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Purdue Pharma, L.P. v. Collegium Pharmaceutical, Inc.

United States District Court, D. Massachusetts

September 28, 2018



          F. Dennis Saylor IV, United States District Judge

         This is a patent dispute concerning a pharmaceutical product: abuse-deterrent, extended-release oxycodone. Plaintiffs Purdue Pharma L.P.; The P.F. Laboratories, Inc.; Purdue Pharmaceuticals L.P.; and Rhodes Technologies (collectively, “Purdue”) have brought suit against Collegium Pharmaceutical, Inc. The amended complaint asserts claims for infringement of three related patents pursuant to 35 U.S.C. §§ 271(a), (b), (c), and (e)(2)(A). The patents at issue are U.S. Patent Nos. 9, 073, 933 (“the '933 patent”), 8, 652, 497 (“the '497 patent”), and 9, 155, 717 (“the '717 patent”). The infringement claims arise out of Collegium's filing of a New Drug Application (“NDA”) for its abuse-deterrent, extended-release oxycodone products, XTAMPZA ER. On November 21, 2017, the Court issued a Memorandum and Order on Claim Construction, in which it construed five disputed claim terms.

         Collegium has moved for summary judgment on three grounds. First, it maintains that the '933 patent is invalid under a theory of issue preclusion, or collateral estoppel. That contention is based on a judgment from the Southern District of New York, affirmed by the Federal Circuit, that three related patents owned by Purdue are invalid. Second, Collegium asserts that even if the '933 patent is valid, it is entitled to judgment of non-infringement as a matter of law because it is not literally infringing and oxycodone myristate (the active ingredient in its product) is not the equivalent of oxycodone hydrochloride (the active ingredient in Purdue's product). Third, it argues that summary judgment of non-infringement of the '497 and '717 patents is appropriate because those patents claim the addition of an “irritant, ” and its product does not contain an “irritant.”

         For the following reasons, Collegium's motion for summary judgment will be granted in part and denied in part.

         I. Background

         Unless otherwise noted, the following facts are undisputed.

         A. Factual Background

         This dispute concerns pharmaceutical products designed to deter abuse of addictive pain medications, such as oxycodone, as well as methods for reducing potentially toxic impurities in oxycodone pharmaceuticals.

         1. Oxycodone Generally

         Oxycodone is an opioid. (Pl. SOF ¶ 91). Opioid drugs are used to treat pain, but are also subject to abuse. (Def. SOF ¶ 3; Pl. SOF ¶ 91). Extended-release (“ER”) formulations of oxycodone are often prescribed to treat severe pain that requires around-the-clock dosing. (Def. SOF ¶ 2; Pl. Response ¶ 2). ER formulations contain a larger amount of oxycodone than other dosage forms because the oxycodone is intended to be released over a 12- to 24-hour period. (Def. SOF ¶ 5; Pl. Response ¶ 5). For example, Purdue's original ER OxyContin, which was approved by the U.S. Food and Drug Administration in 1995, was designed to deliver oxycodone over a 12-hour period. (Pl. SOF ¶ 93).

         2. Abuse-Deterrent Oxycodone

         Unfortunately, the ER formulations of oxycodone are attractive to abusers. To “dose-dump, ” defeat the ER mechanism, and receive a rapid high, abusers may crush or dissolve the drug and then orally ingest, insufflate (that is, snort), smoke, or inject the drug. (Def. SOF ¶¶ 5- 6; Pl. Response ¶¶ 5-6).

         As a result, the FDA has placed a high priority on the development of abuse-deterrent opioids. (Def. SOF ¶ 9; Pl. Response ¶ 9). The FDA approved an abuse-deterring version of OxyContin in 2010. (Pl. SOF ¶ 94). That version incorporated two features: (1) a harder tablet, to resist crushing, and (2) a gelling agent, to impede snorting and injecting of any powder resulting from successful crushing. (Id.). Those features are the subject of two of the patents at issue (the '497 and '717 patents). In April 2013, the FDA granted abuse-deterrent OxyContin the first abuse-deterrent labeling. (Pl. Response ¶ 8).

         Collegium has developed an abuse-deterrent, ER formulation of oxycodone called XTAMPZA ER. (Def. SOF ¶ 14; Pl. Response ¶ 14). Collegium filed an NDA with the FDA for XTAMPZA ER, seeking approval to manufacture and sell the drug. (See, e.g., Def. SOF ¶ 24). That NDA forms the basis of Purdue's First Amended Complaint (“FAC”) for patent infringement.

         3. Removal of Impurities from Oxycodone

         Oxycodone, as manufactured, contains a potentially toxic impurity. The impurity is 14- hydroxycodeinone (“14-hydroxy”), an alpha, beta-unsaturated ketone (“ABUK”).

         The FDA has been concerned about lowering or eliminating the level of 14-hydroxy for some time. In re OxyContin Antitrust Litigation, 994 F.Supp.2d 367, 385 (S.D.N.Y. 2014). In February 2003, Purdue submitted a supplemental NDA to the FDA. Id. In January 2004, the FDA approved the request with several conditions. Id. Among those conditions was to either provide evidence that the level of 14-hydroxy in its oxycodone was safe, to lower the level of 14-hydroxy to less than ten parts per million (10 ppm). Id.

         B. Patents at Issue

         1. The '933 Patent

         a. Description of the Patent

         The '933 patent is entitled “Oxycodone Hydrochloride Having Less Than 25 PPM 14-Hydroxycodeinone.” It was issued on July 7, 2015. ('933 patent). Purdue is a named assignee.[1]

         The '933 patent claims both a product (an oxycodone composition) and a process for preparing it by removing a source of 14-hydroxy from that product-that is, 8α, 14-dihydroxy-7, 8-dihydrocodeinone (“8α”)-during manufacture. Representative claim 1 recites “An oxycodone hydrochloride composition which comprises at least 95% oxycodone hydrochloride and [8α] and less than 25 ppm of [14-hydroxy].” Representative claim 10 recites “A process for preparing an oxycodone hydrochloride composition having less than 25 ppm [14-hydroxy], comprising removing [8α] from an oxycodone base composition and converting the oxycodone base composition to an oxycodone hydrochloride composition having less than 25 ppm [14- hydroxy].”[2]

         According to the patent, methods for reducing the amount of 14-hydroxy in an oxycodone hydrochloride composition were known in the prior art. (Id. col.1, ll. 47-col. 2 ll. 2). At the time of the patent, existing procedures for reducing toxicity in oxycodone hydrochloride produced levels of 14-hydroxy greater than 100 ppm. (Id. col. 2 ll. 12-19).

         b. Prosecution History

         During prosecution of the '933 patent, an examiner from the United States Patent and Trademark Office (“PTO”) rejected all of the claims in Purdue's application on the ground of obviousness-type double patenting. (See Def. Ex. 17 at 5-6). The examiner's determination was based on a comparison to Purdue's existing patents, including the low-ABUK patents. The rejection read: “Although the conflicting claims are not identical, they are not patentably distinct from each other because Oxycodone hydrochloride [API] having less than 25 ppm [14-hydroxy] of the cited patent encompasses [the] instant claims.” (Def. Ex. 17 at 6).

         To avoid the double-patenting rejection, Purdue filed terminal disclaimers on October 1, 2014. (See Def. Ex. 18 at 12-13).[3] Purdue noted that it “traverse[d] these rejections” and that “[t]he filing of these terminal disclaimers is neither an admission of the propriety of the rejections nor an admission that the inventions claimed . . . are not ‘independent and distinct' from the inventions” of the low-ABUK patents. (Def. Ex. 18 at 13).

         The examiner maintained the obviousness rejection of the '933 patent claims in light of the prior art. (See Pl. Ex. 30 at 6-10). In response, on March 4, 2015, Purdue asserted that the examiner acknowledged that “the existence of [8α] was not known prior to the priority date of the present application, ” and that therefore “one skilled in the art would not have ‘figured out to dehydrate [8α]' as asserted by the Examiner.” (Pl. Ex. 30 at 7). On March 23, 2015, after Purdue's response was submitted, the examiner allowed the claims. (See Pl. Ex. 31).

         2. The '497 Patent

         The '497 patent is entitled “Pharmaceutical Formulation Containing Irritant.” It was issued on February 18, 2014. ('497 Patent). Purdue Pharma L.P., is the named assignee on the '497 and '717 patents.[4]

         The '497 patent is generally directed to “provide an oral dosage form of an opioid analgesic which is subject to less parenteral . . . intranasal . . . [and] oral abuse than other dosage forms.” (Id. col. 2 ll. 14-22). The patent is also directed to preventing abuse of drugs other than opioid analgesics that may be the subject of abuse. (Id. col. 5 ll. 35-40). At the time the patent was issued, a number of other techniques were known for deterring opioid abuse. (Id. col. 1 ll. 28-41, 55-67; Id. col. 1 ll. 1-4). In certain embodiments, the patent provides an opioid product that includes “an aversive agent such as an irritant to discourage from tampering with the dosage form and thereafter inhaling, injecting, or swallowing the tampered dosage form. Preferably, the irritant is released when the dosage form is tampered with and provides a burning or irritating effect to the abuser upon inhalation, injection, and/or swallowing of the tampered dosage form.” (Id. col. 2 ll. 52-59).

         3. The '717 Patent

         The '717 patent is entitled “Pharmaceutical Formulation Containing Irritant.” It was issued on October 13, 2015. ('717 Patent). The '717 patent shares a specification with the '497 patent.

         C. Previous Litigation Concerning the Same or Similar Patents

         1. The Teva Litigation

         Prior to the filing of this lawsuit, Purdue sued Teva Pharmaceuticals, USA, Inc. in the Southern District of New York, for infringement. Purdue alleged that Teva's generic drugs infringed U.S. Patent Nos. 7, 674, 799 (“the '799 patent”), 7, 647, 800 (“the '800 patent”), and 7, 683, 072 (“the '072 patent”) (collectively, “the low-ABUK patents”). Teva argued that the asserted claims of the low-ABUK patents were invalid. See In re OxyContin Antitrust Litig., 994 F.Supp.2d 367, 376 (S.D.N.Y. 2014) (“Teva”).

         On January 14, 2014, after a twenty-day bench trial, Judge Sidney H. Stein issued findings of fact and conclusions of law in a lengthy memorandum decision. See Teva, 994 F.Supp.2d at 376. In substance, Judge Stein found that each of the asserted claims was invalid as obvious in light of the prior art.

         Judge Stein reviewed the history of the claimed invention at some length. Id. at 384-87. He noted that Purdue had been attempting to find ways to reduce 14-hydroxy levels in its oxycodone since at least 2001. Id. at 384. He further noted:

         To manufacture oxycodone, Purdue employed these steps:

[F]irst, it oxidized thebaine, a derivative of the opium poppy, to form 14-hydroxy; second, [it] hydrogenated the 14-hydroxy to form oxycodone free base; and third, it added hydrochloric acid to form oxycodone hydrochloric salt.

         Purdue's initial efforts to reduce 14-hydroxy focused on the second step of the synthesis. Id. at 385. Purdue assumed that “the unwanted 14-hydroxy in the end product was merely leftover 14-hydroxy that had not been hydrogenated in [the] second step.” Id. It attempted to ensure that the hydrogenation process was complete, and appeared to have eliminated or nearly eliminated all the 14-hydroxy. Id. But when it finished the third step-adding hydrochloric acid to form a salt-it tested the product “and found that the 14-hydroxy had returned in vast quantities.” Id.

         After experimentation and analysis, Purdue discovered that the “culprit” was 8α, which transformed into 14-hydroxy during the process. Id. at 387. It then developed a dehydration process with two levels of hydrogenation, which permitted the production of oxycodone with 14-hydroxy levels less than 10 ppm. Id. The second hydrogenation process occurred after the third step-that is, after the oxycodone free base had been converted to oxycodone hydrochloric salt. Id.

         In substance, the claims at issue consisted of an oxycodone salt with extremely low levels of 14-hydroxy. See Id. at 376. Judge Stein found that one significant difference between the prior art and the asserted claims was that “the prior art did not disclose the existence of 8α or teach that it converts to 14-hydroxy.” Teva, 994 F.Supp.2d at 397. He observed that “8α was unknown in the prior art: its very existence was unexpected.” Id. at 401. However, that difference between the low-ABUK patents and the prior art did not save them from being held invalid on obviousness grounds.

         Because all of the asserted claims were product-by-process claims, Judge Stein "considered] only the product limitations of [the] claim, not process limitations or source limitations that add no patentable significance to the end product." Id. at 403.[5] "As a matter of law, the 8a-derived limitation . . . [was] disregarded as a process limitation" in determining validity. Id. at 405. Thus, Judge Stein "assesse[d] the validity of the low-ABUK oxycodone API [that is, active pharmaceutical ingredient] product-and its various purity and oral dosage form limitations-not oxycodone API with 14-hydroxy obtained from 8a." Id. at 403.

         Judge Stein found that the invention would have been obvious to a person of skill in the art. Id. at 403-04. First, he concluded that skilled artisans had a reason to develop low-ABUK oxycodone, principally because the FDA had communicated a desire to reduce such impurities in oxycodone. Id. at 404. Second, he concluded that "[f]aced with the problem of excess 14-hydroxy in oxycodone . . ., ordinary skilled artisans would have considered solving the problem by using hydrogenation." Id. Third, he concluded that "[i]t would have been 'obvious to try' to use hydrogenation after the salt formation step." Id. at 405. Fourth, he concluded that "[t]he patent claims extend to the obvious, even if they could be practiced in a nonobvious way." Id. at 406-07. Finally, he concluded that "the secondary considerations do not demonstrate nonobviousness." Id. at 407.

         As to the third point, Purdue contended that the "recognition of 8a as a source of 14-hydroxy in oxycodone salts permitted the inventors to conclude that the application of a hydrogenation step after a salt formation step would produce low-ABUK oxycodone." Id. at 405. Judge Stein disagreed. First, he concluded that the discovery of 8a was "immaterial to the low-ABUK product claimed by the patents." Id. That was true as a matter of law (because he disregarded process limitations) and as a matter of fact (because "identification of a source of the 14-hydroxy in the end product does not have any effect on the structure or nature of the end product."). Id. Second, he concluded that "8a proved largely irrelevant to the process used by Purdue to obtain the product claimed by the patents," because "the low-ABUK process hinges on hydrogenation-not on 8a." Id.

         As to the fourth point-that is, his conclusion that the patent claims extend to the obvious, even if they could be practiced in a non-obvious way-Judge Stein observed as follows:

The Court agrees that with its knowledge of 8a Purdue had the capability to practice its claims in a way that would have been nonobvious. That is, Purdue could practice its claims by tailoring them to 8a. What matters, however, is the objective reach of the claim. If the claim extends to what is obvious, it is invalid under § 103. Instead of claiming 8a directly, Purdue claimed low-ABUK oxycodone API in various forms. Its contribution to the science of that reaction was to identify additional explanations for why known techniques, used for their known purpose, would create the product. Invention requires something more.

Id. at 407 (citations and quotations omitted).

         Finally, as to the low-ABUK patents, Judge Stein's opinion concluded:

The dispute over the low-ABUK patents concerns the line between patentable invention and commendable improvement. The three patents at the center of this dispute describe an improved oxycodone API product containing less of the 14-hydroxy impurity than any oxycodone API available at the time of the invention. This product is an improvement but not an invention. Low-ABUK oxycodone stood within reach of any person of ordinary skill with the desire to use routine science and common sense to improve oxycodone API product.
* * *
Purdue holds out 8a as its contribution to the art. And, indeed, identifying 8a was genuine insight. But the evidence overwhelmingly proved that 8a imparts no significance to the structure of 14-hydroxy. It imparts no distinguishing characteristics to oxycodone. And it imparts no significance to the product claimed by the patents. Knowledge of 8a permits a skilled artisan to understand why 14-hydroxy reappears in a synthetic scheme with a salting step. But knowledge of 8a does not explain how to fix the problem. The solution has everything to do with hydrogenation, and that solution would have been obvious to a person of skill in the art, whether that person knew of 8a or not.
In summary, . . . [t]he Court concludes . . . that Teva has demonstrated by clear and convincing evidence that each of the asserted claims is invalid as obvious pursuantto35U.S.C. § 103.

Id. at 413.

         In 2016, the Federal Circuit affirmed Judge Stein's determination that the asserted claims of the low-ABUK patents were obvious in light of the prior art. See Purdue Pharma L.P. v. Epic Pharma, LLC, 811 F.3d 1345, 1355 (Fed. Cir. 2016) (?Purdue").[6]

         2. The Mylan Litigation

         The '933 patent at issue here was also the subject of a patent infringement action in the District of Delaware filed by Purdue against Mylan Pharmaceuticals, Inc. See Purdue Pharma L.P. v. Mylan Pharmaceuticals, Inc., 2017 WL 784989 (D. Del. Mar. 1, 2017). Mylan moved to dismiss the complaint on the basis of collateral estoppel (that is, issue preclusion) in light of Judge Stein's decision in Teva. Magistrate Judge Sherry R. Fallon issued a report and recommendation to the district judge recommending that the motion to dismiss be denied.

         Magistrate Judge Fallon concluded that "defendants have failed to establish that the invalid claims of the previously-litigated low-ABUK patents are sufficiently identical to the disputed claims of the '933 patent." Id. at *5. Specifically, she found that "[t]he claims of the '933 patent contain limitations not set forth in the low-ABUK patents, but whether these limitations are material to the patentability of the '933 patent is a question of fact to be reserved for a later stage of the proceedings." Id. She found that there were three such limitations in claims 1 and 16 of the '933 patent: (1) the 8a limitation; (2) the 95% limitation, and (3) (as to claim 16) the 5 ppm codeinone limitation.

         First, claims 1 and 16 claim "[a]n oxycodone hydrochloride composition" that "comprises" 8a, among other limitations. Id. Magistrate Judge Fallon noted that the low-ABUK patents litigated in Teva did not contain such a limitation, and that the "8a limitation present in the '933 patent claims must be evaluated to determine the validity of the claims." Id. at *5-6. She rejected the argument that the PTO's double-patenting rejection of the '933 patent, and Purdue's subsequent terminal disclaimer, required the application of issue preclusion. Id. at *6-7. And she rejected the argument that the doctrine of inherency required that the '933 patent be invalidated based on its similarities to the invalid low-ABUK patents. Among other things, she noted that the doctrine applied to prior art references, and that in any event "the inherent teaching of a prior art reference is a question of fact." Id. at *7-8.

         Second, claims 1 and 16 specify that the composition must comprise at least 95% oxycodone hydrochloride. Id. at *8. Magistrate Judge Fallon noted that the invalidated patents contained no such limitation, that "[t]he Teva decision does not discuss the percentages of oxycodone in the prior art." Id. at *9. She concluded that "[t]herefore, it would be inappropriate at this stage of the proceedings for the court to conclusively ...

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