CLAIM CHART – GROUND 3
`
`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
`
`
`
`’118 patent and ’225 patent
`
`
`“Examples 1-10 disclose various formulations for
`preparing tablets or caplets in accordance with the
`invention.” (’118 patent, 6:24-26.)
`
`“[T]he invention comprises pharmaceutical
`compositions and methods [. . . ] comprising [ . . .] a
`gastric acid inhibiting effective amount of [. . .] a
`proton pump inhibitor.” (’118 patent, 3:10-16.)
`
`“Omeprazole, a proton pump inhibitor, irreversibly
`inhibits the enzyme responsible for acid production.”
`(’118 patent, 4:64-66.)
`
`“The composition of the present invention shall
`preferably contain a combination of the following
`compositions or their pharmaceutically acceptable
`salts [. . .] proton pump inhibitor drugs including
`omeprazole from 60 to 500mg per dose”. (’118
`patent, 5:9-11, 30-31.)
`“[T]he invention comprises pharmaceutical
`compositions and methods [. . . ] comprising an
`analgesic effective amount of an NSAID” (’118
`patent, 3:10-14.)
`
`“NSAIDs are commonly used for the treatment of
`pain and inflammation of a variety of etiologies.”
`(’118 patent, 3:10-14.)
`
`“The composition of the present invention shall
`preferably contain [. . .] one of several NSAIDs form
`the group of: [. . .] naproxen from 200 to 500mg per
`dose”. (’118 patent, 5:09-19.)
`“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
`1
`
`Lupin Exh. 1030
`
`

`
`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
`
`iii) said esomeprazole is in
`one or more layers outside
`said core, wherein said one
`“or more layers:
`
`A) do not include an
`
`
`
`(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.)
`
`“The composition of the present invention shall
`preferably contain [. . .] one of several NSAIDs form
`the group of: [. . .] naproxen from 200 to 500mg per
`dose”. (’118 patent, 5:09-19.)
`“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.)“
`“The composition of the present invention shall
`preferably contain a combination of the following
`compositions or their pharmaceutically acceptable
`salts [. . .] proton pump inhibitor drugs including
`omeprazole from 60 to 500mg per dose”. (’118
`patent, 5:9-11, 30-31.)
`“Surrounding the coated inner core is a mantle
`2
`
`

`
`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,
`
`
`
`consisting of [an acid inhibitor]” (’225 patent, 6:41-
`43.)
`“EXAMPLE 11 A tablet consisting of: 500 mg
`acetaminophen; 60 mg of omeprazole; and other
`auxiliary agents and coloring agents.” (’118 patent,
`7:29-35.)
`
`“EXAMPLE 12 A tablet consisting of: 200 mg
`ibuprofen; 60 mg of omeprazole; and other auxiliary
`agents and coloring agents.” (’118 patent, 7:36-42.)
`“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.)
`“The composition of the present invention shall
`preferably contain a combination of the following
`compositions or their pharmaceutically acceptable
`salts [. . .] proton pump inhibitor drugs including
`omeprazole from 60 to 500mg per dose”. (’118
`patent, 5:9-11, 30-31.)
`
`“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
`[acid inhibitor].” (’225 patent, 12:34-40.)
`“The composition of the present invention shall
`preferably contain [. . .] one of several NSAIDs form
`the group of: [. . .] naproxen from 200 to 500mg per
`dose”. (’118 patent, 5:09-19.)
`
`“The composition of the present invention shall
`preferably contain a combination of the following
`3
`
`

`
`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.
`
`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
`
`
`
`compositions or their pharmaceutically acceptable
`salts [. . .] proton pump inhibitor drugs including
`omeprazole from 60 to 500mg per dose”. (’118
`patent, 5:9-11, 30-31.)
`
`
`“The composition of the present invention shall
`preferably contain [. . .] one of several NSAIDs form
`the group of: [. . .] naproxen from 200 to 500mg per
`dose”. (’118 patent, 5:09-19.)
`
`
`“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.)
`
`“[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.)
`
`“Other ingredients both active and inactive can be
`added to the combination pharmaceutical
`compositions of the invention.” (’118 patent, 6:1-3.)
`
`4
`
`

`
`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.
`
`
`“Various excipients such as binders, bulking agents,
`lubricants, fillers and the like, can be combined”
`(’225 patent, 4:28-29.)
`
`“Other ingredients both active and inactive can be
`added to the combination pharmaceutical
`compositions of the invention.” (’118 patent, 6:1-3.)
`
`“Various excipients such as binders, bulking agents,
`lubricants, fillers and the like, can be combined”
`(’225 patent, 4:28-29.)
`
`
`“Other ingredients both active and inactive can be
`added to the combination pharmaceutical
`compositions of the invention.” (’118 patent, 6:1-3.)
`
`“Various excipients such as binders, bulking agents,
`lubricants, fillers and the like, can be combined”
`(’225 patent, 4:28-29.)
`
`
`CLAIM CHART – GROUND 4
`
`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
`
`
`
`’118, ’225, and ’192 patents
`
`
`“Examples 1-10 disclose various formulations for
`preparing tablets or caplets in accordance with the
`invention.” (’118 patent, 6:24-26.)
`
`“[T]he invention comprises pharmaceutical
`compositions and methods [. . . ] comprising [ . . .] a
`gastric acid inhibiting effective amount of [. . .] a
`5
`
`

`
`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
`
`
`
`proton pump inhibitor.” (’118 patent, 3:10-16.)
`
`“Omeprazole, a proton pump inhibitor, irreversibly
`inhibits the enzyme responsible for acid production.”
`(’118 patent, 4:64-66.)
`
`“The composition of the present invention shall
`preferably contain a combination of the following
`compositions or their pharmaceutically acceptable
`salts [. . .] proton pump inhibitor drugs including
`omeprazole from 60 to 500mg per dose”. (’118
`patent, 5:9-11, 30-31.)
`
`“[O]meprazole is a racemic mixture of its two single
`enantiomers, the (+)-enantiomer of omeprazole and
`the (-)-enantiomer of omeprazole.” (’192 patent,
`1:52-54.)
`
`“One previous in vitro study on inhibition of acid
`secretion in isolated gastric glands showed no
`significant difference in effect between the two single
`enantiomers of omeprazole and the racemic mixture [.
`. .] It has also been shown that, when omeprazole was
`administered intravenously to one subject, the plasma
`levels of the two enantiomers were similar.” (’192
`patent, 2:5-13.)
`“[T]he invention comprises pharmaceutical
`compositions and methods [. . .] comprising an
`analgesic effective amount of an NSAID” (’118
`patent, 3:10-14.)
`
`“NSAIDs are commonly used for the treatment of
`pain and inflammation of a variety of etiologies.”
`(’118 patent, 3:10-14.)
`
`“The composition of the present invention shall
`preferably contain [. . .] one of several NSAIDs form
`the group of: [. . .] naproxen from 200 to 500mg per
`dose”. (’118 patent, 5:09-19.)
`“The invention herein is directed to a pharmaceutical
`6
`
`

`
`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
`
`iii) said esomeprazole is in
`one or more layers outside
`said core, wherein said one
`“or more layers:
`
`
`
`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.)
`
`“The composition of the present invention shall
`preferably contain [. . .] one of several NSAIDs form
`the group of: [. . .] naproxen from 200 to 500mg per
`dose”. (’118 patent, 5:09-19.)
`“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.)
`
`“The composition of the present invention shall
`preferably contain a combination of the following
`compositions or their pharmaceutically acceptable
`salts [. . .] proton pump inhibitor drugs including
`7
`
`

`
`omeprazole from 60 to 500mg per dose”. (’118
`patent, 5:9-11, 30-31.)
`
`“[O]meprazole is a racemic mixture of its two single
`enantiomers, the (+)-enantiomer of omeprazole and
`the (-)-enantiomer of omeprazole.” (’192 patent,
`1:52-54.)
`“Surrounding the coated inner core is a mantle
`consisting of [an acid inhibitor]” (’225 patent, 6:41-
`43.)
`“EXAMPLE 11 A tablet consisting of: 500 mg
`acetaminophen; 60 mg of omeprazole; and other
`auxiliary agents and coloring agents.” (’118 patent,
`7:29-35.)
`
`“EXAMPLE 12 A tablet consisting of: 200 mg
`ibuprofen; 60 mg of omeprazole; and other auxiliary
`agents and coloring agents.” (’118 patent, 7:36-42.)
`“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.)
`“The composition of the present invention shall
`preferably contain a combination of the following
`compositions or their pharmaceutically acceptable
`salts [. . .] proton pump inhibitor drugs including
`omeprazole from 60 to 500mg per dose”. (’118
`patent, 5:9-11, 30-31.)
`
`“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
`8
`
`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.
`
`
`
`

`
`[acid inhibitor].” (’225 patent, 12:34-40.)
`
`“The composition of the present invention shall
`preferably contain [. . .] one of several NSAIDs form
`the group of: [. . .] naproxen from 200 to 500mg per
`dose”. (’118 patent, 5:09-19.)
`
`“The composition of the present invention shall
`preferably contain a combination of the following
`compositions or their pharmaceutically acceptable
`salts [. . .] proton pump inhibitor drugs including
`omeprazole from 60 to 500mg per dose”. (’118
`patent, 5:9-11, 30-31.)
`
`“In slow metabolizers 60mg doses of [omeprazole
`and esomeprazole] were given once daily, while the
`rapid metabolisers were given once daily doses of 15
`mg.” (’192 patent, 5:6-8.)
`
`“In general, a suitable oral dosage form may cover a
`dose range from 5 mg to 80 mg total daily dose”
`(’192 patent, 4:40-41.) “[I]n some conditions, it may
`be necessary to use doses outside the ranges stated
`below. Such higher and lower doses of the (-)-
`enantiomer of omeprazole are within the scope of the
`present invention.” (’192 patent, 4:35-39.)
`
`“The composition of the present invention shall
`preferably contain [. . .] one of several NSAIDs form
`the group of: [. . .] naproxen from 200 to 500mg per
`dose”. (’118 patent, 5:09-19.)
`
`
`“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
`9
`
`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.
`
`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,
`
`
`
`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.)
`
`“Other ingredients both active and inactive can be
`added to the combination pharmaceutical
`compositions of the invention.” (’118 patent, 6:1-3.)
`
`“Various excipients such as binders, bulking agents,
`lubricants, fillers and the like, can be combined”
`(’225 patent, 4:28-29.)
`
`“The pharmaceutical compositions [. . .] may also
`contain a pharmaceutically acceptable carrier and
`optionally other therapeutic ingredients.” (’192
`patent, 4:9-13.)
`
`“Other ingredients both active and inactive can be
`added to the combination pharmaceutical
`compositions of the invention.” (’118 patent, 6:1-3.)
`
`“Various excipients such as binders, bulking agents,
`lubricants, fillers and the like, can be combined”
`(’225 patent, 4:28-29.)
`
`“The pharmaceutical compositions [. . .] may also
`contain a pharmaceutically acceptable carrier and
`10
`
`

`
`coloring agents, flavoring
`agents, and aromatic
`substances.
`Claim 15
`The pharmaceutical
`composition of claim 1,
`further comprising at least
`one ingredient to adjust
`pH.
`
`optionally other therapeutic ingredients.” (’192
`patent, 4:9-13.)
`
`
`“Other ingredients both active and inactive can be
`added to the combination pharmaceutical
`compositions of the invention.” (’118 patent, 6:1-3.)
`
`“Various excipients such as binders, bulking agents,
`lubricants, fillers and the like, can be combined”
`(’225 patent, 4:28-29.)
`
`“The pharmaceutical compositions [. . .] may also
`contain a pharmaceutically acceptable carrier and
`optionally other therapeutic ingredients.” (’192
`patent, 4:9-13.)
`
`
`
`
`11