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 .
DETAILED ACTION
Claims 1-4, 6, 11-17, and 19-25 are pending in the instant application.
Claims 1, 3, 6, 11, and 25 are amended.
Claims 2 and 12-24 are cancelled.
Claims 36-38 are new.
Claims 1, 3-4, 6, 11, 25 and 36-38 are examined herein.
Priority
The instant application claims benefit of foreign priority to GB1909454, filed on 01 July 2019, and the benefit of priority to PCT/EP2020/068229, filed on 29 June 2020. The claims to the benefit of priority are acknowledged. As such, the effective filing date of the claims is 01 July 2019.
Information Disclosure Statement
The information disclosure statements (IDS), submitted on 19 April 2022, 19 April 2022, 06 September 2022, and 02 July 2025 are acknowledged and considered. The submissions are in compliance with the provisions of 37 CFR 1.97.
Response to Arguments
The amendment filed on 02 July 2025 has been entered.
In view of applicant amendment to claim 6, the 112(b) rejection of record is withdrawn.
In view of applicant amendment to claim 1, the double patenting rejection of record is withdrawn.
In view of applicant amendment to claim 1, the 103 rejection of record over Melis in view of Rodriguez is withdrawn.
In view of applicant arguments the 103 rejection of record over Wischik in view of Rodriguez is withdrawn.
In addition, new 112(a) and 103 rejections are necessitated by amendment (see below) and address Applicant’s argument that an increase in basal acetylcholine levels and synaptophysin were unknown.
All rejections and objections not found below have been withdrawn.
NEW REJECTIONS FACILITATED BY AMENDMENT
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.
Claims 1, 3-4, 6, 11, 25 and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Wischik et al (WO2018019823; cited by applicant on 1449 IDS) in view of Rodriguez (Radiology. 2016;281(2):516-526), Colovic et al. (Curr Neuropharmacol. 2013;11(3):315–335) and Hedberg et al. (Neurodegener Dis. 2010;7:379-388).
Regarding claim 1, Wischik discloses a method of treating a neurodegenerative disorder of protein aggregation in a subject comprising administering 0.5 to 20 mg of an acetylcholinesterase inhibitor as a MT containing compound (claim 1). Wischik teaches the MT compound can be a LMTX compound of the formula pictured below (claim 11), where the protic acid is methanesulfonic acid (claim 20), which is the instant LMTX compound. Wischik further teaches the neurodegenerative disorder can be mild cognitive impairment (claim 45).
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Wischik does not disclose the method of treatment in a healthy subject. Additionally Wischik does not disclose the increase of basal acetylcholine (ACh) or synaptophysin.
Rodriguez demonstrates that methylthioninium chloride, an acetylcholinesterase inhibitor commonly known as methylene blue (MB), can stimulate cognitive function in healthy individuals (page 524).
Colovic teaches acetylcholinesterase inhibitor increase the level of acetylcholine (page 318, paragraph 4).
Hedberg demonstrates an acetylcholinesterase inhibitor can increase synaptophysin (Abstract).
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious.
In this case at least prong B of KSR applies – substitution of one known element for another. Wischik teaches the treatment of cognitive impairment in an unhealthy subject comprising administering a LMTX compound. Rodriguez teaches the improvement of cognitive function in healthy subjects with the administration of an MT-containing compound. Substitution of the patient population taught by Wischik for that taught by Rodriguez, with a reasonable expectation of success, would be prima facie obvious to one of ordinary skill in the art. Both references teach acetylcholinesterase inhibitor MT-containing compounds, which would exhibit similar properties due to their shared structural core and utility. Colovic further teaches that acetylcholinesterase inhibitors increase acetylcholine. And Hedberg teaches acetylcholinesterase inhibitors increase synaptophysin. It would be prima facie obvious to one skilled in the art that an MT-containing compound utilized as an acetylcholinesterase inhibitor would increase acetylcholine and synaptophysin.
Thus, all of the elements of claims were known to one of ordinary skill in the art at the time the invention was made and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of invention. Therefore, the claimed invention, as a whole, would have been obvious to one of ordinary skill in that art at the time the invention was made.
Regarding claim 3, Rodriguez teaches the improvement of attention (page 524). 1
Regarding claim 4, Wischik discloses administering the LMTX compound to a subject that has not previously received treatment with an acetylcholinesterase inhibitor or an N-methyl-D-aspartate receptor antagonist (claim 76).
Regarding claim 6, Wischik discloses administering 0.5 to 20 mg of a LMTX compound, which overlaps with the range recited in the instant application (claim 1).
Regarding claims 11 and 38, Wischik discloses the compound can be administered two or more times daily (claim 1).
Regarding claim 25, Wischik discloses the composition comprising the LMTX compound and a pharmaceutically acceptable carrier or diluent in the form of a dosage unit (claim 56).
Regarding claim 36, Wischik discloses the compound can be administered as a single daily does (claim 1).
Regarding claim 37, Wischik discloses the compound can be formulated as a dosage unit with a pharmaceutically acceptable carrier or diluent (page 23, line 21).
Claim Objection
Claim 1 is objected to because of the following informalities: As amended, the claim recite “basal choline” levels, but the specification references “basal acetylcholine” levels. The original claims have support for “basal choline”, but the Examiner wants to ensure consistency between the terms “acetylcholine” and “choline”. Appropriate correction is required.
Conclusion
Claims 1, 3-4, 6, 11, 25 and 36-38 are rejected.
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 Jerica K Wilson whose telephone number is (703)756-4690. The examiner can normally be reached Monday-Friday 9:00-5:00.
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/J.K.W./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621