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 claim amendments filed 25 June 2026, amended claims 2-3, 10, 13, 26-27, 39, 46-47, 50-51, 55, 60 and 63. Claims 4-9, 11-12, 14-17, 19-20, 22-24, 28-38, 40-45, 48, 52-54, 56-57, 59, 61-62 and 64-66 are canceled. Consequently, claims 1-3, 10, 13, 18, 21, 25-27, 39, 46-47, 49-51, 55, 58, 60 and 63 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-3, 10, 13, 18, 47, 49-51 and 55, in the reply filed on 25 June 2026 is acknowledged.
Applicant further elected ivacaftor as the CFTR modulator, HPB-cyclodextrin (e.g., HP-β-CD) as the carrier and tablet as the composition form. Since Applicant elected the carrier to be HPB-cyclodextrin and the composition form as a tablet, claims 47, 49-51 and 55 are withdrawn for being directed towards a nonelected species of a composition in the form of particles with a diameter of about 1 µm to about 500 µm and does not a include a carrier including HPB-cyclodextrin.
Claims 13, 21, 25-27, 39, 46-47, 49-51, 55, 58, 60 and 63 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, respectively, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 25 June 2026.
Claims 1-3, 10 and 18 are examined herein to the extent that the CFTR modulator is ivacaftor, the carrier is HPB-cyclodextrin and the composition form is tablet, e.g., applicant's elected species.
Information Disclosure Statement
The information disclosure statement (IDS) filed 06/08/2023, 08/23/2023 (25 pages), 08/23/2023 (2 pages), 11/07/2023, 03/26/2024, 12/27/2024, 04/25/2025, 07/29/2025, 11/06/2025, 06/29/2026 (8 pages), 06/29/2026 (9 pages), and 06/29/2026 (10 pages) have been considered by the Examiner. A signed and initialed copy of the IDS is included with the instant Office Action.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 10, and 18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “composition comprising a carrier comprising a cyclodextrin or a non-ionic surfactant and one or more cystic fibrosis transmembrane conductance regulator (CFTR) modulators” which have 3 possible interpretations of: 1) a cyclodextrin alone, 2) a non-ionic surfactant and one or more cystic fibrosis transmembrane conductance regulator (CFTR) modulators, or 3) a cyclodextrin and one or more cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Therefore, the recitation of “composition comprising a carrier comprising a cyclodextrin or a non-ionic surfactant and one or more cystic fibrosis transmembrane conductance regulator (CFTR) modulators” renders claims 1-3 and 10 indefinite because it is unclear what components are necessary and what components go with what other component. A suggested rewrite of claim 1 in a way that is clearer is:
“A composition comprising
a carrier comprising a cyclodextrin or a non-ionic surfactant;
and
one or more cystic fibrosis transmembrane conductance regulator (CFTR) modulators.”
In the interest of compact prosecution, the recitation of “composition comprising a carrier comprising a cyclodextrin or a non-ionic surfactant and one or more cystic fibrosis transmembrane conductance regulator (CFTR) modulators” is interpreted as a composition comprising cyclodextrin (e.g., elected species) and one or more cystic fibrosis transmembrane conductance regulator (CFTR) modulators (e.g., with ivacaftor as the elected species).
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 1-3, 10 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over ZHA (US 2014/0221424 A1, publication date of 07 August 2014) in view of HUGHES (“Patent Review of Synthetic Routes and Crystalline Forms of the CFTR-Modulator Drugs Ivacaftor, Lumacaftor, Tezacaftor, and Elexacaftor”, Organic Process Research & Development, 23, pages 2302-23022, published 19 September 2019) and SEPULVEDA (KR 2009/0073025 A, publication date of 02 July 2009).
Zha is primarily directed towards pharmaceutical composition comprising N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (ivacaftor) for treatment of cystic fibrosis (abstract).
Regarding claims 1-3 and 18, Zha discloses a composition that includes ivacaftor (paragraph [0011]). Zha discloses that physical stability and/or dissolution and/or solubility of the drug is enhanced by other components (paragraph [0027]). Zha discloses tablet containing ivacaftor (paragraph [0110]).
Zha does not specifically teach that the tablet comprises HP-β-CD (e.g., Applicant elected carrier). The deficiency is made up for by the teachings of Hughes and Sepulveda.
Hughes is primarily directed towards synthetic routes and polymorphic forms of CFTR-modulators including ivacaftor, lumacaftor, and tezacaftor (abstract).
Regarding claims 1-3, Hughes teaches crystalline form C of ivacaftor is the most thermodynamically stable polymorph (page 2308, first column, second paragraph) but that crystalline form are poorly water-soluble and has low bioavailability (page 2308, first column, fourth paragraph).
Sepulveda is primarily directed towards inclusion complex of a drug with low solubility and cyclodextrin including hydroxypropyl-beta-cyclodextrin to improve solubility and bioavailability of the drug (abstract of the English translation of Sepulveda).
Regarding claims 1, 10 and 18, Sepulveda teaches a drug that has low and incomplete gastrointestinal uptake for oral tablets because of the solubility of the drug is limited (second page, seventh paragraph of the English translation). Sepulveda teaches that the complex of the drug and HP-β-CD can be used to obtain a solid form (page 6, sixth paragraph of the English translation). Sepulveda teaches inclusion complex of the drug and cyclodextrin including HP-β-CD (page 9, first paragraph of the English translation). Sepulveda teaches ratio of 1:1 and 1:2 of the drug to cyclodextrin (page 10, sixth paragraph of the English translation). The ratio of 1:1 and 1:2 of drug to cyclodextrin lies inside the range of “3:1 to 1:10” recited in claim 10. Thus, the range in claim 10 is rendered prima facie obvious. See 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). See also MPEP 2144.05. Sepulveda teaches that the drug with HP-β-CD had significant increase solubility (page 11, fourth paragraph of the English translation). Sepulveda teaches that the complex of the drug with cyclodextrin exhibited higher bioavailability (page 12, third paragraph of the English translation).
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 tablet comprising an inclusion complex of HP-β-CD with crystalline ivacaftor including crystalline form C of ivacaftor taught in Hughes, wherein the ratio of HP-β-CD to the ivacaftor is including 1:1. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a composition with ivacaftor that is most stable by using including crystalline for C taught in Hughes; and 2) obtain improved solubility and bioavailability of the ivacaftor that is most stable but poorly water-soluble and has low bioavailability, and reasonably would have expected success because Zha discloses a composition that includes ivacaftor (paragraph [0011]). Zha discloses that physical stability and/or dissolution and/or solubility of the drug is enhanced by other components (paragraph [0027]). Zha discloses tablet containing ivacaftor (paragraph [0110]). Hughes teaches crystalline form C of ivacaftor is the most thermodynamically stable polymorph (page 2308, first column, second paragraph) but that crystalline form are poorly water-soluble and has low bioavailability (page 2308, first column, fourth paragraph). Sepulveda teaches a drug that has low and incomplete gastrointestinal uptake for oral tablets because of the solubility of the drug is limited (second page, seventh paragraph of the English translation). Sepulveda teaches that the complex of the drug and HP-β-CD can be used to obtain a solid form (page 6, sixth paragraph of the English translation). Sepulveda teaches inclusion complex of the drug and cyclodextrin including HP-β-CD (page 9, first paragraph of the English translation). Sepulveda teaches ratio of 1:1 and 1:2 of the drug to cyclodextrin (page 10, sixth paragraph of the English translation). Sepulveda teaches that the drug with HP-β-CD had significant increase solubility (page 11, fourth paragraph of the English translation). Sepulveda teaches that the complex of the drug with cyclodextrin exhibited higher bioavailability (page 12, third paragraph of the English translation).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN P NGUYEN whose telephone number is (571)270-5877. The examiner can normally be reached Monday-Friday 10am-6pm EST.
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/John P Nguyen/
Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600
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