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 .
Application Status
The amendment filed on 8/21/2026 in response to the Non-Final office action is acknowledged and has been entered. Claim 9-10 are currently pending and under consideration.
Rejections Withdrawn:
The rejection of Claims 2-3 and 5 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of Applicants amendments.
The rejection of Claim(s) 1-5 under 35 U.S.C. 102(a)(1) as being anticipated by Zhou and Jiang (US2014/0073648A1, 2014-04-13) as evidenced by Zheng et al (Front. Immunol. 2021; 12: 711939) referred to as Zheng 1 and Zheng et al. (Biomolecules 2022; 12: 1625) referred to herein as Zheng 2 is withdrawn in view of Applicants amendments.
The rejection of Claim(s) 1-5 under 35 U.S.C. 102(a)(1) as being anticipated by Jiang et al. (US9771340B2, 2014-04-13) as evidenced by Song et al. (Life Science 2024; 359: 123232) is withdrawn in view of Applicants amendments.
The rejection of Claims 1-5 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9,771,340 (Issued 2017-09-26) is withdrawn in view of Applicants amendments.
Rejections Maintained:
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.
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.
Claim(s) 9 remains rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. (US9771340B2, 2014-04-13) as evidenced by Song et al. (Life Science 2024; 359: 123232) in view of Shaikh, Aamir, “Levels of PARP-1 immunoreactivity in the Human Brain in Major Depressive Disorder” (2020). Undergraduate Honors Theses. Page 547.
Jiang et al. teach 2-aminothiazole derivatives for use in inhibiting acetylcholine esterase and PARP-1 for treatment of diseases such as Alzheimer’s disease and for use in inhibiting MyD-88 to produce an immunosuppressive effect in treatment of anti-transplant rejection, anti-autoimmune disease, anti-ischemia-reperfusion injury, anti-chronic inflammation and anti-endotoxemia (Column 3, lines 21-30). Regarding the 2-aminothiazole derivatives, Jiang et al. teach the 2-aminothiazole derivatives have the general formula
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and particular species including, but not limited to, the following:
- 2-(4-(4-methoxyphenyl) piperazin-1-yl)-N-(4-phenyl-thiazol-2-yl) acetamide (labeled as TJ-M201005)
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;
- 2-(4-(4-methoxyphenyl) piperazin-1-yl)-N-(4-phenyl-thiazol-2-yl) butyramide (labeled as TJ-M201018);
- 3-(4-benzyl-piperazin-1-yl)-N-(4-phenyl-thiazol-2-yl)-propionamide (labeled as TJ-M201015)
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;
- 3-(4-(4-methoxyphenyl) piperazin-1-yl-N-(4-phenyl-thiazol-2-yl)-propionamide (labeled as TJ-M201021)
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;
- 3-(N,N-pyridylmethyl-ethyl amine)-N-(4-phenyl-thiazole-5-methyl-2-yl)-propionamide (labeled as TJ-M201041), which read on compounds 1616, 1605 and 1604 of instant claim 2 and claim 5 (see specification page 3 for name to structure correlation) (see Examples 4-9 of Jiang et al.). Moreover, Jiang et al. teach numerous in vitro and in vivo models of the use of the inhibitors for treatment of autoimmune diseases and diabetes, wherein the inhibitors were administered via intraperitoneal injection (see Examples 18).
Jiang et al. does not specifically teach that the disease or disorder is depression.
Shaikh, Aamir teaches that PARP-1 inhibition produces antidepressant-like effects in rodents, suggesting that PARP-1 inhibitors hold promise as novel antidepressant drugs. (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by Jiang et al. so as to administer the 2-aminothiazole derivatives to include a patient suffering from depression in view of the teachings of Shaikh, Aamir. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Jiang et al. teach that the 2-aminothiazole derivatives are inhibitors of PARP-1 and
-Shaikh, Aamir teaches that PARP-1 inhibition produces antidepressant-like effects in rodents, suggesting that PARP-1 inhibitors hold promise as novel antidepressant drugs.
In response to this rejection, Applicants refer to Jiang et al. as reporting elevated PARP-1 protein levels in the frontal cortex, but no change in the hippocampus which Applicants contend is the region of the brain critically involved in mood regulation and depressive pathophysiology. Moreover, Applicants assert that Jiang et al. suggests that PARP-1 could be a potential target for antidepressant drugs based on this regional difference. Applicants further point to a more recent and directly relevant article that case doubt on the proposition that inhibiting PARP-1 would be an antidepressant. In particular, Applicants assert that the study by Karen M. Ryan, Declan M. McLoughlin (International Journal of Neuroschopharmacology, 2023; 26: 107-115) which examined the PARP1 mRNA levels in whole blood of depressed patients and reported the following core observations:
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Thus, Applicants contend that Ryan and McLoughlin study actually reports that a decrease in PARP1 expression in depression and no effect of an effective antidepressant intervention (ECT) on PAPR-1 levels.
These arguments have been carefully considered, but are not found persuasive.
In response to these arguments, the Examiner would like to first point out that Applicants reference to Jiang et al. is being interpreted to mean Shaikh since this is the reference teachings PARP-1 and depression. Regarding the teachings of Shaikh, the examiner acknowledges and does not dispute Shaikh teachings, but would like to point out that Shaikh specifically teaches that PARP-1 inhibition produces antidepressant-like effects in rodents, suggesting that PARP-1 inhibitors hold promise as novel antidepressant drugs. Regarding Applicants discussion of Ryan and McLoughlin, the Examiner has reviewed the reference and would like to point out the following passages (p. 113, 1st column, 2nd full paragraph):
-The blood samples were taking from patients who were receiving pharmacotherapy as usual and being treated with ECT. This is important to point out because Ryan and McLoughlin feel that this is a limitation of the study since the baseline/pre-ECT results may reflect an antidepressant effect because, as noted above, antidepressant drugs can alter PARP-1 expression.
-Another limitation of the study is although peripheral blood PARP1 mRNA levels were found to be decreased in patients with depression compared with controls, this does not tell “us” about the activity of PAP1.
Moreover, Ryan and McLoughlin teach that in two rat models of depression, namely the Porsolt swim test and chronic exposure to psychological stress, PARP inhibitors produced antidepressant like behavioral effects similar to those of fluoxetine (p. 108, 1st column, 2nd full paragraph). As such, while Ryan and McLoughlin appear to show reduced PARP-1 mRNA levels in patients following antidepressant treatment, it does not appear that this is a negative teaching which would dissuade PARP-1 inhibition for treatment of depression as asserted by Applicants.
Furthermore, Applicants contend that other studies in the art have also revealed the multifaceted and context-dependent role of PARP-1 in stress and inflammation, further complicating any straightforward casual link between PARP-1 inhibition and mood improvement. Lastly, Applicants assert that known PARP inhibitors such as rucaparib and olaparid have not been reported to possess antidepressant activity in any published study.
These arguments have been carefully considered, but are not found persuasive.
Regarding Applicants arguments pertaining to other studies, the Examiner recognizes that Applicants have not provided any factual evidence of these other studies. With regards to the known inhibitors, the Examiner cannot comment on why there have been no reports. However, the examiner recognizes that Shaikh and Ryan (brought to the attention by Applicants) show that in rodents, PARP inhibitors produced antidepressant like behavioral effects. As such, there is a reasonable expectation of success.
Claim(s) 10 remains rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. (US9771340B2, 2014-04-13) as evidenced by Song et al. (Life Science 2024; 359: 123232) in view of Shaikh, Aamir, “Levels of PARP-1 immunoreactivity in the Human Brain in Major Depressive Disorder” (2020). Undergraduate Honors Theses. Page 547, as applied to claim 9 above, in further view of Mazza et al. (Brain, Behavior, and Immunity 2020; 89: 594-600).
The combination of Jiang et al. as evidenced by Song et al. and Shaikh, Aamir has been discussed above and incorporated herein. In short, the combination teaches a method of treating depression comprising administering a PARP-1 inhibiting amount of a 2-aminothiazole derivative.
The combination does not teach that the depression is induced by COVID-19
Mazza et al. investigated the role of inflammatory and clinical predictors of anxiety and depression in COVID-19 survivors (Title). In particular, Mazza et al. found that a significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms and 40% for insomnia (Abstract, 3rd paragraph). Moreover, Mazza et al. teach that considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions (Abstract, 4th full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by the combination for treating depression to include a patient whom has or has had COVID-19 in view of the teachings of Mazza et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Mazza et al. taches that 31% of COVID-19 patients self-rated as having depression and further, Mazza et al. recognizes that worsening inflammation associated with COVID-19 will lead to worsen depression.
In response to this rejection, Applicants do not appear to provide any arguments against the rejection, but instead point out that the spike model of Example 13 and Figure 33 is merely one of many validated tools for inducing depressive phenotypes.
Conclusion
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 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 BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
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