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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/03/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112(b)
Claim 9 is 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.
The term “about” in claim 9 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 80 wt%” and “about 20 wt%” to mean “80 wt%” and “20 wt%,” disregarding the “about” term. Clarification by amendment in claim 9 is required.
The term “substantially” in claim 9 is also a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the specification at paragraph [0057] provides an example, it does not provide a closed definition. The Examiner will be interpreting “substantially amorphous or amorphous Compound II” as “amorphous Compound II,” disregarding the “substantially” term. Clarification by amendment in claim 9 is required.
Claim 10 is 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.
The term “about” in claim 10 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 80 wt%” and “about 19.5 wt%” to mean “80 wt%” and “19.5 wt%,” disregarding the “about” term. Clarification by amendment in claim 10 is required.
The term “substantially” in claim 10 is also a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the specification at paragraph [0057] provides an example, it does not provide a closed definition. The Examiner will be interpreting “substantially amorphous or amorphous Compound III” as “amorphous Compound III,” disregarding the “substantially” term. Clarification by amendment in claim 10 is required.
Claim 12 is 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.
The term “about” in claim 12 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 10 to about 14 percent by weight” to mean “10 to 14 percent by weight,” disregarding the “about” term. Clarification by amendment in claim 12 is required.
Claim 14 is 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.
The term “about” in claim 14 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 35 to about 40 percent by weight” to mean “35 to 40 percent by weight,” disregarding the “about” term. Clarification by amendment in claim 14 is required.
Claim 17 is 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.
The term “about” in claim 17 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 6 percent by weight” to mean “6 percent by weight,” disregarding the “about” term. Clarification by amendment in claim 17 is required.
Claim 19 is 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.
The term “about” in claim 19 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 1 to about 2 percent by weight” to mean “1 to 2 percent by weight,” disregarding the “about” term. Clarification by amendment in claim 19 is required.
Claim 21 is 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.
The term “about” in claim 21 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 0.5 to about 1.5 percent by weight” to mean “0.5 to 1.5 percent by weight,” disregarding the “about” term. Clarification by amendment in claim 21 is required.
Claim 23 is 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.
The term “about” in claim 23 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 0.5 to about 1.5 percent by weight” to mean “0.5 to 1.5 percent by weight,” disregarding the “about” term. Clarification by amendment in claim 23 is required.
Claim 30 is 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.
The term “about” in claim 30 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 10 mg to about 50 mg” to mean “10 mg to 50 mg,” disregarding the “about” term. Clarification by amendment in claim 30 is required.
The term “substantially” in claim 30 is also a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the specification at paragraph [0057] provides an example, it does not provide a closed definition. The Examiner will be interpreting “amorphous or substantially amorphous Compound II” as “amorphous Compound II,” disregarding the “substantially” term. Clarification by amendment in claim 30 is required.
Claim 31 is 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.
The term “about” in claim 31 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner will be interpreting “about 15 mg to about 75 mg” to mean “15 mg to 75 mg,” disregarding the “about” term. Clarification by amendment in claim 31 is required.
The term “substantially” in claim 31 is also a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the specification at paragraph [0057] provides an example, it does not provide a closed definition. The Examiner will be interpreting “amorphous or substantially amorphous Compound III” as “amorphous Compound II,” disregarding the “substantially” term. Clarification by amendment in claim 31 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.
Claim(s) 1, 6-10, 12-14, 16-17, 19-23, 31, 40, and 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ridley et al. (The Journal of Pediatric Pharmacology and Therapeutics. 2020, 25(3):192–197. doi:10.5863/1551-6776-25.3.192), in view of Chen et al. (WO 2020242935 A1) (hereinafter “Chen”).
The applied references have a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claim 1, Ridley teaches a triple-combination therapy of elexacaftor (Compound I), tezacaftor (Compound 2), and ivacaftor (Compound III). The triple-combination therapy is supplied as a fixed-dose combination tablet of 100 mg of elexacaftor, tezacaftor 50 mg, and ivacaftor 75 mg (Dosing and Administration, page 195). It is noted that fixed-dose reads on the claimed “unit dose form.”
Regarding claim 40, Ridley teaches controlled clinical trials for children (12-17 years old) with cystic fibrosis.
However, in respect to claim 1, Ridley does not teach the range 20 mg to 100 mg of crystalline Compound I Form A or the one or more fillers, wherein the one or more fillers comprise mannitol, a disintegrant, a sweetener, a glidant, and a lubricant of claim 1.
Chen teaches a pharmaceutical composition comprising Compound I (Elexacaftor, the same structure as claimed “Compound I”) ([0011]). Chen specifies a composition additionally comprising one or more APIs (e.g., Compound I, Compound II, Compound Ill-d and/or Compound III) ([00163]), where Compound II is the structure for tezacaftor (the same as the claimed “Compound II”) and Compound III is the structure for ivacaftor (the same as the claimed “Compound III”) (claims 4 and 5). In one composition, there is 10 mg to 110 mg of Compound I ([00150]). Compound I is also described to be in crystalline Form A (Preparation of Form A of Compound I, para. [00218]; para. [0013]). In one embodiment, the pharmaceutical composition for use in the methods of the disclosure comprises one or more fillers, a disintegrant, and a lubricant. Exemplary fillers include: sugars (e.g., mannitol, lactose, sucrose, or the like). In some embodiments, solid forms, including powders comprising one or more APIs (e.g., Compound I, Compound II, Compound Ill-d and/or Compound III) and the included pharmaceutically acceptable excipients (e.g. filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof) can be subjected to a dry granulation process ([00158]).
It would have been obvious for one of ordinary skill in the art to use crystalline Form A Compound I in the composition of Ridley to produce the claimed invention. It would have been obvious to so because both Ridley and Chen are commonly drawn to tablet compositions comprising elexacaftor (Compound I), tezacaftor (Compound 2), and ivacaftor (Compound III). Furthermore, Chen provides the guidance to do so by teaching a method of preparing tablets that includes utilizing dispersions to form a tablet mixture, followed by compression to achieve the tablet form ([00154]). Additionally, Chen specifies that in pharmaceutical applications, a solid dispersion can include a crystalline drug (dispersed phase) in an amorphous polymer (continuous phase); or alternatively, an amorphous drug (dispersed phase) in an amorphous polymer (continuous phase). ([0045]). It would have been obvious to try the crystalline Form A elexacaftor/Compound I in a tablet composition as there a finite number of known ways to form a tablet, and a person of ordinary skill in the art could have pursued the known way of utilizing a crystalline drug within a dispersion with a reasonable expectation of success (See MPEP 2143(I)(E)).
It would have been obvious for one of ordinary skill in the art to optimize the amount of crystalline Form A of Compound I to 10 mg to 110 mg in the composition of Ridley to produce the claimed invention. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because both Ridley and Chen are commonly drawn to compositions comprising elexacaftor (Compound I), tezacaftor (Compound 2), and ivacaftor (Compound III) and Chen provided the guidance to do so by teaching the dosing range of 10 mg to 110 mg of Compound I, which overlaps with the claimed range 20 mg to 100 mg of crystalline Compound I Form A. Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (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); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the amount of Compound I in the composition would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
It also would have been obvious of ordinary skill in the art to combine the fillers, disintegrant, lubricant, glidant, and sugars of mannitol with the composition of Ridley to produce the claimed invention. It would have been obvious to do so because both Ridley and Chen are drawn to compositions containing elexacaftor (Compound I), tezacaftor (Compound 2), and ivacaftor (Compound III) in a tablet form. Furthermore, Chen provides the guidance to do so by teaching the pharmaceutical composition in the tablet mixture further comprises one or more pharmaceutically acceptable excipients (e.g. filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof), and the methods further comprise mixing the first mixture with said one or more excipients to form the tablet mixture ([00153]}. It would have been obvious for an ordinary artisan with reasonable expectation of success to add the fillers, disintegrant, lubricant, glidant, and sugars of mannitol to the triple-combination tablet of Ridley. Thus, there is a teaching, suggestion, or motivation to combine the prior art and achieve the claimed invention (See MPEP 2143(I)(G)).
Regarding claim 6, Chen teaches the pharmaceutical compositions (e.g., tablets) useful in the methods of the invention comprise a first solid dispersion comprising Compound II and a second solid dispersion comprising Compound III or Compound III- d ([0053]). In some embodiments, the solid dispersions of the disclosure can comprise other excipients, such as polymers and/or surfactants ([0056]).
Regarding claim 7 and 9, Chen teaches in some embodiments, the pharmaceutical compositions disclosed herein comprise: 25 mg to 70 mg of a first solid dispersion comprising 80 wt% Compound II relative to the total weight of the first solid dispersion; and 20 wt% of a hydroxypropyl methylcellulose relative to the total weight of the first solid dispersion ([00150]). Additionally, in some embodiments the first and second solid dispersions are comprised of substantially amorphous Compound II or III ([0055]).
Regarding claim 8, Chen teaches in some embodiments, the second solid dispersion comprises a cellulose polymer. For example, the second solid dispersion comprises hydroxypropyl methylcellulose acetate succinate (HPMCAS) ([00118]).
Regarding claim 10, Chen teaches a second solid dispersion comprising 80 wt% of Compound III relative to the total weight of the second solid dispersion; 0.5 wt% of sodium lauryl sulfate relative to the total weight of the second solid dispersion; and 19.5 wt% of a hydroxypropyl methylcellulose acetate succinate to the total weight of the second solid dispersion ([00150]). Additionally, in some embodiments the first and second solid dispersions are comprised of substantially amorphous Compound II or III ([0055]).
Regarding claims 12-14, Chen teaches that mannitol, lactose, sucrose, or the like are suitable fillers for the pharmaceutical composition ([00126]) and in some embodiments, the pharmaceutical compositions comprise one or more fillers in an amount of at least 5 wt% (e.g., at least 20 wt%, at least 30 wt%, or at least 40 wt%) by weight of the pharmaceutical composition ([00127]). These ranges include the claimed “about 10 to about 14 percent by weight” of mannitol and “about 35 to about 40 percent by weight” of lactose of the pharmaceutical composition.
Regarding claim 16, Chen teaches in one embodiment, the disintegrant is croscarmellose sodium ([00128]).
Regarding claim 17, Chen teaches the pharmaceutical compositions comprise 10 wt% or less (e.g., 7 wt% or less, 6 wt% or less, or 5 wt% or less) of croscarmellose sodium, by weight of the pharmaceutical composition ([00129]).
Regarding claim 20, Chen teaches in embodiment, the lubricant is magnesium stearate ([00130]).
Regarding claim 21, Chen teaches the pharmaceutical compositions comprise 5 wt% or less (e.g., 4.0 wt% or less, 3.0 wt% or less, or 2.0 wt% or less, or 1.0 wt% or less) of magnesium stearate, by weight of the pharmaceutical composition ([00131]). These ranges cover the claimed “an amount of about 0.5 to about 1.5 percent by weight of the pharmaceutical composition.”
Regarding claim 44, as previously discussed, Chen describes a composition comprising 10 mg to 110 mg of Compound I [00150], and where Compound I is also described to be in crystalline Form A (Preparation of Form A of Compound I, para. [00218]; para. [0013]). It is noted that 10 mg to 110 mg covers the claimed “80 mg or 100 mg” values.
Claim(s) 1, 6-10, 12-14, 16-17, 19-23, 31, 40, and 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ridley et al. (The Journal of Pediatric Pharmacology and Therapeutics. 2020, 25(3):192–197. doi:10.5863/1551-6776-25.3.192) and Chen et al. (WO 2020242935 A1) (hereinafter “Chen”) as applied to claim Claim(s) 1, 6-10, 12-14, 16-17, 19-23, 31, 40, and 44, and further in view of Dokou et al. (US 10272046 B2) (hereinafter “Dokou”).
The applied references have a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The modified teaching of Ridley is discussed above, said discussion being incorporated herein in its entirety.
However, Ridley and Chen do not teach a pharmaceutical composition in a unit dose form comprising one or a plurality of granules, pellets, particles, or mini-tablets of claims 1-40. Furthermore, Ridley and Chen do not teach sucralose as the specific sweetener in the composition of claims 1-40, wherein the sucralose is present in an amount of about 1 to about 2 percent by weight of claim 19. Ridley and Chen also do not teach the glidant is colloidal silicon dioxide of claim 22-23, or wherein the colloidal silicon dioxide is present in an amount of about 0.5 to about 1.5 percent by weight of the pharmaceutical composition of claim 23. Additionally, the unit dose form comprises from about 15 mg to about 75 mg of amorphous or substantially amorphous Compound III of claim 31 is not taught by Ridley or Chen.
Dokou teaches a pharmaceutical composition containing a solid dispersion of N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1 herein after) (same structure as claimed “Compound III”) (Abstract, column 4, lines 21-33). Dokou teaches one embodiment of the composition comprising about 15 mg to about 75 mg of substantially amorphous or amorphous Compound 1 (column 154, lines 38-53). Furthermore, the present invention provides solid dose forms and unit dose forms comprising a pharmaceutical composition formulated or compressed into a granule, pellet, particle, mini-tablet, sprinkle and the like. The compressed pharmaceutical composition (solid dose forms) such as granules, pellets, particles, mini-tablets and the like can be formulated into unit dose forms such as tablets (column 65, lines 1-19). In still further embodiments, the pharmaceutical compositions also comprise a sweetener (e.g. sucralose, sorbitol, saccharin, fructose, aspartame, or a combination thereof) in a concentration of about 10% or less by weight of this composition (column 7, lines 41-47). In one embodiment, the pharmaceutical composition comprises a glidant in an amount comprise 5 wt % or less (e.g., 1.75 wt %, 1.25 wt % or less, or 1.00 wt % or less) of colloidal silicon dioxide (column 56, lines 46-50). For methods of use, in some embodiments, the method includes treating or lessening the severity of cystic fibrosis in a patient, for example, a pediatric patient, the method comprising administering to the patient one of the pharmaceutical compositions as defined (column 92, lines 4-8). Additionally, Dokou teaches the present invention contemplates novel dosage forms such as granules, pellets, mini-tablets and other solid dose forms which overcome the problems described above with respect to dosing inaccuracies, in particular, for pediatric patients (column 8, lines 2-6).
It would have been obvious for someone of ordinary skill in the art to use the unit dose forms of granules, pellets, particles, or mini-tablets with the modified composition of Ridley to produce the claimed invention. It would have been obvious to try with reasonable expectation of success because both Dokou and Ridley are drawn to pharmaceutical compositions in tablet formulations, and Dokou provides the guidance to do so by teaching that the compressed pharmaceutical composition (solid dose forms) such as granules, pellets, particles, mini-tablets and the like can be formulated into unit dose forms such as tablets. There a finite number of known ways to form a tablet composition, and a person of ordinary skill in the art could have pursued the known ways of formulating granules, pellets, particles, or mini-tablets for compression with reasonable expectation of success (See MPEP 2143(I)(E)).
It also would have been obvious for someone of ordinary skill in the art to use sucralose as the sweetener of the modified composition of Ridley to produce the claimed invention. It would have been obvious to do so because both Dokou and the modified composition of Ridley are commonly drawn to pharmaceutical compositions with sweeteners and Dokou teaches the guidance to do so by disclosing sucralose as a sufficient sweetener example. Thus, [t]he selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).
It also would have been obvious for someone of ordinary skill in the art to optimize the amount of sucralose to about 10% or less by weight of the modified composition of Ridley to produce the claimed invention. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Dokou provides the guidance to do so by teaching the sweetener in a concentration of about 10% or less by weight of this composition, which is a range that overlaps the claimed “amount of about 1 to about 2 percent by weight.” Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (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); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the weight amount of sucralose in the composition would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
It also would have been obvious for someone of ordinary skill in the art to incorporate colloidal silicon dioxide as the glidant of the modified composition of Ridley to produce the claimed invention. It would have been obvious to do so because both Dokou and the modified composition of Ridley are commonly drawn to pharmaceutical compositions comprising glidants and Dokou provides the guidance to do so by teaching silicon dioxide as a potential glidant. Thus, [t]he selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).
It would have been obvious for one of ordinary skill in the art to optimize the amount of silicon dioxide to 5 wt % or less in the modified composition of Ridley to produce the claimed invention. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Dokou provided the guidance to do so by teaching a glidant in an amount comprise 5 wt % or less (e.g., 1.75 wt %, 1.25 wt % or less, or 1.00 wt % or less) of colloidal silicon dioxide (column 56, lines 46-50), which overlaps with the claimed range an amount of about 0.5 to about 1.5 percent by weight. Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (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); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the amount of silicon dioxide in the composition would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
It would have been obvious for one of ordinary skill in the art to optimize to about 15 mg to about 75 mg of substantially amorphous or amorphous Compound 1 in the modified pharmaceutical composition of Ridley to produce the claimed invention. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because both Dokou and Ridley are commonly drawn to pharmaceutical compositions containing the active compound Compound 1/Compound III/ivacaftor and Dokou provided the guidance to do so by teaching a solid dispersion containing about 15 mg to about 75 mg of substantially amorphous or amorphous Compound 1, which is a range that overlaps the claimed about 15 mg to about 75 mg of amorphous or substantially amorphous Compound III. Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (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); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the weight amount of Compound III in the composition would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ridley et al. (The Journal of Pediatric Pharmacology and Therapeutics. 2020, 25(3):192–197. doi:10.5863/1551-6776-25.3.192), Chen et al. (WO 2020242935 A1) (hereinafter “Chen”), and Dokou et al. (US 10272046 B2) (hereinafter “Dokou”) as applied to claim 1, and further in view of Chu et al. (US 20190240197 A1) (hereinafter “Chu”).
The applied references have a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The modified teaching of Ridley is discussed above, said discussion being incorporated herein in its entirety.
Regarding claim 30, Ridley teaches a composition comprising tezacaftor (Compound II). Furthermore, as previously discussed, Ridley teaches fixed-doses (page 195, section Dosing and Administration), which reads on the claimed “unit dose.” Previously discussed for claim 9, Chen teaches substantially amorphous Compound II ([0055]). However, Ridley, Chen, and Dokou do not teach the about 10 mg to about 50 mg of Compound II.
Chu teaches a composition comprising Compound II, which is the same structure as the claimed Compound II. Specifically, Chu teaches a composition where a first solid dispersion comprises 10 mg to 150 mg of Compound II (number 71(b), [0463]) wherein Compound II is independently substantially amorphous (number 90, [0468]).
It would have been obvious for one of ordinary skill in the art to optimize the amount of tezacaftor (Compound II) in the modified composition of Ridley to 10 mg to 150 mg to produce the claimed invention. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because both Chu and the modified composition of Ridley are commonly drawn to compositions containing amorphous tezacaftor/Compound II, and Chu provided the guidance to do so by teaching a composition that comprises 10 mg to 150 mg of amorphous Compound II, which overlaps with the claimed range of about 10 mg to about 50 mg. Thus, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (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); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the amount of Compound II in the composition would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
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/E.L.K./Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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