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 .
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.
Current Status of 18/033,608
This Office Action is responsive to the arguments and amendments received 19 November 2025.
Claims 1-5 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed applications PCT/KR2021/015129 (filed 26 October 2021) and KR 10-2020-0139372 (filed 26 October 2020) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Due to Applicant’s submission of a translation of the foreign priority document, the Examiner has now determined the effective filing date of the instant application to be 26 October 2020.
Response to Amendments
The objections to the drawings, present in the previous office action, are hereby withdrawn due to the replacement drawing sheets.
The objections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The 35 U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2) rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s submission of a translation that allowed the instant effective filing date to be moved 26 October 2020.
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are maintained herein.
Response to Arguments
Applicant argues that the SCERBA reference, within the 35 USC 102 rejections in the previous action, is no longer eligible as prior art due to the submission of a translation of the foreign priority document.
The Examiner has withdrawn the claim rejections under 35 USC 102 in the instant action.
Applicant argues that the LIN reference, cited below, “cites US 8,927,725 for synthesis which teaches Lawesson’s reagent thionation, not P2S5”. Applicant then branches off of this statement and argues that one of ordinary skill in the art would simply follow this Lawesson’s reagent route described by LIN. Applicant argues that a skilled chemist would not have ignored the alleged teaching of LIN and chosen another thionating agent. Applicant argues that GREIG also prefers Lawesson’s reagent, although Applicant admits that GREIG mentions several other thionating agents. Applicant argues that the selection of P2S5 as a thionating reagent for the synthesis of 3,6’-dithiopomalidomide demonstrates impermissible hindsight reasoning on the part of the Examiner. Applicant then shows specific reaction conditions and argues that the synthesis of 3,6’-dithiopomalidomide using P2S5 provided unexpected benefits not previously known.
The Examiner does not agree that LIN cites the US 8,927,725 patent as the synthetic route for producing the 3,6’-dithiopomalidomide. Instead, the Examiner sees that the US 8,927,725 patent is mentioned as being invented by the authors of LIN within the “Competing interests” section of LIN. The Examiner maintains that LIN does not provide a synthetic route for the synthesis of 3,6’-dithiopomalidomide. The Examiner agrees that GREIG clearly prefers the use of Lawesson’s reagent as a thionating agent.
One of ordinary skill in the art, having read the disclosure of LIN, would have wondered what thionating agent was or could be used to synthesize the 3,6’-dithiopomalidomide therein. GREIG shows the thionation of compounds that have a high degree of similarity with pomalidomide (the starting material in LIN), but even if these similar structures were not found in GREIG, GREIG generally shows what thionating agents were known for this type of reaction in the chemical literature. There are 7 total thionating agents taught by GREIG, including Lawesson’s reagent. The Examiner will partially agree with Applicant’s argument as follows: one of ordinary skill in the art, having only a very short period of time or a small amount of starting material would, based upon the prior art, choose to use Lawesson’s reagent and pomalidomide to attempt to synthesize the 3,6’-dithiopomalidomide discussed by LIN. However, given even several minutes to think or review the literature, it would have been obvious to one of ordinary skill in the art to test all 7 thionating agents (taught by GRIEG), to find the ideal thionating agent for the specific thionation reaction at hand. The conception of such reactions and the set up of such test reactions could probably be accomplished by a synthetic chemist of ordinary skill in the art within an afternoon.
Responding to Applicant’s arguments of impermissible hindsight: The Examiner is not stating within their arguments that the benefits of the P2S5-containing synthesis would have been known to one of ordinary skill in the art before the instant effective filing date. The Examiner is also not arguing that one of ordinary skill in the art would have specifically replaced the preferred Lawesson’s reagent with P2S5. Applicant is correct that it is not clear exactly why the artisan would have specifically made that replacement. The Examiner argues that testing all of the relatively small number of thionating agents would have been quickly conceivable, obvious, and relatively easily achievable to one of ordinary skill in the art before the instant effective filing date.
Applicant may consider incorporating the limitations of one of the instant dependent claims, such as claims 3 or 4, into claim 1 to further differentiate the instant invention from the prior art.
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.
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.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over:
LIN (Lin, C.T.; Lecca, D.; Yang, L.Y.; et al. “3,6’-dithiopomalidomide reduces neural loss, inflammation, behavioral deficits in brain injury and microglial activation” eLife June 2020;9:e54726.)
in view of:
GREIG (Cited by Applicant in IDS of 25 April 2023; US 2011/0245210 A1; Publication Date 6 October 2011).
LIN teaches that pomalidomide and 3,6’-dithiopomalidomide were tested against a rat model of cell death and neuroinflammation resulting from traumatic brain injury (TBI). LIN teaches that both tested compounds were able to suppress pro-inflammatory cytokines and autophagy-associated proteins, with 3,6’-dithiopomalidomide having greater efficacy than the non-thiolated compound (abstract). LIN teaches the synthesis of 3,6’-dithiopomalidomide in the first paragraph of the materials and methods section. Therein, LIN teaches that pomalidomide was synthesized and then “selective thionation” was performed in the 3 and 6’ positions. Given the language of that paragraph, it appears that the selective thionation occurs during a single reaction, but the thionation reagent is not described.
LIN does not teach the exact details of the thionation reaction within the synthesis of 3,6’-dithiopomalidomide.
GREIG teaches the use of Lawesson’s reagent to perform the reaction copied below (Pg. 16).
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GREIG also teaches, in paragraph [0173], that phosphorus pentasulfide is an alternative thionation reagent, within a short list, for the syntheses shown therein. GREIG teaches a range of reaction conditions for the related syntheses therein. Paragraph [0149] of GREIG teaches the synthesis of dithiophthalimide from phthalimide as follows: 3.40 mmol (0.436 g) of phthalimide was combined with 3.40 mmol Lawesson’s reagent and refluxed in 50 mL toluene (this would be understood by one of ordinary skill in the art to indicate 110 °C) for 5 hours. Pomalidomide and 3,6’-dithiopomalidomide fall within the general chemical formula taught by claim 3 of GREIG. 3,6’-Dithiopomalidomide can be shown to fall within that general formula by specifying the following variables therein: X is O; Y is S; R2, R3, and R4 are H; R5 is amino; W is O; Z is S; and R15-R20 are all H.
One of ordinary skill in the art would have read LIN and would have been impressed with the anti-traumatic brain injury effects of 3,6’-dithiopomalidomide described therein. The artisan would naturally have been curious how to synthesize this compound. Because LIN does not teach the details of the thionation reaction, the artisan would have consulted the literature and found the teachings of GREIG. It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to test the thionation reagents taught by GREIG, along with the reaction conditions provided by GREIG, in combination with the partially described thionation reaction taught by LIN (producing 3,6’-dithiopomalidomide from pomalidomide), for the purpose of synthesizing the anti-TBI compound taught by LIN and optimizing the synthesis thereof. Using the teachings of GREIG and LIN detailed above, this combination would have resulted in the following reaction conditions: 3.40 mmol (0.93 g) of pomalidomide is combined with 3.40 mmol of phosphorus pentasulfide reagent and refluxed in 50 mL toluene at 110 °C for 5 hours. The artisan would have expected success in this combination, because the compounds of LIN fall within the class of compounds taught to be the subject of GREIG.
Regarding claim 5: It would have been obvious to one of ordinary skill in the art to vary the reaction time to produce a good yield in the shortest possible time. Beginning with 5 hours, as taught by GREIG, it would have been obvious for one of ordinary skill in the art to test shorter reaction times of 1 or 2 hours.
Conclusion
No claims are currently allowable.
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.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625