United States District Court, D. Massachusetts
PURDUE PHARMA L.P.; THE P.F. LABORATORIES, INC.; PURDUE PHARMACEUTICALS, L.P.; and RHODES TECHNOLOGIES, Plaintiffs,
COLLEGIUM PHARMACEUTICAL, INC., Defendant.
MEMORANDUM AND ORDER ON DEFENDANT'S MOTION FOR
Dennis Saylor IV, United States District Judge
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.
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.”
following reasons, Collegium's motion for summary
judgment will be granted in part and denied in part.
otherwise noted, the following facts are undisputed.
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
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).
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
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).
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
Removal of Impurities from Oxycodone
as manufactured, contains a potentially toxic impurity. The
impurity is 14- hydroxycodeinone (“14-hydroxy”),
an alpha, beta-unsaturated ketone (“ABUK”).
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).
Patents at Issue
The '933 Patent
Description of the Patent
'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
'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,
(“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].”
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).
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
avoid the double-patenting rejection, Purdue filed terminal
disclaimers on October 1, 2014. (See Def. Ex. 18 at
12-13). 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).
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).
The '497 Patent
'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.
'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.
The '717 Patent
'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.
Previous Litigation Concerning the Same or Similar
The Teva Litigation
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)
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
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
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.
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
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.
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.
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. "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.
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.
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.
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).
as to the low-ABUK patents, Judge Stein's opinion
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
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.
Id. at 413.
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)
The Mylan Litigation
'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.
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.
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.
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 ...