subject matter in the asserted claims of the reissued patent. Cancelled claim 24 was directed to an anti-bacterial composition comprising daptomycin in substantially pure form; it did not require the inclusion of additional derivatives such as the Formula 1 or Formula 2 compounds that were later required, even if only in small amounts. Thus, the asserted claims are narrower than the cancelled claim 24, and they are not barred by the recapture rule.

Given Hospira’s stipulation to infringement of the remaining patents, the Court proceeded to assess those patents’ validity. The court found that the ’967 patent was invalid as anticipated. Hospira argued that two prior-art references—the Woodworth article and the ’226 patent—anticipated the ’967 patent. The only issue for the Court to decide was whether the claim element “minimizes skeletal muscle toxicity” was present in each of these references, which it did. “Regardless of whether one skilled in the art would be aware of it, following the suggestion disclosed by the Woodworth article [and the ’226 patent] (4-6 mg/kg/day) would have the physiological effect of minimizing skeletal muscle toxicity.” But because the Woodworth article identified the exact dosage amounts and interval claimed by the ’967 patent, only it—and not the ’226 patent—by virtue of its enabling disclosure was deemed to be anticipatory prior art.

Hospira then argued that the Woodworth article and the ’226 patent, in light of the known properties of daptomycin, render the asserted claims of the ’967 and ’689 patents obvious. Those properties include (i) daptomycin’s effectiveness is concentration-dependent; (ii) daptomycin has a longer half-life; (iii) daptomycin has a long post-antibiotic effect; and (iv) skeletal muscle toxicity resulting from daptomycin was known to be reversible in most cases. The Court found that the Woodworth article and the ’226 patent offered the base elements of the claimed invention, and that the additional knowledge and prior art available to one of ordinary skill would have presented a reasonable expectation of success at achieving the claimed invention. The Court did not find that the objective indicia weighed in favor of a finding of non-obviousness. The claims of the ’967 and ’689 patent are not commensurate with the long-felt need Cubist put forth—treatment of serious infections like S. aureusendocarditis (“SAE”)—because the claims cover bacterial infections generally. The weight of the “failure of others” factor becomes considerably more limited when it is acknowledged that others had only failed with respect to SAE. With regard to commercial success, the nexus is strongest for the use of Cubicin to treat SAE only. For Cubicin’s use in other infections, Cubist was unable to establish that the claimed features drove market success.

As to the ’238 and ’342 patents, those patents claim methods of purification as well as daptomycin compositions purified via particular processes: product-by-process claims. Hospira first argued that the ’843 prior-art reference anticipates claim 98 of the ’238 patent because the ’843 patent discloses a method of purifying daptomycin, producing compositions having at most 93% purity with respect to fourteen identified impurities. The issue presented is whether the daptomycin produced via the claim 98 process limitations is structurally and functionally different from that disclosed in the ’843 patent. And the Court found that it was. Both claims disclose methods of purifying daptomycin impurities—perhaps not to the exact same level—but ultimately to the point where the composition is 93% pure. The ’843 patent therefore renders claim 98 anticipated.

Then, Hospira argued that the asserted claims of the ’238 and ’342 patents cover two primary purification steps: (i) micelle or aggregate filtration, followed by (ii) anion exchange chromatography, and both are obvious. The prior art taught a skilled artisan that daptomycin displayed the properties of a surfactant. Other prior-art references taught that micelle filtration “can be further modified and employed for the recovery and purification of most surfactants.” The Court also found that anion exchange chromatography would have been an obvious method of purification to one skilled in the art. Therefore Hospira has established prima facie obviousness concerning the ’238 and ’342 patents. Cubist cited to a long-felt but unmet need to rebut obviousness. But while the processes described in the purity patents may have ultimately led to more efficient production, the claims themselves do not speak of yield. Simply because prior efforts had seen lower yields does not necessarily mean there was a “need” for processes with higher yields. Thus, secondary considerations did not upset the court’s prima facie obviousness finding.