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 Objections
Claim 27 objected to because of the following informalities:
Claim 27 states “wherein the ZIP4 concentration increase accelerator accelerates the increase of jejunal ZIP4 concentration”, should state “wherein DHMBA increases the jejunal ZIP4 concentration”
Appropriate correction is required.
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 21-32 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 21 states “A method of accelerating a decrease in jejunal 8-hydroxydeoxyguanosine ("8- OHdG") concentration in a subject in need thereof, comprising administering to the subject a jejunal 8-OHdG concentration decrease accelerator”.
Claim 24 states “A method of accelerating a decrease in jejunal malondialdehyde ("MDA") concentration in a subject in need thereof, comprising administering to the subject a jejunal MDA concentration decrease accelerator”.
Claim 27 states “A method of accelerating an increase in jejunal zinc transporter ("ZIP4") concentration in a subject in need thereof, comprising administering to the subject a jejunal ZIP4 concentration increase accelerator”.
Claim 30 “A method of inducing an increase in serum zinc concentration in a subject in need thereof, comprising administering to the subject a serum zinc concentration increase inducer”.
The terms “accelerating a decrease”, “accelerating an increase”, and “inducing an increase” are determined to be indefinite. It is undefined how an increase/decrease would be accelerated/induced versus a normal increase/decrease. To accelerate a decrease, or accelerate an increase, the applicant would have to establish the “normal conditions” under which a decrease/increase occurs, and some kind of threshold to show an increase after administration of DHMBA.
For purposes of examination, “A method of accelerating a decrease in jejunal 8-hydroxydeoxyguanosine ("8-OHdG") concentration in a subject in need thereof” is interpreted as a method of decreasing the jejunal 8-hydroxydeoxyguanosine ("8-OHdG") concentration in a subject in need thereof.
For purposes of examination, “A method of accelerating a decrease in jejunal malondialdehyde ("MDA") concentration in a subject in need thereof, comprising administering to the subject a jejunal MDA concentration decrease accelerator” is interpreted as a method of decreasing the jejunal malondialdehyde ("MDA") concentration in a subject in need thereof.
For purposes of examination, “A method of accelerating an increase in jejunal zinc transporter ("ZIP4") concentration in a subject in need thereof” is interpreted as a method of increasing the jejunal zinc transporter ("ZIP4") concentration in a subject in need thereof.
For purposes of examination, “A method of inducing an increase in serum zinc concentration in a subject in need thereof” is interpreted as a method of increasing the serum zinc concentration in a subject in need thereof.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 22, 25, and 28 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Independent Claims 21, 24, and 27 state “wherein said active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol ("DHMBA"), a supernatant fraction obtained by stirring an extraction liquid extracted from oyster meat”. Dependent Claims 22, 25, and 28 state “wherein the DHMBA is extracted from oyster meat”. Independent Claims 21, 24, and 27 state that DHMBA is extracted from oyster meat, so dependent Claims 22, 25, and 28 restating that limitation, does not further narrow the claim scope.
Applicant(s) may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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.
Claims 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over Watanabe (Mitsugi Watanabe, JP 2017132753 A, Pub. Date: 08/03/2017, see IDS dated 12/22/2025), in view of Cai (Xuan Cai et al., “The Protective Effects of Orthosiphon stamineus Extract Against Intestinal Barrier Injury in High-Fat Diet-Induced Mouse and Oxidative Stress Cell Models”, Natural Product Communication, Volume 16, Issue 1, Pgs. 1-9, Pub. Date: January 2021).
Watanabe discloses a method of administering an oyster extract for active amplification comprising 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) to treat oxidative stress, and that oxidative stress contributes to diseases such as aging and cancer (Pg. 5, [0001] and Pg. 6, [0006]).
Watanabe discloses that administration of DHMBA decreases the concentration of 8-OHdG and MDA in the brain (Pg. 30, [0148]). Watanabe also discloses a chemical synthesis reaction for DHMBA, comprising putting oyster meat into the extraction solution containing ethanol, then concentrating the extract, stirring and isolating, separate into a precipitate and supernatant liquid then further extraction with ethyl acetate to obtain DHMBA (Pg. 17, [0059] and [0060]).
Watanabe does not disclose a jejunal concentration of MDA decreased after administration of DHMBA.
Cai discloses “MDA is a secondary oxidation product of lipid peroxidation and is often used as a biomarker of oxidative stress.” In both the cell and mouse models, oxidative stress (H2O2 treated or high-fat diet fed) significantly (P < 0.05) increased the MDA concentrations in jejunum cells and serum, as compared with the control levels (Pg. 6).
Regarding Claims 24-26, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date, to take the method disclosed in Watanabe for treating oxidative stress related diseases with DHMBA, to decrease MDA concentrations in the brain, and administer DHMBA to decrease the MDA concentrations in the jejunum, because Cai teaches oxidative stress increases the MDA concentration in the jejunum. Because Cai and Watanabe both teach MDA as a marker for oxidative stress, and Watanabe teaches DHMBA decreases the levels of MDA in the brain, one of ordinary skill would be motivated to also decrease the jejunum concentration of MDA using DHMBA.
Claims 27-32 are rejected under 35 U.S.C. 103 as being unpatentable over Watanabe (Mitsugi Watanabe, JP 2017132753 A, Pub. Date: 08/03/2017, see IDS dated 12/22/2025), in view of Kawasaki (Ichiro Kawasaki et al., “Zinc Deficiency Enhances the Induction of Micronuclei and 8-Hydroxy-2’-Deoxyguanosine Via Superoxide Radical in Bone Marrow of Zinc-Deficient Rats”, Biological Trace Element Research, Volume 154, pages 120-126, Pub. Date: 29 May 2013) and Hashimoto (Ayako Hashimoto et al., “Properties of Zip4 accumulation during zinc deficiency and its usefulness 1 to evaluate zinc status: A study of the effects of zinc deficiency during lactation”, The Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Pgs. 1-37, Pub. Date: December 23, 2015).
The teachings of Watanabe discussed above with respect to claims 24-26, are incorporated into this rejection.
Watanabe does not disclose that administration of DHMBA, increases the jejunal zinc transporter ZIP4 concentration in a subject.
Kawasaki discloses “Zn deficiency leads to carcinogenesis resulting from superoxide-induced oxidative stress due to a decrease in the activity of Cu/Zn SOD” (Pg. 120, Introduction).
Kawasaki does not teach ZIP4 transporters related to oxidative stress.
Hashimoto discloses systemic and cellular zinc homeostasis is controlled by ZIP and ZnT zinc transporters. Zip4 is the primary transporter that controls systemic zinc homeostasis because of its function of absorbing zinc in the small intestine (Abstract). In the small intestine, Zip4 protein expression was higher in the jejunum than in the duodenum and was accompanied by reduction of ALP activity, suggesting that the jejunum can become zinc deficient more easily (Abstract).
It would have been prima facie obvious for one of ordinary skill, before the effective filing date to take the method disclosed in Watanabe for treating oxidative stress-related diseases with DHMBA, and administer DHMBA to a subject with an elevated concentration of jejunal ZIP4, because Kawasaki teaches that zinc deficiencies contribute to oxidative stress related disease progression and Hashimoto teaches that zinc homeostasis is controlled by ZIP4 in the jejunum and zinc deficiencies accelerate ZIP4 concentrations. Because high ZIP4 jejunal concentrations are associated with oxidative stress, and DHMBA is known in the art to treat oxidative stress, one of ordinary skill would be motivated to administer DHMBA to a patient with high jejunal zip4 concentration and decrease oxidative stress.
Claims 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Watanabe (Mitsugi Watanabe, JP 2017132753 A, Pub. Date: 08/03/2017, see IDS dated 12/22/2025, in view of Zhang (Hao Zhang et al., “Protective Effect of Polydatin on Jejunal Mucosal Integrity, Redox Status, Inflammatory Response, and Mitochondrial Function in Intrauterine Growth-Retarded Weanling Piglets”, Oxidative Medicine and Cellular Longevity, Volume 2020, Pgs. 1-14, Pub. Date: October 12, 2020).
The teachings of Watanabe discussed above with respect to claims 24-26, are incorporated into this rejection.
Watanabe does not teach a method of decreasing the jejunal concentration of 8-OHdG.
Zhang discloses the study used newborn piglets as a model to evaluate the protective effect of polydatin (PD) against IUGR (Intrauterine growth retardation)-induced intestinal injury (Abstract). Zhang also discloses “Disruption of the jejunal barrier function increases the exposure risk of young piglets to exogenous pathogens, antigens, and other noxious factors, which may in turn promote mucosal injury and systemic inflammation. This impaired barrier function may account for the increases in jejunal 8-OHDG and MDA contents…” (Pg. 9, Discussion). Zhang also discloses changes in the jejunum were signs of oxidative stress and inflammation.
It would have been prima facie obvious, for one of ordinary skill in the arts before the effective filing date to take the method disclosed in Watanabe for administering DHMBA to treat oxidative stress related diseases, such as cancer, and administer DHMBA to subjects with high amounts of jejunal 8-OHdG, because Watanabe discloses administration of DHMBA decreases the amount of 8-OHdG and treats oxidative stress related diseases. Because Watanabe discloses administration of DHMBA decreases 8-OHdg in the brain, and Zhang teaches high levels of 8-OHdG found in weanling piglets’ jejunum, it would be obvious for one of ordinary skill to use DHMBA to decrease the amount of jejunal 8-OHdG to treat oxidative stress related diseases. One of ordinary skill, would be motivated to combine the teachings of the above references, because they both relate to oxidative stress, and 8-OHdG concentrations.
Conclusion
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/CIERRA M ROCHELLE/Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
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