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 .
Status of the Application
The amendment and remarks of 19 July 2026 are entered.
Claims 1-20 have been canceled. Claims 1-9 and 21-23 are pending and are being examined on the merits.
The election requirement remains in effect.
The objection to the specification is withdrawn in light of the amendment filed 19 July 2026.
The rejection of claims 1-9 under 35 U.S.C. 112(a) is withdrawn in light of the amendment filed 19 July 2026.
The rejection of claims 4, 5, and 7 under 35 U.S.C. 112(b) is withdrawn in light of the amendment filed 19 July 2026.
The rejection of claims 1 and 4-8 under 35 U.S.C. 103 as being unpatentable over Lin and Peng is maintained, with the Examiner’s response found below.
The rejection of claims 1 and 4-8 under 35 U.S.C. 103 as being unpatentable over Lin and Hopkins is maintained, with the Examiner’s response found below.
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.
1. Claims 1, 4-8, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Lin Jiefu (“Sodium taurocholatehyrate attenuates anesthesia/surgery-induced cognitive impairment and dose-effect relation” Chinese Doctoral Dissertations and Master’s Theses full-text Database, as cited on IDS of 22 September 2023, hereafter referred to as Lin) and Peng et al. (Sci. Rep. 6:29874, published 20 July 2016, hereafter referred to as Peng).
The Lin art discloses usage of WS635 in a study of anesthesia/surgery-induced cognitive impairment in mice (see e.g. p.4). More specifically, Lin indicates that WS635 attenuates cognitive impairment and suggests further studies to determine dose span in providing attenuation of cognitive dysfunction post-surgery (see e.g. p.4, Conclusion). Lin shows that WS635 decreases escape errors in a Barnes maze test when administered at 13.2 mg/kg post anesthesia/surgery (see e.g. Figure 3).
The difference between Lin and the claimed invention is that while Lin shows that WS635 can be used to treat cognitive impairment post-anesthesia or surgery, it does not explicitly discuss treatment of postoperative delirium.
The Peng art discloses that cyclosporin A can treat postoperative delirium induced by anesthesia (see e.g. Figure 5). Peng also notes that CsA has significant side effects that may reduce its effectiveness in clinical treatment of anesthesia/surgery-induced delirium (see e.g. p.8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the WS635 of Lin that is useful for treating cognitive impairment due to anesthesia/surgery could have been applied in place of CsA of Peng for treatment of postoperative delirium. The rationale comes from WS635 being a non-immunosuppressive CsA analog and its demonstrated utility in other post-anesthesia/surgery cognitive issues, such that one of ordinary skill in the art would follow the guidance of Peng and seek out an improved CsA analog. There would have been a reasonable expectation of success because Peng shows CsA is useful for treatment, Lin shows usefulness of a CsA analog in a highly related condition, and Peng directs that CsA usage may be problematic in a clinical setting that is solved by usage of WS635. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claim 4, Peng suggests administration of the CsA 30 minutes prior to anesthesia or surgery (see e.g. p.9).
With respect to claim 5, 21, and 22, CsA in Peng is administered at 10 mg/kg. As noted above Lin uses 13.2 mg/kg. In mice this amounts to less than 900 mg. These also result in the daily dose as found in claims 21 and 22.
With respect to claim 6, both Lin and Peng offer no more than a single administration, i.e. one time per day.
With respect to claims 7, 8, and 23 Peng discloses intraperitoneal injection (see e.g. p.9).
Response to Arguments:
The Applicants argue the Lin art only discloses WS635 as improving POCD but not treatment of POD, and acknowledge this was admitted by the rejection of record.
The Examiner agrees that Lin alone does not teach POD treatment, but rather this is offered by Peng suggesting the highly similar use of CsA in treatment of POD.
The Applicants argue POD and POCD are clinically and pathologically distinct conditions and refer to a reference and discuss the difference between POCD and POD as entities falling under the umbrella of postoperative neurocognitive disorders (PND).
The Examiner has considered the table outlining differences between POCD and POD within the umbrella of PND. The Examiner contends that the arguments while establishing differences between the two still indicate that they fall under a more generic scope of PND, and as such it would be reasonable to utilize treatments for one condition in the other. This is also complicated by the Peng art again specifically suggesting use of CsA in POD. Even disregarding that W635 as in Peng might be utilized for POCD, it is sufficiently similar to CsA that a simple substitution of one known element for another known element would be reasonable and obvious.
The Applicants argue differences in pathophysiological mechanisms between POD and POCD such that if WS635 is targeted at the chronic neurodegenerative damage of POCD WS635 would not work on the different mechanisms in POD.
The Examiner argues that while POD and POCD might have different pathophysiological mechanisms, there is no evidence offered that Peng is specifically targeting a mechanism that would distinguish from POD treatment. Should Applicant be able to provide evidence this argument might be persuasive, but at best the arguments as presented are mere supposition on what Peng targets.
The Applicants argue patent application CA3128410 does not disclose regulatory effects of WS635 on POD pathways, and as such the skilled artisan cannot infer treatment of POD with WS635. The Applicants argue differences in treatment between POD and POCD. The Applicants argue if the potential mechanism of WS635 is focused on the pathological process of POCD it would not be of relevance to POD.
The Examiner argues that CA3128410 is not cited in the rejection of record, and as such it is not clear how the arguments concerning regulatory effects of WS635 are relevant to the rejection of record. Treatment of POD versus POCD might be different, but since the WS635 is highly related to CsA it would have been an obvious substitution in treatment of POD. As to mechanism, again this is merely an argument not supported by any evidence indicating that the mechanism of WS635 would be considered sufficiently distinct to render it unlikely to be a treatment for POD.
The Applicants argue differences in timing of POD and POCD, and that if the dosing regimen of WS635 is designed for chronic treatment then it would not be applicable to acute treatment for POD.
Again, this argument is merely supposition not supported by evidence that the treatment regimen of WS635 would be incompatible with substitution for CsA and subsequent treatment of POD. Furthermore, there is no evidence provided that chronic treatment precludes acute treatment.
The Applicants argue limited correlation between POD and POCD under the umbrella of PND and discuss clinical guidelines and diagnostic criteria. The Applicants argue as such that treatment of one condition would not motivate one of ordinary skill to treat another condition. The Applicants argue undue experimentation.
The Examiner has considered the different diagnostic and clinical criteria in line with the discussion of the previously recited table outlining differences. Again the argument relies upon only differences between the conditions while also ignoring the similarity between CsA and WS635 that would also lead to simple substitution. Furthermore, given that only a change in compound is necessary, there is no evidence to support the notion that such experimentation would be undue.
The Applicants argue Peng discloses CsA as treatment for POD while acknowledging significant side effects. The Applicants argue Peng focuses on an evaluation model for POD rather than drug screening. The Applicants argue this does not lead to analogs, and does not remedy Lin.
The Examiner agrees that Peng discusses CsA and its potential for treatment of POD while acknowledging side effects. This offers the skilled artisan an explicit rationale to test other CsA analogs such as WS635. Even if an evaluation model is present in Peng, the side effects as presented again provide a rationale to utilize other CsA analogs in an attempt to reduce immunosuppressive effects. The Examiner disagrees based on the Peng disclosure that it does not remedy Lin, since it offers treatment of POD and a rationale to utilize CsA analogs.
The Applicants’ arguments have been considered but are not persuasive. The rejection is maintained.
2. Claims 1, 4-8, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Peng et al. (Sci. Rep. 6:29874, published 20 July 2016, hereafter referred to as Peng) and Hopkins et al. (Antimicrob. Agents Chemother. 54:660-672, published 23 November 2009, hereafter referred to as Hopkins).
The relevance of Peng is set forth above. Briefly, Peng discloses that CsA can serve to treat postoperative delirium but notes that CsA is unlikely to be useful clinically due to its immunosuppressive and other side effects.
Hopkins discloses a non-immunosuppressive CsA analog SCY-635 (see e.g. Figure 1). SCY-635 matches the structure of WS635/Formula (I).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the treatment of postoperative delirium of Peng accomplished with CsA could also have been achieved by substituting in SCY-635 as disclosed in Hopkins. The rationale for the substitution comes from the highly similar nature of CsA and SCY-635 as well as Peng explicitly nothing that CsA may present issues for clinical use, which are solved by the SCY-635 analog. There would have been a reasonable expectation of success because SCY-635 is a highly similar CsA analog that lacks the immunosuppressive effects of CsA, such that one of ordinary skill in the art would otherwise expect it to act in a similar manner as CsA. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claim 4, as noted above Peng suggests administration 30 minutes prior to operation.
With respect to claims 5, 21, and 22 as noted above Peng suggests a 10 mg/kg administration. Assuming an 80 kg subject leads to less than 900 mg, and if assuming a murine subject the dosage is far lower than 900 mg. These also are doses within the ranges as claimed.
With respect to claim 6, as noted above Peng suggests only a single administration, i.e. 1 time per day.
With respect to claims 7, 8, and 23 as noted above Peng suggests intraperitoneal administration.
Response to Arguments:
The Applicants reiterate the arguments concerning Peng.
The Examiner has considered those arguments and not found them persuasive.
The Applicants argue Hopkins relates only to the anti-HCV activity of WS635 and does not touch upon POD or any related condition. The Applicants argue the fields are distinct. The Applicants argue a lack of motivation since Hopkins does not consider neural activity or POD treatment. The Applicants argue Hopkins does not disclose or suggest WS635 as effective in treatment of POD.
The Examiner agrees that Hopkins does not discuss POD or related conditions. However, Hopkins does explicitly disclose that SCY-635 as being a non-immunosuppressive analog of CsA. As discussed above, Peng specifically notes that the immunosuppressive side effects of CsA make it an undesirable candidate for treatment of POD. Given this, the skilled artisan would reasonably seek CsA analogs that are non-immunosuppressive, which is offered by SCY-635 as in Hopkins. Even if the fields of HCV treatment and POD are distinct, the underlying core structure linking CsA to SCY-635 links the prior art references. Hopkins need not disclose the neural activity or POD treatment since this is found in Peng, and Hopkins is merely solving a problem Peng notes related to undesirable immunosuppression.
The Applicants argue structural similarity does not guarantee similar biological activity. The Applicants argue CsA has multiple activities while derivatives often maintain only certain activities while losing others. The Applicants argue undue burden on determining such activity based solely on structural similarity.
The Examiner agrees that structural similarity does not guarantee identical biological activity. However, in this case the Peng art sets forth a specific problem with CsA that is solved by the SCY-635 of Hopkins, that being undesirable immunosuppression. Even if the skilled artisan is forced to test SCY-635 in the model of Peng for treatment of POD, this would be routine and ordinary experimentation since it requires only the substitution of a single chemical.
The Applicants arguments have been considered but are not persuasive. The rejection is maintained.
Allowable Subject Matter
Claims 2, 3, and 9 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: While the above art discloses overall dosing, none of Lin, Peng, or Hopkins discuss anything regarding what the effective dose is for a human or a mouse, including values of 4.4 and 40 mg/kg, respectively. Similarly, the prior art references do not disclose use of a second agent that is used to treat, prevent, or lessen cognitive impairment that is distinct from Formula (I). The claims are novel and unobvious pending consideration of any amendments Applicants may make in response to this Action.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
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/ZACHARY J MIKNIS/Patent Examiner, Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
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