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 .
Priority
This patent application is a national phase entry under 35 U.S.C. § 371 of International
Application Number PCT/US2020/031217, filed May 2, 2020, which claims a benefit under 35
U.S.C. § 119(e) to the June 7, 2019 filing date of United States Provisional Patent Application
Serial Number 62/858,621.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 14, 2021; May 30,
2023; January 12, 2024; June 7, 2024; July 19, 2024; and July 23, 2025 were in compliance with the provisions of 37 CPR 1.97. Accordingly, the information disclosure statement are being considered by the examiner. A signed copy of each form 1449 is enclosed herewith.
Status of claims
Claims 1-3, 9, 14, 18, 22-23, 26-27, 29-30, 38-40, 43, 48, 50, and 65 are pending in this application. Claims 1, 18, 22, and 48 have been amended. Claims 4-8, 10-13, 15-17, 19-21, 24-25, 28, 21-37, 41-42, 44-47, 49, 51-64, and 66 are cancelled. Claims 14 and 65 have been withdrawn without traverse via previous election restriction.
Applicant’s arguments, filed September 23, 2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Applicants amended claims make a contribution over the prior art of record. Applicants claim 14 has been cancelled by examiner without prejudice or disclaimer for being dependent on cancelled claim 11. Previously withdrawn claim 65 has been rejoined and therefore claims 1-3, 9, 18, 22-23, 26-27, 29-30, 38-40, 43, 48, 50 and 65 are currently under examination, they constitute the complete set presently being applied to the instant application.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-3, 9, 18, 22, 23, 26, 27, 29, 30, 38-40, 43, 48, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Pakbaz (WO 2018/148262 Al), in view of Maggio (U.S. 2012/0070487 Al).
The instant claims are drawn to a method of treating cognitive, social, or behavioral disabilities and neurodevelopmental disorders by intranasal administration of suramin with a penetration enhancer selected from methyl Beta-cyclodextrin, caprylocaproyl macrogol-8 glycerides, or 2-(2-ethoxyethoxy)ethanol comprising from about 10% to about 75% by weight of the pharmaceutical composition.
Pakbaz et al. discloses in a method of treating neurodevelopmental disorders including
autism spectral disorders (ASDs) by administering a suramin (an anti-purinergic agent)
formulation as an inhalant transmucosally [paragraph 02]. Pakbaz also discloses children diagnosed with autism spectral disorder (ASD) being administered the compound of suramin in example 5 [132] and of ASD encompassing Asperger syndrome and pervasive development disorder not otherwise specified (PDD-NOS) with characteristics of communication difficulties and repetitive behaviors [04]. Pakbaz et al. teaches suramin can be used to improve social behaviors in autism spectrum disorders (ASD's) [17] and that the patient can be an animal or a human [26]. Pakbaz teaches an embodiment wherein the compositions and formulations are formulated to improve the ability of suramin to cross the blood brain barrier with a Non-limiting example including intranasal [39]. Pakbaz also teaches an embodiment in which a suramin composition is using penetration enhancers [10]. Pakbaz teaches inclusion of β-cyclodextrin [85]. Pakbaz further describes "In certain embodiments, it can be desirable to prolong the residence time of the pharmaceutical composition in the nasal cavity, for example, to enhance absorption" with one of the options used to enhance absorption being a microsphere (e.g., starch, albumin, dextran, cyclodextrin) [ 43]. Pakbaz also discloses the use of antioxidants which can further comprise the formulation [61]. Pakbaz also teaches that a treatment daily dosage can range from 1 mg/kg to 1.5g/kg [123] and given as 1-8 doses in a day.
However, Pakbaz does not explicitly identify the amount of cyclodextrin present as a penetration enhancement.
Maggio teaches the addition of penetration enhancer methyl-beta-cyclodextrin, for use in a pharmaceutical composition formulated for administration through nasal or inhalation routes.
Maggio also discloses the purpose of using a penetration enhancer is to provide increased
bioavailability of the compound in the blood plasma of a subject [0035-0036]. Maggio also discloses polyphenol antioxidants are generally believed to be instrumental in combating oxidative stress in humans, a process associated with some neurodegenerative diseases [0028]. Maggio's disclosure relates to "compositions of the invention may be formulated for, and delivered via any suitable administration route, including, for example, oral, buccal, nasal, nasolacrimal, inhalation, pulmonary, transdermal or CSP delivery routes. The terms "administration" or "administering" as used herein are defined to include the act of providing a pharmaceutical composition of the invention to a subject in need of treatment" [0041]. Maggio demonstrates that the addition of 3% penetration enhancer (dodecyl maltoside) increases the blood levels of active agent over 20% [0050].
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention and following the teachings of Pakbaz, to administer suramin intranasally with a prior-art recognized penetration enhancer suitable for intranasal administration such as the methyl-betacyclodextrin taught by Maggio. MPEP 2143. Given that Maggio teaches that penetration enhancers increase the amount of active agent reaching the blood, it would have been prima facie obvious to increase the amount of penetration enhancer in the composition in order to provide the desired levels of active ingredient in the blood (i.e. bioavailability). MPEP 2144.05(II).
From the teachings of the cited references, it is apparent that a person having ordinary skill would have had a reasonable expectation of success in a method of treating ASD in a patient by intranasally administering suramin and methyl-beta-cyclodextrin because it was prior art recognized that suramin is useful in treating ASD, and methyl-betacyclodextrin is taught as a suitable penetration enhancer in intranasal pharmaceutical compositions.
It is noted that a composition of 0.01 mg to 200 mg per unit dosage of suramin would have been prima facie obvious over the teaching of Pakbaz teaching of a daily dosage of suramin ranging from 1 mg/kg to 1.5g/kg and given as 1-8 doses in a day and the average human as 70kg resulting in a daily dose of 70 mg. See MPEP 2144.05(I). Similarly, administration of a pharmaceutical composition of suramin at least every 41-78 days is rendered prima facie obvious over Pakbaz’s teaching of a daily dosage of suramin.
A person of ordinary skill in the art would have been motivated to improve the ability of suramin to cross the blood brain barrier by both using Pakbaz’s disclosure of an intranasal method of delivering Suramin and the disclosure of Maggio to include a penetration enhancer, with the amount w/w administered by the skilled artisan adjusted for severity of disease, size and age of the patient and the patients response to treatment. A skilled artisan would have also recognized the contributions of Maggio wherein antioxidants, beta-cyclodextrin penetration enhancers improved effectiveness an nasally inhaled dosages. A person having ordinary skill in the art would therefore have had a reasonable expectation of success in combining the teachings of Pakbaz and Maggio and administering a nasal formulation of suramin, penetration enhancers, and antioxidants. Therefore, absence of evidence to the contrary (i.e. secondary considerations), the methods of instant claims 1-3, 9, 18, 22, 23, 26, 27, 29, 30, 38-40, 43, 48, and 50 would have been prima facie obvious to one of ordinary skill in the art at the time the instant application was filed.
Response to Arguments
Applicant's arguments filed 09/11/2025 have been fully considered but they are not persuasive.
Applicant clarifies that the elected antipurinergic agent species in the Restriction Requirement, filed January 8, 2025, of suramin or a pharmaceutically acceptable salt, ester, solvate, or prodrug thereof, as named in at least claim 11, includes the hexa-sodium salt as indicated in claim 14. Basis for support is found at least at paragraphs [0159], [0160], [0229], [0234], [238], and [273] of the Specification. Applicant respectfully requests removal of claim 14 from the withdrawn list of claims and formally requests rejoinder of claim 14 among the pending claims.
Claim 11 has been cancelled by Applicants. As such, claim 14 depends from a cancelled claim, so the scope of claim 14 is unknown. Upon Applicants clarifying the dependency and scope of claim 14, the claim will be reevaluated for rejoinder and potentially examine claim 14 at that time. Examiner agrees that support for the hexa-sodium salt can be found in the paragraphs stated by Applicants, but notes that such paragraphs are from the published application rather than the as-filed specification.
Applicant argues Pakbaz provides no working example of suramin administered with a penetration enhancer. Its disclosure of "penetration enhancer" is confined to generic lists of excipients and contains no teaching of a formulation or concentration suitable for use with suramin, let alone one of the specific enhancers ( e.g., methyl Beta-cyclodextrin, caprylocaproyl macrogol-8 glycerides, 2-(2-ethoxyethoxy )ethanol).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art and the unexpected discovery that penetration enhancers, including methyl Beta-cyclodextrin, can be used to safely and effectively deliver suramin with improved brain penetration while maintaining controlled systemic levels. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, to address Pakbaz teaches in [39] In one embodiment, the compositions and formulations are formulated to improve the ability of suramin to cross the blood brain barrier. Non-limiting examples include intranasal and ammonium bets-cyclodextrin nanoparticles. A skilled artisan would have had a reasonable expectation of success in improving suramin’s ability to cross the blood brain barrier resulting from using Maggio’s teaching of beta-cyclodextrin. See MPEP 716.02(d) and MPEP 2144.05.
Conclusion
Claims 1-3, 9, 18, 22-23, 26-27, 29-30, 38-40, 43, 48, 50, and 65 are Rejected, no claims are allowed.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C Milligan can be reached at 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623