DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The submission filed on 10/01/2025 has been entered. Claims 1-20 are pending in this application and are currently under examination.
Priority
This application is a CON of 17/981,348 filed on 11/04/2022, now PAT 12472201, which is a CON of 17/546,880 filed on 12/09/2021, now PAT 11534454, which is a CON of PCT/US21/59760 filed on 11/17/2021, which claims benefit of US PRO 63/115,453 filed on 11/18/2020, US PRO 63/115,451 filed on 11/18/2020, US PRO 63/115,458 filed on 11/18/2020, and US PRO 63/115,445 filed on 11/18/2020.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed application, Application No. 63/115,453, 63/115,451, 63/115,458, or 63/115,445, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claim 15 recites “an antibiotic, an anti-coagulant”, “an antifungal”, and “an anti-migraine, an anti-neoplastic, an antiviral, a piperazine, a naphthylpropylamine, or a phenidate”, which are not disclosed or supported by the prior-filed Application No. 63/115,453, 63/115,451, 63/115,458, and 63/115,445.
Also, this application repeats a substantial portion of prior Application No. 17/981,348, filed on 11/04/2022, and adds disclosure not presented in the prior application. Because this application names the inventor or at least one joint inventor named in the prior application, it may constitute a continuation-in-part of the prior application. Should applicant desire to claim the benefit of the filing date of the prior application, attention is directed to 35 U.S.C. 120, 37 CFR 1.78, and MPEP § 211 et seq. The presentation of a benefit claim may result in an additional fee under 37 CFR 1.17(w)(1) or (2) being required, if the earliest filing date for which benefit is claimed under 35 U.S.C. 120, 121, 365(c), or 386(c) and 1.78(d) in the application is more than six years before the actual filing date of the application. Claims 1-20 recite “cationic pharmaceutical compound… an anionic substituted cyclodextrin… free of crystalline material”, “pharmaceutical compound is a cation… a plurality of anionic conjugate bases… free of crystalline material” and/or ”characterized by increased solubility compared to a corresponding crystalline form of the solid salt”, which are not disclosed in the prior application. Thus, the priority date of claims 1-20 is 10/01/2025 as filed.
Information Disclosure Statement
The information disclosure statement (IDS) with appropriate assertion under 37 CFR 1.98 filed on 01/02/2026 has been considered.
Claim Objections
Claims 2 and 11 are objected to because of the following informalities: In claim 2, change the incorrect recitation “is substituted with” (lines 1 to 2) to “has” because the preceding “the anionic substituted cyclodextrin” has recited the “substituted”. In claim 11, change the improper recitation “at least 98% free of impurities” (lines 1 to 2) to “at least 98% purity by High Performance Liquid Chromatography” to indicate how the 98% is obtained and is based on. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims 1, 2, 10, 12, and 19 recite "cationic pharmaceutical compound… an anionic substituted cyclodextrin… free of crystalline material”, “pharmaceutical compound is a cation… a plurality of anionic conjugate bases… free of crystalline material” and/or ”characterized by increased solubility compared to a corresponding crystalline form of the solid salt”, which are not disclosed in the originally filed application. Applicants’ specification only supports "formula [A]n[B] wherein A is an pharmaceutical compound comprising at least one basic nitrogen atom… B is a complexing agent comprising a plurality of acidic functional groups”, “the total number of basic nitrogen atoms of A is equal to the number of acidic functional groups of B, thus resulting in a compound of neutral charge, wherein the acidic functional groups of B are deprotonated (and thus anionic) and the basic nitrogen atom or atoms of A are protonated (and thus cationic)”, and “In some embodiments, the solid form is a crystalline form or an amorphous form” (p. 41-43, [0185 and 0189]; p. 46, [0202]).
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 3, 4, and 12-20 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. Claims 4, 13-18, and 20 depend from claim 3, 12, or 19.
Claims 3, 12, and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: There is no parent compound recited to support the recitations “a conjugate base” (line 2 of claim 3) and “conjugate bases” (line 5 of claim 12; line 8 of claim 19). It is not clear what the “conjugate base” refers to. Applicant is advise to insert the phrase “of an acid” and “of acids” immediately after the recitations “a conjugate base” and “conjugate bases”, respectively.
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.
(I) Claims 1-15 and 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hong et al. (JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 100, NO. 7, p. 2703-2716, JULY 2011, hereinafter referred to as Hong ‘2011, also listed in IDS filed on 01/02/2026) as evidenced by Kim et al. (Journal of Pharmaceutical Sciences, Vol. 87, No. 12, p. 1560-1567, December 1998, hereinafter referred to as Kim ‘1998, , also listed in IDS filed on 01/02/2026).
With regard to structural limitations “an amorphous solid salt comprising: at least one (or at least two; or having an ionizable nitrogen) cationic pharmaceutical compound; and an anionic substituted cyclodextrin (or having at least one anionic functional group or a conjugate base of a carboxylic acid or a sulfonic acid), wherein the anionic substituted cyclodextrin is a counter-anion to the at least one cationic pharmaceutical compound (or the molar ratio of the cationic pharmaceutical compound to the anionic substituted cyclodextrin is greater than 1:1 or from about 2: 1 to about 8: 1), and wherein the amorphous solid salt is substantially (defined as the term is used herein means completely or almost completely) free of crystalline material” (claims 1-8 and 10), and “an amorphous solid salt comprising (or a method of dissolving an amorphous solid salt, comprising dissolving the amorphous solid salt comprising) the formula: [pharmaceutical compound]n[substituted cyclodextrin], wherein the pharmaceutical compound is a cation (or a piperazine); the substituted cyclodextrin comprises a plurality of anionic conjugate bases of acids which are counter-anions to the pharmaceutical compound, n is at least 1 (or at least 2; or 6, 7, or 8), and the amorphous solid salt (or a powder; or characterized by scanning electron microscopy, IR spectral analysis, differential scanning calorimetry) is substantially free of crystalline material” (claims 9, 12-15, and 17-19):
Hong ‘2011 disclosed Preparation of Lyophilized Ziprasidone–CD Complexes: To form the complex, cyclodextrins (CDs), including sulfobutylether-ß-cyclodextrin (SBEßCD) and carboxyethyl-ß-cyclodextrin (CEßCD), were added to 15 mL of sterile water for injection (sWFI) in a small beaker and stirred until fully dissolved. When the temperature reached 70◦C, ziprasidone mesylate was slowly added to the solution and stirred until dissolved. Solution pH for all solutions was below pH 4.0, dictated by the solution pH of ziprasidone mesylate. After filtering 3 mL of CD–ziprasidone complex into clean 10 mL glass vials, the samples were freeze-dried. Preparation of Ziprasidone–SBEβCD Salts: SBEßCD polysulfonic acid contains approximately six polymethylenesulfonic acid groups per ß-CD. Different stoichiometric salts of ziprasidone with SBEßCD were then prepared by adding the free acid form of SBEßCD to 3–6 molar equivalents of ziprasidone free base. The solid forms of ziprasidone–SBEßCD salts were isolated by removal of reaction medium at reduced pressure and moderate heat. Analysis of samples included potency and purity analysis by HPLC, and solid form characterization by X-ray diffraction, microscopy, and NMR to confirm the solid form of the test article. Table 2. Physical Nature of Ziprasidone in Different Chemical Forms for Solid State-Stability Study:
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(page 2705, right col., para. 3; page 2706, left col., para. 4 and 5; right col., para. 5; page 2708, Table 2). The fact that ziprasidone dissolved at high concentration from the isolated solid into an aqueous solution provided indirect evidence that a complex was formed and the sample remained as a complex in the isolated solid state. This is further supported by the fact that the lyophilized complex can be rapidly reconstituted with water (page 2709, left col., para. 1; right col., para. 1). Inclusion complexation of ziprasidone with SBEßCD at a molar stoichiometry of 1:1 was confirmed using proton nuclear magnetic resonance (NMR) of ziprasidone solubilized in SBEßCD in dimethyl sulfoxide (DMSO) previously by Kim et al. (page 2705, left col., para. 1, ref #7 on page 2715). Kim ‘1998 (cited here as evidence only) disclosed that Ziprasidone, 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazin-yl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one, is a weak base with an apparent pKa of about 6.5. The solubility of the free base in water is 0.3 µg/mL, a factor of 104 to 105 below the targeted solution concentration of 20-40 mg/mL for the im formulation. This target concentration can be achieved by preparing an inclusion complex of the mesylate salt of ziprasidone (ZM) with ß-cyclodextrin sulfobutyl ether (SBECD). Figure 1 - Chemical structure of ziprasidone mesylate:
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, X, X’, Y, Y’, A, B, Z1, and Z2 indicate the protons at those particular positions. A piperazine nitrogen (N* in Figure 1) is protonated (page 1560, left col., para. 2; right col., para. 1 and Figure 1; page 1562, right col., para. 2).
Thus, these teachings of Hong ‘2011 as evidenced by Kim ‘1998 anticipate Applicant’s claims 1-15 and 17-20, and would carry the same properties and/or would achieve the same intended results, including “substantially free of crystalline”, “at least 98% purity by HPLC”, and/or “characterized by increased solubility compared to a corresponding crystalline form of the solid salt”, required by claims 1, 11, 12, 19, and 20.
(II) Claims 1-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Szabo et al. (Heliyon 7:e07581, 2021, Accepted 12 July 2021, hereinafter referred to as Szabo ‘2021).
With regard to structural limitations “an amorphous solid salt comprising: at least one (or at least two; or having an ionizable nitrogen) cationic pharmaceutical compound; and an anionic substituted cyclodextrin (or having at least one anionic functional group or a conjugate base of a sulfonic acid), wherein the anionic substituted cyclodextrin is a counter-anion to the at least one cationic pharmaceutical compound (or the molar ratio of the cationic pharmaceutical compound to the anionic substituted cyclodextrin is greater than 1:1 or from about 2: 1 to about 8: 1), and wherein the amorphous solid salt is substantially (defined as the term is used herein means completely or almost completely) free of crystalline material” (claims 1-8 and 10), and “an amorphous solid salt comprising (or a method of dissolving an amorphous solid salt, comprising dissolving the amorphous solid salt comprising) the formula: [pharmaceutical compound]n[substituted cyclodextrin], wherein the pharmaceutical compound is a cation (or an anti-neoplastic; or formulated for oral administration); the substituted cyclodextrin comprises a plurality of anionic conjugate bases of acids which are counter-anions to the pharmaceutical compound, n is at least 1 (or at least 2; or 6, 7, or 8), and the amorphous solid salt (or a powder; or characterized by IR spectral analysis or differential scanning calorimetry) is substantially free of crystalline material” (claims 9 and 12-19):
Szabo ‘2021 disclosed inclusion complexation between pomalidomide (POM) and sulfobutylether-β-cyclodextrin (SBE-β-CD, degree of substitution ~7). Solid state complexation in a 1:1 M ratio was carried out by lyophilization and investigated by infrared spectroscopy (IR) and X-ray powder diffraction method (XRD). The complex exhibited fast-dissolution with immediate release of POM, when compared to the pure drug at acidic and neutral pH. POM (
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) has a low oral bioavailability mainly due to its poor solubility in water. Increasing the solubility of POM could enhance its bioavailability. POM has a pKa of 1.89±0.01 and is in its protonated form only in very acidic pH values. Preparation of POM - SBE-β-CD inclusion complex by lyophilization: Equimolar amounts of POM (0.1 M) and SBE-β-CD (0.1 M) were dissolved in ethanol-water mixture (1:1 v/v ratio). The mixture was stirred for 8 h at room temperature and filtered through a 0.45 mm Millipore membrane filter. The yellow filtrate was frozen and then lyophilized in a freeze-dryer for 24 h. The obtained powders were sieved (125 μm) and kept in a desiccator until use. The XRD analysis of lyophilized product (LP) clearly shows that the inclusion complex is totally in the amorphous state, no sign of crystalline character is present on this diffraction pattern (page 1, Abstract; page 4, right col., para. 1; page 5, Table 1; page 3, right col., para. 3; page 7, left col., para. 1; ). The 1H NMR chemical shifts (δ) were measured at different POM concentration/SBE-β-CD concentration ratios, while the sum of CPOM + CSBE-B-CD was kept constant. The calculated factors (ΔδχPOM) were plotted as a function of POM molar ratio (χPOM). Representative Job plot curves of POM with SBE-β-CD:
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(page 4, right col., para. 4; page 5, Figure 4).
Thus, these teachings of Szabo ‘2021 anticipate Applicant’s claims 1-20, and would carry the same properties and/or would achieve the same intended results, including “at least 98% purity by HPLC”, and/or “characterized by increased solubility compared to a corresponding crystalline form of the solid salt”, required by claims 11 and 20.
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691