DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
The preliminary amendment filed 08 January 2024 amended claims 1, 4, 5-6, 8, 10-12, 14,-17, and canceled claims 20-25. Consequently, claims 1-19 are pending and presented for examination herein.
Priority
Receipt is acknowledged of certified copies of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
Information Disclosure Statement
The information disclosure statement (IDS) filed 06/23/2023 has been considered by the Examiner. A signed and initialed copy of the IDS is included with the instant Office Action.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-9, 12-16 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over PLACHETKA (US 8,557,285 B2; date of patent: 15 October 2013) in view of TAKAHASHI (US 8,648,080 B2; date of patent: 11 February 2014) as evidenced by TAKAHASHI (Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid Secretion and Motility, Journal of Pharmacology and Experimental Therapeutics, 364, pages 275-286, February 2018; hereafter Takahaski2).
Plachetka is primarily directed towards drug dosage forms that release an agent that raises the pH of the patient’s gastrointestinal tract, followed by a non-steroidal anti-inflammatory drug (abstract).
Regarding claims 1, 3-6, 13 and 19, Plachetka discloses a method of reducing the risk of gastrointestinal side effects in people taking NSAIDs for pain relief and for other conditions. The method involves the administration of a single, coordinated, unit-dose product that combines: a) an agent that actively raises intragastric pH to levels associated with less risk of NSAID-induced ulcers; and b) an NSAID that is specially formulated to be released in a coordinated way that minimizes the adverse effects of the NSAID on the gastroduodenal mucosa (column 3, lines 11-20). Plachetka discloses that acid inhibitors including compounds which competes with potassium at the acid pump that are referred to as “reversible proton pump inhibitors”. Plachetka discloses a pharmaceutical composition that contains a non-steroidal anti-inflammatory drug in an amount effective to reduce or eliminate pain or inflammation and that the NSAID is most preferred naproxen in an amount of between 50 mg and 1500 mg (paragraph bridging columns 3 and 4). Plachetka discloses that the pharmaceutical composition is in the form of a tablet or capsule that has the acid inhibitor present in an amount effective to raise the gastric pH of the patient to at least 3.5 upon administration of the unit dosage form, the non-steroidal anti-inflammatory drug (NSAID) present in an amount effective to reduce or eliminate pain or inflammation in a patient upon administration of the unit dosage form, wherein the NSAID in the dosage form is in a core (e.g., first compartment) for tablets and several cores for capsules (column 4, second paragraph). Plachetka disclose that the NSAID does not release until the pH of the surrounding medium is 3.5 or higher (e.g., controlled release). Plachetka discloses that the acid inhibitor is in including one layer (e.g., second compartment) outside of the core and not surrounded by an enteric coating and upon ingestion of the tablet or capsule by a patient, release of acid inhibitor is in the patient’s stomach (column 4, second paragraph). Plachetka disclose that an enteric coating layer delays the release of the naproxen until the pH is a specific level (column 6, lines 1-2). Plachetka discloses that that the acid inhibitor is in the outermost layer in an effective amount that releases from the dosage form immediately after administration to the patient (column 9, fifth paragraph). Plachetka teaches including pellets of naproxen (column 18, lines 62-67).
Regarding claims 7-9, Plachetka discloses an outer layer comprising the acid inhibitor (e.g., second active ingredient layer) and an inner core which comprises the NSAID (column 4, lines 52-53).
Regarding claim 12, Plachetka discloses a barrier layer (e.g., a separation layer between the core and the enteric coated layer of the first compartment) that protects the first layer (e.g., core) containing naproxen (column 14, second paragraph).
Regarding claims 16, Plachetka discloses capsules filled with fast release acid inhibitor granules and naproxen delayed release pellets that are cores with an enteric coating (column 19, lines, 9-10, 24-25, and 28-30).
Plachetka does not specifically teach that the acid inhibitor is tegoprazan and in the amount of about 20 mg to about 100 mg. The deficiencies are made up for by the teachings of Takahashi.
Takahashi is primarily directed towards compounds having an acid pump antagonistic activity, a pharmaceutically acceptable salt thereof (abstract).
Regarding claim 1, Takahashi teaches reversible inhibitory activity of a compound with gastric proton pump activity (column 1, lines 11-15). Takahashi teaches acid pump antagonists that inhibit acid secretion via reversible potassium-competitive inhibition and can be used for treating non-steroidal anti-inflammatory drug (NSAID)-induced ulcers (column 12, third paragraph). Takahashi teaches acid pump antagonist that is known to suppress gastric acid secretion and found to enhance gastrointestinal motility (column 12, fourth paragraph). Takahashi teaches that acid pump antagonistic activity includes (S)-(-)-4-[(5,7-difluoro-3,4-dihydro-2H-chromen-4-yl)oxy]-N,N,2-t- rimethyl-1H-benzimidazole-6-carboxamide (column 11, line 52-53; claim 3). As evidenced by Takahashi2, (S)-4-((5,7-difluorochroman-4-yl)oxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide is tegoprazan (page 275, second column). Takahashi teaches that the administration of an acid pump antagonistic activity in an amount of from 0.1 to about 3,000 mg/day (column 21, lines 52-54).
Regarding claim 2, Takahashi teaches that the compounds may be administered as crystalline or amorphous products (column 17, lines 29-30).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition that is in the form of a tablet or capsule and comprises naproxen that is in a core that is coated by an enteric coating that delays the release of the naproxen until the pH is a specific level (e.g., controlled release), tegoprazan in the form of a layer for a tablet or in the form of granules for a capsule; wherein the tegoprazan is released immediately; wherein the amount of the naproxen is between 50 mg and 1500 mg; and wherein the amount of the tegoprazan is from 0.1 to about 3,000 mg. The person of ordinary skill in the art would have been motivated to make those modifications to obtain a composition that not only suppresses gastric acid secretion but also provides enhanced gastrointestinal motility by substituting tegoprazan as the acid inhibitor which also provides enhanced gastrointestinal motility, as taught by Takahashi, and reasonably would have expected success because Plachetka discloses a method of reducing the risk of gastrointestinal side effects in people taking NSAIDs for pain relief and for other conditions. The method involves the administration of a single, coordinated, unit-dose product that combines: a) an agent that actively raises intragastric pH to levels associated with less risk of NSAID-induced ulcers; and b) an NSAID that is specially formulated to be released in a coordinated way that minimizes the adverse effects of the NSAID on the gastroduodenal mucosa (column 3, lines 11-20). Plachetka discloses that acid inhibitors including compounds which competes with potassium at the acid pump that are referred to as “reversible proton pump inhibitors”. Plachetka discloses a pharmaceutical composition that contains a non-steroidal anti-inflammatory drug in an amount effective to reduce or eliminate pain or inflammation and that the NSAID is most preferred naproxen in an amount of between 50 mg and 1500 mg (paragraph bridging columns 3 and 4). Plachetka discloses that the pharmaceutical composition is in the form of a tablet or capsule that has the acid inhibitor present in an amount effective to raise the gastric pH of the patient to at least 3.5 upon administration of the unit dosage form, the non-steroidal anti-inflammatory drug (NSAID) present in an amount effective to reduce or eliminate pain or inflammation in a patient upon administration of the unit dosage form, wherein the NSAID in the dosage form is in a core (e.g., first compartment) for tablets and several cores for capsules (column 4, second paragraph). Plachetka disclose that the NSAID does not release until the pH of the surrounding medium is 3.5 or higher (e.g., controlled release). Plachetka discloses that the acid inhibitor is in including one layer (e.g., second compartment) outside of the core and not surrounded by an enteric coating and upon ingestion of the tablet or capsule by a patient, release of acid inhibitor is in the patient’s stomach (column 4, second paragraph). Plachetka disclose that an enteric coating layer delays the release of the naproxen until the pH is a specific level (column 6, lines 1-2). Takahashi teaches reversible inhibitory activity of a compound with gastric proton pump activity (column 1, lines 11-15). Takahashi teaches acid pump antagonists that inhibit acid secretion via reversible potassium-competitive inhibition and can be used for treating non-steroidal anti-inflammatory drug (NSAID)-induced ulcers (column 12, third paragraph). Takahashi teaches acid pump antagonist that is known to suppress gastric acid secretion and found to enhance gastrointestinal motility (column 12, fourth paragraph).
Claims 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Plachetka in view of Takahashi as evidenced by Takahashi2 as applied to claims 1-9, 12-16 and 19 above, and further in view of MAEDA (US 2018/0214460 A1, cited in IDS filed 06/23/2023).
Regarding claims 10-11, the composition of claim 9 is described above in section 10.
Plachetka and Takahashi do not specifically teach that the layer comprising the acid inhibitor comprises particles comprising the acid inhibitor. The deficiency is made up for by the teachings of Maeda.
Maeda is primarily directed towards a tablet that comprises a potassium-competitive acid blocker (abstract).
Regarding claims 10-11, Maeda teaches potassium-competitive acid blocker that are in the form of outer layer granulated powder free of enteric coating that coats an inner tablet with an enteric coating (paragraphs [0115] and [0157]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition that is in the form of a tablet or capsule and comprises naproxen that is in a core that is coated by an enteric coating that delays the release of the naproxen until the pH is a specific level (e.g., controlled release), tegoprazan in the form of a outer layer granulated powder; wherein the tegoprazan is released immediately; wherein the amount of the naproxen is between 50 mg and 1500 mg; and wherein the amount of the tegoprazan is from 0.1 to about 3,000 mg. The person of ordinary skill in the art would have been motivated to make those modifications to obtain other forms of immediate release of acid inhibitors including outer layer granulated powder free of enteric coating, as taught by Maeda. The person of ordinary skill in the art would have reasonably expected success because Plachetka discloses that the acid inhibitor is in including one layer (e.g., second compartment) outside of the core and not surrounded by an enteric coating and upon ingestion of the tablet or capsule by a patient, release of acid inhibitor is in the patient’s stomach (column 4, second paragraph). Maeda teaches potassium-competitive acid blocker that are in the form of outer layer granulated powder free of enteric coating that coats an inner tablet with an enteric coating (paragraphs [0115] and [0157]).
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Plachetka in view of Takahashi as evidenced by Takahashi2 as applied to claims 1-9, 12-16 and 19 above, and further in view of WEINBACH (WO 03/017940 A2).
Regarding claim 17, the composition of claim 13 is described above in section 10.
Plachetka and Takahashi do not specifically teach that the capsule is filled with a tablet comprising naproxen in the form of enteric coated particles and including the acid inhibitor in a second active ingredient layer. The deficiencies are made up for by the teachings of Weinbach.
Weinbach is primarily directed towards a modified release pharmaceutical formulation (abstract).
Regarding claim 17, Weinbach teaches solid dosage forms including capsules comprising minitablets (paragraph [0147]). Weinbach teaches that minitablet in capsule formulations resulted in significantly higher bioavailabilities than the large tablets (paragraph [0155]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition that is in the form of a capsule and comprises minitablets comprising naproxen that is in a core that is coated by an enteric coating that delays the release of the naproxen until the pH is a specific level (e.g., controlled release) and tegoprazan in the form of a layer coating the enteric coated core comprising naproxen; wherein the tegoprazan is released immediately; wherein the amount of the naproxen is between 50 mg and 1500 mg; and wherein the amount of the tegoprazan is from 0.1 to about 3,000 mg. The person of ordinary skill in the art would have been motivated to make those modifications to obtain a composition with better bioavailability compared to large tablets by producing a form that comprises minitablets in a capsule, and reasonably would have expected success because Plachetka discloses that the pharmaceutical composition is in the form of a tablet (column 4, second paragraph). Plachetka discloses NSAID in the dosage form is in a core (e.g., first compartment) for tablets and several cores for capsules (column 4, second paragraph). Plachetka disclose that the NSAID does not release until the pH of the surrounding medium is 3.5 or higher (e.g., controlled release). Plachetka discloses that the acid inhibitor is in including one layer (e.g., second compartment) outside of the core and not surrounded by an enteric coating and upon ingestion of the tablet or capsule by a patient, release of acid inhibitor is in the patient’s stomach (column 4, second paragraph). Plachetka disclose that an enteric coating layer delays the release of the naproxen until the pH is a specific level (column 6, lines 1-2). Weinbach teaches solid dosage forms including capsules comprising minitablets (paragraph [0147]). Weinbach teaches that minitablet in capsule formulations resulted in significantly higher bioavailabilities than the large tablets (paragraph [0155]).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Plachetka in view of Takahashi as evidenced by Takahashi2 as applied to claims 1-9, 12-16 and 19 above, and further in view of BENGTSSON (WO 96/01622 A1).
Regarding claim 18, the composition of claim 4 is described above in section 10.
Plachetka and Takahashi do not specifically teach that the enteric coating is about 5 wt% or more and about 20 wt% or less based on the total weight of the core. The deficiency is made up for by the teachings of Bengtsson.
Bengtsson is primarily directed towards an oral formulation used for inhibiting gastric acid secretion (abstract and page 1, lines 16-18).
Regarding claim 18, Bengtsson teaches an enteric coating applied onto a core (page 6, last paragraph). Bengtsson teaches that the enteric coating protects a compound from acid. Bengtsson teaches that the enteric coating constitutes including more than 8.0% (page 7, lines 13-16).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition that is in the form of a tablet or capsule and comprises naproxen that is in a core that is coated by an enteric coating that delays the release of the naproxen until the pH is a specific level (e.g., controlled release), tegoprazan in the form of a layer for a tablet or in the form of granules for a capsule; wherein the tegoprazan is released immediately; wherein the amount of the naproxen is between 50 mg and 1500 mg; wherein the amount of the tegoprazan is from 0.1 to about 3,000 mg; and wherein the enteric coating constitutes more than 8.0% of the core weight. The person of ordinary skill in the art would have been motivated to make those modifications in order to obtain an enteric coating that protects the core from stomach acid by optimizing using the range of more than 8.0% of the core weight, as taught by Bengtsson, and reasonably would have expected success because Plachetka disclose that an enteric coating layer delays the release of the naproxen until the pH is a specific level (column 6, lines 1-2). Bengtsson teaches an enteric coating applied onto a core (page 6, last paragraph). Bengtsson teaches that the enteric coating protects a compound from acid. Bengtsson teaches that the enteric coating constitutes including more than 8.0% (page 7, lines 13-16).
Thus, the claimed invention as a whole is clearly prima facie obvious over the teachings of the prior art.
Conclusion and Correspondence
No claims are found allowable.
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/John P Nguyen/
Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600