United States District Court, D. New Jersey
MEMORANDUM AND ORDER
G. SHERIDAN, U.S.D.J.
matter comes before the Court on joint claim construction
submitted by Plaintiff Bracco Diagnostics, Inc.
("Bracco") and Defendant Maia Pharmaceuticals, Inc.
("Maia") concerning United States Patent No. 6,
803, 046 (the "'046 Patent"). The '046
Patent is listed to market and sell the drug Kinevac®
which is an injectable solution used for treating,
preventing, and diagnosing gall bladder-related disorders.
The parties dispute the meaning of three terms in the patent:
(1) buffer; (2) surfactant/solubilizer; and (3) surfactant.
was originally introduced in 1976 as a lyophilized white
powder for parenteral (by injection) administration. The
active ingredient in Kinevac is sincalide, a peptide molecule
composed of eight amino acids bound together. ('046
Patent at 1:9-16). The patent also claims five other
ingredients: at least one stabilizer, a
surfactant/solubilizer, a chelator, a bulking agent/tonicity
adjuster, and a buffer. (Id. at 37:41-49).
currently has three uses approved by the FDA: (1) to
stimulate gallbladder contraction; (2) to stimulate
pancreatic secretion; and (3) to accelerate the transit of a
barium meal through the small bowel. (See
Declaration of Donald L. Rhoads ("Rhoads Decl."),
Ex. 63, Labeling for Kinevac). Kinevac is a synthetic analog
of a hormone produced by the human body known as CCK-8
(cholecystokinin). "CCK-8 acts on receptors within the
gallbladder wall causing it to contract, cleaning out any
remaining sludge or bile that may have accumulated within the
gallbladder." ('046 Patent at 13:42-45). Kinevac
"has a more rapid physiological effect on the
gallbladder in terms of contraction and relaxation than the
endogenous hormone (CCK-8)." (Id. at 13:49-51).
Kinevac is "administered before and/or after diagnostic
imaging ... to improve visualization and/or diagnosis of
various disease states." (Id. at 13:55-58).
"Typically, the gallbladder contracts within 15 minutes
after sincalide [(Kinevac)] injection and the hepatobiliary
imaging agent... is injected 30 minutes later."
(Id. at 14:17-20). Once the gallbladder is emptied
it "is better able to take up and accumulate imaging
agent. . . which helps to reduce the number of false positive
studies." (Id. at 14:20-23).
originally introduced, Kinevac suffered from some drawbacks.
The '046 Patent identifies "potency
variability" as one such drawback, which meant "a
20% overage of sincalide was required in previous sincalide
formulations to compensate for the limitations of the
bioassay." ('046 Patent at 1:27-40). The new
invention "satisfie[d] the need for improved sincalide
formulations by providing formulations that eliminate the
need for a 20% overage of sincalide." (Id. at
1:43-45). "The sincalide formulations of the invention
are also purer than prior art formulations, and have fewer
degradants and more consistent potency." (Id.
'046 Patent sets forth 108 total claims, which are
directed to sincalide formulations (claims 1-20 and 106);
methods for making sincalide formulations (claims 21-39);
kits containing sincalide formulations (claims 40-55 and
107-108); and methods for using sincalide formulations
(claims 56-105). Claim 1 provides:
stabilized, physiologically acceptable formulation of
(a) an effective amount of sincalide,
(b) at least one stabilizer,
(c) a surfactant/solubilizer
(d) a chelator
(e) a bulking agent/tonicity adjuster, and
(f) a buffer.
('046 Patent at 37:41-49).
August 2017, Maia filed a new drug application with the FDA
seeking approval to market a sincalide product. The FDA
granted the product priority review and then approved it in
February 2018. In a notice letter required under the statute,
Maia notified Bracco of several reasons that Maia argued its
product does not infringe the '046 Patent:
• Maia's product does not include either a buffer or
• The amino acids in Maia's product are not used as
buffers and have no buffering capacity over the pH range of
Maia's formulation. An excipient generally only provides a
buffering capability when the pH of the formulation is within
1 pH unit of the excipient's pKa.
• The amino acids in Maia's product provide no
surfactant or solubilizing effect because they do not have a
suitable hydrophobic tail, and are not surface active by
themselves, and do not function as solubilizers.
• Maia's product does not contain either polysorbate
20 or dibasic potassium phosphate.
filed this action pursuant to the Hatch-Waxman Act on
December 15, 2017, claiming that Maia's proposed product
infringes its claims in its '046 Patent. Maia challenges
the validity of the asserted claims.
purposes of this hearing, the definition of three terms is at
issue: (1) buffer, (2) surfactant/solubilizer; (3)
surfactant. The following proposed definitions are proposed:
Excipients that “stabilize the pH” and
“include, but are not limited to, phosphoric
acid, phosphate (e.g. monobasic or dibasic sodium
phosphate, monobasic or dibasic potassium
phosphate, etc.), citric acid, citrate (e.g. sodium
citrate, etc.), sulfosalicylate, acetic acid,
acetate (e.g. potassium acetate, sodium acetate,
etc.), methyl boronic acid, boronate, disodium
succinate hexahydrate, amino acids, including amino
acid salts (such as histidine, glycine, lysine,
imidazole), lactic acid, lactate (e.g. sodium
lactate, etc.), maleic acid, maleate, potassium
chloride, benzoic acid, sodium benzoate, carbonic
acid, carbonate (e.g. sodium carbonate, etc.),
bicarbonate (e.g. sodium bicarbonate, etc.), boric
acid, sodium borate, sodium chloride, succinic
acid, succinate (e.g. sodium succinate), tartaric
acid, tartrate (e.g. sodium tartrate, etc.),
tris(hydroxymethyl) aminomethane, biological
buffers (such as N-2- hydroxyethylpiperazine,
N'-2- ethanesulfonic acid (HEPES), CHAPS and
other ‘Good's' buffers), and the
SOURCES: ‘046 Patent at 9:45-65, claims 3,
23, 41, 60, and 87, 9:65-10:9, Forrest Deci. at J
31-62; Exs. 15-39.
A compound that stabilizes the pH of a sincalide
SOURCES: ‘046 Patent at 9:44-47; Kilbanov
DecI. at ¶ 92, 93, 95; Websters Ninth
Collegiate Dictionary at 185 (1985); Webster's
II New College Dictionary at 144 (1986);
McGraw-Hill Dictionary of Scientific and Technical
Terms at 278 (5th ed. 1994).
Excipients that “may reduce the interfacial
tension or aid in solubilization” and
“include, but are not limited to, pluronics
(e.g., Lutrol F68, Lutrol F127), Poloxamers, SDS,
Triton-l00, polysorbates such as TWEEN® 20 and
TWEEN® 80, propylene glycol, PEG and similar
compounds, Brij58 (polyoxyethylene 20 cetyl ether),
cremophor EL, cetyl trimethylammonium bromide
(CTAB), dimethylacetamide (DMA), NP-40 (Nonidet P
40), and N-methyl-2- pyrrolidone (Pharmasolve),
glycine and other amino acids/amino acid salts and
anionic surfactants containing alkyl, aryl or
heterocyclic structures, and cyclodextrins.”
SOURCES: ‘046 Patent 11:26-12:14; Forrest
Decl. ¶Â¶ 63-72.
A surfactant that is also a solubilizer.
A solubilizer is a compound that aids in
solubilization, thus preventing or reducing
sincalide denaturation and/or degradation caused by
peptide aggregation, precipitation, surface
adsorption, or agitation at air/liquid or
liquid/solid interfaces in solution.
SOURCES: ‘046 Patent at 11:27-35, 11:51,
claims 1, 6, 21, 26 Klibanov Decl. at ¶ 63,
Excipients that “may reduce the interfacial
tension” and “include, but are not
limited to, pluronics (e.g., Lutrol F68, Lutrol F
127), Poloxamers, SDS, Triton-100, polysorbates
such as TWEEN® 20 and TWEEN® 80, propylene
glycol, PEG and similar compounds, Brij58
(polyoxyethylene 20 cetyl ether), cremophor EL,
Dictionary of Scientific and cetyl
trimethylammonium Technical Terms. bromide (CTAB),
dimethylacetamide (DMA), NP-40 (Nonidet P-40), and
N-methyl-2-pyrrolidone (Pharmasolve), glycine and
other amino acids/amino acid salts and anionic
surfactants containing alkyl, aryl or heterocyclic
structures, and cyclodextrins.”
SOURCES: ‘046 Patent at 9:49-65, 11:26-36,
claims 44, 63, 90; Forrest Decl. at ¶Â¶ 74-
A compound that reduces the tension of the
air/liquid or liquid/solid interface.
SOURCES: ‘046 Patent at 11:29-34; Klibanov
Decl. at ¶ 35-39, 43-48; Condensed Chemical
Dictionary; Webster's Ninth Collegiate
Dictionary; McGraw-Hill Dictionary of Scientific
and Technical Terms.
is a 'bedrock principle' of patent law that 'the
claims of a patent define the invention to which the patentee
is entitled the right to exclude.'" Phillips v.
AWH Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005) (en
banc) (quoting Innova/Pure Water Inc. v. Safari Water
Filtration Sys., Inc., 381 F.3d 1111, 1115 (Fed. Cir.
2004)). Claim construction determines the correct claim scope
and is a determination exclusively for the court as a matter
of law. Markman v. Westview Instruments, Inc., 52
F.3d 967, 978-79 (Fed. Cir. 1995) (en banc),
aff'd, 517 U.S. 370 (1996). The focus in
construing disputed terms in claim language "is on the
objective test of what one of ordinary skill in the art at
the time of the invention would have understood the term to
mean." Id. at 986.
determine the meaning of the claims, courts start by
considering the intrinsic evidence. Phillips, 415
F.3d at 1313; C.R. Bard, Inc. v. U.S. Surgical
Corp., 388 F.3d 858, 861 (Fed. Cir. 2004); BellAtl.
Network Servs., Inc. v. Covad Comms. Group, Inc., 262
F.3d 1258, 1267 (Fed. Cir. 2001). The intrinsic evidence
includes the claims themselves, the specification, and the
prosecution history. Phillips, 415 F.3d at 1314;
C.R. Bard, Inc., 388 F.3d at 861.
court "begin[s] [its] analysis with the claim language
itself." Microsoft Corp. v. Multi-Tech Sys.,
Inc., 357 F.3d 1340, 1347 (Fed. Cir. 2004). The
"claims 'must be read in view of the specification
of which they are a part."' Phillips, 415
F.3d at 1315 (quoting Markman, 52 F.3d at 979).
"[T]he specification 'is always highly relevant to
the claim construction analysis. Usually, it is dispositive;
it is the single best guide to the meaning of a disputed
term.'" Id. (quoting Vitronics Corp. v.
Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir.
1996)). This is true because a patentee may define his own
terms, give a claim term a different meaning than the term
would otherwise possess, or disclaim or disavow the claim
scope. Id. at 1316. In these circumstances, the
inventor's lexicography governs. Id. But,
although "the specification often describes very
specific embodiments of the invention," the Federal
Circuit has "repeatedly warned against confining the
claims to those embodiments." Phillips, 415
F.3d at 1323.
parties first disagree as to the definition of
"buffer." Both claim their construction derives
from the intrinsic evidence but also rely on some extrinsic
evidence. As previously stated, Bracco urges the following
Excipients that "stabilize the pH" and
"include, but are not limited to, phosphoric acid,
phosphate (e.g. monobasic or dibasic sodium phosphate,
monobasic or dibasic potassium phosphate, etc.), citric acid,
citrate (e.g. sodium citrate, etc.), subsalicylate, acetic
acid, acetate (e.g. potassium acetate, sodium acetate, etc.),
methyl boronic acid, boronate, disodium succinate
hexahydrate, amino acids, including amino acid salts (such as
histidine, glycine, lysine, imidazole), lactic acid, lactate
(e.g. sodium lactate, etc.), maleic acid, maleate, potassium
chloride, benzoic acid, sodium benzoate, carbonic acid,
carbonate (e.g. sodium carbonate, etc.), bicarbonate (e.g.
sodium bicarbonate, etc.), boric acid, sodium borate, sodium
chloride, succinic acid, succinate (e.g. sodium succinate),
tartaric acid, tartrate (e.g. sodium tartrate, etc.),
tris(hydroxymethyl)-aminomethane, biological buffers (such as
N-2-hydroxyethylpiperazine, N'-2- ethanesulfonic acid
(HEPES), CHAPS and other 'Good's' buffers), and
(See Brief of Bracco, ECF No. 50 at 11). Maia
proposes a much shorter definition: "A compound that
stabilizes the pH of a sincalide formulation."
(See Brief of Maia, ECF No. 50 at 30).
the parties generally agree that a buffer stabilizes pH.
However, the critical difference is whether the phrase
"of a sincalide formulation" should be included in
the definition. Maia argues that buffer must be directed to
sincalide formulations for two reasons: (1) the invention -
as stated in the claims and specifications - is directed to
sincalide formulations and (2) a compound, which may operate
as a buffer in a formulation within a specific pH range, may
not act ...