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 .
In the event the determination of the status of the application as subject to AIA 35
U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any
correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will
not be considered a new ground of rejection if the prior art relied upon, and the rationale
supporting the rejection, would be the same under either status.
Claim Status
Claims 1-7 are currently pending.
Priority
The instant application claims foreign priority to JP2023-116398 filed on 07/18/2023 as reflected in the filing receipt dated on 09/06/2024. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/12/2024 and 05/07/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the Examiner.
Election/Restrictions
Applicant's election without traverse of Group I, claims 1-6, in the reply filed on 05/21/2026 is acknowledged. Claims 1-7 are pending in the application. Claim 7 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/21/2026. Accordingly, claims 1-6 are being examined on the merits herein.
Claim Objections
Claim 6 is objected to because of the following informalities:
Claim 6 recites the limitation “a basic material: and” in line 3, which contains a typographical error wherein the colon should be replaced with a semicolon.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 2 and 3 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 2 recites the limitation “wherein the basic material is contained in an amount of 0.2 to 2.0 molar equivalents relative to the acidic groups of the acidic polymer”. The claim is indefinite because it appears to claim a relative amount, i.e. a ratio, but it does not clearly define how many moles of the basic material relative to the moles of acidic groups of the acidic polymer are permitted. For example, does the claim mean that the molar equivalent of basic material:acidic groups is 0.2:2, or that the molar equivalent ranges from 0.2:1 to 2:1? For the purposes of compact prosecution in the prior art rejections below, the Examiner is interpreting the claim broadly to mean the latter.
Claim 3 recites the limitation “100 µm or less”. It is unclear how the basic material can have a volume-based average particle diameter in a range of 100 µm or less, which encompasses embodiments wherein the average particle diameter is 0 µm (i.e., there are no particles), and also comprise the required basic material. Therefore, the scope of the claim is indefinite.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 4-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (European J. of Pharm. Sci., vol. 168, pg. 1-14; published: 11/16/2021; IDS of 05/07/2025) as evidenced by Chemical Book (Synthesis and Application of Toltrazuril, pg. 1-3; published: 08/29/2022; PTO-892).
Zhang, throughout the reference, teaches the preparation of a poorly water-soluble model drug, toltrazuril (TOL), as an enteric micro-environmental pH-modifying solid dispersion (micro pHm SD) with enteric, hydrophilic polymers and alkalizer, wherein the enteric polymer exhibits protective effects on the alkalizer, thereby improving the dissolution and bioavailability of the active pharmaceutical ingredient [abstract].
Zhang further teaches a method wherein TOL enteric micro pHm SDs were prepared by dissolving polyvinylpyrrolidone k30 (PVPk30) in methanol and dissolving an enteric polymer selected from a poly(methacrylic acid-co-methyl methacrylate) polymer (Eudragit® L100, S100, or L100-55) or hydroxypropyl methylcellulose acetate succinate (HPMCAS) in N,N-dimethylformamide (DMF), mixing, dissolving TOL in DMF, adding the TOL to the liquid polymer mixture, suspending Ca(OH)2 in methanol, then adding the Ca(OH)2 and stirring to obtain a uniform liquid mixture for solid dispersion [pg. 2-3, sec. 2.2].
Regarding claims 1 and 4: The poly(methacrylic acid-co-methyl methacrylate) polymers and HPMCAS each read on the instantly claimed acidic polymer, as evidenced by instant claim 4. The Ca(OH)2 reads on the instantly claimed basic material, as evidenced by Applicant’s instant specification [0044]. Methanol and DMF are each organic solvents and thus meet the claim limitation.
Regarding the instantly claimed poorly water-soluble drug: Applicant’s instant specification teaches "poorly water-soluble drug" refers to a drug listed in the Japanese Pharmacopoeia Eighteenth Edition as "slightly soluble", "very slightly soluble", or "practically insoluble or insoluble" as defined by a series of listed experimental conditions [0051]. While Zhang does not expressly define the conditions used to characterize toltrazuril as “poorly water-soluble” in the reference, Chemical Book states that toltrazuril is insoluble in water [pg. 1, “General description”]. Therefore, an ordinarily skilled artisan would reasonably conclude that toltrazuril meets the claim limitation. The Examiner notes that since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed poorly water-soluble drug with the toltrazuril of Zhang, the burden of proof is upon the Applicant to show an unobvious distinction between the structural and functional characteristics of the claimed poorly water-soluble drug and that of the prior art. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, USPQ 2d 1922 (PTO Bd. Pat. App. & Int.).
Regarding the claim limitation “wherein the basic material is dispersed in the organic solvent”: Applicant’s instant specification teaches that “dispersed” refers to a state in which all or part of the basic material is not dissolved in a solvent [0067]. Because Zhang teaches that the Ca(OH)2 is “suspended in” methanol, whereas other ingredients are explicitly described as “dissolved in” their respective solvents, one of skill in the art would reasonably conclude that Zhang’s distinction indicates that Ca(OH)2 is not fully dissolved in solvent and thus meets the claim limitation wherein the basic material is “dispersed in” solvent [pg. 2-3, sec. 2.2].
Regarding claim 5: The liquid mixture comprises methanol, which reads on the instantly claimed “organic solvent”. The Examiner notes that while the mixture of Zhang also includes DMF, the open claim language “comprising” recited in parent claim 1 does not exclude the presence of an additional organic solvent. Claim 5 is met so long as the prior art composition includes an organic solvent selected from those recited in the claim, which it does.
Regarding claim 6: Zhang teaches that the uniform liquid mixture taught above is freeze dried to obtain a solid dispersion in powder form comprising Ca(OH)2, TOL, PVPk30, and enteric polymer [pg. 2-3, sec. 2.2].
Regarding the limitation “wherein the basic material has a surface that is partially or entirely coated with the acidic polymer”: In observing the tablet surface of the SD, Zhang further teaches that the alkalizer, e.g., the Ca(OH)2, was well wrapped inside the tablets by the enteric polymers, which successfully protected the Ca(OH)2 in the SD from being dissolved by the acidic medium due to their insolubility under acidic conditions [pg. 4-5, sec. 3.2, fig. 2]. Under broadest reasonable interpretation, “wrapped inside the tablets by the enteric polymers” reads on the instantly claimed structure “surface…coated with the acidic polymer”.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (European J. of Pharm. Sci., vol. 168, pg. 1-14; published: 11/16/2021; IDS of 05/07/2025) as evidenced by Chemical Book (Synthesis and Application of Toltrazuril, pg. 1-3; published: 08/29/2022; PTO-892).
Zhang as evidenced by Chemical Book teaches the invention(s) of claims 1-2 and 4-6 as discussed in detail above and further incorporated herein.
Regarding claim 2: Zhang teaches embodiments wherein the weight ratio of Ca(OH)2:enteric polymer is 8:3, 8:6, 8:12, 8:18, or 8:24 [pg. 2-3, sec. 2.2]. While Zhang is silent as to the amount of Ca(OH)2 molar equivalents relative to the acidic groups of the enteric polymers, which may in fact lie within the instantly claimed range, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to manipulate the molar equivalents of alkalizer relative to acidic groups in the enteric polymer in order to achieve a desired dissolution profile because Zhang expressly teaches that protection of Ca(OH)2-, which ultimately prevents neutralization of the alkalizer in the acidic stomach and promotes dissolution of drug in the intestinal tract, increases with increased proportion of enteric polymer [pg. 5-6, sec. 3.3; pg. 12-13, sec. 4].
It is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 3: While Zhang is silent as to the volume-based average particle diameter of the Ca(OH)-2, the reference further teaches that the resulting solid dispersion has a particle size of <100 µm [pg. 3, l. col.]. Accordingly, it would have been prima facie obvious to manipulate the particle size of the Ca(OH)-2 according to known methods to yield the predictable result of particles having a diameter of 100 µm or less, which would necessarily result in a volume-based average particle diameter of 100 µm or less, because the reference teaches that particles in the final dried solid dispersion cannot exceed this size range.
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 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10,493,161 B2 in view of Zhang et al. (European J. of Pharm. Sci., vol. 168, pg. 1-14; published: 11/16/2021; IDS of 05/07/2025).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US ‘161 recite a solution for spray drying comprising all features of the instantly claimed composition for a solid dispersion except the claims of US ‘161 do not expressly recite the instantly claimed basic material or the additional features of instant claims 2-3 and 5, or the solid dispersion of instant claim 6.
The teachings of Zhang are as set forth and further incorporated herein.
Regarding claim 1: It would have been obvious to one of ordinary skill in the art to modify the solution recited in the claims of US ‘161 by further including a basic material, such as Ca(OH)-2, because Zhang demonstrates that dispersing an alkalizer in an organic solvent, such as those recited in the claims of US ‘161, and then mixing the suspension with a solution comprising an enteric polymer, poorly water-soluble drug, and organic solvent, such as the hypromellose acetate succinate solution recited in the claims of US ‘161, is an effective way to improve the dissolution and bioavailability of the drug.
Regarding claim 2: It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to manipulate the molar equivalents of basic material relative to acidic groups in the enteric polymer in order to achieve a desired dissolution profile because Zhang expressly teaches that protection of the alkalizer (i.e., coating of the alkalizer with the enteric polymer), which ultimately prevents neutralization of the alkalizer in the acidic stomach and promotes dissolution of drug in the intestinal tract, increases with increased proportion of enteric polymer.
Regarding claim 3: It would have been obvious to one of ordinary skill in the art to manipulate the particle size of the basic material according to known methods to yield the predictable result of particles having a diameter of 100 µm or less, which would necessarily result in a volume-based average particle diameter of 100 µm or less, because Zhang teaches that particles in dried solid dispersions should exceed this size range.
It is generally noted that differences in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 6: Zhang teaches that organic solvent can be removed from solutions comprising poorly water-soluble drug, alkalizer, and enteric polymer to form a dried solid dispersion [pg. 3, sec. 2.2]. It would have been obvious to one of ordinary skill in the art to use the known method of Zhang to remove organic solvent from the solution recited in the claims of US ‘161 claims to yield the predictable result of a solid dispersion comprising a basic material that has a surface partially or completely coated with the hypromellose acetate succinate. An ordinarily skilled artisan would have been motivated to do so because Zhang teaches that solid dispersions formulated in this manner are known to improve the dissolution and bioavailability of poorly water-soluble drugs.
Claim 6 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 8-9 of copending Application No. 19/175,646 in view of Zhang et al. (European J. of Pharm. Sci., vol. 168, pg. 1-14; published: 11/16/2021; IDS of 05/07/2025).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims recite a composite comprising a solid dispersion comprising all features of the instantly claimed solid dispersion except the instantly claimed basic material.
The teachings of Zhang are as set forth above and further incorporated herein.
It would have been obvious to one of ordinary skill in the art to modify the solid dispersion recited in the claims of App. ‘646 by further including an alkalizer, such as the Ca(OH)2, having a surface partially or entirely coated with an acidic enteric polymer, such as the hydroxypropyl methyl cellulose succinate recited in the copending claims, because Zhang teaches that formulating poorly water-soluble drugs in a solid dispersion comprising an alkalizer wrapped by (i.e., coated within) an enteric polymer is an effective way to improve the dissolution and bioavailability of the drug.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH CLINKSCALES WISTNER whose telephone number is (571)270-7715. The examiner can normally be reached Monday - Thursday 8:00 AM - 5:00 PM ET.
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/SARAH C WISTNER/Examiner, Art Unit 1616
/Mina Haghighatian/Primary Examiner, Art Unit 1616
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