`
`In re patent application of:
`
`
`
` THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Plachetka, John R.
`
`Group Art Unit: 1615
`
`Appl.No.: 10/158,216
`
`Examiner: Spear, J.
`
`Filed: May 31,2002
`
`Atty. Dkt.: 7569/73281
`
`For:
`
`Pharmaceutical Compositions for the
`Coordinated Delivery of NSAIDs
`
`Amendment and Response Under 37 C.F.R. § 1.116
`
`Commissioner for Patents
`US. Patent and Trademark Office
`220 20th Street South
`
`Customer Window, MS RCE
`Crystal Plaza Two, Lobby, Room 1B03
`Arlington, VA 22202
`
`Sir:
`
`In response to the Office Action dated October 20, 2004, Applicant respectfully requests
`
`reconsideration of the above-captioned application in View of the following amendments and
`
`remarks.
`
`Amendments to the Claims begin on page 2 of the present document.
`
`Remarks begin on page 10 of the present document.
`
`CFAD EXHIBIT 1023
`
`

`

`—2—
`
`Plachetka, John R.
`
`10/158,216
`
`Amendments to the Claims
`
`Please cancel claims 51 and 52 without prejudice. Please add new claims 55-57 and
`
`amend the remaining claims as indicated below in the “List of Claims.”
`
`List of Claims
`
`1.
`
`(Currently amended) A pharmaceutical composition in unit dose form suitable for oral
`
`administration to a patient, comprising:
`
`(a)
`
`an acid inhibitor 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)
`
`a non-steroidal anti-inflammatory drug (N SAID) 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 said unit dosage form provides for coordinated release such thatz—said—aeiel
`
`
`
`said NSAID is surrounded by a coating that, upon ingestion of said
`
`unit dosage form by said patient, prevents the release of essentially
`
`any NSAID from said dosage form unless the pH of the surrounding
`
`medium is 3.5 or higher;
`
`m
`
`at least a portion of said acid inhibitor is not surrounded by an enteric
`
`coating and, upon ingestion of said unit dosage fonn by said patient, is
`
`released regardless of whether the pH of the surrounding medium is
`
`below 3.5 or above 3.5.
`
`2.
`
`(Currently amended) The pharmaceutical composition of claim 1, wherein said acid
`
`inhibitor is seleeted—fi=em:—a—pfeten—pum-p—inhibiter—and an H2 blocker.
`
`3.
`
`(Currently amended) The pharmaceutical composition of claim 2, wherein said acid
`
`mlaibiter—is—an H2 blocker i_s_ selected from the group consisting of: cimetidine; ranitidine;
`
`ebrotidine; pabutidine; lafutidine; loxtidine and famotidine.
`
`

`

`-3-
`
`Plachetka, John R.
`10/158,216
`
`(Original) The .pharmaceutical composition of claim 3, wherein said H2 blocker is
`
`famotidine, present in said unit dosage form in an amount of between 5 mg and 100 mg.
`
`(Original) The pharmaceutical composition of claim 1, wherein said acid inhibitor is a
`
`proton pump inhibitor selected from the group consisting of: omeprazole, esomeprazole,
`
`lansoprazole, pantoprazole and rabeprazole.
`
`(Original) The pharmaceutical composition of claim 5, wherein said proton pump
`
`inhibitor is pantoprazole, present in said unit dosage form in an amount of between 10
`
`mg and 200 mg.
`
`(Original) The pharmaceutical composition of claim 1, wherein said NSAID is a
`
`cyclooxygenese-2 (COX-2) inhibitor.
`
`(Original) The pharmaceutical composition of claim 7, wherein said COX—2 inhibitor is
`
`selected from the group consisting of celecoxib; rofecoxib; meloxicam; piroxicam;
`
`valdecoxib, parecoxib, etoricoxib, CS-502, JTE-522; L-745,337; and NS398.
`
`(Original) The pharmaceutical composition of claim 1, wherein said NSAID is selected
`
`from the group consisting of:
`
`aspirin; acetaminophen;
`
`ibuprofen;
`
`flurbiprofen;
`
`ketoprofen; lornoxicam; naproxen; oxaprozin; etodolac; indomethacin; ketorolac; and
`
`nabumetone.
`
`10.
`
`(Original) The pharmaceutical composition of claim 9, wherein said NSAID is naproxen
`
`present in an amount of between 50 mg and 1500 mg.
`
`ll.
`
`011'
`
`inal‘ The
`
`3
`hannaceutical com osition of claim 10 wherein said na roxen is
`
`present in an amount of between 200 mg and 600 mg.
`
`

`

`-4-
`
`Plachetka, John R.
`10/ 1 58,2 1 6
`
`12.
`
`(Currently amended) The pharmaceutical composition of claim 1 wherein said unit
`
`dosage form is a multilayer tablet comprising a single core and one or more layers
`
`outside of said single core, wherein:
`
`i)
`
`i_i_)
`
`said NSAID is present in said core;
`
`said coating that does not release said NSAID unless the pH of the surrounding
`
`medium is‘ 3.5 or higher surrounds said core; and
`
`iii)
`
`said acid inhibitor is in said one more layers outside said core.
`
`13.
`
`14.
`
`(Currently amended) The pharmaceutical composition of claim 12, wherein said—unit
`
`
`
`eereef—said—NSMB—said one or more layers outside of said core do not contain NSAID
`
`and are not surrounded by an enteric coating.
`
`(Currently amended) The phannaceutical composition of claim 17’!- Q, wherein said unit
`
`dosage form is a bilayer tablet having an outer layer of said acid inhibitor and an inner
`
`core of said NSAID and wherein said outer layer of said tablet is surrounded by a non—
`
`enteric film coating that releases said acid inhibitor upon ingestion by a patient.
`
`15.
`
`
`(Currently amended) The pharmaceutical composition of any one of claims 42-1-4 1 or 7-
`
`E, wherein said :
`
`
`inhibitor is a proton pump inhibitor.
`
`16.
`
`
`(Currently amended) The pharmaceutical composition of any—eneef elaims—l-Q—J4 claim
`
`l_5_,whereinsaid := ‘
`
`-:- :-
`
`-: -
`
`= ~:: - - .
`
`e -.- =.‘:-= :. : ;:--- coating
`
`that surrounding said core does not dissolve unless the pH of the surrounding medium is
`
`4 or greater.
`
`17.
`
`
`(Currently amended) The pharmaceutical composition of Mme—1244 claim
`
`l_5_,whereinsaid :; -
`
`-:‘ :-
`
`-: -
`
`:
`
`‘:
`
`:
`
`‘ -‘ 2 -.-:.-:-: ;- : ;:--- coating
`
`

`

`—5-
`
`Plachetka, John R.
`10/158,216
`
`that surrounding said core does not dissolve unless the pH of the surrounding medium is
`
`5 or greater.
`
`18.
`
`
`(Currently amended) The pharmaceutical composition of any one of elem-1244 claims
`
`
`7—14, wherein said—tablethas an inner-core of said—NSAID—surreunded—by—a—bafiier
`.-.-,-.-.--V.....-..-..-...‘in...- .....
`.
`.-.,.
`
`surreand-mg—medr-um—rséé—or—greatef said acid inhibitor is an H2 blocker.
`
`19.
`
`
`(Currently amended) The pharmaceutical composition of any—efie-etlel-aims—l—Z-M claim
`
`3, wherein said tablet has an inner core of said NSAID surrounded by a barrier coating
`
`that dissolves at a rate such that said NSAID is not released until
`
`the pH of the
`
`surrounding medium is 4 or greater.
`
`20.
`
`
`(Currently amended) The pharmaceutical composition of any—meef—elaims—l—Z—M claim
`
`lfi, wherein said tablet has an inner core of said NSAID surrounded by a barrier coating
`
`that dissolves at a rate such that said NSAID is not released until
`
`the pH of the
`
`surrounding medium is 5 or greater.
`
`21.
`
`22.
`
`23.
`
`24.
`
`(Original) The pharmaceutical composition of claim 1, wherein said unit dosage form is
`
`a capsule.
`
`(Original) A method of treating a patient
`
`for pain or
`
`inflammation, comprising
`
`administering to said patient the pharmaceutical composition of any one of claims 1-14.
`
`(Previously presented) The method of claim 22, wherein said pain or inflammation is
`
`due to either osteoarthritis or rheumatoid arthritis.
`
`(Original) A method of treating a patient for pain or inflammation, comprising:
`
`(a)
`
`orally administering to said patient an acid inhibitor at a dose effective to
`
`raise the gastric pH of said patient to at least 3.5; and
`
`

`

`-6-
`
`Plachetka, John R.
`10/158,216
`
`25.
`
`26.
`
`27.
`
`28.
`
`29.
`
`30.
`
`31.
`
`32.
`
`(b)
`
`orally administering to said patient an NSAID that is coated in a polymer
`
`that only dissolves at a pH of 3.5 or greater.
`
`(Original) The method of claim 24, wherein said acid inhibitor is an H2 blocker.
`
`(Original) The method of claim 25, wherein said H-2 blocker is selected from the group
`
`consisting of: cimetidine; ranitidine; ebrotidine; pabutidine;
`
`lafutidine;
`
`loxtidine and
`
`famotidine.
`
`(Original) The method of claim 26, wherein said H2 blocker is famotidine administered
`
`at a dose of between 5 mg and 100 mg.
`
`(Original) The method of claim 24, wherein said acid inhibitor is a proton pump
`
`inhibitor.
`
`(Original) The method of claim 28, wherein said proton pump inhibitor is selected from
`
`the group consisting of: omeprazole, esomeprazole,
`
`lansoprazole,
`
`rabeprazole and
`
`pantoprazole.
`
`(Original) The method of claim 29, wherein said proton pump inhibitor is pantoprazole
`
`administered at a dose of between 10 mg and 200 mg.
`
`(Original) The method of any one of claims 24 — 30, wherein said NSAID is a COX-2
`
`inhibitor selected from the group consisting of: celecoxib;
`
`rofecoxib; meloxicam;
`
`piroxicam; valdecoxib, parecoxib, etoricoxib, CS-502, JTE-522; L-745,337; and NS398.
`
`(Original) The method of any one of claims 24 — 30, wherein said NSAID is selected
`
`from the group consisting of:
`
`aspirin; acetaminophen;
`
`ibuprofen;
`
`flurbiprofen;
`
`ketoprofen; lomoxicam; naproxen; oxaprozin; etodolac; indomethacin; ketorolac; and
`
`nabumetone.
`
`

`

`-7—
`
`Plachetka, John R.
`10/158,216
`
`(Original) The method of claim 32, wherein said NSAID is naproxen administered at a
`
`dose ofbetween 50 mg and 1500 mg.
`
`(Original) The method of claim 33, wherein said naproxen is administered at a dose of
`
`between 200 mg and 600 mg.
`
`(Original) The method of claim 24, wherein said acid inhibitor and said NSAID are
`
`delivered as part of a single dosage form providing for the coordinated release of
`
`therapeutic agents.
`
`(Original) The method of claim 35, wherein said single dosage form is a bilayer tablet
`
`with an outer layer comprising an H2 blocker and an inner core comprising an NSAID.
`
`(Original) A method of treating a patient for pain or inflammation, comprising:
`
`(a)
`
`orally administering to said patient an acid inhibitor at a dose effective to
`
`raise the gastric pH of said patient to at least 3.5; and
`
`(b)
`
`concurrently administering to said patient an NSAID that is coated in a
`
`polymer that dissolves at a rate such that said NSAID is not released until
`
`said gastric pH is at 3.5 or higher.
`
`(Original) The method of claim 37, wherein said acid inhibitor is an H2 blocker.
`
`(Original) The method of claim 38, wherein said H-2 blocker is selected from the group
`
`consisting of: cimetidine; ranitidine; ebrotidine; pabutidine;
`
`lafutidine;
`
`loxtidine and
`
`famotidine.
`
`(Original) The method of claim 39, wherein said H2 blocker is famotidine administered
`
`at a dose ofbetween 5 mg and 100 mg.
`
`(Original) The method of claim 37, wherein said acid inhibitor is a proton pump
`
`inhibitor.
`
`33.
`
`34.
`
`35.
`
`36.
`
`37.
`
`38.
`
`39.
`
`40.
`
`41.
`
`

`

`-8-
`
`Plachetka, John R.
`10/158,216
`
`42.
`
`43.
`
`44.
`
`45.
`
`46.
`
`47.
`
`48.
`
`49.
`
`(Original) The method of claim 41, wherein said proton pump inhibitor is selected from
`
`the group consisting of: omeprazole, esomeprazole,
`
`lansoprazole,
`
`rabeprazole and
`
`pantoprazole.
`
`(Original) The method of claim 42, wherein said proton pump inhibitor is pantoprazole
`
`administered at a dose ofbetween 10 mg and 200 mg.
`
`(Original) The method of any one of claims 37 - 43, wherein said NSAID is a COX—2
`
`inhibitor selected from the group consisting of: celecoxib;
`
`rofecoxib; meloxicam;
`
`piroxicam; valdecoxib, parecoxib, etoricoxib, CS-502, JTE—522; L-745,337; and NS398.
`
`(Original) The method of any one of claims 37 — 43, wherein said NSAID is selected
`
`from the group consisting of:
`
`aspirin;
`
`acetaminophen;
`
`ibuprofen;
`
`flurbiprofen;
`
`ketoprofen; lomoxicam; naproxen; oxaprozin; etodolac; indomethacin; ketorolac; and
`
`nabumetone.
`
`(Original) The method of claim 45, wherein said NSAID is naproxen administered at a
`
`dose of between 50 mg and 1500 mg.
`
`(Original) The method of claim 46, wherein said naproxen is administered at a dose of
`
`between 200 mg and 600 mg.
`
`(Original) The method of claim 47, wherein said acid inhibitor and said NSAID are
`
`delivered as part of a single dosage form providing for the coordinated release of
`
`therapeutic agents.
`
`Ori
`
`g
`
`g
`g
`y
`inal The method of claim 48, wherein said sin le dosa e form is a bila‘er tablet
`
`with an outer layer comprising an H2 blocker and an inner core comprising an NSAID.
`
`

`

`-9-
`
`Plachetka, John R.
`10/158,216
`
`50.
`
`(Original) A method of improving compliance in patients requiring frequent daily
`
`dosages of an acid inhibitor and an NSAID comprising administering said dosages in a
`
`coordinated unit dosage form in accordance with claim 1.
`
`51-52.
`
`Cancelled
`
`53.
`
`54.
`
`55.
`
`56.
`
`57.
`
`(Currently amended) A method of treating a patient for pain or inflammation, comprising
`
`administering to said patient the pharmaceutical composition of elaimé-l claim15.
`
`(Previously presented) The method of claim 53, wherein said pain or inflammation is due
`
`to either osteoarthritis or rheumatoid arthritis.
`
`(New) The pharmaceutical composition of any one of claims 5-11 wherein said unit
`
`dosage form is a multilayer tablet comprising a single core and one or more layers
`
`outside of said single core, wherein:
`
`i)
`
`ii)
`
`said NSAID is present in said core;
`
`said coating that does not release said NSAID unless the pH of the surrounding
`
`medium is 3.5 or higher surrounds said core; and
`
`iii)
`
`said acid inhibitor is in said one more layers outside said core.
`
`(New) The pharmaceutical composition of claim 55, wherein said one or more layers
`
`outside of said core do not contain NSAID and are not surrounded by an enteric coating.
`
`(New) The pharmaceutical composition of claim 56, wherein said unit dosage form is a
`
`bilayer tablet having an outer layer of said acid inhibitor and an inner core of said
`
`NSAID and wherein said outer layer of said tablet is surrounded by a non—enteric film
`
`coating that, upon ingestion by a patient, releases said acid inhibitor into the stomach of
`
`said patient.
`
`

`

`—10—
`
`Remarks
`
`Plachetka, John R.
`
`10/158,216
`
`‘ 1.
`
`Status of the Application and Claims
`
`As originally filed, the present application had a total of 50 claims. Applicant added
`
`claims 51-54 in a previous submission to the PTO. Claims 51 and 52 have been cancelled herein
`
`and new claims 55-57 have been added. Thus, the claims pending in the application afier the
`
`entry of the present amendments will be claims 1-50, 53—57.
`
`11.
`
`The Amendments
`
`Claims to pharmaceutical compositions were amended both to comply with suggestions
`
`in the Office Action and to emphasize characteristics that Applicants believe are central to their
`
`invention. Amended claims require that NSAID be surrounded by a coating that prevents its
`
`release from the dosage form unless the pH of the surrounding medium is 3.5 or higher, and that
`
`at least a portion of the acid inhibitor in compositions is not surrounded by an enteric coating
`
`and is released regardless of whether the pH is above 3.5 or below 3.5. Amendments were
`
`introduced into claims 12—14 to indicate that that the recited tablet dosage forms contain a single
`
`core with NSAID that is surrounded by the coating that prevents drug release and that acid
`
`inhibitor is in separate outer layers that are not enterically coated (claim 12). Other amendments
`
`indicate that the outer layers of the tablets do not contain NSAID (claim 13) and may be
`
`surrounded by a non-enteric film that allows for the release of acid inbitor into a patient’s
`
`stomach (claim 14). New claims 55-57 introduce these same requirements but refer back to
`
`claims 5—11 rather than to claim 1. The dependency of other claims was changed and an attempt
`
`was made to restrict certain claims to either dosage forms containing H2 blockers or proton
`
`pump inhibitors.
`
`These amendments do not add new matter to the application and their entry is therefore
`
`respectfully requested.
`
`I.
`
`Rejection of Claims Under 35 USC § 102(b)
`
`The Rejections
`
`On pages 2 and 3 of the Office Action, the Examiner rejects claims under 35 USC
`
`§102(b) based upon Goldman et al.
`
`(US 5,204,118). However, Applicant has amended
`
`

`

`-1 l—
`
`Plachetka, John R.
`10/1 58,216
`
`pharmaceutical composition claims so that they now require that NSAID be surrounded by a
`
`‘ coating that does not release the NSAID until the pH of the surrounding medium is at least 3.5.
`
`Based upon statements made in the Office Action, Applicant believes that
`
`this should be
`
`sufficient to obviate the rejection.
`
`II.
`
`Rejection of Claims Under 35 USC § 102(e)
`
`On page 3 of the Office Action, claims 1, 2, 5, 6, 9-12, 21 and 23 are rejected under 35
`
`USC §102(e) based upon Depui, et a]. (US 6,613,354). The arguments made by the Examiner
`
`are a little confusing. In one part, it appears that the Examiner seems to say that Applicant’s
`
`previous arguments are not persuasive because the claims failed to include a requirement that
`
`NSAID be coated to prevent it from being released until the pH of the surrounding medium
`
`rises. If this is the case, then Applicant submits that the rejection has been overcome by the
`
`amendments made herein.
`
`However, at the very end of page 3, the Examiner seems to imply that Depui would serve
`
`as an inherent anticipation of Applicant’s composition claims even if a limitation concerning the
`
`coating of NSAID is included. If this is the case, then Applicant respectfully traverses the
`
`rejection.
`
`An inherent anticipation occurs in cases where a reference fails to literally disclose an
`
`element required by a claim but it can be shown that the missing element is necessarily present
`
`based upon the other teachings in the reference. The fact that the missing element might be
`
`present is insufficient. For example, all of the physical properties of a compound are inherent in
`
`its chemical structure but the amount of the compound added to a chemical reaction is not. In the
`
`present case, the disclosure of a drug composition containing an NSAID and acid inhibitor in
`
`which the acid inhibitor is coated (Depui) certainly does not inherently anticipate a claim to a
`
`composition containing these drugs in which the NSAID is coated and acid inhibitor is not
`
`(Applicant’s claims). The coating of one component does not mean that the other component
`
`must necessarily also be coated. It should also be recognized that Depui’s compositions would
`
`act in a very different way than those claimed by Applicant. Specifically, release of acid
`
`inhibitor in Depui’s compositions would be delayed whereas acid inhibitor release from
`
`

`

`-l 2—
`
`Plachetka, John R.
`10/158,216
`
`Applicant’s compositions is immediate and only the release of NSAID is delayed. The basic
`
`' concept of coating NSAIDs in a way that will prevent them from being released until the
`surrounding pH rises to at least 3.5 is entirely missing from the Depui reference. Applicant
`
`therefore submits that that the reference cannot be validly used to reject the presently pending
`
`claims as inherently anticipated.
`
`III.
`
`Claim Objections
`
`On page 4 of the Office Action, the Examiner objects to claims 7, 8, 13-20 and 51-54 as
`
`being dependent on a rejected base claim but indicates that they would be allowable if rewritten
`
`in independent
`
`form. Since Applicant believes that the base claims should now be allowable, it
`
`is respectfully submitted that the Examiner’s objection has been overcome.
`
`Conclusion
`
`In light of the amendments and discussion above, Applicant believes that all of the
`
`rejections and objections in the present Office Action have been overcome and that the claims
`
`are now in condition for allowance. Early notice to this effect is earnestly solicited.
`
`If, in the opinion of the Examiner, a phone call may help to expedite the prosecution of
`
`this application, the Examiner is invited to call Applicant’s undersigned attorney at (202) 419—
`
`7013.
`
`Respectfully submitted,
`
`FITCH, EVEN, TABIN & FLANNERY
`
`. Mafia/£57
`
`By
`
`Michael A. Sanzo
`
`Reg. No. 36,912
`Attorney for Applicant
`
`
`Date: MW /7 ,2004
`1801 K Street, NW, Suite 401L
`
`Washington, DC 20006
`(202) 419—701 3
`
`