CLAIM CHART – GROUND 1
`
`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;
`
`
`
`’556 patent and Chandramouli
`
`
`
`“In preferred embodiments of the invention, the
`pharmaceutical compositions containing the proton
`pump inhibitors and NSAIDs set forth herein are
`administered orally.” (7:31-33.)
`
`“The invention is further directed to a dosage form
`comprising a therapeutically effective amount of an
`NSAID and an amount of a proton pump inhibitor
`effective to substantially inhibit gastrointestinal side
`effects of the NSAID” (4:4-7.)
`
`“In certain preferred embodiments, the proton pump
`inhibitor is omeprazole, either in racemic mixture or
`only the (-)enantiomer of omeprazole (i.e.
`esomeprazole)” (6:53-56.)
`
`U.S. Patent No. 5,877,192, which is incorporated by
`reference, teaches esomeprazole may raise intragastric
`pH to 3.5 or higher. (See 6:53-58.)
`“The invention is further directed to a dosage form
`comprising a therapeutically effective amount of an
`NSAID and an amount of a proton pump inhibitor
`effective to substantially inhibit gastrointestinal side
`effects of the NSAID” (4:4-7.)
`
`“For many years NSAIDs have been used for treating
`pain and/or inflammation.” (5:40-42.)
`
`“The term NSAID includes, but is not limited to, the
`group consisting of [. . .], naproxen, [. . .]” (5:60-63.)
`“In certain preferred embodiments, the oral dosage
`form of the present invention comprises a compressed
`matrix comprising the NSAID or a salt thereof and a
`retardant material in an effective amount to provide a
`controlled release of the NSAID for at least about 24
`hours; a proton pump inhibitor coated on the surface
`1
`
`Lupin Exh. 1024
`
`

`
`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:
`
`
`
`of the matrix” (12:54-59.)
`“In certain preferred embodiments, the oral dosage
`form of the present invention comprises a compressed
`matrix comprising the NSAID or a salt thereof and a
`retardant material in an effective amount to provide a
`controlled release of the NSAID” (12:54-59.)
`
`“In one embodiment, coatings are provided to permit
`either pH-dependent or pH-independent release”
`(12:17-19.)
`
`“Coatings which are pH-dependent may be used in
`accordance with the present invention” (12:40-41.)
`
`“As enteric coating layer polymers one or more,
`separately or in combination, of the following can be
`used; e.g. solutions or dispersions of methacrylic acid
`copolymers, cellulose acetate phthalate,
`hydroxypropyl methylcellulose phthalate,
`hydroxypropyl methylcellulose acetate succinate,
`polyvinyl acetate phthalate, cellulose acetate
`trimellitate, carboxymethylethylcellulose, shellac or
`other suitable enteric coating layer polymer(s).”
`(13:13-22.)
`“In certain preferred embodiments, the oral dosage
`form of the present invention comprises a compressed
`matrix comprising the NSAID [. . .]; a proton pump
`inhibitor coated on the surface of the matrix, wherein
`the proton pump inhibitor is in an amount effective to
`inhibit gastrointestinal side effects normally
`associated with oral administration of the NSAID”
`(’556 patent, 12:54-62.)
`
`“The proton pump inhibitor is coated onto the tablet.
`Preferably, a solution of the proton pump inhibitor is
`spray dried onto the surface of the tablet using any
`spray technique known to those skilled in the art.”
`(14:8-11.)
`
`“In certain preferred embodiments, the proton pump
`2
`
`

`
`inhibitor is omeprazole, either in racemic mixture or
`only the (—)enantiomer of omeprazole (i.e.
`esomeprazole)” (6:53-56.)
`“In certain preferred embodiments, the oral dosage
`form of the present invention comprises a compressed
`matrix comprising the NSAID [. . .]; a proton pump
`inhibitor coated on the surface of the matrix” (12:54-
`59)
`“Formulations according to the invention that utilize
`pH-dependent coatings to obtain formulations may
`also impart a repeat-action effect whereby
`unprotected drug [. . .] is coated over the enteric coat
`and is released in the stomach, while the remainder, [.
`. .] being protected by the enteric coating, is released
`further down the gastrointestinal tract.” (12:33-40.)
`“In one embodiment, coatings are provided to permit
`either pH-dependent or pH-independent release”
`(12:17-19.)
`
`“Formulations according to the invention that utilize
`pH-dependent coatings to obtain formulations may
`also impart a repeat-action effect whereby
`unprotected drug [. . .] is coated over the enteric coat
`and is released in the stomach, while the remainder, [.
`. .] being protected by the enteric coating, is released
`further down the gastrointestinal tract.” (12:33-40.)
`
`“In certain preferred embodiments, the oral dosage
`form of the present invention comprises a compressed
`matrix comprising the NSAID or a salt thereof and a
`retardant material in an effective amount to provide a
`controlled release of the NSAID for at least about 24
`hours; a proton pump inhibitor coated on the surface
`of the matrix” (12:54-59.)
`
`“The term NSAID includes, but is not limited to, the
`group consisting of [. . .], naproxen, [. . .]” (5:60-63.)
`
`“In certain preferred embodiments, the proton pump
`
`3
`
`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
`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
`patient for pain or
`inflammation, comprising
`administering to said
`patient a therapeutically
`effective amount of the
`pharmaceutical
`composition of claim 1.
`
`
`
`inhibitor is omeprazole, either in racemic mixture or
`only the (—)enantiomer of omeprazole (i.e.
`esomeprazole)” (6:53-56.)
`
`“Thus, in certain embodiments of the invention, the
`amount of proton pump inhibitor which is included in
`the dosage form is an amount which is considered to
`be therapeutically effective, in accordance with the
`dosages set forth above for a variety of disease
`states.” (7:1-5.)
`
`“For example, when the drug is omeprazole, the
`dosage form may contain from about 0.1mg to about
`120 mg omeprazole. Lansoprazole is typically
`administered about 15-30 mg/day; rabeprazole is
`typically administered 20 mg/day and pantoprazole is
`typically administered 40 mg/day. However, any
`therapeutic or sub-therapeutic dose of these agents is
`considered within the scope of the present invention”
`(7:7-14.)
`
`“The invention is further directed to a dosage form
`comprising a therapeutically effective amount of an
`NSAID and an amount of a proton pump inhibitor
`effective to substantially inhibit gastrointestinal side
`effects of the NSAID” (4:4-7.)
`
`Listing commonly prescribed naproxen dosage as
`250-500mg, and 750-1000mg per day (Chandramouli,
`34)
`
`“Also disclosed is a method of treating a human
`patient in need of antiinflammatory, analgesic and/or
`antipyretic therapy, comprising orally administering
`to the patient an oral pharmaceutical dosage form
`which includes a therapeutically effective amount of
`an NSAID and an amount of a proton pump inhibitor
`effective to substantially inhibit gastrointestinal side
`effects of the NSAID.” (Abstract.)
`
`
`4
`
`

`
`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.
`Claim 15
`The pharmaceutical
`composition of claim 1,
`further comprising at least
`one ingredient to adjust
`pH.
`
`
`
`“For many years NSAIDs have been used for treating
`pain and/or inflammation.” (5:40-42.)
`
`“Pain includes, but is not limited to, chronic pains,
`such as arthritis pain (e.g. pain associated with
`osteoarthritis and rheumatoid arthritis)” (5:46-48.)
`
`
`“The combination of proton pump inhibitor and a
`NSAID can be employed in admixtures With
`conventional excipients, i.e., pharmaceutically
`acceptable organic or inorganic carrier substances
`suitable for oral, parenteral, nasal, intravenous,
`subcutaneous, enteral, or any other suitable mode of
`administration, known to the art. Suitable
`pharmaceutically acceptable carriers include but are
`not limited to [. . .].” (7:31-44.)
`
`
`“The pharmaceutical preparations can be sterilized
`and if desired mixed with auxiliary agents, e.g.,
`lubricants, preservatives, stabilizers, wetting agents,
`emulsifiers, salts for influencing osmotic pressure
`buffers, coloring, flavoring and/or aromatic
`substances and the like.” (7:44-48.)
`
`
`“A further ingredient which can be added to the
`matrix is a pH modifying agent” (13:48-49.)
`
`5
`
`

`
`CLAIM CHART – GROUND 2
`
`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
`
`
`
`’556 patent and ’225 patent
`
`
`“In preferred embodiments of the invention, the
`pharmaceutical compositions containing the proton
`pump inhibitors and NSAIDs set forth herein are
`administered orally.” (’556 patent, 7:31-33.)
`
`“The invention is further directed to a dosage form
`comprising a therapeutically effective amount of an
`NSAID and an amount of a proton pump inhibitor
`effective to substantially inhibit gastrointestinal side
`effects of the NSAID” (’556 patent, 4:4-7.)
`
`“In certain preferred embodiments, the proton pump
`inhibitor is omeprazole, either in racemic mixture or
`only the (—)enantiomer of omeprazole (i.e.
`esomeprazole)” (’556 patent, 6:53-56.)
`
`U.S. Patent No. 5,877,192, which is incorporated by
`reference, teaches esomeprazole may raise intragastric
`pH to 3.5 or higher. (See ’556 patent, 6:53-58.)
`
`“As enteric coating layer polymers one or more,
`separately or in combination, of the following can be
`used; e.g. solutions or dispersions of methacrylic acid
`copolymers, cellulose acetate phthalate,
`hydroxypropyl methylcellulose phthalate,
`hydroxypropyl methylcellulose acetate succinate,
`polyvinyl acetate phthalate, cellulose acetate
`trimellitate, carboxymethylethylcellulose, shellac or
`other suitable enteric coating layer polymer(s).”
`(’556 patent, 13:13-22.)
`“The invention is further directed to a dosage form
`comprising a therapeutically effective amount of an
`NSAID and an amount of a proton pump inhibitor
`effective to substantially inhibit gastrointestinal side
`effects of the NSAID” (’556 patent, 4:4-7.)
`
`
`6
`
`

`
`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;
`
`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
`
`
`
`“For many years NSAIDs have been used for treating
`pain and/or inflammation.” (’556 patent, 5:40-42.)
`
`“The term NSAID includes, but is not limited to, the
`group consisting of [. . .], naproxen, [. . .]” (’556
`patent, 5:60-63.)
`“In certain preferred embodiments, the oral dosage
`form of the present invention comprises a compressed
`matrix comprising the NSAID or a salt thereof and a
`retardant material in an effective amount to provide a
`controlled release of the NSAID for at least about 24
`hours; a proton pump inhibitor coated on the surface
`of the matrix” (’556 patent, 12:54-59.)
`
`“The term NSAID includes, but is not limited to, the
`group consisting of [. . .], naproxen, [. . .]” (’556
`patent, 5:60-63.)
`
`“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
`misoprostol.” (’225 patent, 12:34-40.)
`“In certain preferred embodiments, the oral dosage
`form of the present invention comprises a compressed
`matrix comprising the NSAID or a salt thereof and a
`retardant material in an effective amount to provide a
`controlled release of the NSAID” (’556 patent, 12:54-
`59.)
`
`“In one embodiment, coatings are provided to permit
`either pH-dependent or pH-independent release”
`(’556 patent, 12:17-19.)
`
`
`7
`
`

`
`“Coatings which are pH-dependent may be used in
`accordance with the present invention” (’556 patent,
`12:40-41.)
`
`“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.)
`“In certain preferred embodiments, the oral dosage
`form of the present invention comprises a compressed
`matrix comprising the NSAID [. . .]; a proton pump
`inhibitor coated on the surface of the matrix, wherein
`the proton pump inhibitor is in an amount effective to
`inhibit gastrointestinal side effects normally
`associated with oral administration of the NSAID”
`(’556 patent, 12:54-62.)
`
`“The proton pump inhibitor is coated onto the tablet.
`Preferably, a solution of the proton pump inhibitor is
`spray dried onto the surface of the tablet using any
`spray technique known to those skilled in the art.”
`(’556 patent, 14:8-11.)
`
`“In certain preferred embodiments, the proton pump
`inhibitor is omeprazole, either in racemic mixture or
`only the (—)enantiomer of omeprazole (i.e.
`esomeprazole)” (’556 patent, 6:53-56.)
`
`“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-
`8
`
`iii) said esomeprazole is in
`one or more layers outside
`said core, wherein said one
`“or more layers:
`
`
`
`

`
`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.)
`“In certain preferred embodiments, the oral dosage
`form of the present invention comprises a compressed
`matrix comprising the NSAID [. . .]; a proton pump
`inhibitor coated on the surface of the matrix” (’556
`patent, 12:54-59)
`
`“Surrounding the coated inner core is a mantle
`consisting of [an acid inhibitor]” (’225 patent, 6:41-
`43.)
`“Formulations according to the invention that utilize
`pH-dependent coatings to obtain formulations may
`also impart a repeat-action effect whereby
`unprotected drug [. . .] is coated over the enteric coat
`and is released in the stomach, while the remainder, [.
`. .] being protected by the enteric coating, is released
`further down the gastrointestinal tract.” (’556 patent,
`12:33-40.)
`“In one embodiment, coatings are provided to permit
`either pH-dependent or pH-independent release”
`(’556 patent, 12:17-19.)
`
`“Formulations according to the invention that utilize
`pH-dependent coatings to obtain formulations may
`also impart a repeat-action effect whereby
`unprotected drug [. . .] is coated over the enteric coat
`and is released in the stomach, while the remainder, [.
`. .] being protected by the enteric coating, is released
`further down the gastrointestinal tract.” (’556 patent,
`12:33-40.)
`“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
`the lower G.I. tract as opposed to the stomach [where
`the acid inhibitor is released].” (’225 patent, 6:33-36.)
`
`“In certain preferred embodiments, the oral dosage
`9
`
`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
`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.
`
`
`
`form of the present invention comprises a compressed
`matrix comprising the NSAID or a salt thereof and a
`retardant material in an effective amount to provide a
`controlled release of the NSAID for at least about 24
`hours; a proton pump inhibitor coated on the surface
`of the matrix” (’556 patent, 12:54-59.)
`
`“The term NSAID includes, but is not limited to, the
`group consisting of [. . .], naproxen, [. . .]” (’556
`patent, 5:60-63.)
`
`“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.)
`
`“In certain preferred embodiments, the proton pump
`inhibitor is omeprazole, either in racemic mixture or
`only the (—)enantiomer of omeprazole (i.e.
`esomeprazole)” (’556 patent, 6:53-56.)
`
`“Thus, in certain embodiments of the invention, the
`amount of proton pump inhibitor which is included in
`the dosage form is an amount which is considered to
`be therapeutically effective, in accordance with the
`dosages set forth above for a variety of disease
`states.”
`
`“For example, when the drug is omeprazole, the
`dosage form may contain from about 0.1mg to about
`120 mg omeprazole. Lansoprazole is typically
`administered about 15-30 mg/day; rabeprazole is
`typically administered 20 mg/day and pantoprazole is
`10
`
`

`
`typically administered 40 mg/day. However, any
`therapeutic or sub-therapeutic dose of these agents is
`considered within the scope of the present invention”
`(’556 patent, 7:7-14.)
`
`“The invention is further directed to a dosage form
`comprising a therapeutically effective amount of an
`NSAID and an amount of a proton pump inhibitor
`effective to substantially inhibit gastrointestinal side
`effects of the NSAID” (’556 patent, 4:4-7.)
`
`
`“Also disclosed is a method of treating a human
`patient in need of antiinflammatory, analgesic and/or
`antipyretic therapy, comprising orally administering
`to the patient an oral pharmaceutical dosage form
`which includes a therapeutically effective amount of
`an NSAID and an amount of a proton pump inhibitor
`effective to substantially inhibit gastrointestinal side
`effects of the NSAID.” (’556 patent, Abstract.)
`
`“For many years NSAIDs have been used for treating
`pain and/or inflammation.” (’556 patent, 5:40-42.)
`
`“A method of treating inflammation" comprising
`orally 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.)
`
`“Pain includes, but is not limited to, chronic pains,
`such as arthritis pain (e.g. pain associated with
`osteoarthritis and rheumatoid arthritis)” (’556 patent,
`5:46-48.)
`
`“[NSAIDs] comprise a class of drugs which have long
`11
`
`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
`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.
`
`
`
`

`
`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.)
`
`“The combination of proton pump inhibitor and a
`NSAID can be employed in admixtures With
`conventional excipients, i.e., pharmaceutically
`acceptable organic or inorganic carrier substances
`suitable for oral, parenteral, nasal, intravenous,
`subcutaneous, enteral, or any other suitable mode of
`administration, known to the art. Suitable
`pharmaceutically acceptable carriers include but are
`not limited to [. . .].” (’556 patent, 7:31-44.)
`
`
`“The pharmaceutical preparations can be sterilized
`and if desired mixed with auxiliary agents, e.g.,
`lubricants, preservatives, stabilizers, wetting agents,
`emulsifiers, salts for influencing osmotic pressure
`buffers, coloring, flavoring and/or aromatic
`substances and the like.” (’556 patent, 7:44-48.)
`
`
`“A further ingredient which can be added to the
`matrix is a pH modifying agent” (’556 patent, 13:48-
`49.)
`
`12
`
`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.
`Claim 15
`The pharmaceutical
`composition of claim 1,
`further comprising at least
`
`
`
`

`
`one ingredient to adjust
`pH.
`
`
`
`
`13