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 . Claims 20-22, 25-33 and 35-37 filed January 28, 2026 are currently pending.
Response to Amendment
Applicant’s amendments, filed 01/28/2026 are acknowledged. Claims 23-24 and 34 have been canceled in their entirety. Claim 20 is amended as follows: A method of preventing peptic ulcer in a subject, comprising administering to the subject an effective amount of tegoprazan, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, solvate thereof, or a mixture of the foregoing for a period of 4 weeks to 24 weeks, wherein the subject had received treatment for a peptic ulcer prior to the administration of tegoprazan.
Claim 33 has also been amended to the following: A method of preventing recurrence of a peptic ulcer in a subject, comprising administering to the subject for a period of 4 weeks to 24 weeks a pharmaceutical composition comprising an effective amount of tegoprazan, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, solvate thereof, or a mixture of the foregoing, wherein the peptic ulcer was caused by a non- steroidal anti-inflammatory drug (NSAID) taken by the subject for at least 4 week or more prior to the administration of tegoprazan.
Claim 36 has additionally been amended to the following: A method of inhibiting development of a peptic ulcer in a subject, comprising administering to the subject a pharmaceutical composition comprising about 25mg to about 25mgan effective amount of tegoprazan, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, solvate thereof, or a mixture of the foregoing, wherein the subject has previously been treated for peptic ulcer.
In view of amendments to claims 20, 33, and 36, the pending 35 U.S.C 102(a)(1) rejection by Kim (JPET Vol. 369 pages 318-327 published 2019) is withdrawn as Kim does not specifically teach wherein the subject has been previously treated for peptic ulcer, nor the treatment duration of 4-24 weeks..
Next, in view of amendments to claims 20, 33, and 36, the pending 35 U.S.C 103 (a) rejection by Hanazawa (US2007/0142448 published 06/21/2007) is withdrawn as Hanazawa does not specifically teach wherein the subject has been previously treated for peptic ulcer does not specifically teach wherein the subject has been previously treated for peptic ulcer, nor the treatment duration of 4-24 weeks.
Applicant's arguments, filed 01/28/2026 have been fully considered. Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and objections presently being applied to the instant application.
Claim Rejections - 35 USC § 103-Rejection Maintained
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 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.
Claim(s) 20-22, 25-29, 31-33, 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Mizokami (Gut Vol.67 pages 1042-1051 published 2018), Takahashi (Journal of Pharmacology and Experimental Therapeutics Vol. 364 pages 25-286 published February 2018) and Hanazawa (US2007/0142448 published 06/21/2007).
Mizokami (Gut Vol.67 pages 1042-1051 published 2018) teaches the method of preventing peptic ulcer reoccurrence during continued long term NSAID therapy comprising administering a therapeutically effective amount of a potassium-competitive acid blocker (P-CAB) inhibitor vonoprazan (title, abstract). Mizokami teaches that arthritis patients receiving NSAID therapy including the acetic-acid derivative diclofenac developed peptic ulcers and were treated with once-a-day administration of the P-CAB inhibitor in combination with the NSAID agent (page 1043 left col. to page 1044 right col. Table 1). Mizokami teaches that the P-CAB inhibitor is efficacious at preventing reoccurrence of the NSAID-induced peptic ulcer in said patients and was better than lansoprazole at blocking reoccurring peptic ulcers (abstract, page 1046, page 1049, Figure 2). In Table 2, recurrent peptic ulcers were prevented with vonoprazan in patients receiving NSAID therapy wherein administration of said P-CAB inhibitor for 12 weeks prevented reoccurrence of peptic ulcers in 203 of 209 patients (10 mg). Continued treatment with said P-CAB inhibitor for an additional 12 weeks continued to prevent recurrent peptic ulcers in 202 of 209 patients (page 1047, Table 2). Mizokami teaches that the P-CAB inhibitor vonoprazan is efficacious at inhibiting gastric H+/K+-ATPase activity ((0.019 mM ref 10 of Mizokami; page 1043 left-right col.).
However, Mizokami does not specifically teach the administration of the claimed tegoprazan to treat the reoccurrence of peptic ulcers in patients receiving P-CAB therapy for peptic ulcers induced by long-term NSAID therapy for at least 12 weeks.
Takahashi (Journal of Pharmacology and Experimental Therapeutics Vol. 364 pages 25-286 published February 2018) teaches tegoprazan as a novel potassium-competitive acid blocker (P-CAB) that potently and reversibly inhibits gastric H+/K+-ATPase activity compared to esomeprazole (0.53 mM vs 42 mM; abstract, Figure 1, page 275 right col., page 278). Takahashi teaches that P-CAB is a new class of drugs for acid-related gastrointestinal diseases and clinical evaluation of the P-CAB inhibitor vonoprazan has demonstrated its potent and long acting efficacy in patients with GERD and peptic ulcers compared with that of the currently available proton-pump inhibitors. Takahashi further states that in-vitro and in-vivo pharmacology studies have demonstrated that tegoprazan has similar pharmacological properties to those of vonoprazan (pages 284-285).
Therefore, one of ordinary skill in the art prior to the time of the invention, knowing that administration of the P-CAB inhibitor vonoprazan is efficacious at preventing reoccurrence of peptic ulcers induced by long-term NSAID therapy for at least 12 weeks and continued prevention of NSAID induced peptic ulcers in a subject in need when administered for a duration of at least 12 weeks as taught by Mizokami, said artisan would have found it prima facie obvious that substituting the P-CAB inhibitor vonoprazan in the regimen of Mizokami, for an alternative P-CAB inhibitor, such as tegoprazan of Takahashi, the resulting P-CAB inhibitor therapeutic regimen would have prevented peptic ulcer reoccurrence in the patient in need.
MPEP 2143 provides rationale for a conclusion of obviousness including (B): Simple substitution of one known element for another to obtain predictable results;
In the present case, it was known in the prior art that administering a P-CAB inhibitor in combination with an NSAID agent was efficacious at preventing NSAID induced peptic ulcer reoccurrence in a subject in need. Accordingly, said artisan would have been inspired with a reasonable expectation of success, that substituting the P-CAB inhibitor vonoprazan in the regimen of Mizokami, for an alternative, such as tegoprazan of Takahashi, said resulting P-CAB inhibitor and NSAID regimen would have effectively prevented peptic ulcer reoccurrence in the afflicted patient. The resulting substitution of the P-CAB inhibitor from vonoprazan to tegoprazan in the regiment of Mizokami and Takahashi reads on the limitation of wherein the subject has received treatment for a peptic ulcer prior to the administration of tegoprazan.
However, the combination of Mizokami and Takahashi do not specifically teach administering tegoprazan in a dose of 25-50 mg tegoprazan, nor does the combination of Mizokami and Takahashi teach administering tegoprazan in the frequency of once or twice a day.
Hanazawa teaches treating peptic ulcers and NSAID induced ulcers in a subject in need comprising administering a therapeutically effective amount of a compound of Formula (I). Embraced within Formula (I) is 7-[[(4S)-5,7-Difluoro-3,4-dihydro-2H-1-benzopyran-4-yl]oxy]-N,N,2-trimethyl-1H-benzimidazole-5-carboxamide for Example 2 shown below, which is art-recognized as tegoprazan ([0333]-[0337], [0400]-[0435], Table 1, claims 1, 5, 8-9).
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582
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Hanazawa teaches administration of said compound in doses of 0.5 mg to 300 mg, which overlaps with the 25 mg to 50 mg embraced within the claims ([0289]). Applicant is reminded of MPEP 2144.05 wherein the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Regarding claims 31-32, administration of said compound once or in multiple doses per day is embodied within the teachings of Hanazawa ([0289]).
Therefore, one of ordinary skill in the art prior to the time of the invention knowing that administration of the P-CAB inhibitor tegoprazan in combination with an NSAID is efficacious at preventing peptic ulcer reoccurrence in a subject as taught by the combination of Mizokami and Takahashi, said skilled artisan would have found it prima facie obvious to administer the art-recognized P-CAB inhibitor tegoprazan in a dose of 25 mg to 50 mg in a frequency of once or twice a day in view of Hanazawa.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, it was known in the prior art of Hanazawa that doses of 0.5 mg to 300 mg of tegoprazan are efficacious at treating peptic ulcers in a subject in need, administered once or in multiple times per day ([0289], claims 1, 5, 8-9). Accordingly said artisan would have applied the tegoprazan dosing methodology of Hanazawa to the P-CAB inhibitor tegoprazan and NSAID therapeutic regimen of Mizokami and Takahashi above, arriving at the presently claimed with a reasonable expectation of success.
Applicant traverses. Applicant asserts that Mizokami fails to teach the presently claimed methodology and the combination of Takahashi and Hanazawa fail to cure the deficiencies of Mizokami. Applicant asserts that Mizokami teaches management of acid-related disorders in context of H. Pylori and does not teach post-ulcer treatment prophylaxis nor preventive dosing following ulcer resolution. Applicant argues that Takahashi does not teach post treatment prevention of peptic ulcers with tegoprazan, but instead is directed to acid suppression therapy. Applicant further argues that Hanazawa does not teach preventing recurrence of peptic ulcers in NSAID using subjects but lists “NSAID induced ulcers” among a broad list of treatable conditions. Applicant argues that Hanazawa does not teach continued NSAID use during or after treatment, nor NSAID associated ulcer recurrence and that the examiner exhibited significant hindsight reconstruction to select the instantly claimed tegoprazan and arrive at the presently claimed methodology.
Response to Arguments
Applicant’s arguments, filed 01/28/2026 are acknowledged and have been carefully considered. Regarding Applicant’s contention that Mizokami teaches management of acid-related disorders in context of H. Pylori and does not teach post-ulcer treatment prophylaxis nor preventive dosing following ulcer resolution, this argument is unavailing.
Post-ulcer treatment prophylaxis afforded by P-CAB inhibitor therapy and preventive dosing following ulcer resolution is taught by Mizokami. As shown in Table 2, recurrent peptic ulcers were prevented with administration of the art-recognized P-CAB inhibitor vonoprazan in patients receiving long term NSAID therapy wherein administration of said P-CAB inhibitor for 12 weeks prevented reoccurrence of peptic ulcers in 203 of 209 patients (10 mg). Preventive dosing is also taught as continued treatment with said P-CAB inhibitor for an additional 12 weeks continued to prevent recurrent peptic ulcers in 202 of 209 patients (page 1047, Table 2).
Next, regarding Applicant’s contention that Takahashi does not teach post treatment prevention of peptic ulcers with tegoprazan, but instead is directed to acid suppression therapy, Applicant is reminded that “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references” In re Merck and Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
In the present case, post-treatment prevention of peptic ulcers with a P-CAB inhibitor in long term NSAID treated patients was established in the prior art of Mizokami as discussed above. Takahashi establishes that tegoprazan shares the same mechanism-of-action of vonoprazan of Mizokami above ((potassium-competitive acid blocker (P-CAB)), potently and reversibly inhibits gastric H+/K+-ATPase activity compared to esomeprazole (0.53 mM vs 42 mM; abstract, Figure 1, page 275 right col., page 278) and comprises similar pharmacological properties to those of vonoprazan used in the methodology of Mizokami above. Coupled with the knowledge that Hanazawa teaches tegoprazan or 7-[[(4S)-5,7-Difluoro-3,4-dihydro-2H-1-benzopyran-4-yl]oxy]-N,N,2-trimethyl-1H-benzimidazole-5-carboxamide is efficacious treating peptic ulcers and NSAID induced ulcers in a subject in need, said skilled artisan would have been inspired with a reasonable expectation of success, that substituting the P-CAB inhibitor vonoprazan in the regimen of Mizokami, for an alternative, such as tegoprazan of Takahashi, said resulting P-CAB inhibitor and NSAID regimen would have effectively continued to prevent peptic ulcer reoccurrence in the afflicted patient.
Thirdly, Regarding Applicant’s contention that Hanazawa does not teach continued NSAID use during or after treatment, nor NSAID associated ulcer recurrence,
Applicant is reminded that “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references” In re Merck and Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). In the present case, post-treatment prevention of peptic ulcers with a P-CAB inhibitor in long term NSAID treated patients was established in the prior art of Mizokami as discussed above.
Lastly, in regards to Applicant’s contention that the examiner exhibited significant hindsight reconstruction to select the instantly claimed and art-recognized P-CAB inhibitor tegoprazan, Applicant is reminded that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. However, so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the Applicant’s disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971) and MPEP 2145.
Considering the fact that the present rejection under 35 U.S.C. 103(a) relies solely on the knowledge and motivation that was generally available to one of ordinary skill in the art of preventing recurrence of induced peptic ulcers in long-term NSAID administered patients with P-CAB inhibitor therapy (as clearly elucidated with the combined teachings of Mizokami, Takahashi and Hanazawa above), as well as in the previous Office Action) and does not improperly rely upon Applicant’s disclosure, the assertion that the present rejection is made with impermissible hindsight reconstruction is properly found unpersuasive.
Claim(s) 30 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Mizokami (Gut Vol.67 pages 1042-1051 published 2018), Takahashi (Journal of Pharmacology and Experimental Therapeutics Vol. 364 pages 25-286 published February 2018) and Hanazawa (US2007/0142448 published 06/21/2007) as applied to claims 20-22, 25-29, 31-33, 35-37 above in view of Lai (The American Journal of Medicine Vol. 118 pages 1271-1278 published 2005) and Varas-Lorenzo (Pharmacoepidemiology and Drug Safety Vol. 16 pages 366-376 published 2006).
As discussed above, the combination of Mizokami, Takahashi and Hanazawa render obvious the method of preventing the reoccurrence of an NSAID-induced peptic ulcer in a subject comprising the method of administering the P-CAB inhibitor tegoprazan in combination with the NSAID therapeutic agent as tegoprazan is art-recognized as a potent P-CAB inhibitor coupled with the knowledge that combinations comprising P-CAB inhibitors and NSAID agents are efficacious at preventing reoccurrence of peptic ulcers in patients receiving NSAID therapy.
However, the combination of Mizokami, Takahashi and Hanazawa does not specifically teach wherein the NSAID agent is celecoxib.
Lai (The American Journal of Medicine Vol. 118 pages 1271-1278 published 2005) teaches proton pump inhibitor co-therapy has been shown to reduce relapse of endoscopic peptic ulcers and peptic ulcer complications in patients receiving NSAID therapy (abstract, page 1277). Lai teaches that the NSAID agent celecoxib is as effective with the proton-pump inhibitor lansoprazole in the prevention of peptic ulcer reoccurrence in patients with a history of NSAID-related complicated peptic ulcers (abstract, page 1277 left and right col.)
Varas-Lorenzo (Pharmacoepidemiology and Drug Safety Vol. 16 pages 366-376 published 2006) teaches that celecoxib results in fewer peptic ulcer complications than diclofenac or naproxen in patients receiving daily NSAID therapy (abstract, page 370 right col., page 371 left col. Tables 2-3, Figure 2).
Therefore, one of ordinary skill in the art knowing that administering a combination comprising the P-CAB inhibitor tegoprazan with an NSAID therapeutic agent is efficacious at preventing reoccurrence of peptic ulcers in patients receiving NSAID therapy as taught by the combination of Mizokami, Takahashi and Hanazawa above, said skilled artisan would have found it prima facie obvious to administer the NSAID agent celecoxib in the P-CAB inhibitor and NSAID agent in view of Lai and Varas-Lorenzo.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, Lai teaches that the NSAID agent celecoxib is efficacious to use in therapeutic combinatorial regimens to prevent the reoccurrence of peptic ulcers in patients in need, coupled with the knowledge that celecoxib results in fewer ulcer complications than diclofenac or naproxen in patients receiving daily NSAID therapy. Accordingly, said artisan would have readily predicted that administration of the P-CAB inhibitor tegoprazan in combination with the NSAID agent celecoxib would have prevented the reoccurrence of celecoxib-induced peptic ulcers in the afflicted patient.
Response to Arguments
Applicant’s arguments filed 01/28/2026 are acknowledged and have been carefully considered. Arguments pertaining to the rejection of claims 20-22, 25-29, 31-33, 35-37 by the combination of Mizokami (Gut Vol.67 pages 1042-1051 published 2018), Takahashi (Journal of Pharmacology and Experimental Therapeutics Vol. 364 pages 25-286 published February 2018) and Hanazawa (US2007/0142448 published 06/21/2007) have been addressed above. Secondly, Applicant has not specifically pointed out the deficiencies of Lai and Varas-Lorenzo, and as such, the rejections of record are maintained for the reasons above.
Conclusion
In view of the rejections set forth above, no claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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