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 .
Response to Amendments
Applicant’s amendments to the claims of February 18, 2026, in response to the Office Action of September 18, 2025, are acknowledged.
Response to Arguments
Applicant argues that Maeda provides a general reference to cyclodextrin, but the experiments only use SBE beta CD.
The examiner notes that Maeda, Pitha, and Lee each teach cyclodextrin inclusion complexes. Maeda and Lee teach using equol and Pith teaches any biologically active material. It is this combination that renders obvious an equol CD inclusion complex. Lee teaches enhanced bioavailability of soy isoflavones with inclusion complexes with beta-CD. This includes daidzein of which equol is a metabolite. Thus, Lee explicitly teaches that using an inclusion complex of beta-cyclodextrin with a soy isoflavone will improve aqueous solubility and bioavailability. All of the isoflavones tested exhibited an increase in bioavailability. As such, there is a reasonable and predictable expectation of success in using arriving at an inclusion complex of a beta cyclodextrin and a soy isoflavone. Maeda uses equol as the choice API in a derivative of beta CD inclusion complex while Lee using beta-CD with soy isoflavones. Thus, a POSA would under that equol can be used in an inclusion complex beta-CD and have an enhanced bioavailability as all isoflavones tested were shown to have.
With regard to new claims 13-15, the examiner notes that these are each product by process claims/limitations with a method claim. The process is used to describe how the administered product is formed. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983).
As such, the burden is on Applicant to show that the product produced by the steps described in claims 13-15 yield a patentably distinct product that is used in a method that is rendered obvious by the combination of cited prior art.
The examiner also cites: Florez et al., “Transcriptional Regulation of the Equol Biosynthesis Gene Cluster in Adlercreutzia equolifaciens DSM19450T,” Nutrient. 2019 Apr 30;11(5):993. Florez teaches that equol is known to be beneficial to our health and equol producing bacteria including Adlercreutzia equolifaciens DSM19450T is known to produce equol from daidzein isoflavone. Equol is the strongest antioxidant, e.g., and the bacteria metabolized all cultures of daidzein after only 10 hours of incubation. The bacterial conversion is known to produce only (S) equol enantiomer.
Jackson et al., “Emerging evidence of the health benefits of S-equol, an estrogen receptor beta agonist,” August 1, 2011, Nutrition Reviews, Volume 69, Issue 8, teaches: S-equol may provide therapeutic benefits for a number of medical needs. See Abstract. Gut bacteria is known to convert daidzein to S-equol. See p433, Figure 2. S-equol was shown to be beneficial in osteoporosis, vasomotor symptoms in postmenopausal women, prostate disease, and cardiovascular conditions, e.g. S-equol inhibits prostate cell growth, e.g. See p442, 2nd full par.
As such, using a known process to produce S-equol that is the naturally occurring form produced in the human gut and is known to be a more beneficial enantiomeric form would be obvious to use and produce in a known manner for inclusion in a complex shown to have advantages including providing an enhanced bioavailability.
There is no allegation and showing of unexpected results. As such, the examiner is determining if a prima facie showing of obviousness has been established in view of the cited prior art. He has determined for the reasons set forth below that the claims are obvious in view of the cited prior art.
Status of the Claims
Claims 10 and 12-15 are pending and examined.
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.
Claims 10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al., “Preparation and characterization of the inclusion complexes of equol with sulfobutylether-β-cyclodextrin: their antioxidant activity and dissolution evaluation,” Journal of Inclusion Phenomena and Macrocyclic Chemistry (2018) 91:125–131, in view of Pitha, (US2004/0048831), in view of Lee et al., “Enhanced Bioavailability of Soy Isoflavones by Complexation with beta-Cyclodextrin in Rats,” Biosci. Biotechnol. Biochem., 71 (12), 2927–2933, 2007.
Maeda teaches an inclusion complex of equol and cyclodextrins (CDs). See Abstract. In conclusion Maeda explains, the antioxidant activity of SEq can be increased by complex. See p129, 6th par. “Solid SEq/CD inclusion complexes were prepared by physical mixing, kneading, and freeze-drying methods, and the antioxidant activities of the solid complexes were examined. Also, the improvement in solubility of SEq was examined in the dissolution test.” See p125, last par. A complex was formed with water, which was removed by freeze drying. See p126, 3rd par.
Similarly, Pitha teaches producing solid dosage forms of a cyclodextrin inclusion complex by absorbing an aqueous solution of an API with cyclodextrin and evaporating water and any other volatiles. See prior art claim 1. The dosage can be a tablet-like dose for oral administration. See par. 34.
Lee teaches enhancing bioavailability of soy isoflavones with beta-cyclodextrin inclusion complexes. See Abstract. Further, the bioavailability of equol, a metabolite of daidzein, was detected. Daidzein, genistein and glycitein were spiked in the plasma at various concentrations. See p2931, last par. When orally administered the plasma concentrations are shown in Figure 3. Data also showed substantial increases in AUC for each compound by complexation with beta-CD.
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Similar results exist for Cmax. “These findings suggest that the amount of (isoflavone aglycones) IFA absorbed into the blood following administration of inclusion complexes (IFE beta-CD) was five times higher than that following the administration of IFE alone.” See p2931, 1st par. Lee explains that applications of isoflavones are well-known and have been restricted by poor water solubility. However, complexation increase solubility in aqueous solution. See p2932, 1st par. “In conclusion, these results suggest that the complexation of isoflavones with beta-CD would be a useful method for increasing their solubility and bioavailability for food, pharmaceutical, and cosmetic uses.” See p2932, final par.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods. One would be motivated to do so because inclusion complexes comprising isoflavones generally and equol with beta-cyclodextrins are taught. Further, Maeda and Pitha teaches forming such complexes in the presence of water. Moreover, the use of inclusion complexes has been shown in different isoflavones, including one that metabolizes to equol, to substantially includes solubility, Cmax, and AUC of compounds that were included in inclusion complexes as compared to those compounds not in an inclusion complex. As such, there is a reasonable and predictable expectation of success that the oral forms of inclusion complexes of beta-cyclodextrin comprising equol would have an improved blood absorption, Cmax, and AUC.
Claims 10 and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al., “Preparation and characterization of the inclusion complexes of equol with sulfobutylether-β-cyclodextrin: their antioxidant activity and dissolution evaluation,” Journal of Inclusion Phenomena and Macrocyclic Chemistry (2018) 91:125–131, in view of Pitha, (US2004/0048831), in view of Lee et al., “Enhanced Bioavailability of Soy Isoflavones by Complexation with beta-Cyclodextrin in Rats,” Biosci. Biotechnol. Biochem., 71 (12), 2927–2933, 2007, in view of Florez et al., “Transcriptional Regulation of the Equol Biosynthesis Gene Cluster in Adlercreutzia equolifaciens DSM19450T,” Nutrient. 2019 Apr 30;11(5):993, and in view of Jackson et al., “Emerging evidence of the health benefits of S-equol, an estrogen receptor beta agonist,” August 1, 2011, Nutrition Reviews, Volume 69, Issue 8.
Maeda teaches an inclusion complex of equol and cyclodextrins (CDs). See Abstract. In conclusion Maeda explains, the antioxidant activity of SEq can be increased by complex. See p129, 6th par. “Solid SEq/CD inclusion complexes were prepared by physical mixing, kneading, and freeze-drying methods, and the antioxidant activities of the solid complexes were examined. Also, the improvement in solubility of SEq was examined in the dissolution test.” See p125, last par. A complex was formed with water, which was removed by freeze drying. See p126, 3rd par.
Similarly, Pitha teaches producing solid dosage forms of a cyclodextrin inclusion complex by absorbing an aqueous solution of an API with cyclodextrin and evaporating water and any other volatiles. See prior art claim 1. The dosage can be a tablet-like dose for oral administration. See par. 34.
Lee teaches enhancing bioavailability of soy isoflavones with beta-cyclodextrin inclusion complexes. See Abstract. Further, the bioavailability of equol, a metabolite of daidzein, was detected. Daidzein, genistein and glycitein were spiked in the plasma at various concentrations. See p2931, last par. When orally administered the plasma concentrations are shown in Figure 3. Data also showed substantial increases in AUC for each compound by complexation with beta-CD.
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551
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Similar results exist for Cmax. “These findings suggest that the amount of (isoflavone aglycones) IFA absorbed into the blood following administration of inclusion complexes (IFE beta-CD) was five times higher than that following the administration of IFE alone.” See p2931, 1st par. Lee explains that applications of isoflavones are well-known and have been restricted by poor water solubility. However, complexation increase solubility in aqueous solution. See p2932, 1st par. “In conclusion, these results suggest that the complexation of isoflavones with beta-CD would be a useful method for increasing their solubility and bioavailability for food, pharmaceutical, and cosmetic uses.” See p2932, final par.
Florez teaches that equol is known to be beneficial to our health and equol producing bacteria including Adlercreutzia equolifaciens DSM19450T is known to produce equol from daidzein isoflavone. Equol is the strongest antioxidant, e.g., and the bacteria metabolized all cultures of daidzein after only 10 hours of incubation. The bacterial conversion is known to produce only (S) equol enantiomer.
Jackson teaches S-equol provides therapeutic benefits for a number of medical needs. See Abstract. Gut bacteria is known to convert daidzein to S-equol. See p433, Figure 2. S-equol was shown to be beneficial in osteoporosis, vasomotor symptoms in postmenopausal women, prostate disease, and cardiovascular conditions, e.g. S-equol inhibits prostate cell growth, e.g. See p442, 2nd full par.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods. One would be motivated to do so because inclusion complexes comprising isoflavones generally and equol with beta-cyclodextrins are taught. Further, equol is taught to the most potent antioxidant with specific benefits. Further, Maeda and Pitha teach forming such complexes in the presence of water. The use of inclusion complexes has been shown in different isoflavones, including one that metabolizes to equol, to substantially enhance solubility, Cmax, and AUC of compounds that were included in inclusion complexes as compared to those compounds not in an inclusion complex. As such, there is a reasonable and predictable expectation of success that the oral forms of inclusion complexes of beta-cyclodextrin comprising equol would have an improved blood absorption, Cmax, and AUC. Even further, using a process that is known to produce the naturally occurring and produced S-enantiomer of equol would be obvious. One would be motivated to use a known process to produce the naturally occurring form produced in the human gut because s-equol is known to be a more potent and beneficial form. As such, selecting a process for use in producing an inclusion complex with S-equol would have a reasonable and predictable expectation of success in view of the cited prior art.
As such, no claim is allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628