CLAIM CHART – GROUND 5
`
`8,945,636
`Claim 1
`A pharmaceutical
`composition in unit dose
`form suitable for oral
`administration to a patient,
`comprising:
`
`(a) esomeprazole present
`in an amount effective to
`raise the gastric pH of said
`patient to at least 3.5 upon
`the administration of one
`or more of said unit
`dosage forms;
`
`
`(b) naproxen present in an
`amount effective to reduce
`or eliminate pain or
`inflammation in said
`patient upon
`administration of one or
`more of said unit dosage
`forms; and wherein:
`i) said unit dosage form is
`a tablet in which said
`naproxen is present in a
`core;
`
`
`
`’225 patent, Chandramouli, and WO’185
`
`
`“The invention herein is directed to a pharmaceutical
`composition which consists of a core/mantle tablet
`having an inner core and an outer mantle coating
`surrounding the inner core.” (’225 patent, 1:11-14.)
`
`“The solid formulation of the present invention could
`be in the form of [. . .] a tablet.” (WO’185, 26:27-28.)
`“The proton pump inhibitor is administered and dosed
`in accordance with good medical practice, taking into
`account the clinical condition of the individual
`patient, the site and method of administration,
`scheduling of administration, and other factors known
`to medical practitioners. The ‘effective amount’ for
`purposes herein thus determine by such
`considerations as are known in the art. The amount
`must be effective to achieve improvement, including
`but not limited to, raising of gastric pH [. . .].”
`(WO’185, 21:12-20.)
`“Today, NSAIDs are the most frequently prescribed
`medication for chronic pain and remain the most
`widely used drug category for the treatment of
`rheumatoid arthritis, osteoarthritis [. . .].”
`Chandramouli at 28. “NSAIDs having enterohepatic
`recirculation include indomethacin, naproxen,
`diclofenac and piroxicam.” Chandramouli at 31.
`
`“The invention herein is directed to a pharmaceutical
`composition which is a core/mantle tablet consisting
`of a core of a nonsteroidal anti-inflammatory drug
`(NSAID).” (’225 patent, 3:9-11.)
`
`“We claim: 1. A pharmaceutical composition
`comprising: a. a core consisting of a therapeutically-
`effective amount of a nonsteroidal anti-inflammatory
`agent; and b. a mantle coating surrounding the core
`comprising a therapeutically-effective amount of
`1
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`Lupin Exh. 1031
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`

`
`ii) said tablet comprises a
`coating, wherein said
`coating surrounds said
`core and does not release
`said naproxen until the pH
`of the surrounding
`medium is 3.5 or higher;
`and
`
`iii) said esomeprazole is in
`one or more layers outside
`said core, wherein said one
`“or more layers:
`
`A) do not include an
`naproxen;
`
`B) are not surrounded by
`an enteric coating; and
`
`C) upon ingestion of said
`tablet by a patient, release
`said esomeprazole into
`
`
`
`misoprostol.” (’225 patent, 12:34-40.)
`“Surrounding the [NSAID] core is an enteric
`coating.” (’225 patent, 6:28-29.) “The coating aids in
`segregating the NSAID [. . .] and in directing the
`dissolution of the NSAID core in the lower G.I. tract
`as opposed to the stomach.” (’225 patent, 6:33-36.)
`
`Examples 3-6 include “methacrylic acid copolymer
`type C” within the enteric coating, which is known to
`prevent release of contents until pH is above 3.5.
`(’225 patent, 8:30-32, 9:5-7, 42-43; 10:12-13.)
`“Surrounding the coated inner core is a mantle
`consisting of [an acid inhibitor]” (’225 patent, 6:41-
`43.)
`
`“We claim: 1. A pharmaceutical composition
`comprising: a. a core consisting of a therapeutically-
`effective amount of a nonsteroidal anti-inflammatory
`agent; and b. a mantle coating surrounding the core
`comprising a therapeutically-effective amount of
`[acid inhibitor].” (’225 patent, 12:34-40.)
`
`“Omeprazole [. . .] reduce[s] gastric acid production [.
`. .]. Because this drug maintains gastric pH
`throughout the dosing interval and has a very good
`safety profile, it is a logical choice”. (WO’185, 4:8-
`15.)
`“Surrounding the coated inner core is a mantle
`consisting of [an acid inhibitor]” (’225 patent, 6:41-
`43.)
`“[I]t would be desirable to have a proton pump
`inhibitor formulation which is convenient to prepare
`and administer [. . .] which is rapidly absorbed, can be
`orally or enterally delivered as a liquid form or solid
`form [. . . ]” (WO’185, 16:2-6.) “[. . .] wherein said
`dosage form is not enteric coated or time-released.”
`(WO’185, 57:23-24.)
`“Surrounding the [NSAID] core is an enteric
`coating.” (’225 patent, 6:28-29.) “The coating aids in
`[. . .] directing the dissolution of the NSAID core in
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`

`
`said patient's stomach.
`
`Claim 2
`The pharmaceutical
`composition of claim 1,
`wherein there is a single
`core comprising said
`naproxen.
`
`Claim 3
`The pharmaceutical
`composition of claim 2,
`wherein said esomeprazole
`is present in said unit
`dosage form in an amount
`of between 5 mg and 100
`mg.
`Claim 4
`The pharmaceutical
`composition of claim 2,
`wherein naproxen is
`present in said unit dosage
`form in an amount of 200-
`600 mg.
`Claim 5
`A method of treating a
`
`
`
`the lower G.I. tract as opposed to the stomach [where
`the acid inhibitor is released].” (’225 patent, 6:33-36.)
`“[I]t would be desirable to have a proton pump
`inhibitor formulation [. . .] which is rapidly absorbed,
`can be orally or enterally delivered as a liquid form or
`solid form [. . . ] in the stomach”. (WO’185, 16:2-7.)
`
`“The invention herein is directed to a pharmaceutical
`composition which is a core/mantle tablet consisting
`of a core of a nonsteroidal anti-inflammatory drug
`(NSAID).” (’225 patent, 3:9-11.)
`
`“We claim: 1. A pharmaceutical composition
`comprising: a. a core consisting of a therapeutically-
`effective amount of a nonsteroidal anti-inflammatory
`agent; and b. a mantle coating surrounding the core
`comprising a therapeutically-effective amount of
`[acid inhibitor].” (’225 patent, 12:34-40.)
`
`“Table 2. Features and Costs of Commonly
`Prescribed NSAIDs. [. . .] naproxen”. Chandramouli
`at 34.
`
`“The dosage range of omeprazole or other proton
`pump inhibitors such as substituted benzimidazoles
`and derivatives thereof can range from approximately
`2 mg/day to approximately 100 mg/day.” (WO’185,
`21:27-22:1.)
`
`
`Table 2. Features and Costs of Commonly Prescribed
`NSAIDs states that the commonly known dose for
`naproxen (Naprosyn®) is 250-500mg. Chandramouli
`at 34.
`
`
`“A method of treating inflammation comprising orally
`
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`

`
`patient for pain or
`inflammation, comprising
`administering to said
`patient a therapeutically
`effective amount of the
`pharmaceutical
`composition of claim 1.
`
`Claim 6
`The method of claim 5,
`wherein said pain or
`inflammation is due to
`either osteoarthritis or
`rheumatoid arthritis.
`
`Claim 13
`The pharmaceutical
`composition of claim 1,
`further comprising at least
`one carrier.
`Claim 14
`The pharmaceutical
`composition of claim 1,
`further comprising at least
`one auxiliary agent chosen
`from the group consisting
`of lubricants,
`preservatives,
`disintegrants, stabilizers,
`wetting agents,
`emulsifiers, salts, buffers,
`coloring agents, flavoring
`agents, and aromatic
`substances.
`
`
`
`administering to a patient in need of such treatment, a
`therapeutically effective amount to treat inflammation
`of a composition comprising a. a core consisting of a
`therapeutically effective amount of a nonsteroidal
`anti-inflammatory agent [. . .]; and b. a mantle coating
`surrounding the core comprising a therapeutically-
`effective amount of [acid inhibitor].” (’225 patent,
`12:42-44.)
`
`“[NSAIDs] comprise a class of drugs which have long
`been recognized as having high therapeutic value
`especially for the treatment of inflammatory
`conditions such as exhibited in inflammatory diseases
`like osteoarthritis (OA) and rheumatoid arthritis
`(RA).” (’225 patent, 1:18-22.) “It would be desirable
`to provide a pharmaceutical composition which would
`exhibit the beneficial properties of an NSAID and
`which composition would exhibit the beneficial
`properties of [an acid inhibitor] for countering [. . .]
`the ulcerogenic side effects attendant to NSAID
`administration.” (’225 patent, 1:57-62.)
`
`“[A]dministering to a patient a pharmaceutical
`composition including a proton pump inhibitor in a
`pharmaceutically acceptable carrier”. (WO’185,
`Abstract.)
`
`“The formulations can be made more palatable by
`adding flavorings such as chocolate, root beer, and
`others.” (WO’185, 22:10-12.)
`
` “Additionally, various additives including ambicin
`which enhance the stability, sterility, and isotonicity
`of the compositions. Additionally, antimicrobial
`preservatives, antioxidants, chelating agents, and
`buffers can be added.” (WO’185, 22:13-17.)
`
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`
`Claim 15
`The pharmaceutical
`composition of claim 1,
`further comprising at least
`one ingredient to adjust
`pH.
`
`
`
`“[A]dministering to a patient a pharmaceutical
`composition including a proton pump inhibitor in a
`pharmaceutically acceptable carrier including a
`bicarbonate salt”. (WO’185, Abstract.)
`
`
`
`5