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
Claims 1-8, 11-12, and 15-17 are pending.
Priority
Instant application 18/720,436, filed 06/14/2024 claims priority as follows:
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
All references from IDS(s) received 06/14/2024 have been considered unless marked with a strikethrough.
Claim Objections
Claim 8 is objected to because of the following informalities: claim 8 appears to contain a typographical error. Depends from claim 5, but follows claims 6 and 7 and recites “wherein the crystalline form further comprises” additional XRPD peaks not already set forth in claim 6 or 7. It appears that claim 8 should depend from claim 6 or claim 7. Appropriate correction is required.
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, 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 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.
Claims 1-2, 5, 11-12, 15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over YOON (US20230192650A1; filed 16 June 2021) in view of ARIKAWA (Journal of Medicinal Chemistry, vol. 55, no. 9, May 2012, pp. 4446–56).
Yoon discloses the compound 1-(5-(2-fluorophenyl)-4-methoxy-1-(pyridin-2-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine or a pharmaceutically acceptable salt thereof as a potassium competitive acid blocker (P-CAB) (Yoon, [0057]-[0058], Example 1).
While Yoon discloses pharmaceutically acceptable salts generically, Yoon does not disclose the fumarate salt instantly claimed.
However, Arikawa teaches P-CABs bearing substantial structural similarity to instant formula I (see, for example the compounds of Table 2 and Table 3). In particular, Arikawa teaches the lead candidate compound TAK-438 (also known as vonoprazan), which is a fumarate salt having the structure:
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Arikawa teaches that preparation of several compounds (including TAK-438) as the fumarate salts improved the ligand-lipophilicity efficiency (LLE) value of the compounds (abstract, conclusion).
Finding of prima facie obviousness
The skill level in the art of pharmaceutical salt formation is relatively high. Applying KSR example rationale (A) and/or (G), it would have been prima facie obvious to prepare the fumarate salt of Yoon’s Example 1 compound in view of Arakawa’s teaching of improved bioavailability. The motivation is derived explicitly from Arakawa, but also from general knowledge in the art about the common use of salts such as fumarate, and the “normal desire of scientists or artisans to improve upon what is already generally known”. See In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003). See also Pfizer, Inc. v. Apotex, Inc. 82 USPQ2d 1321. The Arikawa reference above provides a reasonable expectation of success that a fumarate salt of Yoon’s example 1 compound would have superior properties to the free base.
Claim 1 is therefore obvious over Yoon in view of Arikawa.
With respect to claim 2, the limitation reciting that the fumarate salt has a TGA pattern showing a weight loss of less than 0.1 wt% at 120 °C or less effectively means that the fumarate salt of claim 2 is anhydrous (i.e. the compound is not a hydrate or solvate). In view of Arikawa’s disclosure of anhydrous 13e, a person having ordinary skill would have reasonably expected that the fumarate of Yoon’s example 1 compound prepared by Arikawa’s method would have been anhydrous. Moreover, obtaining an anhydrous pharmaceutical salt of a compound through ordinary drying and recrystallization is the predictable result of routine optimization. Claim 2 is therefore obvious over Yoon in view of Arikawa.
With respect to claim 5, Arikawa’s fumarate salts are isolated by crystallization and the resulting compounds are in crystalline form. A person having ordinary skill, applying Arikawas’s conditions for preparing the fumarate salt of Yoon’s example 1 compound, would have therefore reasonably expected to prepare Yoon’s compound as the fumarate salt in crystalline form. Claim 5 is therefore obvious over Yoon in view of Arikawa.
With respect to claims 11-12, Yoon teaches the claimed methods with the free base (or generic salt) of Example 1. It would have therefore been prima facie obvious to use the fumarate salt of Example 1 taught by Yoon in view of Arikawa in the same method of treatment taught by Yoon. Claims 11-12 are therefore obvious over Yoon in view of Arikawa.
With respect to claims 15 and 17, Arikawa teaches a preparation method comprising dissolving a compound in ethyl acetate and adding fumaric acid in methanol at room temperature; precipitating the compound; and filtering/drying the product (page 4453, left side, preparation of 13e). It would have been prima facie obvious to apply Arikawa’s fumarate salt preparation method to Yoon’s example 1 compound in order to prepare the fumarate salt of Yoon’s compound. The resulting method renders instant claims 15 and 17 obvious.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over YOON (US20230192650A1; filed 16 June 2021) in view of ARIKAWA (Journal of Medicinal Chemistry, vol. 55, no. 9, May 2012, pp. 4446–56), and further in view of FENGLUAN (CN104860923A; published 2018).
The teachings of Yoon and Arikawa are disclosed above and at least those teachings are incorporated herein by reference. As set forth above, Yoon in view of Arikawa teaches the preparation method of claim 15.
With respect to claim 16, neither Yoon nor Arikawa discloses recrystallization from the single organic solvent of isopropyl alcohol or acetone.
However, Fengluan discloses an alternative method for preparing TAK-438 (vonoprazan fumarate) comprising a final step of recrystallization from isopropyl alcohol. See example 2 of Fengluan.
It would have therefore been prima facie obvious to recrystallize Yoon example 1 fumarate compound from isopropyl alcohol; and a person having ordinary skill would have enjoyed a reasonable expectation of success in view of Fengluan’s example 2.
Moreover, the solvent used for recrystallization is considered a result effective variable which impacts, for example, the yield of the recrystallization. Differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization.
Therefore, claim 16 is obvious over Yoon in view of Arikawa and Fengluan.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
US 11,767,311 B2
Claims 1-2, 5, 11-12, 15, and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. US 11,767,311 in view of ARIKAWA (Journal of Medicinal Chemistry, vol. 55, no. 9, May 2012, pp. 4446–56).
The reference patent issued from YOON which was cited above in the rejection under section 103. The reference patent recites the compound 1-(5-(2-fluorophenyl)-4-methoxy-1-(pyridin-2-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine or a pharmaceutically acceptable salt thereof (claim 8).
The reference patent does not recite the fumarate salt of the compound.
However, Arikawa teaches P-CABs bearing substantial structural similarity to instant formula I (see, for example the compounds of Table 2 and Table 3). In particular, Arikawa teaches the lead candidate compound TAK-438 (also known as vonoprazan), which is a fumarate salt having the structure:
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Arikawa teaches that preparation of several compounds (including TAK-438) as the fumarate salts improved the ligand-lipophilicity efficiency (LLE) value of the compounds (abstract, conclusion).
Finding of prima facie obviousness
The skill level in the art of pharmaceutical salt formation is relatively high. Applying KSR example rationale (A) and/or (G), it would have been prima facie obvious to prepare the fumarate salt of the reference patent compound in view of Arakawa’s teaching of improved bioavailability. The motivation is derived explicitly from Arakawa, but also from general knowledge in the art about the common use of salts such as fumarate, and the “normal desire of scientists or artisans to improve upon what is already generally known”. See In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003). See also Pfizer, Inc. v. Apotex, Inc. 82 USPQ2d 1321. The Arikawa reference above provides a reasonable expectation of success that a fumarate salt of the reference patent compound would have superior properties to the free base.
Claim 1 is therefore obvious over the reference patent in view of Arikawa.
With respect to claim 2, the limitation reciting that the fumarate salt has a TGA pattern showing a weight loss of less than 0.1 wt% at 120 °C or less effectively means that the fumarate salt of claim 2 is anhydrous (i.e. the compound is not a hydrate or solvate). In view of Arikawa’s disclosure of anhydrous 13e, a person having ordinary skill would have reasonably expected that the fumarate of the reference patent’s compound prepared by Arikawa’s method would have been anhydrous. Moreover, obtaining an anhydrous pharmaceutical salt of a compound through ordinary drying and recrystallization is the predictable result of routine optimization. Claim 2 is therefore obvious over the reference patent in view of Arikawa.
With respect to claim 5, Arikawa’s fumarate salts are isolated by crystallization and the resulting compounds are in crystalline form. A person having ordinary skill, applying Arikawas’s conditions for preparing the fumarate salt of the reference patent’s compound, would have therefore reasonably expected to prepare the reference patent compound as the fumarate salt in crystalline form. Claim 5 is therefore obvious over the reference patent in view of Arikawa.
With respect to claims 11-12, the reference patent recites the claimed applications of the free base (or generic salt) of the claimed compound. It would have therefore been prima facie obvious to use the fumarate salt of Example 1 taught by the reference patent in view of Arikawa in the same method of treatment taught by the reference patent. Claims 11-12 are therefore obvious over the reference patent in view of Arikawa.
With respect to claims 15 and 17, Arikawa teaches a preparation method comprising dissolving a compound in ethyl acetate and adding fumaric acid in methanol at room temperature; precipitating the compound; and filtering/drying the product (page 4453, left side, preparation of 13e). It would have been prima facie obvious to apply Arikawa’s fumarate salt preparation method to the reference patent compound in order to prepare the fumarate salt of the compound. The resulting method renders instant claims 15 and 17 obvious.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. US 11,767,311 in view of ARIKAWA, and further in view of FENGLUAN (CN104860923A; published 2018).
The recitations of the reference patent and the teachings of Arikawa are disclosed above and at least those teachings are incorporated herein by reference. As set forth above, the reference patent in view of Arikawa teaches the preparation method of claim 15.
With respect to claim 16, neither the reference patent nor Arikawa discloses recrystallization from the single organic solvent of isopropyl alcohol or acetone.
However, Fengluan discloses an alternative method for preparing TAK-438 (vonoprazan fumarate) comprising a final step of recrystallization from isopropyl alcohol. See example 2 of Fengluan.
It would have therefore been prima facie obvious to recrystallize the fumarate salt of the reference patent compound from isopropyl alcohol; and a person having ordinary skill would have enjoyed a reasonable expectation of success in view of Fengluan’s example 2.
Moreover, the solvent used for recrystallization is considered a result effective variable which impacts, for example, the yield of the recrystallization. Differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization.
Therefore, claim 16 is obvious over the reference patent in view of Arikawa and Fengluan.
18/228,672
Claims 11-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/228/672 in view of ARIKAWA (Journal of Medicinal Chemistry, vol. 55, no. 9, May 2012, pp. 4446–56).
The reference application claims priority to YOON which was cited above in the rejection under section 103. The reference application recites a method of treating gastrointestinal ulcers, gastrointestinal inflammatory diseases, or gastric acid-related diseases, comprising administering the compound 1-(5-(2-fluorophenyl)-4-methoxy-1-(pyridin-2-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine or a pharmaceutically acceptable salt thereof (claim 8).
The reference application does not recite the fumarate salt of the compound.
However, Arikawa teaches P-CABs bearing substantial structural similarity to instant formula I (see, for example the compounds of Table 2 and Table 3). In particular, Arikawa teaches the lead candidate compound TAK-438 (also known as vonoprazan), which is a fumarate salt.
Arikawa teaches that preparation of several compounds (including TAK-438) as the fumarate salts improved the ligand-lipophilicity efficiency (LLE) value of the compounds (abstract, conclusion).
Finding of prima facie obviousness
The skill level in the art of pharmaceutical salt formation is relatively high. Applying KSR example rationale (B) and/or (G), it would have been prima facie obvious to substitute the free base of the fumarate salt of the reference application compound with the fumarate salt in the recited method in view of Arakawa’s teaching of improved bioavailability. The motivation is derived explicitly from Arakawa, but also from general knowledge in the art about the common use of salts such as fumarate, and the “normal desire of scientists or artisans to improve upon what is already generally known”. See In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003). See also Pfizer, Inc. v. Apotex, Inc. 82 USPQ2d 1321. The Arikawa reference above provides a reasonable expectation of success that a fumarate salt of the reference application compound would have superior properties to the free base.
Claims 11-12 are therefore obvious over the reference application in view of Arikawa.
This is a provisional nonstatutory double patenting rejection.
18/719,710
Claims 1-2, 5, 11-12, 15, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/719,710 in view of ARIKAWA (Journal of Medicinal Chemistry, vol. 55, no. 9, May 2012, pp. 4446–56).
The reference application recites the HCl, succinate, or tartrate salt of the compound 1-(5-(2-fluorophenyl)-4-methoxy-1-(pyridin-2-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine.
The reference application does not recite the fumarate salt of the compound.
However, Arikawa teaches P-CABs bearing substantial structural similarity to instant formula I (see, for example the compounds of Table 2 and Table 3). In particular, Arikawa teaches the lead candidate compound TAK-438 (also known as vonoprazan), which is a fumarate salt.
Arikawa teaches that preparation of several compounds (including TAK-438) as the fumarate salts improved the ligand-lipophilicity efficiency (LLE) value of the compounds (abstract, conclusion).
Finding of prima facie obviousness
The skill level in the art of pharmaceutical salt formation is relatively high. Applying KSR example rationale (B) and/or (G), it would have been prima facie obvious to substitute the hydrochloride counterion the reference application HCl salt with the fumarate counterion in view of Arakawa’s teaching of improved bioavailability. The motivation is derived explicitly from Arakawa, but also from general knowledge in the art about the common use of salts such as fumarate, and the “normal desire of scientists or artisans to improve upon what is already generally known”. See In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003). See also Pfizer, Inc. v. Apotex, Inc. 82 USPQ2d 1321. The Arikawa reference above provides a reasonable expectation of success that a fumarate salt of the reference application compound would have superior properties to the HCl salt.
Claims 1-2, 5, 11-12, 15, and 17 are therefore obvious over the reference application in view of Arikawa.
This is a provisional nonstatutory double patenting rejection.
Claim 16 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/719,710 in view of ARIKAWA (Journal of Medicinal Chemistry, vol. 55, no. 9, May 2012, pp. 4446–56), and further in view of FENGLUAN (CN104860923A; published 2018). A machine-translated copy of FENGLUAN is appended.
The recitations of the reference application and the teachings of Arikawa are disclosed above and at least those teachings are incorporated herein by reference. As set forth above, the reference application in view of Arikawa teaches the preparation method of claim 15.
With respect to claim 16, neither the reference appilcation nor Arikawa discloses recrystallization from the single organic solvent of isopropyl alcohol or acetone.
However, Fengluan discloses an alternative method for preparing TAK-438 (vonoprazan fumarate) comprising a final step of recrystallization from isopropyl alcohol. See example 2 of Fengluan.
It would have therefore been prima facie obvious to recrystallize the fumarate salt of the reference patent compound from isopropyl alcohol; and a person having ordinary skill would have enjoyed a reasonable expectation of success in view of Fengluan’s example 2.
Moreover, the solvent used for recrystallization is considered a result effective variable which impacts, for example, the yield of the recrystallization. Differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization.
Therefore, claim 16 is obvious over the reference application in view of Arikawa and Fengluan.
Allowable Subject Matter
Please note: in the interest of compact prosecution, the Examiner strongly recommends amending independent claim 1 to incorporate the limitations of claims 5 and 6 in order to place the application in condition for allowance.
Claims 3-4 and 6-7 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-2, 5, 11-12, and 15-17 are rejected. Claims 3-4 and 6-8 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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