United States District Court, D. New Jersey, Camden Vicinage
RENÉE MARIE BUMB, UNITED STATES DISTRICT JUDGE
Reckitt Benckiser LLC (“Reckitt” or
“Plaintiff”) brings this Hatch-Waxman action for
patent infringement against Defendants Amneal Pharmaceuticals
LLC (“Amneal”) and Dr. Reddy's Laboratories,
Inc. (“DRL”) (collectively,
“Defendants”) pursuant to 35 U.S.C. §
271(e)(2)(A) and §§ 271(a), (b), and (c).
Reckitt's Guaifenesin Drug Mucinex® and the
case involves Reckitt's Mucinex® product, an
extended-release guaifenesin tablet used as an expectorant
that thins and loosens mucus and relieves chest congestion.
Reckitt initially alleged that Amneal's generic 600 mg
and 1200 mg guaifenesin sustained-release tablets
(“Amneal's ANDA products”) will infringe U.S.
Patent Nos. 6, 372, 252 (the “'252 Patent”),
6, 955, 821 (the “'821 Patent”), and 7, 838,
032 (the “'032 Patent”). Similarly, Reckitt
initially alleged that DRL's generic 600 mg and 1200 mg
guaifenesin and pseudoephedrine hydrochloride
sustained-release tablets (“DRL's ANDA
Products”) will infringe the '252, '821, and
'032 Patents. After the filing of the Complaints, Reckitt
dismissed its claims under the '252 Patent as to both
Defendants [Docket Nos. 64, 65] and its claims under the
'821 Patent against Defendant DRL [Docket No.
heart of the dispute is whether Defendants' ANDA Products
have two distinct formulations, an immediate release
formulation (“IR formulation”) and a sustained
release formulation (“SR formulation”). Reckitt
contends that they do. Defendants counter that their ANDA
products are single formulation matrix tablets and
therefore do not infringe the Patents-in-Suit.
The '821 Patent
'821 Patent is entitled “Sustained Release
Formulations of Guaifenesin and Additional Drug
Ingredients” and is a continuation-in-part of the
'252 Patent. Stipulated Facts (“SF”) [Docket
No. 157] ¶ 8-9. The named inventors are Robert D. Davis,
Ralph W. Blume, and Donald Jeffery Keyser. SF ¶ 10. The
'821 Patent was filed on April 15, 2002, as Application
No. 10/121, 706. The '821 Patent expires on April 28,
2020. SF ¶ 11. Reckitt is the owner and current assignee
of the '821 Patent. SF ¶ 12.
30, 35, 36, 41, and 70 of the '821 Patent are asserted
against Defendant Amneal only. SF ¶ 20. Amneal has
stipulated that its ANDA products satisfy every limitation of
the asserted claims of the '821 Patent except
for the elements: “modified release drug
product;” “first quantity of guaifenesin in an
immediate release formulation;” and “second
quantity of guaifenesin in a sustained release
form/release-delaying matrix.” SF ¶ 24.
The '032 Patent
'032 Patent is entitled “Sustained Release of
Guaifenesin” and is a continuation-in-part of the
'821 Patent, which is a continuation-in-part of the
'252 Patent. SF ¶ 14-15. The named inventors are
Robert D. Davis, Ralph W. Blume, and Donald Jeffery Keyser.
SF ¶ 16. The '032 Patent was filed on April 4, 2003
as Application No. 10/406, 557. The '032 Patent expires
on April 28, 2020. SF ¶ 17. Reckitt is the owner and
current assignee of the '032 Patent. SF ¶ 18.
1, 2, 5, and 6 of the '032 Patent are asserted against
both DRL and Amneal. SF ¶ 25. DRL and Amneal have
stipulated that their respective 1200 mg ANDA products
satisfy every limitation of claims 1 and 2 except for the
following claim elements directed to the drug product
“having two portions” of guaifenesin: “a
first portion comprises guaifenesin in an immediate release
form;” and “a second portion comprises
guaifenesin in a sustained release form.” SF ¶ 27.
DRL and Amneal have also stipulated that their respective 600
mg ANDA products satisfy every limitation of claims 5 and 6
except for the following claim elements directed to the drug
product “having two portions” of guaifenesin:
“a first portion comprises guaifenesin in an immediate
release form;” and “a second portion comprises
guaifenesin in a sustained release form.” SF ¶ 28.
approved NDA No. 21-282 in July 2002 for 1200 mg guaifenesin
extended-release tablets and in December 2002 for 600 mg
guaifenesin extended-release tablets, both of which are
marketed by Reckitt under the trademark Mucinex®. SF
¶ 29-30. Mucinex® is approved for use as an
expectorant. SF ¶ 30. The FDA approved NDA No. 21-585 in
June 2004 for 600 mg/60 mg and 1200 mg/120 mg guaifenesin and
pseudoephedrine hydrochloride extended-release tablets, which
are marketed by Reckitt under the trademark Mucinex® D.
SF ¶ 31-32. Mucinex® D is approved for use as an
expectorant and nasal decongestant. SF ¶ 32.
claims asserted by Reckitt cover both Mucinex® SE and
Mucinex® D. Mucinex® SE products contain guaifenesin
as the only active pharmaceutical ingredient
(“API”) and Mucinex® D products contain both
guaifenesin and pseudoephedrine as the two APIs. SF ¶
Reckitt's Mucinex® products are bi-layer tablets, one
layer containing guaifenesin in an IR form that provides
fast-acting relief, and the other layer containing
guaifenesin in a SR form that continues to release
guaifenesin for 12 hours. SF ¶ 37. Mucinex® is a
preferred example of and is disclosed as Formulation IV in
the Patents-it-Suit. Tr. 101:14-102:2; 652:1-6; Tr. 829:22-23.
Amneal's ANDA and ANDA Product
filed an Abbreviated New Drug Application
(“ANDA”) No. 207342 with the FDA seeking
regulatory approval to market guaifenesin extended-release
tablets in 1200 mg and 600 mg dosages. SF ¶ 38-39.
Amneal's ANDA identifies the listed drug product that is
the basis for the submission as Mucinex®. SF ¶ 45.
Amneal's ANDA included a paragraph IV certification
asserting that the '252, '821, and '032 Patents
are invalid, unenforceable, or will not be infringed by the
manufacture or sale of its generic extended-release
guaifenesin tablets. SF ¶ 44. Amneal's ANDA is
is no dispute that Amneal intended to develop generic
products that are therapeutically equivalent to Mucinex®
SE, nor any dispute that Amneal has concluded that its
products have comparable dissolution profiles to, and are
bioequivalent with, Mucinex® SE products. SF ¶ 53,
60-61. Moreover, the parties have stipulated that the
Amneal's ANDA products have the following composition:
DRL's ANDA and ANDA Product
filed ANDA No. 208369 with the FDA seeking regulatory
approval to market guaifenesin extended-release tablets. SF
¶ 46-47. DRL's ANDA identifies the listed drug
product that is the basis for the submission as Mucinex®.
SF ¶ 52. DRL's ANDA included a paragraph IV
certification asserting that the '252, '821, and
'032 Patents are invalid, unenforceable, or will not be
infringed by the manufacture or sale of its generic
extended-release guaifenesin tablets. SF ¶ 51. DRL's
ANDA is currently pending.
Amneal, there is no dispute that DRL intended to develop
generic products that are therapeutically equivalent to
Mucinex® D, nor any dispute that DRL has concluded that
its products have comparable dissolution profiles to, and are
bioequivalent with, Mucinex® SE products. SF ¶
66-68. The parties have also stipulated that DRL's ANDA
products have the following composition:
Procedural History Before This Court
August 14, 2015, and September 25, 2015, Amneal and DRL each
filed motions for judgment on the pleadings under Rule 12(c)
arguing that their ANDA products do not infringe the
Patents-in-Suit because their products are single-formulation
matrix tablets that were disclaimed during the prosecution of
the '252 Patent. On January 15, 2016, the Court denied
the motions on the ground that Reckitt should be afforded
limited discovery regarding the actual structure of the
Defendants' ANDA products.
11, 2016, Defendants, contending their products were single
formulation release tablets, filed a summary judgment motion
of non-infringement. They argued that the disclaimer of
single formulation sustained release tablets that Reckitt had
made during the prosecution of the '252 Patent should
also apply to the '821 and '032 Patents. On December
22, 2016, the Court denied the motions, without opinion, and
thereafter scheduled a trial on the merits.
March 28, 2017, the Court issued an Order adopting the claim
constructions of Judge Stark set forth in Reckitt
Benckiser LLC v. Aurobindo Pharma Ltd., C.A. No.
14-1203-LPS, 2016 U.S. Dist. LEXIS 152337 (D. Del. Nov. 3,
2016) (“Aurobindo I”) and Reckitt Benckiser
LLC v. Aurobindo Pharma Ltd., C.A. No. 14-1203-LPS, 2017
U.S. Dist. LEXIS 31985 (D. Del. Mar. 6, 2017)
(“Aurobindo II”), appeal docketed, No.
17-1895 (3d Cir. Apr. 12, 2017). [Docket No. 127]. The Court
set the matter down for trial, limiting the trial to the
issue of infringement only.
Prior Related Litigation
case that comes before this Court is not Reckitt's first
challenge against a manufacturer of a generic Mucinex®.
Three other courts have found no infringement by three other
manufacturers of generic single formulation matrix tablets.
Reckitt contends that Defendants' reliance on prior
litigation is misplaced because the prior cases involve a
different patent (the '252 Patent), different claim
construction, and different products. The Court disagrees, in
part. While it is true that the '252 Patent is no longer
part of this case, Defendants' products must have a
discrete IR formulation and SR formulation to infringe.
Reckitt has rehashed some of its earlier arguments and the
prior courts' discussions of those arguments are
instructive. Moreover, whether or not Reckitt adequately
addressed the deficiency of proof identified by the
Aurobindo court (infra) requires analysis
of that court's decision whose claim construction this
Court has adopted.
April 24, 2009, Reckitt filed an infringement lawsuit against
Watson Laboratories, Inc. - Florida and Watson
Pharmaceuticals, Inc. (“Watson”) for infringement
of the '252 and '821 Patents, subsequently dismissing
the '821 Patent claim. Plaintiff's Responses to
Defendants' Proposed Findings of Fact
(“PRDFF”), ¶ 12 (citing Reckitt
Benckiser, Inc. v. Watson Laboratories, Inc. Florida,
Case No. 09-60609 (S.D. Fla. 2009)).The District Court held that Watson
did not infringe the '252 Patent, either literally or
under the doctrine of equivalents. Reckitt Benckiser,
Inc. v. Watson Laboratories, Inc. Florida, Case No.
09-60609, 2011 U.S. Dist. LEXIS 83090, ¶ 238 (S.D. Fla.
Feb. 18, 2011). In relevant part, that Court found that
Watson's products were prepared from a single uniform
blend. Id.at ¶ 143. Moreover,
the Court found that the “guaifenesin granules that
touch the surface are not part of a separate structure from
the balance of the guaifenesin and the other ingredients; all
are part of a single structure. Watson's ANDA products do
not have two structural portions.”
Id.at ¶ 204. On July 7, 2011,
the Court of Appeals for the Federal Circuit affirmed the
District Court's judgment of non-infringement, holding
that “[t]he district court correctly concluded that
Watson's products do not have two structural portions and
that guaifenesin granules on the surface of Watson's
tablets do not constitute the claimed first portion of
guaifenesin in an IR form.” Reckitt Benckiser Inc.
v. Watson Laboratories, Inc., Florida, 430 Fed.Appx.
871, 877 (Fed. Cir. 2011).
2007, Adams Respiratory Therapeutics, Inc., Reckitt's
predecessor-in-interest, and related entities filed an
infringement lawsuit against Perrigo Company
(“Perrigo”) and related entities for infringement
of the '252 Patent. Adams Respiratory Therapeutics,
Inc. et al v. Perrigo Co., Case No. 1:07-CV-993 (W.D.
Mich. 2007). The Perrigo District Court granted
summary judgment of non-infringement. In relevant part the
Court held that “[i]n spite of its attempts to
distinguish Watson, [Reckitt] made substantially the
same argument to the Federal Circuit in Watson
(including that the Guaifenesin on the surface of
Watson's tablets was uninhibited by polymer) that it now
makes in this case with regard to Perrigo's
tablet.” Perrigo, Case No. 1:07-CV-993, 2012
U.S. Dist. LEXIS 3288, at *16 (W.D. Mich. Jan. 11, 2012). In
short, the Court held that Perrigo, like Watson, made a
single formulation tablet which was disclaimed in the
September 14, 2014, Reckitt filed an infringement suit
against Aurobindo Pharma Ltd. (“Aurobindo”) for
infringement of the '821, '032 and '252 Patents,
later dismissing the '252 Patent from its suit. See
generally Aurobindo I, 2016 U.S. Dist. LEXIS 152337 and
Aurobindo II, 2017 U.S. Dist. LEXIS 31985. The Court
found that the asserted claims of the '821 and '032
Patents require “two distinct formulations.”
See Aurobindo I, 2016 U.S. Dist. LEXIS 152337, at
*6-8. The Court then granted summary judgment of
non-infringement concluding that “a reasonable
factfinder could only conclude that Aurobindo seeks FDA
approval of a single-formulation, extended-release
product.” Aurobindo II, 2017 U.S. Dist. LEXIS
31985, at *15. (The Aurobindo decisions will be
discussed in greater detail infra.)
Trial Before This Court
on the issue of infringement commenced on May 15, 2017, and
lasted four days. Closing arguments were heard on June 29,
2017. Defendants' invalidity claims were stayed pending
the outcome of the infringement trial. Reckitt presented the
testimony of Dr. Martyn C. Davies, a professor of biomedical
surface chemistry at the University of Nottingham School of
general, relying on his Raman analyses, Dr. Davies opined
that Defendants' ANDA Products have two distinct
formulations of guaifenesin, an IR formulation without
rate-controlling polymers on the surface and a SR formulation
including rate-controlling polymers in the interior.
presented five experts at trial. Dr. Harry Brittain and Dr.
Richard Gemeinhart, two experts in pharmaceutical
formulation, generally testified that Defendants' ANDA
products are matrix tablets made from a single uniformly
distributed blend of ingredients. Two experts, Dr. Robin Rogers and Dr.
Neil Spingarn, generally testified about the flaws and
weaknesses of Dr. Davies's Raman analyses. Finally, Dr. Jeffrey
Rodriguez, a computer imaging expert called by DRL testified
about his count of the guaifenesin and (XXXXX) pixels in Dr. Davies's Raman
considering all the evidence, and the parties'
submissions, for the reasons set forth herein, the Court
finds that Amneal and DRL will not infringe the '032 and
'821 Patents. The Court declines to exercise jurisdiction
over the counterclaims asserting invalidity. This Opinion
constitutes the Court's findings of fact and conclusions
of law pursuant to Federal Rule of Civil Procedure 52(a).
prove infringement, the patentee must show that it is more
likely than not that the proposed ANDA product would, if
commercially marketed, meet all of the claim limitations of
the Patents-in-Suit. See Adams Respiratory Therapeutics,
Inc. v. Perrigo Co., 616 F.3d 1283, 1289 (Fed. Cir.
2010); Abbott Labs. v. TorPharm, Inc., 300 F.3d
1367, 1373 (Fed. Cir. 2002) (infringement analysis turns on
whether accused product satisfies every limitation of the
claim in question); Laitram Corp. v. Rexnord, Inc.,
939 F.2d 1533, 1535 (Fed. Cir. 1991) (“To establish
infringement, every limitation set forth in a patent claim
must be found in an accused product . . . .”). In other
words, the patentee “has the burden of proving
infringement by a preponderance of the evidence.”
Kegel Co., Inc. v. AMF Bowling, Inc., 127 F.3d 1420,
1425 (Fed. Cir. 1997); SmithKline Diagnostics, Inc. v.
Helena Labs. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988).
Determining whether an accused product infringes the patent
involves a two-step analysis. Kegel, 127 F.3d at
1425. The Court must first construe the scope and meaning of
the asserted patent claims and then compare the accused
product to the properly construed claims. Id.
The Asserted Claims and Claim Construction
asserts claims 30, 35, 36 and 41 of the '821 Patent
against Amneal, and claims 1 and 5 of the '032 Patent
against Amneal and DRL. The claims are as follows:
29. A modified release drug product comprising a
first quantity of guaifenesin in an
immediate release formulation wherein the guaifenesin becomes
bioavailable in a subject's stomach; a second
quantity of guaifenesin in a sustained release form,
. . .
30. The modified release drug product according to claim 29,
wherein a total quantity of guaifenesin is from about 600 mg
to about 1200 mg.
35. The modified release drug product according to claim 30,
wherein the guaifenesin has a Cmax of about 800 to 1250 ng/ml
and an AUCinf of about 2800 to 4375 hr*ng/ml.
36. The modified release drug product according to claim 30,
wherein the guaifenesin has a Cmax of least 1000 ng/ml and an
AUCinf of at least 3500 hr*ng/ml.
41. The modified release drug product according to claim 29,
wherein the drug product is approximately equally effective
when administered to the human subject with an empty or full
'821 Patent (emphasis added).
1. A drug product comprising guaifenesin and having two
portions, wherein a first portion comprises
guaifenesin in an immediate release form, which releases
guaifenesin in a human's stomach, and a second portion
comprises guaifenesin in a sustained release form.
5. A drug product comprising guaifenesin and having two
portions, wherein a first portion comprises
guaifenesin in an immediate release form, which releases
guaifenesin in a human subject's stomach, and a second
portion comprises guaifenesin in a sustained release form, .
'032 Patent (emphasis added).
noted, this Court adopted Judge Stark's claim
construction from Aurobindo I as follows:
“a distinct formulation” ('032
“Modified release drug product”
“a dosage form comprising a sustained release
quantity and an immediate release quantity, and
having both immediate release and sustained release
properties” ('821 Patent)
“Immediate release formulation wherein the
guaifenesin becomes bioavailable in a subject's
“a form intended to rapidly release in the
stomach guaifenesin for absorption” ('821
“a combination of hydrophilic and water
insoluble polymers of the sustained release
formulation which gels in the stomach”
the two formulations need not be physically separate - except
where there is a limitation regarding the spatial orientation
of them, like a bi-layered tablet - they must be
“inherently physically ‘separate'”
because they are distinct formulations. This construction is in
line with the Federal Circuit's decision that construed
the same term in the context of the related (not asserted
here) '252 Patent. See Watson, 430 Fed.Appx. at
Aurobindo court, much like the Perrigo
court, turned to the Federal Circuit's construction of
the “portion” limitation in the '252 Patent.
See Aurobindo I, 2016 U.S. Dist. LEXIS 152337, at
*6-8. The Federal Circuit construed “portion” as
a discrete part of the product. Watson, 430
Fed.Appx. at 875-77. Based on the nearly-identical language
of the '032 Patent, the Aurobindo court
construed “portion” to mean “distinct
formulation.” Aurobindo I, 2016 U.S. Dist.
LEXIS 152337, at *6, *8 n.5 (“[I]n order to avoid
confusion . . . the Court has (non-substantively) modified
the Federal Circuit's construction of
“portion” by substituting “distinct
formulation” for “discrete part of the
product.”) Similarly, regarding the '821 Patent, as
Judge Stark found and this Court adopted, the plain language
of the claim - a “modified release drug product”
comprising a “first quantity” and “second
quantity” of guaifenesin - imposes a requirement that
the product comprises two distinct formulations. Id.
parties squabble over whether “discrete” means
“distinct.” Reckitt contends that the words have
different meanings and, thus, the Federal Circuit's
construction of “portion” in Claim 1 as a
“discrete part of the product” cannot be squared
under the doctrine of claim differentiation with Claim 3
which provides “the drug product according to claim 1,
wherein the first and second portions are discrete.”
See Watson, 430 Fed.Appx. at 876 (construing
'252 Patent). The Watson case involved a
bi-layered tablet. As the Watson court explained,
the two-portion limitation distinguished the product from the
defendant's non-layered tablet. The Aurobindo case, like
this case, however, did not involve a bilayer tablet. The
Aurobindo court modified the construction by substituting
“distinct formulation” for “discrete part
of the product.” Aurobindo I, 2016 U.S. Dist.
LEXIS 152337, at *8 n.5. Notably, the Aurobindo
court declined to impose a construction that required any
particular spatial relationship. Id. at *13. The
To the extent the parties' dispute centers on whether the
IR and SR formulations must be
“physically separate, ” as in, for example, a
bi-layered tablet . . . the Court finds that the claims do
not impose limitations regarding the spatial orientation of
the two. The Court recognizes that the two different
formulations of guaifenesin in the claimed products are
inherently physically “separate” because they are
distinct formulations. However, the intrinsic record does not
support additional structural or spatial limitations being
imposed by the word “portion.”
Id. (emphasis in original) (citation omitted).
court explained in its second opinion
In discussing spatial relationships, the Court considered,
and rejected, Aurobindo's suggestion that the claims
require the two distinct formulations to exist in a
particular relationship, such as being layered. But the
Court's rejection of any particular spatial relationship
simply means that the two distinct formulations can be put
together into a tablet in any physical combination. See,
e.g., '821 [P]atent col. 4 ll. 8-16 (describing
tablet embodiments composed of two types of beads or granules
mixed together; a sustained-release core with
immediate-release outer coating; or two layers). It does not
eliminate the requirement for two distinct
formulations, which are defined in
the patents by their ingredients. See, e.g.,
'821 [P]atent col. 20 l. 54-col. 21 l. 37 (defining IR
and SR formulations by listing components).
Aurobindo II, 2017 U.S. Dist. LEXIS 31985, at *24
(emphasis in original).
Court's view, the Aurobindo court recognized
that Claims 1 and 3 used the terms “distinct” and
“discrete” with somewhat different meanings.
Although the words are often used interchangeably, the Court
finds that “discrete” in Claim 3 means
“separate and distinct.” See
Webster's New World College Dictionary 411 (Michael Agnes
eds., 4th ed. 2010). Thus, Claim 3 added a particular spatial
relationship, see '821 Patent col. 4:10-12 (“beads
or granules of both immediate release formulation and beads
or granules of sustained release formulation”), not
present in Claim 1. Cf. Claim 4 (“The drug
product according to claim 3, which is in a form of a
Court must next determine whether the accused product
contains every limitation of the properly construed claims.
Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448, 1467
(Fed. Cir. 1998), abrogated on other grounds by
Teva Pharm. USA, Inc. v. Sandoz, Inc., 135 S.Ct. 831
Thus, the relevant question is whether the Defendants'
ANDA Products contain two distinct formulations, an IR
Formulation and a SR Formulation. Because Reckitt believed
that the Aurobindo court had granted summary
judgment against it due to Reckitt's failure to present
any evidence of structural or spatial limitations,
 the trial
before this Court primarily involved testimonial evidence
focused on that issue.
Dr. Davies's Raman Imaging
introduced the testimony of Dr. Davies who relied on Raman
chemical imaging maps of Defendants' Products to attempt
to show that the accused products have a distinct IR
formulation on the surface and a distinct SR formulation
below the surface. Tr. 98:24 - 99:7. In general, Dr. Davies
identified a region where there was guaifenesin and other
excipients, without (XXXXX) (a
rate-changing polymer), on and near the surface of the
tablets from which guaifenesin would rapidly release,
i.e., an IR portion. He then identified another
region beneath the surface of the tablets where the rate of
guaifenesin would be slower, i.e., an SR portion,
because (XXXXX) is present, which
effects the release of guaifenesin. Dr. Davies then testified
how the IR and SR portions were, in his opinion, distinct in
location, composition, and in release properties.
argue that the analyses done by Dr. Davies are flawed for
numerous reasons. Principally, Defendants aver that Dr.
Davies's images merely portray what is well known, that
in a non-coated tablet there is always guaifenesin on the
surface that rapidly dissolves in the stomach before the
rate-controlling polymers have swelled to exert a
rate-controlling effect. Defendants also contend that Dr.
Davies equated two distinct formulations with dissolution
behavior, a theory rejected by the Aurobindo court.
See Aurobindo II, 2017 U.S. Dist. LEXIS 31985, at
*18, 19-23 ("[That the drugs have similar dissolution
profiles] is unsurprising, as bioequivalence to an
already-approved product is a requirement for ANDA
approval”). The Court now turns to the parties'
analyses of the evidence.
initial matter, the parties do not dispute that Raman
microscopy testing is used in the pharmaceutical industry as
a means to characterize the structure of solid oral dosage
forms. Tr. 134:17-20. Raman spectroscopy and microscopy
produces unique chemical fingerprints which may enable a
person skilled in the art to identify the molecules at any
given position. Id. at 134:21-23.
of his Raman analysis, Dr. Davies cut a single tablet of each
of the Defendants' products in half and then used a
microtome to obtain an extremely thin and flat substrate for
imaging. Id. at 135:6-12. The spot size of the laser
used for imaging was two microns. Id. at 139:9.
After a spectrum was obtained the laser moved to a new spot
five microns away to repeat the process. Id. at
139:14-16. For each spectrum, the acquisition time was 400
milliseconds. Id. at 139:21-22. This process was
repeated 230, 000 times and each spectrum was matched to a
compound, using K-means cluster analysis, and a corresponding
location in order to create a colored Raman map. Id.
at 145:21; 176:17-177:10.
Imaging of DRL Tablet
Davies generated the following two maps which he testified
are representative of the structure of DRL's tablets (PTX
35). (XXXXX) In the third
demonstrative map (PDX 237), the red arrows illustrate where,
allegedly, guaifenesin is present on the surface.
to Dr. Davies, the surface of DRL's tablet was
“dominated” by guaifenesin. Tr. 147:25-148:15. He
explained that regions on and near the surface of DRL's
tablet dominated by guaifenesin and other excipients, but
without the rate-controlling (XXXXX)
polymers, constitute the first portion of guaifenesin in IR
form. Id. at 148:15-20. Because the guaifenesin
present in the IR region is uninhibited by (XXXXX) (which is rate-controlling), it rapidly
releases in the gastric fluid upon contact. Id. at
148:21-23. The consistent release rate in the first hour is
about 23%. Id. at 118:20-24. In his opinion, this is
a distinct immediate release formulation within the meaning
of the asserted claims. Id. at 118:22-25; 191-198.
Dr. Davies further testified that DRL's products contain
a second portion of guaifenesin in SR form, which is
guaifenesin in the interior of the tablet in the presence of
the rate- controlling polymers, a second formulation within
the asserted claims. Id. at 118:25-119:4; 191-198.
Imaging of Amneal Tablet
Davies also generated the following map (PTX 36), which he
testified is representative of the structure of Amneal's
to the DRL tablet, the red arrows in the demonstrative map
above, (PDX 241), illustrate where guaifenesin is present on
the surface of the Amneal tablet. According to Dr. Davies,
the surface is dominated by guaifenesin and other excipients
without Methocel, which constitutes the IR formulation.
Id. at 160:6-10. Dr. Davies testified that
Amneal's tablets provide a consistent release in the
first hour, about 20% and 24% for the 1200 mg and 600 mg
products, respectively. Id. 422:6-10. In his
opinion, this is a distinct immediate release formulation.
Id. at 160:7-9. He further provided that, similar to
the DRL tablet, the guaifenesin below the surface is
inhibited by the rate-controlling polymers and is the SR
Dr. Davies's Analysis is Flawed and Unreliable
the parties spent a considerable amount of time either
defending or attacking Dr. Davies's Raman analyses, the
Court first turns to some of the parties' specific
arguments. In the Court's final analysis, however, it is
not so much that Dr. Davies's images were flawed - as
they were for the reasons set forth herein - but that his
interpretation of those images was fundamentally flawed.
Defendants argue as a general principle that Dr. Davies's
Raman maps should be given no evidentiary weight because they
are nothing more than “window dressing.” They
essentially rely on an exchange between Dr. Davies and the
The Court: But it seems to me, correct me if I'm wrong,
that if you have to do content blending, uniformity blending,
you are going to get this mixture. You know the significant
percentages of guaifenesin going into it. It seems to me that
that picture could have been painted without the imaging.
The Witness: Your Honor, to me it could because . . .
I think looking at the dissolution and the PK data, somebody
of ordinary skill in the art would know thatsuch formulations would be able to achieve that
because they have the first portion and an immediate-release
portion and they have a sustained-release portion that can
give you that long term effect. It's - I guess ...