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 .
Claim Status
Applicant’s remarks and amendments, filed 10 November 2025 in response to the non-final rejection mailed 11 July 2025, are acknowledged and have been fully considered. Applicant’s amendments to the claims are acknowledged. The listing of claims filed 10 November 2025 replaces all prior versions and listings of the claims.
Claims 1-8 and 10-15 are pending. Claim 9 is canceled by Applicant’s amendment. Claims 1, 3, 8, 11, and 12 are amended. Claims 1-8 and 10-15 are being examined on the merits.
Response to Amendment
Any previous rejection or objection not mentioned herein is withdrawn. The affidavit submitted on 10 November 2025 is hereby acknowledged.
Applicant’s amendments to the specification have overcome the specification objection in regards to minor informalities. The objection to the specification has thus been withdrawn.
Applicant’s arguments and amendments, on page 5 of the reply filed 10 November 2025 with respect to the rejection of Claim 9 under 35 USC § 112(d) have been fully considered. The rejections of Claim 9 is withdrawn due to cancellation of the claim.
Claim Rejections - 35 USC § 103
(grounds modified as necessitated by amendment)
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.
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.
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.
Claims 1, 2, 4-11, and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Food Res Int, 2012, 444-449) in view of Ribas-Latre et al. (Mol Nutr Food Res, 2015, 865-878) and Ho et al. (J Agric Food Chem, 2007, 10664-10670) as evidenced by Zhao et al. (Front Endocrin, 2019, 16 pages) and Walther and Bader (Biochm Pharm, 2003, 1673-1680).
The instant claims are as of record, drawn to methods for increasing melanin content in a subject or regulating gene expression of TPH, DDC, AANAT, and ASMT, comprising administering to a subject in need thereof a composition comprising an effective amount of longan flower extract obtained via aqueous alcoholic solvent extraction.
Liu et al. teach a longan flower extract obtained from dried longan flowers using water (pharmaceutically acceptable carrier; as required for instant Claims 6 and 14) as a solvent to steep the flowers at 100°C for 30 minutes (Liu et al., Materials and Methods, page 445; as required for instant Claims 1 and 8). The extract was fed (administered) to rats and analyzed for phytochemical content (Liu et al., Table 1, page 446; as required for instant Claims 1, 8, and 9). Rats were fed the longan flower extract as solution at a dose of 12.5 g/L or 25.0 g/L (at least 0.2 wt%; pharmaceutical composition; Liu et al., Animal and diets, page 445; as required for instant Claims 2, 5, 7, 13, and 15). The longan flower extract naturally comprises the proanthocyanidins catechin and epicatechin, which were provided to rats at the following doses: 8.4 mg/100 mL catechin and 17.7 mg/100 mL epicatechin in the 12.5 g/L longan flower extract solution and 16.6 mg/100 mL catechin and 37.9 mg/100 mL epicatechin in the 25.0 g/L longan flower extract solution (effective amount; Liu et al., Table 1, page 446; as required for instant Claims 1 and 8).
Liu et al. do not teach increasing melanin content in a subject or regulating gene expression of TPH, DDC, AANAT, and ASMT or an aqueous alcoholic extraction solvent.
Ribas-Latre et al. teach that a grape seed proanthocyanidin extract comprising 58 μmol/g catechin and 52 μmol/g epicatechin administered to rats, including jet-lagged rats (subject in need thereof), resulted in increased melatonin levels during daylight (Ribas-Latre et al., Figure 1, page 869; as required for instant Claims 1 and 8). This increase in melatonin is either due to proanthocyanidins acting on the hypothalamic suprachiasmatic nucleus, which controls secretion of melatonin by the pineal gland, or by proanthocyanidins causing an increase in melatonin which then acts on the hypothalamic suprachiasmatic nucleus (Ribas-Latre et al., Discussion, page 875). Since melatonin biosynthesis in animals inherently occurs via a signal cascade comprising tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (DOPA decarboxylase), serotonin N-acetyltransferase (aralkylamine N-acetyltransferase), and N-acetylserotonin O-methyltransferase, an increase in melatonin biosynthesis would inherently increase (i.e., regulate) the expression of the corresponding genes, TPH, DDC, AANAT, and ASMT (Zhao et al., Figure 4, page 7 and page 9; as required for instant Claims 1 and 8). The specific gene TPH1 is expressed in the pineal gland and would inherently be the gene affected by proanthocyanidins (Walther and Bader, Abstract, page 1673; as required for instant Claim 10).
Ho et al. teach a proanthocyanidin-rich extract of longan flowers obtained via extraction with 95% ethanol (mixture of alcohol and water) for 24 hours at room temperature using a ratio of 20 mL of solvent per gram of dried longan flower (Ho et al., Extraction of Longan Flower, page 10665; as required for instant Claims 1 and 8).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instant application to combine the teachings of Liu et al., Ribas-Latre et al., and Ho et al. to arrive at the instantly claimed invention. A skilled artisan would be able to take the longan flower extract of Liu et al. extracted using the method of Ho et al. in order to obtain an extract with a higher proanthocyanidin content compared to a water extract. The positive teaching of Ribas-Latre et al. that proantocyanidin-rich extracts, comprising catechin and epicatechin that are also found in longan flower extracts (Liu et al., Table 1, page 446) would motivate a skilled artisan to apply an proanthocyanidin-rich extract obtained from another source such as a longan flower to a subject in need of improved insomnia, sleep quality, or sleep disturbance in order to increase melatonin production and thus expression of the genes controlling melatonin production with a reasonable expectation of success. Additionally, a skilled artisan would be further motivated to use a longan flower extract because of the additional health benefits such as antioxidant properties (Liu et al., Results and Discussion, page 447), anticancer activity, memory enhancing effect (Liu et al., Introduction, page 445), and lack of cytotoxicity (Hu et al., Discussion, page 10669).
Liu et al., Ribas-Latre et al., and Ho et al. are relied upon for the reasons discussed above. If not expressly taught by the prior art, based upon the overall beneficial teaching provided by these reference with respect to proanthocyanidin activity, doses provided to rats and mice in the manner disclosed therein, and extraction conditions such as mass to volume ratios, temperatures, and durations the adjustments of particular conventional working conditions (e.g., determining one or more suitable longan flower extract concentration with which to perform such a method (as required for instant Claim 11); determining a volume ratio; and determining an extraction temperature (as required for instant Claims 1 and 8)), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
Claims 1-8 and 10-15 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Food Res Int, 2012, 444-449) in view of Ribas-Latre et al. (Mol Nutr Food Res, 2015, 865-878) and Ho et al. (J Agric Food Chem, 2007, 10664-10670) as evidenced by Zhao et al. (Front Endocrin, 2019, 16 pages) and Walther and Bader (Biochm Pharm, 2003, 1673-1680) as applied to Claims 1, 2, 4-11, and 13-15 above, and further in view of Wang et al. (Molec, 2017, 15 pages).
The claims and teachings of Liu et al. in view of Ribas-Latre et al. and Ho et al. as evidenced by Zhao et al. and Walther and Bader are as of record.
Liu et al. in view of Ribas-Latre et al. and Ho et al. as evidenced by Zhao et al. and Walther and Bader do not teach wherein the longan is hydrolyzed with a complex cellulase prior to solvent extraction.
Wang et al. teach that enzyme-assisted extraction using complex cellulase (hydrolyzed; Wang et al., Enzyme Pre-Treatment, page 10; as required for instant Claims 3 and 12) prior to solvent extraction increases the extraction yield of phenolics from plants (Wang et al., Abstract, page 1; Introduction, page 2).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instant application to combine the teachings of Liu et al., Ribas-Latre et al., and Ho et al. with those of Wang et al. to arrive at the instantly claimed invention. Using cellulase enzyme-assisted extraction would increase the yield of the beneficial proanthocyanidins, and thus a skilled artisan could incorporate this extraction method into the claimed invention with a reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments and affidavit filed 10 November 2025 have been fully considered but they are not persuasive.
Applicant argues that the extract obtained by the specifically claimed extraction conditions are capable of increasing melatonin content based upon Examples 1 to 3 in the instant Specification and also due to support from the Abstract of Frenkel et al., which states that resveratrol causes a significant increase in serum melatonin content. Since the extract prepared by the claimed method has higher polyphenol content than other extracts of the instant disclosure, Applicant is concluding that higher content of polyphenols such as resveratrol lead to a higher content of serum melatonin. Since the disclosure of Liu et al. does not have the same extraction method and the proanthocyanidins of Ribas-Latre et al. were obtained from a different plant source, Applicant concludes that a skilled artisan would not be motivated to consider the disclosure of Ribas-Latre et al. Finally, Applicant argues that because Ribas-Latre et al. utilized a proanthocyanidin-rich extract and the specific proanthocyanidins responsible for increasing melatonin content were not disclosed, a skilled artisan could not conclude that a proanthocyanidin-rich extract from a different plant source comprising different proanthocyanidin content.
Firstly, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the specific extract providing a higher increase in melatonin content) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Additionally, it is noted that at [0048] of the specification it is stated that “in the following examples, water was used as the extraction solvent,” and the examples following this statement are those related to increase of melatonin content (Example 2), improving insomnia and sleep quality (Example 3), and gene expression modification (Example 4). The applicant does not provide evidence in the instant disclosure that the different aqueous ethanolic extracts have an unexpected effect of increasing melatonin. The conclusion drawn from Frenkel et al. that the longan flower extracts with higher polyphenol content must lead to higher serum melatonin content is flawed because Frenkel et al. do not look at polyphenol content as a whole, and instead only consider pure resveratrol (e.g., there are no other constituents that would be present in a plant extract; see Materials and Methods, page 38). Frenkel et al. also do not provide any data on dose-dependence, and thus the conclusion that a higher overall polyphenol content in a plant extract would necessarily lead to higher production of serum melatonin in a subject is flawed.
It is additionally noted that regarding the product-by-process recited in instant Claims 1 and 8, determination of patentability is based upon the product itself, e.g., a longan flower extract. As noted above, the instant specification shows that water extracts of longan flower are effective at producing the effects of increasing melatonin in a subject and regulating expression of the claimed genes. The prior art additionally indicates that proanthocyanidin-rich extracts obtained using aqueous alcoholic solvents was known in the art. 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 the instant case, the product required for the method claim made by the claimed process is obvious from a product of the prior art, as discussed in the rejection above.
Regarding the proanthocyanidin-rich grape extract of Ribas-Latre et al., it is first noted that neither the prior art nor the instant disclosure indicate which polyphenolic components specifically contribute to an increase in melatonin and modulation of gene expression. A skilled artisan, however, would be aware that proanthocyanidins are a class of polyphenols found in various plant sources such as vegetables and fruits (Ribas-Latre et al., Introduction, page 866). They would therefore be able to conclude that an extract rich in proanthocyanidins from another plant source, such as the water extracts of Liu et al. comprising 26.1-54.5 mg/100 mL of proanthocyanidins (Liu et al., Table 1, page 446) or the water and ethanolic extracts of Ho et al. comprising 112.5-187.7 mg/g of proanthocyanidins could be used for increasing melatonin and modulating the genes thereof with a reasonable expectation of success.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 JENNIFER L CAIN whose telephone number is (703)756-1318. The examiner can normally be reached M-Th 11:00am to 5:00pm EST.
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/J.L.C./Examiner, Art Unit 1655
/AARON J KOSAR/Primary Examiner, Art Unit 1655
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