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
Claims 17-27 were canceled.
Claims 1-16 are pending.
Claims 4-10 and 14 were withdrawn from further consideration (see below).
Claims 1-3, 11-13 and 15-16 are under consideration.
Election/Restrictions
Applicant’s election without traverse of Species A (exercise) in the reply filed on 6/22/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim(s) 4-10 and 14 were/was withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/22/2026.
Claim Objections
Claim 12 is objected to because of the following informalities: “including a) the gut” in line 8 should read “including the gut” (i.e. “a)” should be deleted) because “a)” is repeated twice in line 7 and 8 and because the therapy comprises a) an agent for modulating …, b) exercise, c) fecal transplantation, and d) an agent to decrease bacteria producing valeric acid. 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 11 and 15-16 is 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.
Claims 11 and 16 recite “further comprising measuring blood valeric acid concentration in the subject” but do not recite how this measuring step is related to treating neuroinflammation. Therefore, it is not clear how this measuring step is related to other active steps. Does measuring step treat neuroinflammation? Or does measuring step result in determination of whether neuroinflammation was successfully treated or not?
Claim 15 recites “further comprising modulating a valeric acid interleukin (IL)-17 pathway in the subject” and therefore it seems that Applicant intends to recite additional active process step in addition to the active process step of “administering to the subject a therapy for reducing valeric acid in a subject” of claim 12. However, “for reducing valeric acid in a subject” recited by claim 12 is also encompassed by “modulating a valeric acid interleukin (IL)-17 pathway in the subject” recited by claim 15. Furthermore, instant claim 1 also recites “a therapy for modulating a valeric acid interleukin (IL)-17 pathway in the subject” and therefore the limitation “modulating a valeric acid interleukin (IL)-17 pathway in the subject” is the expected result of administered therapy of exercise, not the active process step of the claimed method. Thus, it is unclear if Applicant intends to recite additional active process step or expected result by “further comprising modulating a valeric acid interleukin (IL)-17 pathway in the subject” of claim 15.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3 and 12-13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kingsbury et al (Journal of Cerebral Blood Flow & Metabolism, 2021, vol. 41(12) 3200-3212; first published online 8/24/2021 (see below); 3/18/2024 IDS).
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Regarding claim 1 and 3, Kingsbury teaches “We, and others, have implicated the role of inflammatory microbiota in stroke secondary cell death. Elucidating this inflammation microbiome as a biomarker may improve stroke diagnosis and treatment. Here, adult Sprague-Dawley rats performed 30 minutes of exercise on a motorized treadmill for 3 consecutive days prior to transient middle cerebral artery occlusion (MCAO). Stroke animals that underwent exercise showed 1) robust behavioral improvements, 2) significantly smaller infarct sizes and increased peri-infarct cell survival and 3) decreasing trends of inflammatory microbiota BAC303, EREC482, and LAB158 coupled with significantly reduced levels of inflammatory markers ionized calcium binding adaptor molecule 1, tumor necrosis factor alpha, and mouse monoclonal MHC Class II RT1B in the brain, gut, spleen, and thymus compared to non-exercised stroke rats. These results suggest that a specific set of inflammatory microbiota exists in central and peripheral organs and can serve as a disease biomarker and a therapeutic target for stroke.” (abstract). Kingsbury teaches “For the first time, we report that a microbiome signature closely approximated the inflammation that predominated in brain (corresponds to “neuroinflammation” of instant claim 1), gut, spleen, and thymus after stroke. Such inflammation-plagued microbiota profile reveals a novel biomarker for stroke. In tandem, we provide evidence that such microbiome was sensitive to the neuroprotective effects of exercise, supporting the additional use of microbiome profiling as a sensitive index of stroke therapeutics” (Discussion section). Kingsbury teaches that exercise reduces inflammatory microbiota and thus reduce stroke symptoms (Figure 6; reproduced below). Therefore, Kingsbury teaches same method comprising same active process step of administering exercise to a subject as instant claims. Although Kingsbury does not expressly teach the limitation “for modulating a valeric acid-interleukin (IL)-17 pathway in the subject” in line 2-3 of instant claim 1, this limitation is the expected result of the active process step of administering exercise and because Kingsbury teaches same active process step of administering exercise, the method taught by Kingsbury will also have same expected result. As shown in Figure 6 below, Kingsbury teaches that inflammation in brain (neuroinflammation) is treated by exercise as recited by instant claim 1.
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Regarding claim 12, as discussed above, Kingsbury teaches exercise mediates inflammatory response in a subject suffering from ischemic stroke as recited by instant claim 12. As shown in Figure 6 of Kingsbury, Kingsbury teaches that the inflammatory response in the subject is reduced by exercise as recited by wherein-clause of instant claim 12.
Regarding claim 13, as discussed above in Figure 6, Kingsbury teaches that exercise decreases the increase of inflammatory microbiota which is gut microbiota change after the stroke. Furthermore, Kingsbury expressly teaches “On the other hand, exercise decreased microbiota expression in each organ, which was accompanied by a lower level of inflammatory cytokines.” (Discussion section). Kingsbury teaches “the gut and brain communicate via the gut-brain axis has been recently advanced. Inflammation in the brain may be either upregulated or downregulated by the over- or under-expression, or dysbiosis, of certain microbiota in the gut.” (Discussion section).
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.
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.
Claim(s) 1-3 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Feng et al (Front. Immunol., 11 December 2017, vol.8, Article 1768; PTO-892).
Regarding claim 1-3 and 12, Feng teaches “exercise prevents enhanced postoperative neuroinflammation (corresponds to “post-surgery neuroinflammation” of instant claim 2) and cognitive decline and rectifies the gut microbiome in a rat model of metabolic syndrome” (title). Feng teaches “Postoperative cognitive decline (PCD) can affect in excess of 10% of surgical patients and can be considerably higher with risk factors including advanced age, perioperative infection, and metabolic conditions such as obesity and insulin resistance. To define underlying pathophysiologic processes, we used animal models including a rat model of metabolic syndrome generated by breeding for a trait of low aerobic exercise tolerance. After 35 generations, the low capacity runner (LCR) rats differ 10-fold in their aerobic exercise capacity from high capacity runner (HCR) rats. The LCR rats respond to surgical procedure with an abnormal phenotype consisting of exaggerated and persistent PCD and failure to resolve neuroinflammation. We determined whether preoperative exercise can rectify the abnormal surgical phenotype.” (abstract).
Feng teaches “Postoperatively, LCR rats exhibited exaggerated cognitive decline both at 3 days and at 3 months that was prevented by preoperative exercise. Similarly, LCR rats had excessive postoperative neuroinflammation that was normalized by preoperative exercise. Diversity of the gut microbiome in the LCR rats improved after exercise.” (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered exercise to subject to treat post-surgery neuroinflammation because Feng teaches that excessive postoperative neuroinflammation of LCR rats can be normalized by exercise and that diversity of the gut microbiome in the LCR rats improved after exercise. One of ordinary skill in the art would understand that exercise treat postoperative neuroinflammation by improving gut microbiome in the LCR rats. Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art.
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 because Feng teaches that excessive postoperative neuroinflammation of LCR rats can be normalized by exercise. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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