DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Preliminary Amendments and Remarks, filed 6 May 2025, in the matter of Application N° 18/999,125. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application is being examined under the pre-AIA first to invent provisions.
Claims 1-34 have been canceled. Claims 35-54 have been added and are supported by the originally-filed disclosure. None of the newly added claims has been further amended.
No new matter has been added.
Thus, claims 35-54 now represent all claims currently under consideration.
Information Disclosure Statement
One Information Disclosure Statement (IDS) filed 6 May 2025 is acknowledged and has been considered.
Specification
Applicants are reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The disclosure is objected to at ¶[0008] because it contains an embedded hyperlink and/or other form of browser-executable code. Applicants are required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP §608.01.
Nonstatutory 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 35-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of Dokou et al. (USPN 8,883,206 B2). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 35 recites:
A pharmaceutical composition in a unit dose form comprising a plurality of granules or mini-tablets, comprising:
a solid dispersion in an amount from about 5 mg to about 125 mg, wherein the solid dispersion comprises:
about 80 wt % of substantially amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion,
about 19.5 wt % of HPMCAS by weight of the dispersion, and
about 0.5 wt % SLS by weight of the dispersion;
a binary filler comprising mannitol and lactose in a ratio of about 1:3 mannitol to lactose;
sucralose; and
at least one excipient selected from a disintegrant, a glidant, and a lubricant.
Instant claim 43 recites:
“The pharmaceutical composition of claim 35, wherein the solid dispersion is present in an amount of about 35 wt% of the pharmaceutical composition…”
The foregoing is read on by claims 1, 2 and 5 of the reference ‘206 patent. The key differences are emphasized below:
A pharmaceutical composition consisting of:
about 35 wt% of a solid dispersion by weight of the composition, wherein the dispersion comprises about 80 wt % of substantially amorphous or amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide by weight of the dispersion, and about 19.5 wt % of HPMCAS by weight of the dispersion, and about 0.5 wt % SLS by weight of the dispersion;
about 13.5 wt% of mannitol by weight of the composition;
about 41 wt% of lactose by weight of the composition;
about 2 wt% of sucralose by weight of the composition;
about 6 wt% of croscarmellose sodium by weight of the composition;
about 1 wt% of colloidal silicon dioxide by weight of the composition; and
about 1.5 wt% of magnesium stearate by weight of the composition.
The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a unit dose form comprising one or a plurality of granules, pellets, particles or mini-tablets, and wherein the unit dose form comprises from about 1 mg to about 100 mg of substantially amorphous or amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.
Claim 5 additionally discloses that the unit-dose comprises about 25-40 mini-tablets.
The foregoing additionally reads on the limitations of instant claims 35-46.
The remaining limitations disclosed in claims 3-10 of the reference ‘206 patent read immediately upon the instant limitations of claims 36-46 of the claimed composition.
The limitations of the instantly claimed method of treating require each of the compositional limitations of claim 35.
As no restriction requirement was made in either the instant or reference application, the instant method claims are also considered to be read on by the reference composition.
Thus, the instant recitations of claims 35 and 47, though compositionally broader, would be anticipated by the composition of claim 1, were the reference available as prior art.
Thus, the Examiner concludes that the ‘206 patent presents a prima facie showing of obviousness such that a person of ordinary skill in the art at the time of the filed invention would have had a reasonably high expectation of successfully practicing the instantly claimed invention, absent a clear showing of evidence to the contrary.
Claims 35-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of Dokou et al. (USPN 10,272,046 B2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations recited by instant independent claims 35, 43, and 47 are discussed above.
Claim 1 of the reference ‘046 patent discloses:
A pharmaceutical composition in a unit dose form comprising one or a plurality of granules, pellets, particles, or mini-tablets, wherein the composition comprises:
a solid dispersion in an amount from about 30 to about 50 percent by weight of the composition, wherein the dispersion comprises about 80 wt% of substantially amorphous or amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion, about 19.5 wt % of HPMCAS by weight of the dispersion, and about 0.5 wt % SLS by weight of the dispersion;
mannitol and lactose in amount from about 30 to about 60 percent by weight of the composition, wherein mannitol and lactose are present in a ratio of about 1:3 mannitol to lactose;
sucralose in an amount from about 1.5 to about 2.5 percent by weight of the composition;
croscarmellose sodium in an amount from about 4 to about 8 percent by weight of the composition;
colloidal silicon dioxide in an amount from about 0.5 to about 1.5 percent by weight of the composition; and
magnesium stearate in an amount from about 0.5 to about 1.5 percent by weight of the composition;
wherein the composition does not comprise SLS outside of the solid dispersion.
Claim 9 discloses that the solid dispersion is present in an amount of about 35 weight percent of the pharmaceutical composition.
Claims 5, 7, and 9 additionally disclose that the dosage for will comprise from about 25-40 mini-tablets, about 26 mini-tablets and about 39 mini-tablets, respectively.
Claims 2-4, 8, and 10 disclose varying amounts of amorphous Compound 1.
The foregoing reads on the limitations of instant claims 35-46.
The remaining limitations disclosed in claims 2-12 of the reference ‘046 patent read immediately upon the instant limitations of claims 36-46 of the claimed composition.
The limitations of the instantly claimed method of treating require each of the compositional limitations of claim 35.
As no restriction requirement was made in either the instant or reference application, the instant method claims are also considered to be read on by the reference composition as does the reference method presented in claims 13-23.
Thus, the instant recitations of claims 35 and 47 are compositionally narrower, and would thus be anticipated by the practiced compositions, were the reference available as prior art.
Thus, the Examiner concludes that the ‘046 patent presents a prima facie showing of obviousness such that a person of ordinary skill in the art at the time of the filed invention would have had a reasonably high expectation of successfully practicing the instantly claimed invention, absent a clear showing of evidence to the contrary.
Claims 35-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of Dokou et al. (USPN 11,147,770 B2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations recited by instant independent claims 35 and 49 are discussed above.
Claim 1 of the reference ‘770 patent discloses:
A pharmaceutical composition comprising a unit dose form comprising one or a plurality of granules, pellets, particles, or mini-tablets, wherein the composition comprises:
a solid dispersion in an amount of 30 to 40 percent by weight of the composition;
a binary filler;
a sweetener;
a disintegrant;
a glidant; and
a lubricant;
wherein the unit dose form comprises from 1 mg to 250 mg of substantially amorphous or amorphous Compound 1,
wherein the solid dispersion comprises about 80 wt % of substantially amorphous or amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion, about 19.5 wt % of hydroxypropyl methylcellulose acetate succinate (HPMCAS) by weight of the dispersion, and about 0.5 wt % sodium lauryl sulfate (SLS) by weight of the dispersion,
wherein the binary filler comprises mannitol and lactose in a ratio of about 1:3 mannitol to lactose;
wherein the sweetener is sucralose, and
wherein substantially amorphous Compound 1 has less than 15% crystallinity.
Claim 12 additionally discloses that the solid dispersion is present in an amount of about 35 percent by weight of the pharmaceutical composition.
The foregoing disclosed composition reads on instant claims 35-37, 43, and 45. The key difference between the two compositions resides with the range of the amount of Compound 1 that is recited.
Claims 11, 12, and 14 read on the ranges and amounts of mini-tablets recited by instant claims 43 and 45.
Instant claims 42-44 are also read on by reference claims 8-10, 13, and 15.
Reference claims 38-46 respectively read on instant claims 8-15.
As no restriction requirement was made in either the instant or reference application, the instant method claims are also considered to be read on by the reference composition.
The method recited by instant claim 47 is read on by reference claim 17.
The dependent method limitations recited by instant claims 48 and 51-54 are read on directly by claims 18-22 of the reference.
Thus, the Examiner concludes that the ‘770 patent presents a prima facie showing of obviousness such that a person of ordinary skill in the art at the time of the filed invention would have had a reasonably high expectation of successfully practicing the instantly claimed invention, absent a clear showing of evidence to the contrary.
Claims 35-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of Dokou et al. (USPN 11,752,106 B2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations recited by instant independent claims 35 are discussed above.
Claim 1 of the reference ‘106 patent discloses:
A pharmaceutical composition comprising a unit dose form comprising one or a plurality of granules, pellets, particles, or mini-tablets, wherein the composition comprises:
a solid dispersion in an amount of 30 to 40 percent by weight of the composition, wherein the dispersion comprises:
about 80 wt % of substantially amorphous or amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion,
about 19.5 wt % of hydroxypropylmethylcellulose acetate succinate (HPMCAS) by weight of the dispersion, and
about 0.5 wt % sodium lauryl sulfate (SLS) by weight of the dispersion;
a binary filler, wherein the binary filler comprises mannitol and lactose in a ratio of about 1:3 mannitol to lactose;
a sweetener, wherein the sweetener is sucralose;
a disintegrant;
a glidant; and
a lubricant;
wherein the unit dose form comprises at least about 5 mg of substantially amorphous or amorphous Compound 1; and
wherein substantially amorphous Compound 1 has less than 15% crystallinity.
The foregoing disclosure reads on instant claims 35-42.
The added disclosure of claims 11-13 are considered to read further on instant claims 43-46 with respect to the quantities and ranges of mini-tablets present in the instantly claimed dosage form.
The method limitations disclosed by claims 15-20 of the reference are considered to teach and suggest the limitations recited by instant claims 47-54.
Thus, the Examiner concludes that the ‘106 patent presents a prima facie showing of obviousness such that a person of ordinary skill in the art at the time of the filed invention would have had a reasonably high expectation of successfully practicing the instantly claimed invention, absent a clear showing of evidence to the contrary.
Claims 35-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5-20 of Dokou et al. (USPN 12,214,083 B2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations recited by instant independent claims 35 are discussed above.
Claim 1 of the reference ‘083 patent discloses:
A pharmaceutical composition in a unit dose form comprising a plurality of granules or mini-tablets, wherein the composition comprises:
a) a solid dispersion in an amount from about 30 to about 40 percent by weight of the composition, wherein the dispersion comprises:
i. about 80 wt % of amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion,
ii. about 19.5 wt % of hydroxypropylmethylcellulose acetate succinate (HPMCAS) by weight of the dispersion, and
iii. about 0.5 wt % of sodium lauryl sulfate (SLS) by weight of the dispersion;
b) mannitol and lactose in an amount from about 30 to about 60 percent by weight of the composition, wherein mannitol and lactose are present in a ratio of about 1:3 mannitol to lactose;
c) sucralose in an amount from about 0.1 to about 5 percent by weight of the composition;
d) croscarmellose sodium in an amount from about 1.5 to about 8 percent by weight of the composition;
e) colloidal silicon dioxide in an amount from about 0.1 to about 5 percent by weight of the composition; and
f) magnesium stearate in an amount from about 0.1 to about 7 percent by weight of the composition;
wherein the unit dose form comprises at least about 5 mg of amorphous Compound 1, and
wherein less than about 15 wt % of the Compound 1 is crystalline.
The foregoing disclosure reads on instant claims 35 and 38-40.
The limitations disclosed in claims 2 and 3 read on instant claims 36 and 37.
The limitations disclosed in claims 5 and 6 read on instant claims 41 and 42.
The limitations disclosed in claims 7-9 and 11 read on instant claims 43 and 45.
The limitations disclosed in claims 10-12 read on instant claims 44-46.
The method limitations disclosed by claims 13-20 of the reference are considered to teach and suggest the limitations recited by instant claims 47-54.
Thus, the Examiner concludes that the ‘083 patent presents a prima facie showing of obviousness such that a person of ordinary skill in the art at the time of the filed invention would have had a reasonably high expectation of successfully practicing the instantly claimed invention, absent a clear showing of evidence to the contrary.
Claims 35-37, 39-42, and 47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-10, 12-14, 16, 17, 19-23, 30, 31, 40, and 44 of copending Application No. 19/100,776 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations of instant claim 35 are discussed above.
Reference claim 1 discloses:
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Claim 12 additionally defines the one or more fillers as containing about 10-14 wt% mannitol of the composition. Claims 13 and 14 disclose that the one or more fillers comprise lactose in an amount ranging from about 35-40 wt% of the composition.
The combined disclosure of claims 12-14 present the ordinarily-skilled artisan with a reasonable expectation of producing a dosage form with a binary filler that contains mannitol and lactose in a weight ratio ranging from about 1:3.
Of particular note regarding copending claim 1 is that the dosage form comprises Compound III, which reads on instantly claimed Compound I (aka ivacaftor). However, the additional disclosure of Compound I (Form A), and Compound II, does not present a teaching away from the instantly claimed composition since the scope of the instantly claimed invention does not exclude the other two compounds.
Thus, the limitations of claims 6-10, 16, 17, 19-23, and 30 do not present a teaching away, but in fact, are considered to provide added teachings that define the composition in terms of the excipients that are instantly recited.
The disclosure of the amount of Compound III present in claim 31 is considered to teach that the compound is amorphous as instantly claimed and present in amounts that read on instant dependent claims 36, 37, and 39-42.
Lastly, the limitations of claims 40 and 41 are considered to read on the instantly recited method of claim 47.
Thus, the Examiner concludes that the ‘776 application presents a prima facie showing of obviousness such that a person of ordinary skill in the art at the time of the filed invention would have had a reasonably high expectation of successfully practicing the instantly claimed invention, absent a clear showing of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 35-54 are free of the prior art. As discussed in the Notice of Allowance for application 17/475,622, mailed on 21 April 2023:
Applicants’ remarks and Rule 132 Declaration, filed 12 April 2023 have been carefully considered in response to the remaining Nonstatutory Double Patenting rejection raised over Rowe et al. (USPN 10,646,481 B2).
Of particular interest within the totality of the response was Mr. Hayden’s filed affidavit discussing evidence of criticality for the claimed 1:3 ratio of mannitol to lactose in the binary filler of the composition. Specifically, ¶¶10-11 of the declaration submitted evidence not previously found in the entirety of the prosecution history discussing Applicants’ discovered advantages for reciting the above ratio.
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What the above chart shows is a comparative plot of the force (y) required to eject a dosage form from the die in which it was compressed against the compression force used. The third variable of the plot is a greyscale differentiation of the different blends of lactose and mannitol used. The blends range from 100% mannitol (100:0) to 100% lactose (0:100). The latter formulation employing 100% lactose (the lowest-plotted, dark groupings at the bottom of the box) required the least amount of force to be removed from the die. This blend is also understood to be a singular filler blend.
The next groupings are faint data points also within the box and are representative of the claimed binary filler of 1:3 mannitol to lactose. Applicants attest that their research revealed this particular blend to not only provide an aesthetically pleasing masking for the bitter tasting drug, but more critically, it provided a low enough ejection force to be able to remove the completed dosage forms from their dies without damaging the dosage form itself. This critical feature allowed the dosage forms to be repeatedly produced with the quality and validation aspects (i.e., lack of damage, content uniformity, etc.) required to consistently deliver the same dose of ivacaftor from each tablet.
Those dosage blends tested that employed higher quantities of mannitol in the ratio (i.e., 1:1 and 3:1) were reported as requiring far greater force to eject them from the die which summarily resulted in damage to enough of the tablets to warrant the higher ratios as being undesirable.
This evidence, on its own, is persuasive in overcoming the teachings of Rowe, alone or in combination with the secondary teachings.
The Examiner maintains that Rowe does teach and suggest: (1) the combination of mannitol with lactose as the filler component, (2) total amounts of the filler that may be used in the overall composition, and (3) amounts of lactose within the totality of the filler component. Ultimately, Rowe is considered to provide teachings that encompass the recited filler and ratio. However, in view of the newly filed evidence, Rowe does not provide the motivation to the skilled artisan to arrive at the instantly claimed ratio.
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
Prosecution Insights