DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Applicant’s amendment and response filed on 2/20/2026 have been received and entered into the case. Claims 1-18, 23-24, 28-35, and 39-64 have been canceled. Claims 19-22, 25-27, 36-38, and 65-68 are pending, Claims 38 and 65-68 have been withdrawn, and Claims 19-22, 25-27 and 36-37 have been considered on the merits, insofar as they read on the elected species of a combination of broccoli seed extract, red orange extract and grape seed extract. All arguments have been fully considered.
Claim Rejections - 35 USC § 112
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 19-22, 25-27 and 36-37 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 pre-AIA the applicant regards as the invention.
Claim 19, line 4 & 11-12, the recitation of “consist essentially of” is indefinite. The transitional phrase "consisting essentially of" limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising.". (MPEP 2111.03 III) Applicant has failed to disclose the basic and novel characteristics. It is also noted that different extraction methods and solvents produce different extract products. Applicant has failed to clearly define the term “extract”. Therefore, the claimed “extract” can be interpreted to include a variety of ingredients.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 19-22 and 25-27 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sinnott (US 2007/0190209 A1; 8/16/2007. Cited on IDS) in view of Dallas et al (Phytomedicine. 2008;15:783-792.), Fujishita et al (Cell Mol Neurobiol. 2009;29:1121-1129.), Yanaka et al (Cancer Prev Res. 2009;2(4):353-360.), and Han et al (Int. J. Mol. Sci. 2007;8:950-988.).
The instant claims recite a method of modulating expression of Nrf2-associated genes in a subject comprising: orally administering to the subject an effective amount of an oral formulation including active agent that consist essentially of a plurality of agents that modulate expression of Nrf2-associated genes upon ingestion of the oral formulation, wherein the Nrf2-associated genes include at least one gene encoding intrinsic antioxidants, and at least one gene encoding cellular detoxifiers, and wherein the effective amount attenuates inflammation, and wherein the Nrf2-associated genes are genes that encode for Nuclear Factor erythroid derived 2 protein and genes modulated by the binding of Nrf2 to antioxidant response elements (ARE) associated with these genes; and wherein the plurality of agents that modulate expression of Nrf2-associated genes consist essentially of broccoli seed extract, red orange extract, and grape seed extract.
Sinnott teaches compositions and methods for a dietary supplement formulation (an oral formulation) containing a therapeutically effective amount of a standardized source of one or more natural plant extracts, for human and animal consumption (a subject) (Abstract, para 0009, 0049), wherein said compositions are administered orally (para 0035, 0039, 0079), and said one or more standardized include sulforaphanes (broccoli seed extract), glucosinolates (broccoli seed extract), polyphenolics (red orange extract, see Dallas, p.784 col left – para 4), grape seed extract), and quercetin (a polyphenol, abundant in grape seeds, see Fujishita, p.1121 col right – para 1) (para 0011), e.g., broccoli extract standardized to 6.0% glucosinolates - 1.2 to 20 mg/capsule (para 0016-0017, 0074), and grape pomace extract standardized to 50% polyphenols - 20 mg/capsule (para 0074). At the time of the claimed invention, it was well-known in the art that sulforaphane is a Nrf-2 inducer with anti-oxidative and anti-inflammatory properties (p.354 col left – para 1, p.358 col right – para 2), as evidenced by Yanaka. Since sulforaphane activates Nrf-2 pathway, Nrf-2 associated genes must be selected. In addition, it was well-known in the art that dietary polyphenols possess diverse biological properties such as antioxidant and anti-inflammation (Abstract), and they modulate cellular signaling processes such as the translocation into the nucleus of nuclear factor erythroid 2 related factor 2 (Nrf2) (Abstract), quercetin increases glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity (p.955 last para, Table 2), increases the expression and activity of NADPH:quinone oxidoreductase-1 (NQO1) (Table 2), and quercetin-induced ARE activity involves upregulation of Nrf2 (p.956 first para), as evidenced by Han. Therefore, a subject orally administering the sulforaphanes and polyphenolics-containing formulation of Sinnott would modulate expression of Nrf2-associated genes upon ingestion of the oral formulation in the subject, modulate at least one gene encoding intrinsic antioxidants and at least one gene encoding cellular detoxifiers, attenuates inflammation and stimulates autophagy in a tissue of the subject, wherein the Nrf2-associated genes are genes that encode for Nuclear Factor erythroid derived 2 proteins and genes modulated by the binding of Nrf2 to antioxidant response elements (ARE) associated with these genes.
Sinnott does not teach the claimed concentration and dosage of broccoli seed extract, red orange extract and grape seed extract (claims 25-27).
However, Sinnott does teach compositions and methods comprising a therapeutically effective amount of a standardized source of one or more plant extracts (para 0049), wherein said one or more standardized include sulforaphanes (broccoli seed extract), glucosinolates (broccoli seed extract), polyphenolics (red orange extract (see Dallas, p.784 col left – para 4), grape seed extract), and quercetin (a polyphenol, abundant in grape seeds, see Fujishita, p.1121 col right – para 1) (para 0011), e.g., broccoli extract standardized to 6.0% glucosinolates - 1.2 to 20 mg/capsule (para 0016-0017, 0074), and grape pomace extract standardized to 50% polyphenols - 20 mg/capsule (para 0074). The skilled artisan will recognize that the total amount of said compositions may be varied according to the dosage requirement of the user, number of doses and other requirements (para 0017, 0079). In addition, Yanaka does teach that sulforaphane is a Nrf-2 inducer with anti-oxidative and anti-inflammatory properties (p.354 col left – para 1, p.358 col right – para 2). Finally, Han does teach dietary polyphenols possess diverse biological properties such as antioxidant and anti-inflammation (Abstract), and they modulate cellular signaling processes such as the translocation into the nucleus of nuclear factor erythroid 2 related factor 2 (Nrf2) (Abstract), quercetin increases glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity (p.955 last para, Table 2), increases the expression and activity of NADPH:quinone oxidoreductase-1 (NQO1) (Table 2), and quercetin-induced ARE activity involves upregulation of Nrf2 (p.956 first para).
Thus, at the time of the claimed invention, it would have been obvious to one of ordinary skill in the art to optimize concentration and dosage of broccoli seed extract, red orange extract and grape seed extract for their well-known biological significance in the art, as evidenced by Sinnott, Yanaka and Han. Generally, differences in concentration will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. (MPEP 2144.05 II) Moreover, at the time of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference and routine practice to optimize concentration and dosage of broccoli seed extract, red orange extract and grape seed extract, with a reasonable expectation for successfully obtaining a dietary supplement formulation.
Claims 36-37 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sinnott (US 2007/0190209 A1; 8/16/2007. Cited on IDS) in view of Dallas et al (Phytomedicine. 2008;15:783-792.), Fujishita et al (Cell Mol Neurobiol. 2009;29:1121-1129.), Yanaka et al (Cancer Prev Res. 2009;2(4):353-360.), and Han et al (Int. J. Mol. Sci. 2007;8:950-988.) as applied to claims 19-22 and 25-27 above, further in view of Puetter (Personal vitamin/supplement use and practice. 2000;1-12. Cited on IDS).
References cited above do not teach administering the oral formulation to the subject at night (claim 36), and administering the oral formulation to the subject when the subject retires to bed (claim 37).
However, Sinnott does teach the dietary supplement formulation comprises vitamin sources, mineral sources and phytochemicals (para 0009). Puetter teaches that vitamins and supplements are taken at different times of the day, depending on their uses and the user (p.1 last para).
Thus, at the time of the claimed invention, it would have been obvious to one of ordinary skill in the art to administer an oral formulation containing vitamins and supplements to a subject at night or when the subject retires to bed, since Puetter discloses that vitamins and supplements are taken at different times of the day, depending on their uses and the user. Moreover, at the time of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to administer an oral formulation containing vitamins and supplements to a subject at night or when the subject retires to bed with a reasonable expectation of success.
Response to Arguments
Applicant argues that the transitional phrase “consisting essentially of” has a well-established meaning in patent law and limits the claim to the recited ingredients while permitting the presence of additional components that do not materially affect the basic and novel characteristics of the invention. See MPEP $2111.03. These characteristics, which are found at least in independent claim 19, are clearly modulation ofNRf2-associated gene expression involved in intrinsic antioxidant and cellular detoxification pathways, and attenuation of inflammation upon oral administration. Thus, Applicant submits that the basic and novel characteristics are identified in both the specification and claims.
These arguments are not found persuasive. According to MPEP 2111, "A ‘consisting essentially of’ claim occupies a middle ground between closed claims that are written in a ‘consisting of’ format and fully open claims that are drafted in a ‘comprising’ format." In the instant case, the rejected claim 19 recites “an oral formulation including active agent that consist essentially of a plurality of agents that modulate expression of Nrf2-associated genes upon ingestion of the oral formulation, … and wherein the plurality of agents that modulate expression of Nrf2-associated genes consist essentially of broccoli seed extract, red orange extract, and grape seed extract”. Broccoli seed extract, red orange extract, and grape seed extract are plant extracts contain highly diverse bioactive compounds. Is each and every one of these highly diverse bioactive compounds modulates expression of Nrf2-associated genes? What compounds are included as active agents for modulating expression of Nrf2-associated genes, and what compounds are excluded from the transitional phrase “consist essentially of” recited in claim 19?
Applicant argues that Sinnott does not disclose a formulation limited to broccoli seed extract, red orange extract, and grape seed extract, that the cited references do not teach that the claimed three extracts should be used together, that they should be used without additional ingredients, suggest that their combination would modulate multiple Nrf2-assocaited genes as claimed, or suggest that the combination would attenuate inflammation as claimed.
These arguments are not found persuasive. Applicant’s arguments regarding “consist essentially of”, please see above 112b rejections as well as above response to 112b arguments. In addition, according to MPEP 2111, if an applicant contends that additional steps or materials in the prior art are excluded by the recitation of "consisting essentially of," applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of the claimed invention.
Applicant argues that the examiner uses improper hindsight.
These arguments are not found persuasive because it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In addition, please see above responses to arguments.
Conclusion
No claims are allowed.
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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN Y FAN whose telephone number is (571)270-3541. The examiner can normally be reached on M-F 7am-4pm.
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/Lynn Y Fan/
Primary Examiner, Art Unit 1759