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
Claims 1-4, 18-21, and 25-34 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 04/23/2026 are acknowledged. Claims 1, 19-21, and 30 are amended. Claims under consideration in the instant office action are claims 1-4, 18-21, and 25-34.
Applicants' arguments, filed 04/23/2026, have been fully considered but they are not deemed to be persuasive. The double patenting rejection of claims 1-4, 15-21, and 25-33 is withdrawn due to Applicant’s Terminal Disclaimer, filed 04/23/2026. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 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.
Claims 1-4, 18-21, and 25-34 are rejected under 35 U.S.C. 103 as being unpatentable over Mahuran (WO 2014/172776, as disclosed in IDS) in view of Rius (Trans- but Not Cis-Resveratrol Impairs Angiotensin-II–Mediated Vascular Inflammation through Inhibition of NF-kB Activation and Peroxisome Proliferator-Activated Receptor-γ Upregulation, The Journal of Immunology, 2010, 185(6), pp. 3718-3727 as disclosed in IDS).
Mahuran teaches methods of treating mucopolysaccharidoses (MPS) by administering a compound that decreases activity of N-deacetylase/N-sulfotransferase (NDST) (see abstract). Mahuran teaches such compounds to include resveratrol, which exhibits anti-inflammatory properties and inhibits NDST1 promoter activity by between 50-75%. (see Table 5, pg. 45). Regarding claims 2-4, Mahuran teaches the mucopolysaccharidoses is selected from the group consisting of MPS I (Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome), MPS II (Hunter syndrome), MPS IIIA (Sanfilippo syndrome A), MPS IIIC (Sanfilippo syndrome C), MPS 1110 (Sanfilippo syndrome D), and MPS IIIE (Sanfilippo syndrome E) (paragraph 0010). Mahuran teaches a dosage of from about 0.001 mg to about 10000 mg per kilogram of body weight per day at hourly or daily intervals (paragraph 00159), and the composition administered via oral, parenteral, or intravenous routes (paragraph 00162). Mahuran teaches the composition in the dosage form of tablet or liquid form (paragraph 0157). Mahuran also teaches combination therapy to include enzyme replacement therapy (paragraph 00138). Mahuran teaches testing compounds for inhibitory activity using human fibroblast cells (paragraph 00202). Mahuran teaches that “Substrate reduction therapy has recently been shown to be a promising strategy for the treatment of neuronopathic forms of MPS and other lysosomal storage diseases [6-8]. This therapeutic strategy is based on the use of small molecules that may cross the blood brain barrier and act in the CNS.” (paragraph 0004).
Mahuran does not teach administering trans-resveratrol for the treatment of MPS cells.
Rius is drawn towards the anti-inflammatory activity resveratrol isomers (see abstract). Rius teaches that the anti-inflammatory activity of resveratrol is produced by its trans isomer (see abstract).
It would have been obvious to one of ordinary skill in the art to treat MPS cells by administering trans-resveratrol, as suggested by Rius, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Mahuran teaches that resveratrol can be administered to treat MPS, and trans-resveratrol has superior anti-inflammatory activity over the cis isomer of resveratrol as taught by Rius, with a reasonable expectation of success absent evidence of criticality of the particular steps.
Even though the range for the dosage of resveratrol as taught by Mahuran is not the same as the claimed dosages, Mahuran teaches a dosage of from about 0.001 mg to about 10000 mg per kilogram of body weight per day at hourly or daily intervals (paragraph 00159), and it has been held that in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP § 2144.05(I). Furthermore, the determination of dosage is well within the purview of those skilled in the art through routine experimentation, and it has been held that “it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05(II). It would have been obvious to one of ordinary skill in the art to optimize the dosage in order to increase the efficacy of the composition.
The amounts of active agents to be used, the pharmaceutical forms, e.g., tablets, etc; mode of administration, flavors, surfactant are all deemed obvious since they are all within the knowledge of the skilled pharmacologist and represent conventional formulations and modes of administration.
Furthermore, no unobviousness is seen in the ratio claimed because once the usefulness of a compound is known to treat a condition, it is within the skill of the artisan to determine the optimum ratio.
Response to Arguments
Applicant argues that “neither Mahuran nor Rius alone or in combination teach administering trans-resveratrol or piceatennol for treating MPS-I, or for increasing alpha-L-iduronidase activity in vivo. Further, the ability to increase IDUA is an entirely unexpected result.” The Examiner respectfully disagrees since Mahuran does teach a method of treating MPS (claim 1), wherein the mucopolysaccharidoses is selected from the group consisting of MPS I (Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome), MPS II (Hunter syndrome), MPS IIIA (Sanfilippo syndrome A), MPS IIIC (Sanfilippo syndrome C), MPS 1110 (Sanfilippo syndrome D), and MPS IIIE (Sanfilippo syndrome E) (claim 2). Although Mahuran does not teach a method of administering a trans-stilbene or trans-stilbenoid compound, Mahuran does teach the use of resveratrol, which exhibits anti-inflammatory properties and inhibits NDST1 promoter activity by between 50-75%. (see Table 5, pg. 45). Additionally, Rius teaches that the anti-inflammatory activity of resveratrol is produced by its trans isomer (see abstract). Although Mahuran and Rius do not explicitly teach that a trans-stilbene or trans-stilbenoid compound increases alpha-L-iduronidase activity, the teachings of Mahuran and Rius do read on the active steps of the claimed invention, and disclose an overlapping dosage of a trans-stilbene or trans-stilbenoid compound as recited in claims 32 and 34, which would thus be an effective amount that increases alpha-L-iduronidase activity as recited in claim 1. When the composition recitations are met, the desired properties are met, as any component that materially affects the composition and its properties would have to be present in the claim to be commensurate in scope (i.e. claim 1). Additionally, when the composition is delivered in the same manner as claimed, the effects of the composition would be the same such as the therapeutic profile, as they are a direct result of the components of the composition and the mode of administration which are met by the art, whereby the resulting properties and effects would intrinsically be met. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. The court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). (MPEP 2111.04 I).
Regarding Applicant’s unexpected results, although Applicant has demonstrated that resveratrol and piceatannol increased transcription of the IDUA gene as outlined in the 2023 Swift Declaration (pp. 4-5) and Fig. 3 of the Specification, Applicant has not provided a comparative of the claimed invention and the prior art regarding the treatment of MPS-I. Applicant has not demonstrated how the unexpected increased transcriptional activity improves efficacy in treating MPS-I. Additionally, Applicant’s unexpected are not commensurate in scope with the claims, particularly the dosage necessary to achieve such unexpected activity.
Conclusion
Claims 1-4, 18-21, and 25-34 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 ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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