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 .
DETAILED ACTION
2. This Office Action is responsive to Applicant’s Amendment and Remarks, filed April 9, 2026. The amendment, filed April 9, 2026, is entered, wherein claims 44 and 50 are amended, claims 1 – 2, 4 – 6, 9 – 19, and 40 are withdrawn, and claims 3, 7 – 8, 20 – 39, 41 – 43, and 45 – 49 are canceled.
Claims 1 – 2, 4 – 6, 9 – 19, 40, 44, and 50 – 51 are pending in this application and claims 44 and 50 – 51 are currently examined.
Priority
3. This application is a national stage application of PCT/US2019/061171, filed November 13, 2019, which claims benefit of domestic application 62/767,202, filed November 14, 2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/09/2026 was filed after the mailing date of the previous Office Action on December 10, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Rejections
5. The rejection of claims 44 and 50 – 51 in the previous Office Action, mailed December 10, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2 and 4 – 5 of U.S. Patent No. 12186306B2 has been considered and is withdrawn in view of the amended claim 44.
The rejection of claims 44 and 50 – 51 in the previous Office Action, mailed December 10, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 40 – 41 and 46 – 47 of U.S. Patent No. 11066417B2 in view of Miller et al. has been considered and is withdrawn in view of the amended claim 44.
The rejection of claims 44 and 50 – 51 in the previous Office Action, mailed December 10, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1, 37, and 40 – 41 of U.S. Patent No. 11866450B2 in view of Miller et al. has been considered and is withdrawn in view of the amended claim 44.
The rejection of claims 44 and 50 – 51 in the previous Office Action, mailed December 10, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 3 and 6 – 9 of U.S. Patent No. 11873300B2 in view of Miller et al. has been considered and is withdrawn in view of the amended claim 44.
The rejection of claims 44 and 50 – 51 in the previous Office Action, mailed December 10, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 21 of copending Application No. 18/020,802 in view of Miller et al. has been considered and is withdrawn in view of the amended claim 44.
The rejection of claims 44 and 50 – 51 in the previous Office Action, mailed December 10, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9 and 21 – 26 of copending Application No. 18/835,221 in view of Miller et al. has been considered and is withdrawn in view of the amended claim 44.
The rejection of claims 44 and 50 – 51 in the previous Office Action, mailed December 10, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9 – 10, 13 – 16, and 18 of copending Application No. 19/185,978 in view of Miller et al. has been considered and is withdrawn in view of the amended claim 44.
The following are new grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed April 9, 2026, wherein claims 44 and 50 are amended, claims 1 – 2, 4 – 6, 9 – 19, and 40 are withdrawn, and claims 3, 7 – 8, 20 – 39, 41 – 43, and 45 – 49 are canceled. Previously and newly cited references have been used to establish the new grounds of rejection.
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.
Claims 44 and 50 – 51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2 and 4 – 5 of U.S. Patent No. 12186306B2 (previously cited as copending Application No. 17/546,649) in view of Morgan (WO2012/158885A1).
a. Regarding claims 44 and 50 – 51, ‘306B2 teaches a method of treating cystic fibrosis comprising daily administration of 250 mg of compound I:
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21.24 mg of compound II:
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and 100 mg of compound III:
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(claim 1).
The compounds are administered in a single composition (claim 4). Compounds I, II, and III are also administered as two compositions once daily, each composition comprising 125mg of compound I, 10.62 mg of compound II, and 50 mg of compound III (claim 5).
However, ‘306B2 does not explicitly teach 50 mg of the claimed Compound III-d.
Morgan teaches pharmaceutical composition comprising an effective amount of a compound of Formula I:
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and a pharmaceutically acceptable carrier (para. [52]), wherein the compound of Formula I is compound 106 (para. [34]):
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In one embodiment, an effective amount of a compound of this invention can range from about 0.02 to 2500 mg per treatment (para. [74]). In one embodiment, such treatment is for treating cystic fibrosis (para. [79]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the amount of compound II as taught by ‘306B2 because ‘306B2 teaches the reduced amount of compound II from 21.24 to 10.62 mg. It would have been prima facie obvious for one of ordinary skill in the art to consider the teachings of Morgan for determining the dosing of Compound III-d because Morgan’s teaching of deuterated ivacaftor-type CFTR potentiators and effective amounts thereof, it would have been obvious to one of ordinary skill in the art to determine a therapeutically effective amount of Compound III-d, including about 50 mg, through routine dose optimization. One would have performed a routine experimentation to discover the best dosage of these compounds for optimal treatment characteristics. One would also have been motivated to seek the lowest effective dosage. Furthermore, it would have expected that a skilled artisan will formulate the claimed pharmaceutical composition with a pharmaceutically acceptable carrier to achieve the desired route of administration. Therefore, one of the skills in the art would have had a reasonable expectation of success as ‘306B2 teaches the reduced amount of the components are still effective for the same purpose and Morgan provides the effective dose range of deuterated ivacaftor-type CFTR potentiators.
Claims 44 and 50 – 51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 40 – 41 and 46 – 47 of U.S. Patent No. 11066417B2 in view of Miller et al. (US9782408B2, cited in the previous Office Action mailed August 7, 2024) and Morgan (WO2012/158885A1).
b. Regarding claims 44 and 50 – 51, ‘417B2 teaches a compound of the formula (claims 40 – 41):
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or a pharmaceutically acceptable salt thereof. ‘417B2 also teaches a pharmaceutical composition comprising the compound in combination with Compound II and/or Compound III (claims 46 – 47):
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and
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and a pharmaceutically acceptable carrier.
However, ‘417B2 does not teach the composition comprising 5 mg of Compound I and 50 mg of Compound III-d.
Miller et al. teach a compound of formula I:
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for the treatment of cystic fibrosis (Abstract). Miller et al. specifically teach a few compounds as shown below (Col. 403 – 404; Col. 405 – 406; Col. 623 – 624):
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Miller et al. also teach that the pharmaceutical compositions of the invention are administered as oral formulations containing about 25 mg of a compound of Formula I (Col. 2138, lines 66 – 67). Moreover, Miller et al. teach that a compound of Formula I can be used with other therapeutic agents (claim 81):
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Miller et al. teach that Compound II and III are CFTR modulators (Col. 2150, lines 20 – 50; Col. 2151, lines 40 – 65).
Morgan teaches pharmaceutical composition comprising an effective amount of a compound of Formula I:
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and a pharmaceutically acceptable carrier (para. [52]), wherein the compound of Formula I is compound 106 (para. [34]):
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In one embodiment, an effective amount of a compound of this invention can range from about 0.02 to 2500 mg per treatment (para. [74]). In one embodiment, such treatment is for treating cystic fibrosis (para. [79]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine ‘417B2 in view of Morgan to substitute Compound III with compound 106 taught by Morgan in the method to treat cystic fibrosis. It would have been obvious for one of ordinary skill in the art to do this because both Compound III and compound 106 are known separately in the prior art for the purpose of treating cystic fibrosis, and it would have been obvious to substitute equivalent drug known to treat the same disease. One of ordinary skill in the art would have had a reasonable expectation of success to modify ‘417B2 with the teachings of Morgan because it is well known to combine drugs to treat the same disease. ‘417B2 does not disclose 5 mg of Compound I, the amount of an active pharmaceutical ingredient in a pharmaceutical composition, however, is a result-effective variable because the amount affects therapeutic efficacy, exposure, tolerability, and safer. In addition, Miller et al. teach structurally related CFTR modulator compounds having a related core/scaffold to Compound I, and further teaches that such CFTR modulator compounds useful for treating cystic fibrosis may be formulated for oral administration in milligram amounts, including about 25 mg. Thus, Miller et al. provide both structural and dosage guidance showing that compounds in this CFTR-modulator class are conventionally formulated in milligram quantities and that selection of the amount of active ingredient is subjected to routine dose optimization. In view of ‘417B2’s teaching of pharmaceutical compositions comprising Compound I with additional CFTR modulating agents, Miller et al.’s teaching of related CFTR modulators and oral milligram dosing, and Morgan’s teaching of deuterated ivacaftor-type CFTR potentiators and effective amounts thereof, it would have been obvious to one of ordinary skill in the art to determine a therapeutically effective amount of Compound I, including about 5 mg, through routine dose optimization.
Claims 44 and 50 – 51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 37, and 40 – 41 of U.S. Patent No. 11866450B2 in view of Miller et al. (US9782408B2, cited in the previous Office Action mailed August 7, 2024) and Morgan (WO2012/158885A1).
c. Regarding claims 44 and 50 – 51, ‘450B2 teaches a method of treating cystic fibrosis comprising administering to a patient in need a compound of Formula I (claim 1):
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‘450 further teaches a method of treating cystic fibrosis comprising administering to a patient in need thereof a compound of (claim 37):
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or a pharmaceutically acceptable salt thereof. Compound 195 is administered in combination with one or more of compound II and compound III or compound III-d (claims 40 – 41):
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However, ‘450B2 does not teach the composition comprising 5 mg of Compound I and 50 mg of Compound III-d.
Miller et al. teaches a compound of formula I:
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for the treatment of cystic fibrosis (Abstract). Miller et al. specifically teaches a few compounds as shown below (Col. 403 – 404; Col. 405 – 406; Col. 623 – 624):
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Miller et al. also teaches that the pharmaceutical compositions of the invention are administered as oral formulations containing about 25 mg of a compound of Formula I (Col. 2138, lines 66 – 67). Moreover, Miller et al. teaches that a compound of Formula I can be used with other therapeutic agents (claim 81):
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Miller et al. teaches that Compound II and III are CFTR modulators (Col. 2150, lines 20 – 50; Col. 2151, lines 40 – 65).
Morgan teaches pharmaceutical composition comprising an effective amount of a compound of Formula I:
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and a pharmaceutically acceptable carrier (para. [52]), wherein the compound of Formula I is compound 106 (para. [34]):
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In one embodiment, an effective amount of a compound of this invention can range from about 0.02 to 2500 mg per treatment (para. [74]). In one embodiment, such treatment is for treating cystic fibrosis (para. [79]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of ‘450B2 in view of Miller et al. and Morgan to arrive at the claimed pharmaceutical composition. ‘450B2 teaches administering Compound 195, corresponding to presently claimed Compound I, in combination with additional CFTR modulators, including Compound II and Compound III-d, for treating cystic fibrosis. Miller et al. teach structurally related CFTR modulator compounds having a related core/scaffold to Compound I, and further teaches that such CFTR modulator compounds useful for treating cystic fibrosis may be formulated for oral administration in milligram amounts, including about 25 mg. Thus, Miller et al. provide both structural and dosage guidance showing that compounds in this CFTR-modulator class are conventionally formulated in milligram quantities and that selection of the amount of active ingredient is subjected to routine dose optimization. Morgan teaches deuterated ivacaftor-type CFTR potentiators corresponding to Compound III-d, pharmaceutical compositions thereof, and effective amounts for treating cystic fibrosis, including amounts encompassing about 50 mg. Therefore, one of ordinary skill in the art would have been motivated to formulate the known CFTR-modulator combination taught by ‘450B2 as a pharmaceutical composition and to select therapeutically effective milligram amounts of the active ingredients, including about 5 mg of Compound I and about 50 mg of Compound III-d, through routine dose optimization. One of ordinary skill in the art would have had a reasonable expectation of success because ‘450B2, Miller et al., and Morgan each relate to CFTR modulators useful for treating cystic fibrosis, and the selected amounts merely optimize known active agents for their known therapeutic purpose.
Claims 44 and 50 – 51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 3 and 6 – 9 of U.S. Patent No. 11873300B2 in view of Miller et al. (US9782408B2, cited in the previous Office Action mailed August 7, 2024) and Morgan (WO2012/158885A1).
d. Regarding claims 44 and 50 – 51, ‘300B2 teaches a pharmaceutical composition comprising Compound I calcium salt hydrate Form D (claims 1 – 2):
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‘300B2 further teaches that the pharmaceutical composition further comprising one or more additional CFTR modulating compounds (claim 3), wherein the CFTR modulating compounds are
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(claim 6).
Finally, ‘300B2 teaches that the pharmaceutical composition is for treating cystic fibrosis (claims 7 – 9).
However, ‘300B2 does not teach the composition comprising 5 mg of Compound I and 50 mg of Compound III-d.
Miller et al. teaches a compound of formula I:
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for the treatment of cystic fibrosis (Abstract). Miller et al. specifically teaches a few compounds as shown below (Col. 403 – 404; Col. 405 – 406; Col. 623 – 624):
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Miller et al. also teaches that the pharmaceutical compositions of the invention are administered as oral formulations containing about 25 mg of a compound of Formula I (Col. 2138, lines 66 – 67). Moreover, Miller et al. teaches that a compound of Formula I can be used with other therapeutic agents (claim 81):
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Miller et al. teaches that Compound II and III are CFTR modulators (Col. 2150, lines 20 – 50; Col. 2151, lines 40 – 65).
Morgan teaches pharmaceutical composition comprising an effective amount of a compound of Formula I:
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and a pharmaceutically acceptable carrier (para. [52]), wherein the compound of Formula I is compound 106 (para. [34]):
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In one embodiment, an effective amount of a compound of this invention can range from about 0.02 to 2500 mg per treatment (para. [74]). In one embodiment, such treatment is for treating cystic fibrosis (para. [79]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of ‘300B2 in view of Miller et al. and Morgan to arrive at the claimed pharmaceutical composition. ‘300B2 teaches administering Compound I, corresponding to presently claimed Compound I, in combination with additional CFTR modulators, including Compound II and Compound III-d, for treating cystic fibrosis. Miller et al. teach structurally related CFTR modulator compounds having a related core/scaffold to Compound I, and further teaches that such CFTR modulator compounds useful for treating cystic fibrosis may be formulated for oral administration in milligram amounts, including about 25 mg. Thus, Miller et al. provide both structural and dosage guidance showing that compounds in this CFTR-modulator class are conventionally formulated in milligram quantities and that selection of the amount of active ingredient is subjected to routine dose optimization. Morgan teaches deuterated ivacaftor-type CFTR potentiators corresponding to Compound III-d, pharmaceutical compositions thereof, and effective amounts for treating cystic fibrosis, including amounts encompassing about 50 mg. Therefore, one of ordinary skill in the art would have been motivated to formulate the known CFTR-modulator combination taught by ‘300B2 as a pharmaceutical composition and to select therapeutically effective milligram amounts of the active ingredients, including about 5 mg of Compound I and about 50 mg of Compound III-d, through routine dose optimization. One of ordinary skill in the art would have had a reasonable expectation of success because ‘300B2, Miller et al., and Morgan each relate to CFTR modulators useful for treating cystic fibrosis, and the selected amounts merely optimize known active agents for their known therapeutic purpose.
Claims 44 and 50 – 51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 21 of copending Application No. 18/020,802 in view of Miller et al. (US9782408B2, cited in the previous Office Action mailed August 7, 2024) and Morgan (WO2012/158885A1).
e. Regarding claims 44 and 50 – 51, ‘802 teaches a crystalline Compound I (claim 1):
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‘802 teaches a pharmaceutical composition comprising the crystalline Compound I and further comprising one or more additional CFTR modulating compounds (claims 7 – 8). ‘802 teaches a method of treating cystic fibrosis comprising administering the crystalline Compound I with one or more additional CFTR modulating compounds (claims 15 – 16). ‘802 further teaches a method of preparing this crystalline Compound I (claim 21).
However, ‘802 does not teach the composition comprising 5 mg of Compound I, and ‘802 does not teach the specific CFTR modulating compounds and amounts recited in the instant claims.
Miller et al. teaches a compound of formula I:
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for the treatment of cystic fibrosis (Abstract). Miller et al. specifically teaches a few compounds as shown below (Col. 403 – 404; Col. 405 – 406; Col. 623 – 624):
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Miller et al. also teaches that the pharmaceutical compositions of the invention are administered as oral formulations containing about 25 mg of a compound of Formula I (Col. 2138, lines 66 – 67). Moreover, Miller et al. teaches that a compound of Formula I can be used with other therapeutic agents (claim 81):
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Miller et al. teaches that Compound II and III are CFTR modulators (Col. 2150, lines 20 – 50; Col. 2151, lines 40 – 65).
Morgan teaches pharmaceutical composition comprising an effective amount of a compound of Formula I:
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and a pharmaceutically acceptable carrier (para. [52]), wherein the compound of Formula I is compound 106 (para. [34]):
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In one embodiment, an effective amount of a compound of this invention can range from about 0.02 to 2500 mg per treatment (para. [74]). In one embodiment, such treatment is for treating cystic fibrosis (para. [79]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition taught by ‘802 in view of Miller et al. and Morgan to arrive at the claimed pharmaceutical composition, ‘802 teaches crystalline Compound I, pharmaceutical compositions comprising crystalline Compound I and compositions further comprising one or more additional CFTR modulating compounds for treating cystic fibrosis. ‘802 does not explicitly identify the specific additional CFTR modulators or the specific amounts recited in the instant claims, Miller et al. teach that Compound II and Compound III are known CFTR modulators useful for treating cystic fibrosis, and Morgan teaches deuterated ivacaftor-type CFTR potentiators corresponding to Compound III-d, pharmaceutical compositions thereof, and effective amounts for treating cystic fibrosis, including amounts encompassing about 50 mg. One of ordinary skill in the art would have been motivated to select Compound II and/or Compound III-d as the additional CFTR modulating compounds in the pharmaceutical composition of ‘802 because each was known in the art as a CFTR modulator useful for treating the same disease. One of ordinary skill in the art would have had a reasonable expectation of success because the selected compounds would have been expected to perform their known CFTR modulating functions in the compositions for their known therapeutic purpose. Regarding the “5 mg of Compound I”, the amount of an active CFTR modulator in an oral pharmaceutical composition is a result-effective variable because the amount effects therapeutic efficacy, systemic exposure, safety, and tolerability. Miller et al. teach structurally related CFTR modulator compounds, pharmaceutical compositions thereof, and oral milligram dosing, including about 25 mg, thereby providing guidance that CFTR modulators of this class are conventionally administered in milligram quantities and that dosage amount is subjected to routine optimization. Accordingly, selecting therapeutically effective milligram amounts of the active agents, including about 5 mg of Compound I and about 50 mg of Compound III-d, would have involved no more than routine dose optimization of known CFTR modulators for their known therapeutic purpose.
Claims 44 and 50 – 51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9 and 21 – 26 of copending Application No. 18/835,221 in view of Miller et al. (US9782408B2, cited in the previous Office Action mailed August 7, 2024) and Morgan (WO2012/158885A1).
f. Regarding claims 44 and 50 – 51, ‘221 teaches a method of treating cystic fibrosis comprising administering to a patient in need thereof 0.1 mg to about 50 mg of Compound I: crystalline Compound I (claims 1 – 9):
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‘221 teaches that the method further comprises administering one or more additional therapeutic agents with CFTR-modulating activity (claims 21 – 23). The one or more additional therapeutic agents are (claims 24 – 26)
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However, ‘221 does not teach the composition comprising 5 mg of Compound I and 50 mg of Compound III-d.
Miller et al. teaches a compound of formula I:
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for the treatment of cystic fibrosis (Abstract). Miller et al. specifically teaches a few compounds as shown below (Col. 403 – 404; Col. 405 – 406; Col. 623 – 624):
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Miller et al. also teaches that the pharmaceutical compositions of the invention are administered as oral formulations containing about 25 mg of a compound of Formula I (Col. 2138, lines 66 – 67). Moreover, Miller et al. teaches that a compound of Formula I can be used with other therapeutic agents (claim 81):
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Miller et al. teaches that Compound II and III are CFTR modulators (Col. 2150, lines 20 – 50; Col. 2151, lines 40 – 65).
Morgan teaches pharmaceutical composition comprising an effective amount of a compound of Formula I:
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and a pharmaceutically acceptable carrier (para. [52]), wherein the compound of Formula I is compound 106 (para. [34]):
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In one embodiment, an effective amount of a compound of this invention can range from about 0.02 to 2500 mg per treatment (para. [74]). In one embodiment, such treatment is for treating cystic fibrosis (para. [79]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of ‘221 in view of Miller et al. and Morgan to arrive at the claimed pharmaceutical composition. ‘221 teaches administering the presently claimed Compound I, in combination with additional CFTR modulators, including Compound II and Compound III-d, for treating cystic fibrosis. Miller et al. teach structurally related CFTR modulator compounds having a related core/scaffold to claimed Compound I, and further teaches that such CFTR modulator compounds useful for treating cystic fibrosis may be formulated for oral administration in milligram amounts, including about 25 mg. Thus, Miller et al. provide both structural and dosage guidance showing that compounds in this CFTR-modulator class are conventionally formulated in milligram quantities and that selection of the amount of active ingredient is subjected to routine dose optimization. Morgan teaches deuterated ivacaftor-type CFTR potentiators corresponding to Compound III-d, pharmaceutical compositions thereof, and effective amounts for treating cystic fibrosis, including amounts encompassing about 50 mg. Therefore, one of ordinary skill in the art would have been motivated to formulate the known CFTR-modulator combination taught by ‘221 as a pharmaceutical composition and to select therapeutically effective milligram amounts of the active ingredients, including about 5 mg of Compound I and about 50 mg of Compound III-d, through routine dose optimization. One of ordinary skill in the art would have had a reasonable expectation of success because ‘221, Miller et al., and Morgan each relate to CFTR modulators useful for treating cystic fibrosis, and the selected amounts merely optimize known active agents for their known therapeutic purpose.
Claims 44 and 50 – 51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9 – 10, 13 – 16, and 18 of copending Application No. 19/185,978 in view of Miller et al. (US9782408B2, cited in the previous Office Action mailed August 7, 2024) and Morgan (WO2012/158885A1).
g. Regarding claims 44 and 50 – 51, ‘978 teaches a pharmaceutical composition comprising Compound I (free form) Form A (claims 1 and 9):
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115
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.
The composition further comprises one or more additional CFTR modulating compounds (claim 10), wherein the one or more additional CFTR modulating compounds are
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108
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,
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110
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,
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(claim 13).
‘978 also teach a method of treating cystic fibrosis comprising administering Compound I to a subject in need thereof (claim 14), wherein Compound I is administered along with one or more additional CFTR modulating compounds (claim 15), wherein the CFTR modulating compounds are:
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108
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,
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,
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(claim 16).
However, ‘978 does not teach the composition comprising 5 mg of Compound I and 50 mg of Compound III-d.
Miller et al. teaches a compound of formula I:
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for the treatment of cystic fibrosis (Abstract). Miller et al. specifically teaches a few compounds as shown below (Col. 403 – 404; Col. 405 – 406; Col. 623 – 624):
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,
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302
314
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, and
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178
412
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.
Miller et al. also teaches that the pharmaceutical compositions of the invention are administered as oral formulations containing about 25 mg of a compound of Formula I (Col. 2138, lines 66 – 67). Moreover, Miller et al. teaches that a compound of Formula I can be used with other therapeutic agents (claim 81):
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Miller et al. teaches that Compound II and III are CFTR modulators (Col. 2150, lines 20 – 50; Col. 2151, lines 40 – 65).
Morgan teaches pharmaceutical composition comprising an effective amount of a compound of Formula I:
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and a pharmaceutically acceptable carrier (para. [52]), wherein the compound of Formula I is compound 106 (para. [34]):
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.
In one embodiment, an effective amount of a compound of this invention can range from about 0.02 to 2500 mg per treatment (para. [74]). In one embodiment, such treatment is for treating cystic fibrosis (para. [79]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of ‘978 in view of Miller et al. and Morgan to arrive at the claimed pharmaceutical composition. ‘978 teaches administering the presently claimed Compound I, in combination with additional CFTR modulators, including the claimed Compound II and Compound III-d, for treating cystic fibrosis. Miller et al. teach structurally related CFTR modulator compounds having a related core/scaffold to claimed Compound I, and further teaches that such CFTR modulator compounds useful for treating cystic fibrosis may be formulated for oral administration in milligram amounts, including about 25 mg. Thus, Miller et al. provide both structural and dosage guidance showing that compounds in this CFTR-modulator class are conventionally formulated in milligram quantities and that selection of the amount of active ingredient is subjected to routine dose optimization. Morgan teaches deuterated ivacaftor-type CFTR potentiators corresponding to Compound III-d, pharmaceutical compositions thereof, and effective amounts for treating cystic fibrosis, including amounts encompassing about 50 mg. Therefore, one of ordinary skill in the art would have been motivated to formulate the known CFTR-modulator combination taught by ‘978 as a pharmaceutical composition and to select therapeutically effective milligram amounts of the active ingredients, including about 5 mg of Compound I and about 50 mg of Compound III-d, through routine dose optimization. One of ordinary skill in the art would have had a reasonable expectation of success because ‘978, Miller et al., and Morgan each relate to CFTR modulators useful for treating cystic fibrosis, and the selected amounts merely optimize known active agents for their known therapeutic purpose.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed April 9, 2026, have been fully considered. Applicant’s arguments regarding the amendment of claim 44 is persuasive; therefore, the rejections are withdrawn. However, insofar as Applicant’s arguments are applied to the new rejections set forth above, the arguments are not persuasive for the reasons discussed below.
Regarding ‘306B2, Applicant argues that ‘306B2 does not teach the “50 mg of Compound III-d” required by the amended claim 44. However, the rejection is moot because the rejection no longer relies on ‘306B2 alone. Morgan is introduced to address the new limitation “50 mg of Compound III-d”. As Morgan teaches a method of treating cystic fibrosis by administering 0.02 to 2500 mg of the claimed Compound III-d per treatment. The combination of ‘306B2 and Morgan render the claimed invention obvious.
Regarding ‘417B2 and Miller et al., Applicant argues that ‘417B2 and Miller et al. do not teach the “50 mg of Compound III-d” required by the amended claim 44. However, the rejection is moot because the rejection no longer relies on ‘417B2 and Miller et al. Morgan is introduced to address the new limitation “50 mg of Compound III-d”. As Morgan teaches a method of treating cystic fibrosis by administering 0.02 to 2500 mg of the claimed Compound III-d per treatment. The combination of ‘417B2, Miller et al., and Morgan render the claimed invention obvious.
Regarding ‘450B2 and Miller et al., Applicant argues that ‘450B2 and Miller et al. do not teach the “50 mg of Compound III-d” required by the amended claim 44. However, the rejection is moot because the rejection no longer relies on ‘450B2 and Miller et al. Morgan is introduced to address the new limitation “50 mg of Compound III-d”. As Morgan teaches a method of treating cystic fibrosis by administering 0.02 to 2500 mg of the claimed Compound III-d per treatment. The combination of ‘450B2, Miller et al., and Morgan render the claimed invention obvious.
Regarding ‘300B2 and Miller et al., Applicant argues that ‘300B2 and Miller et al. do not teach the “50 mg of Compound III-d” required by the amended claim 44. However, the rejection is moot because the rejection no longer relies on ‘300B2 and Miller et al. Morgan is introduced to address the new limitation “50 mg of Compound III-d”. As Morgan teaches a method of treating cystic fibrosis by administering 0.02 to 2500 mg of the claimed Compound III-d per treatment. The combination of ‘300B2, Miller et al., and Morgan render the claimed invention obvious.
Regarding ‘802 and Miller et al., Applicant argues that ‘802 and Miller et al. do not teach the “50 mg of Compound III-d” required by the amended claim 44. However, the rejection is moot because the rejection no longer relies on ‘802 and Miller et al. Morgan is introduced to address the new limitation “50 mg of Compound III-d”. As Morgan teaches a method of treating cystic fibrosis by administering 0.02 to 2500 mg of the claimed Compound III-d per treatment. The combination of ‘802, Miller et al., and Morgan render the claimed invention obvious.
Regarding ‘221 and Miller et al., Applicant argues that ‘221 and Miller et al. do not teach the “50 mg of Compound III-d” required by the amended claim 44. However, the rejection is moot because the rejection no longer relies on ‘221 and Miller et al. Morgan is introduced to address the new limitation “50 mg of Compound III-d”. As Morgan teaches a method of treating cystic fibrosis by administering 0.02 to 2500 mg of the claimed Compound III-d per treatment. The combination of ‘221, Miller et al., and Morgan render the claimed invention obvious.
Regarding ‘978 and Miller et al., Applicant argues that ‘978 and Miller et al. do not teach the “50 mg of Compound III-d” required by the amended claim 44. However, the rejection is moot because the rejection no longer relies on ‘978 and Miller et al. Morgan is introduced to address the new limitation “50 mg of Compound III-d”. As Morgan teaches a method of treating cystic fibrosis by administering 0.02 to 2500 mg of the claimed Compound III-d per treatment. The combination of ‘978, Miller et al., and Morgan render the claimed invention obvious.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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