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 .
Priority
This application claims priority as follows:
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Claim amendments
Receipt of claim amendments and arguments filed on May 13, 2026 is acknowledged. Claims 1-69 and 71-85 have been canceled. Claims 70, 86 and 87 are now pending and are newly drawn to a method of reversing deterioration in memory in a subject,
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All rejections have been withdrawn in view of the claim amendments.
The claim amendments have necessitated the new grounds of rejection presented in this Final Office action.
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.
Claims 70, 86 and 87 are rejected under 35 U.S.C. 103 as being unpatentable over Bourque et al. (WO 2012/129084-cited previously) in view of Sardi et al. (Proc. Natl. Acad. Sci. U.S.A. (2011), 108 (29) 12101-12106) and Biegstraaten et al. (J. Inherit Metab Dis (2012) 35:1093-1099).
Bourque discloses a method for treating Gaucher’s disease (types 1, 2 and 3) in a subject diagnosed as having a lysosomal storage disease of the lysosomal enzyme glucocerebrosidase (GCase, GBA1), comprising administering small molecule inhibitors of glucosylceramide synthase (GCS), of formula
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(venglustat) or pharmaceutically acceptable salts. See pages 64-67. (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2- yl)carbamate (S)-2-hydroxysuccinate salt was exemplified. The maleate salt of the compound was suggested at page 99:
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Unlike enzyme replacement therapy (ERT), and other small molecule GCS inhibitors (SRTs) for Gaucher’s disease, this compound crosses the blood-brain barrier and reduces the accumulation of glucosylceramide (also known as GlcCer or glucocerebroside) and glucosylsphingosine (GlcSph) build-up in the brain. See whole document, particularly, page 140, 144, Figures and Examples 122-125.
Sardi teaches that memory deficits in Gaucher mice that exhibited impaired memory (page 12102-12103) can be corrected by augmenting glucocerebrosidase activity in the CNS. At page 12105, Sardi disclosed that clearing the neurotoxin GlcSph and reduction of alpha-syn/ubiquitin aggregates ameliorated memory impairment. See at least the following excerpts:
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Biegstraaten discloses that “GD1 patients exhibit mild deficits in power of attention and speed of memory, reflecting a decreased ability to focus attention and process information, together with a slowing in the speed of retrieval of items from memory.” See the conclusion. They disclosed that GD1 as well as GD3 patients exhibit decreased speed measures. They hypothesized that the toxic metabolite glucosylsphingosine is elevated in the brain of neuronopathic GD patients. The other hypothesis is the accumulated glucosylceramide in the CNS.
Ascertainment of the difference between the prior art and the claims
Bourque did not disclose that the GD patients have deterioration in memory.
Finding of prima facie obviousness – rationale and motivation
A person of ordinary skill in the art is a person with the knowledge and level of skill of the authors of the references cited in this action. It would have been prima facie obvious to a POSITA to treat memory deterioration in Gaucher’s disease (GD) patients having GBA1 mutations associated with GD with the compositions of Bourque. The compositions of Bourque are to be used to treat GD by reducing glucosylceramide (GlcCer or glucocerebroside) and glucosylsphingosine (GlcSph) build-up in the brain. Since the secondary references teach that memory impairment/deficits in Gaucher’s disease (GD) subjects having glucocerebrosidase (GCase) dysfunction due to GBA1 mutations is associated with the brain accumulation of alpha-syn/ubiquitin aggregates and of GlcSph and, since Sardi additionally teaches that promoting their clearance improved (corrected) memory performance, the artisan would have reasonably expected that treatment with the compositions of Bourque would ameliorate the memory deficits in said subjects.
Conclusion
Claims 70, 86 and 87 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 VALERIE RODRIGUEZ-GARCIA whose telephone number is (571)270-5865. The examiner can normally be reached Monday-Friday 9:30am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
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