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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/16/2026 has been entered.
Status of the Application
Claims 1-4, 15-16, 18-21, and 25-34 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 03/16/2026 are acknowledged. Claim 1 is amended and claim 34 is added. Claims under consideration in the instant office action are claims 1-4, 15-16, 18-21, and 25-34.
Applicants' arguments, filed 03/16/2026, have been fully considered but they are not deemed to be persuasive regarding the rejections under 35 U.S.C. 103. Additionally, the obviousness-type double patenting rejection is maintained since a terminal disclaimer has not been filed. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 Interpretation
The claimed invention is interpreted as a method of treating a MPS-I in a subject in need thereof comprising administering a therapeutically effective amount of a composition comprising a stilbene or stilbenoid compound in the trans configuration. However, the Examiner suggests reciting a limitation such as “wherein the trans-stilbene or trans-stilbenoid compound is in the trans configuration”.
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, 15-16, 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 “Submitted herewith is a Terminal Disclaimer that disclaims the terminal portion of any patent issuing from the present application that would extend beyond the expiration of the '706 patent, subject to the terms set forth in the Terminal Disclaimer. Accordingly, withdrawal of the double-patenting rejections is respectfully requested.” The Examiner respectfully disagrees since a terminal disclaimer has not been filed as of 03/16/2026.
Applicant also argues that “Mahuran does not teach any compound for increasing alphaL-iduronidase (IDUA) activity in vivo. Rather, Mahuran describes compounds for decreasing the activity of NDSTl, for use in Substrate Reduction Therapy for treating mucopolysaccharidoses. Mahuran also does not specifically teach use of a trans-stilbene or trans-stilbenoid compound… Rius does not teach administering trans-resveratrol for treating MPS-I, or for increasing alphaL-iduronidase activity in vivo.” 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).
Applicant also argues that “In the present invention, the increased transcription of the IDUA gene is an entirely unexpected result that is not obvious over the combination of Mahuran and Rius. Figure 1 shows that treatment of MPS I patient cells with resveratrol and various stilbenoid compounds resulted in an increase in IDUA activity. CTI-101 is piceatannol, CTI-102 is resveratrol, CTI-111 is 4,4'stilbenedicarboxylic acid. Figure 2 shows that treatment of MPS I patient cells with resveratrol and piceatannol increased the mRNA level of a -L-iduronidase (IDUA). Figure 3 shows the elevation of a-iduronidase activity in plasma of mice treated with piceatannol (top) or resveratrol (bottom) for one month: both resveratrol and piceatannol provided substantial boosts in enzyme activity. (page 3, lines 1-8). Further, the 2023 Swift Declaration, of record, states that trans-resveratrol increases alpha-Liduronidase expression which is believed to be beneficial for treating MPS-I. (para 15).” The Examiner respectfully disagrees since 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. Additionally, Applicant has not demonstrated unexpected results over the entire genus of compounds of the recited formula.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-4, 15-16, 18-21, and 25-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12,029,706.
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims both recite similar methods of treating MPS-I comprising administering trans-resveratrol. U.S. Patent No. 12,029,706 is drawn towards a method of treating MPS-I comprising administering trans-resveratrol wherein the composition increases plasma alpha-L-iduronidase activity in vivo, and wherein the effective amount is from 25 to 50 mg/kg daily.
U.S. Patent No. 12,029,706 does not recite administering the same range of dosages.
It would have been obvious to one of ordinary skill in the art to administer trans-resveratrol over the same range of dosages, as suggested by U.S. Patent No. 12,029,706, and produce the instant invention.
Even though the range for the dosage of resveratrol as taught by U.S. Patent No. 12,029,706 is not the same as the claimed dosages, U.S. Patent No. 12,029,706 teaches a dosage of from about 10 mg to about 5,000 mg daily, 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.
Conclusion
Claims 1-4, 15-16, 18-21, and 25-34 are rejected.
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