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 .1 Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 24 October 2025 has been entered.
Drawings
Receipt of the drawings by the Examiner is acknowledged. Note that formal acceptance of the drawings for publication purposes is subject to review by the Office of Patent Application Processing (OPAP). See MPEP 507 and 608.02(b)(I.).
Status of Claims
Claims 1-3, 5, and 9-12 are pending and are directed to Applicant’s elected species (with traverse) a compound of formula I, the hydrophilic alpha adrenergic blocker (HAAB) compound prazosin.2
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The species election had been modified to account for doxazosin, a compound of the specification 2, as a species of HAAB.
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Claim Interpretation and Background Prior Art
Claims 1 and 11 have been amended to recite the limitations of now canceled claims 4, 6 and 8.
Specifically, the claims have been amended to recite the following intended uses of the claimed composition:
wherein an elution rate when adding the complex to an eluate of pH 1.2 is slower
than the elution rate when adding the hydrophilic alpha adrenergic blocker compound to the eluate of pH 1.2,
wherein an elution rate when adding the complex to an eluate of pH 7.8 is slower
than the elution rate when adding the hydrophilic alpha adrenergic blocker compound
to the eluate of pH 7 .8,
wherein a time to maximum plasma concentration (tmax) in the oral
administration of the composition is longer than a time to maximum plasma concentration (tmax) in the oral administration of a hydrophilic alpha adrenergic blocker compound aqueous solution,
wherein the maximum plasma concentration (Cmax) in the oral administration of the composition is lower than the maximum plasma concentration (Cmax) in the oral administration of the hydrophilic alpha adrenergic blocker compound aqueous solution,
Note: these intended use limitations of the claimed controlled-release composition regarding elution rate and maximum plasma concentration time (tmax) and maximum plasma concentration (Cmax) would be inherent to prior art teaching the claimed composition.
Note the specification Examples 1-6, pages 35-37 exemplify and detail specific methods to formulate doxazosin, prazosin, terazosin and alfuzosin in 1:1 to 1:2 ratios complexed with bentonite, formulated by the specific process of Example 1 on page 35. See also Table 1 on page 38.
Note especially, Example 1 of the specification where doxazosin was formulated with hydrochloric acid solution to prepare the claimed doxazosin complex with bentonite (aka Sodium montmorillonite (Na-MMT)). See SciFinder search identifying bentonite, the smectite clay complexing agent of the examined application, as Sodium montmorillonite (Na-MMT or Na-MTM), aka CAS Reg. No. 1318-93-0.
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See also the specification where it notes the limitation of a “smectite-based minerals,” is defined as “for example, montmorillonite or bentonite, smectite, vermiculite, beidellite, nontronite, saponite, hectorite . . . . “ See page 14.
On examination of the specification, those intended use limitations of pH and pharmacokinetics of claims 1 and 11 are supported by the particular details of Experimental Examples 4 and 5, limited to doxazosin and prazosin and where the composition is formulated by the process of Example 1.
It is pointed out that by way of background prior art, smectite/bentonite/clay based complexes drug formulations for extended and/or controlled release of drugs are known in the art.
For Example, Bello teaches the use of sodium montmorillonite suitable to complex amine containing drugs (such as the claimed doxazosin drug) intercalated and layered into controlled release drug complex. See title and abstract. See also, Park 20163 that teaches a clay/bentonite/MTM complex with a cationic drug or provide an oral sustained release dosage form. While the previous rejection over Park 2016 was withdrawn, it remains relevant to the patentability of the claimed subject matter as detailed below.
Response to Arguments
Applicant’s arguments and amendments, filed 24 October 2025, with respect to the obviousness rejection of Claims 1-12 rejected under 35 U.S.C. 103 over
KR 369 English in view of Pavli have been fully considered and are persuasive. The rejection of claims 1-12 has been withdrawn. However, see new rejections detailed below.
The provisional rejection of claims 1-12 on the ground of nonstatutory double patenting as being unpatentable over claim 1-13 and 15 of copending Application No. 18/013919 (reference application) has been withdrawn, as necessitated by the amendment of claims of the reference application, that have been allowed by the Examiner of the 18/013919 reference application. Note the new rejection over of claims 1-3, 5, and 9-12 for double patenting over Application No. 18/013919 in view of Bello as detailed below.
New Claim Rejections - 35 USC § 102 Necessitated by Amendment
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.
Claims 1-3, 5, 9, and 11-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bello et al. Sodium Montmorillonite/Amine-Containing Drugs Complexes: New Insights on Intercalated Drugs Arrangement into Layered Carrier Material PLoS ONE 10(3): e0121110 (2015).4 Bello is cited on the PTO-892 form.
Amended claim 1 is directed to a controlled-release composition for oral administration comprising:
a complex of a hydrophilic alpha adrenergic blocker compound or its salt; and a clay mineral,
wherein the clay mineral is a plate-like carrier with interlayer expandability and includes smectite-based minerals,
wherein the hydrophilic alpha adrenergic blocker compound is adsorbed onto the clay mineral in an amorphous state;
wherein an elution rate when adding the complex to an eluate of pH 1.2 is slower
than the elution rate when adding the hydrophilic alpha adrenergic blocker compound to the eluate of pH 1.2,
wherein an elution rate when adding the complex to an eluate of pH 7.8 is slower
than the elution rate when adding the hydrophilic alpha adrenergic blocker compound
to the eluate of pH 7 .8,
wherein a time to maximum plasma concentration (tmax) in the oral
administration of the composition is longer than a time to maximum plasma concentration (tmax) in the oral administration of a hydrophilic alpha adrenergic blocker compound aqueous solution,
wherein the maximum plasma concentration (Cmax) in the oral administration of the composition is lower than the maximum plasma concentration (Cmax) in the oral administration of the hydrophilic alpha adrenergic blocker compound aqueous solution,
and wherein the release of the hydrophilic alpha adrenergic blocker compound in the composition is controlled.
As noted by the specification, and regarding claim 1, “present disclosure is a clay
mineral which has a plate-like structure, specifically, interlayer expansibility, and may be used as a carrier by inserting . . . [a drug, antibiotic] into the clay mineral. See page 14.
As detailed in the specification, the limitation of a “smectite-based minerals,” is defined as “for example, montmorillonite or bentonite, smectite, vermiculite, beidellite, nontronite, saponite, hectorite . . . . “ See page 14.
Accordingly, prior art directed to a composition with clay mineral as a carrier containing/comprising a drug will be relevant the novelty analysis.
Regarding claim 1, Bello teaches sodium montmorillonite (Na-MMT)/amine containing drug complexes, especially claimed drug doxazosin (a hydrophilic alpha adrenergic blocker). See Title and Abstract. As required by claim 1, Bello teaches Na-MMT has adsorption properties. See page 2 of 20, first paragraph. Bello teaches layered drug deliver carrier are able to accommodate pharmacologically active substances and are effect of modulating drug release. See abstract.
Bello teaches Na-MMT complexed with doxazosin. See Table 1, page 3. As taught by the Example 1 of the examined invention’s specification, where the clay complex of claim 1 is formed by dispersion of doxazosin in an acidic HCl solution, stirred to form the bentonite (aka Na-MMT)/doxazosin sustained release complex. Similarly, Bello teaches its amine compounds, including doxazosin, were complexed with Na-MMT (aka bentonite) in various acidic (HCl) conditions to form the various Na-MMT complexes including Na-MMT complexed with doxazosin. See page 3 of 20, section titled Sodium Montmorillonite Inclusion Complex Preparation.
Regarding the intended use limitation, where the elution rate of the complex added to an elute of pH 1.2 or 7.8 is slower than the elution rate of adding HAAB in an aqueous solution at the same pH 1.2 or 7.8, while such property is not recited in the Bello, it would be inherent as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
Regarding the intended use pharmacokinetic limitations of tmax and Cmax, while such properties are not recited Bello, it would be necessarily present as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
Regarding the intended use controlled release limitation, while such property is not recited in Bello, it would be necessarily present as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
Regarding claim 2, Bello teaches doxazosin. See Table 1 and abstract.
Regarding claim 3, where the time to reach tmax (maximum plasma concentration) of the claimed HAAB complex composition is longer than the HAAB compound in aqueous solution, while such property is not recited Bello, it would be inherent as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
Regarding claim 5 and the Cmax (Maximum plasma concentration) in the oral administration of the composition is 15% to 80%, while such property is not recited in the Bello, it would be inherent as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
Regarding claim 9 and the intended use limitation of the pharmaceutical composition of preventing/treating hypertension or prostate hypertrophy, while such property is not recited in the Bello, it would be inherent as the claimed clay/bentonite complex of doxazosin (known to have such intended uses) is taught by the prior art.
Claim 11 is directed to a method for preparing a controlled-release composition for oral administration, comprising preparing a complex by mixing a drug
aqueous solution prepared by dissolving a hydrophilic alpha adrenergic blocker
compound or its pharmaceutically acceptable salt in an acidic aqueous solvent; and a
clay mineral suspension as a plate-like carrier with interlayer expandability to adsorb
the compound onto the clay mineral,
wherein an elution rate when adding the complex to an eluate of pH 1.2 is slower
than the elution rate when adding the hydrophilic alpha adrenergic blocker compound to the eluate of pH 1.2,
wherein an elution rate when adding the complex to an eluate of pH 7.8 is slower
than the elution rate when adding the hydrophilic alpha adrenergic blocker compound
to the eluate of pH 7 .8,
wherein a time to maximum plasma concentration (tmax) in the oral
administration of the composition is longer than a time to maximum plasma concentration (tmax) in the oral administration of a hydrophilic alpha adrenergic blocker compound aqueous solution,
wherein the maximum plasma concentration (Cmax) in the oral administration of the composition is lower than the maximum plasma concentration (Cmax) in the oral administration of the hydrophilic alpha adrenergic blocker compound aqueous solution,
and wherein the release of the hydrophilic alpha adrenergic blocker compound in the composition is controlled.
Bello teaches Na-MMT complexed with doxazosin. See Table 1, page 3. As required by claim 11’s method to form the claimed clay complex, Bello teaches its amine compounds, including doxazosin, were complexed with Na-MMT (aka bentonite) in various acidic (HCl) conditions to form the various Na-MMT complexes including Na-MMT complexed with doxazosin. See page 3 of 20, section titled Sodium Montmorillonite Inclusion Complex Preparation.
Regarding the intended use limitation, where the elution rate of the complex added to an elute of pH 1.2 or 7.8 is slower than the elution rate of adding HAAB in an aqueous solution at the same pH 1.2 or 7.8, while such property is not recited in the Bello, it would be inherent as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
Regarding the intended use pharmacokinetic limitations of tmax and Cmax, while such properties are not recited Bello, it would be inherent as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
Regarding the intended use controlled release limitation, while such property is not recited in Bello, it would be necessarily present as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
Regarding claim 12, where the pH is more than 0 and less than 7, as detailed on page 3 of Bello, the HCl solution is acidic, which means it has a pH between 0 and 7.
New Claim Rejections - 35 USC § 103 Necessitated by Amendment
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3, 5, and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Bello et al. Sodium Montmorillonite/Amine-Containing Drugs Complexes: New Insights on Intercalated Drugs Arrangement into Layered Carrier Material PLoS ONE 10(3): e0121110 (2015).
As detailed above, claims 1-3, 5, 9 and 11-12 are taught by the teachings of Bello.
In summary, as required by claims 1 and 11, Bello teaches the claimed Na-MMT-doxazosin clay complex, as well as a method for producing such in an acidic HCl solution, as detailed above in the title, abstract and pages 1-3 of Bello. Note that Bello teaches its drug-clay (Na-MMT) complex can be characterized as a powder by X-Ray powder diffraction (XRPD). See page 3, section Characterization of the Sodium Montmorillonite Inclusion Complex.
Bello does not teach (anticipate) the particular species of claim 1, as spelled out in claim 10, where the composition is a food composition, thus necessitating this obviousness rejection. However, as Bello teaches a powder of the complex, while not explicitly reciting a food composition, it would be routine for a person having ordinary skill in the art (PHOSITA) to optimize a food composition from a powder complex of Na-MMT-doxazosin, especially as these complexes are known to be administered to patients as drugs to a subject in need of treatment of a disease.
Regarding claim 2, Bello teaches doxazosin. See Table 1 and abstract.
Regarding claims 3, 5, and 9, and the intended use limitations of tmax, Cmax, treatment of hypertension/prostate hypertrophy, while such properties are not recited in the Bello, they would be inherent, i.e. necessarily present, as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
Regarding claim 12, where the pH is more than 0 and less than 7, as detailed on page 3 of Bello, the HCl solution is acidic, which means it has a pH between 0 and 7.
New Double Patenting Rejections Necessitated by Amendment
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 1-3, 5, and 9-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 6-11, 13 and 15-16 of copending Application No. 18/013919 (reference application) in view of Bello et al. Sodium Montmorillonite/Amine-Containing Drugs Complexes: New Insights on Intercalated Drugs Arrangement into Layered Carrier Material PLoS ONE 10(3): e0121110 (2015).
Reference application 18013919 has been allowed by its Examiner.
Although the claims at issue are not identical, they are not patentably distinct from each other because the examined claims and reference application claims are directed to sustained release clay complexes (bentonite) mineral type composition with plate layers) comprising drugs with an amine group. See claim 1.
Regarding examined claims 1 and 11 and the claimed orally administered clay complex comprising a hydrophilic alpha adrenergic blocker (HAAB) compounds and clay, reference application claim 1 discloses a drug clay mineral complex, where the drug has an amine group. See also reference claims 5 and 13 where the clay mineral bentonite. See also claims 13, and 15-16 teaching a process of making with an acidic solution with a pH of less than 5, with hydrochloric acid.
Note the reference application does not teach the claimed amine group containing drug, doxazosin.
Bellow teaches the complexation of Na-MMT (aka bentonite) with doxazosin, and the process to form the complex in an acidic solution. See title, abstract and pages 1-3
Prior to the filing the instant application, a PHOSITA following the teachings of the reference application, noting an amine containing drug in a clay/bentonite complex, would have found it prima facie obvious to use doxazosin (a known amine containing drug ) in a clay based complex as claimed based on the teachings of Bello (see MPEP 2143 (b), simple substitution of one known element for another to obtain predictable results).
Regarding claim 2, Bello teaches doxazosin. See Table 1 and abstract.
Regarding claims 3, 5, and 9, and the intended use limitations of tmax, Cmax, treatment of hypertension/prostate hypertrophy, while such properties are not recited in the Bello, they would be inherent, i.e. necessarily present, as the claimed clay/bentonite complex of doxazosin is taught by the prior art.
See also reference claim 7 that discloses a maximum drug release rate in a release solution at pH 7.4 is increased by 1.5 times greater than a drug-clay mineral complex having the same composition except that the phospholipids is not included.
See also reference application claim 8 wherein the maximum drug release rate in the release solution at pH 7.4 is 80% or more of the drug content.
Regarding claim 10, Bello teaches its drug-clay (Na-MMT) complex can be characterized as a powder by X-Ray powder diffraction (XRPD). See page 3, section Characterization of the Sodium Montmorillonite Inclusion Complex.
As Bello teaches a powder of the complex, while not explicitly reciting a food composition, it would be routine for a person having ordinary skill in the art (PHOSITA) to optimize a food composition from a powder complex of Na-MMT-doxazosin, especially as these complexes are known to be administered to patients as drugs to a subject in need of treatment of a disease.
Regarding claim 12, where the pH is more than 0 and less than 7, as detailed on page 3 of Bello, the HCl solution is acidic, which means it has a pH between 0 and 7.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion and Correspondence
In summary, no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a 371 of PCT/KR2020/006991 filed 05/29/2020. PCT/KR2020/006991 claims earlier foreign priority to KR10-2019-0073749 filed on 06/20/2019.
2 CAS Reg. No. 19216-56-9
Furazosin, Prazosine, Prazosinum, Prazosina, Prazocin
2-(4-(2-Furoyl)piperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline
1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)piperazine
Methanone, [4-(4-amino-6,7-dimethoxy-2-quinazolinyl)-1-piperazinyl]-2-furanyl-
[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(furan-2-yl)methanone
https://pubchem.ncbi.nlm.nih.gov/compound/Prazosin
3 Park et al. "Application of montmorillonite in bentonite as a pharmaceutical excipient in drug delivery systems," J. Pharm. Investig. (2016) 46:363-375 (Park 2016)
Previously cited in the Non-Final Rejection dated Dec 27 2024.
4 https://doi.org/10.1371/journal.pone.0121110
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