DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 3, 2026 has been entered.
Claims 1-18, 23-24, 28-35, 39-64, and 66 have been canceled. Claims 19-22, 25-27, 36-38, 65, and 67-68 are pending, Claims 38, 65 and 67-68 have been withdrawn, and Claims 19-22, 25-27 and 36-37 have been considered on the merits, insofar as they read on the elected species of a combination of broccoli seed extract,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) It is unclear what agents are excluded from the phrase “consisting essentially of”. For instance, is cauliflower extract standardized to sulphoraphane included or excluded from the phrase, is green tea extract standardized to polyphenols included or excluded from the phrase? In the interest of compact prosecution, the phrase “consist essentially of” is interpreted as “comprising”.
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 Procaps (https://www.procapslabs.com/Products/Cruciferous-Extracts/302183/?srsltid=AfmBOorZUP1EgXxEWgEw_XzpHjN8QS1VLM_izceUQYV-3FQ4LygOcQTa. 2009;1-3.), 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 and wherein the broccoli seed extract is standardized to include from 1% to 20% sulphoraphane, the red orange extract is standardized to include from 2.5% to 25% polyphenols, and the grape seed extract is standardized to include from 50% to 99% polyphenols.
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, see Procaps, p.1 col right - Ingredients), 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., 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 19 and 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, see Procaps, p.1 col right - Ingredients), 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., 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, Procaps does teach a composition comprising broccoli seed extract standardized to 1.2% sulforaphane or 80 mg (p.1 col right - Ingredients), and 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, Procaps, 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 Procaps (https://www.procapslabs.com/Products/Cruciferous-Extracts/302183/?srsltid=AfmBOorZUP1EgXxEWgEw_XzpHjN8QS1VLM_izceUQYV-3FQ4LygOcQTa. 2009;1-3.), 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 cited references do not teach or suggest the claimed method as recited in claim 19, specifically the claimed standardized three-extract active-agent combination.
These arguments are not found persuasive because 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, see Procaps, p.1 col right - Ingredients), 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., grape pomace extract standardized to 50% polyphenols - 20 mg/capsule (para 0074). In addition, Procaps does teach a composition comprising broccoli seed extract standardized to 1.2% sulforaphane or 80 mg (p.1 col right - Ingredients), and 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). Therefore, a skill in the art would have been motivated by the cited references 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.
Conclusion
No claims are allowed.
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.
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, Curtis Mayes can be reached on (571)272-1234. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Lynn Y Fan/
Primary Examiner, Art Unit 1759
Prosecution Insights