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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/22/25 has been entered.
Claims 1, 11, 13 have been cancelled. Claims 26-28 have been added. Claims 2-10, 12, 14-28 are pending. Claim 7 has been withdrawn. Claims 2-6, 9-10, 12, 14-25 have been amended. Claims 2-6, 8-10, 12, 14-28 are examined herein.
Applicant’s arguments have been fully considered but found not persuasive. The rejection of the last Office Action is maintained for reasons of record and modified below as a result of the new claim amendments.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham vs 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(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 2-6, 8-10, 23-24, 28 are rejected under 35 U.S.C. 103(a) as being obvious over Stocks et al. (US Patent Application 2022/0016128 A1, of record) in view of Mekonnen et al. (US Patent Application 2022/0274996 A1, of record).
The instant claims are directed to a method of treating autism spectrum disorder by administering a molindone formulation.
Stocks et al. teach a method of treating autism by administering molindone as an add-on therapy where patients are already receiving treatment for the underlying disorder (abstract). Molindone is marketed as Moban, which is an immediate release tablet formulation (paragraph 0006). Molindone may be in the single (-) enantiomer, or in the form of a single (+) enantiomer, or in the form of the racemic mixture, or in the form of a non-racemic mixture of enantiomers with varying amounts of the (-) and (+) enantiomers (paragraph 0121).
However, Stocks et al. fail to disclose topically administering to the subject’s pre-gastric mucosa.
Mekonnen et al. teach methods of treating cognitive impairment associated with CNS disorders in a subject in need thereof, for example autism spectrum disorders, fragile X disorder (abstract, paragraph 0209), Prader-Willi syndrome, and Smith-Lemli-Opitz syndrome (paragraph 0211) by administering the antipsychotic, molindone (paragraph 0856). The compounds or agents of this invention may be administered topically, orally, buccally, sublingually, nasally, or through inhalation (paragraph 0837).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, at the time the claimed invention was made, to have topically administered molindone in the subject’s pre-gastric mucosa, as taught by Mekonnen et al., in the method of treating autism, as taught by Stocks et al.
A person of ordinary skill in the art would have been motivated to topically administer molindone in the subject’s pre-gastric mucosa because Mekonnen et al. teach that molindone can be topically, orally, buccally, sublingually, or nasally administered.
It is noted that the limitations drawn to “reduce or eliminate one or more motor and/or behavioral symptoms” and “bypasses the first-pass effect” and “Tmax (hr) of less than 1.5 and/or a Cmax (ng/ml) of more than 174.66” are obvious to occur since all elemental steps of the method claim has been taught by the cited prior art.
Claims 12, 14-22, 25-27 are rejected under 35 U.S.C. 103(a) as being obvious over Stocks et al. (US Patent Application 2022/0016128 A1, of record) and Mekonnen et al. (US Patent Application 2022/0274996 A1, of record), as applied to claims 2-6, 8-10, 23-24, 28, in view of Sopper et al. (WO 2021/228358 A1, of record), Talalay et al. (WO 2016/054475 A1, of record).
The instant claims are directed to a method of treating autism spectrum disorder by administering a molindone formulation.
Stocks and Mekonnen et al. teach as disclosed above, however, fail to disclose a mucosal penetration enhancer, a nano-structured carrier, an oro-dispersible formulations, and an Aberrant Behavioral Checklist.
Sopper et al. teach a solid mucoadhesive composition comprising at least one active agent, at least one carrier, and at least one mucoadhesive polymer (abstract) for oral care preparations (paragraph 0001). Oral disintegrable films, which can disintegrate in the mouth within 1 minute and adhere to the buccal mucosa, are taught (paragraph 0013). Oro-dispersible tablets are taught (paragraph 0015). Lyophilisates are taught (paragraph 0050 and claim 13). The active substance can be loaded in a nanoparticle or nanostructure (carriers), which is dispersed within a mucoadhesive polymer matrix (paragraphs 0010-0011) (oro-dispersible fiber formulation). Carriers for the oral active agents can be from silicon dioxide, silica gels, and silicates with pore sizes in the nanometer range. Silica xero gel is usually commercialized as coarse granules (paragraphs 0036-0037). Chitosan (paragraphs 0040-0041, 0081, claim 4), surfactants, and high molecular weight polyethylene glycol (paragraph 0066) (known penetration enhancers) are taught.
Talalay et al. teach methods of treating autism spectrum disorder (abstract). The goal is to produce at least a 30-90% decrease in total Aberrant Behavior Checklist score (paragraph 0011). Figures 3-6 show changes in total Aberrant Behavior Checklist score of patients during treatment compared to a placebo, with many data points greater than 50. The Aberrant Behavior Checklist assesses irritability, lethargy, stereotypy, hyperactivity, and verbal communication (paragraph 00132).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, at the time the claimed invention was made, to have used a mucosal penetration enhancer, a nano-structured carrier, an oro-dispersible formulations, and an Aberrant Behavorial Checklist, as taught by Sopper and Talalay et al., in the method of treating autism by administering an immediate release molindone formulation, as taught by Stocks and Mekonnen et al.
A person of ordinary skill in the art would have been motivated to have used a mucosal penetration enhancer and a nano-structured carrier in an oro-dispersible formulations because Sopper et al. teach that these components and formulations are commonly used in a solid mucoadhesive composition, which is what Stocks teaches. Furthermore, a person of ordinary skill in the art would have been motivated to use the Aberrant Behavorial Checklist because it can determine the extent and progression of the disease and treatment.
Response to Arguments
The Kovacs Declaration 2 under 37 CFR 1.132 filed 10/22/25 is insufficient to overcome the rejection of claims 2-6, 8-10, 12, 14-28 based upon Stocks et al. (US Patent Application 2022/0016128 A1, of record), Mekonnen et al. (US Patent Application 2022/0274996 A1, of record), Sopper et al. (WO 2021/228358 A1, of record), and Talalay et al. (WO 2016/054475 A1, of record) as set forth in the last Office action.
Applicant submits evidence that only non-toxic molindone hydrochloride tablets and capsules for oral administration were available as of June 2015 and/or 2016.
This is not persuasive because none of the evidence explicitly states that only non-toxic molindone hydrochloride tablets and capsules for oral administration were available as of June 2015 and/or 2016, therefore nothing can be said regarding non-oral dosage forms.
Applicant argues that the Stocks et al. (2012) reference provides support that for the propensity of molindone to create motor abnormalities or aberrant behavioral symptoms. Several patients in this study dropped out due to due to adverse events. Applicant also argues that the Cerilliant reference shows that liquid concentrations of molindone were severely toxic, therefore could not be used for pre-gastric administration without significant alterations, which the Mekonnen publication fails to teach.
This is not persuasive because none of these references supplied by the Applicant were used in the rejections of record. Furthermore, none of these references reflect the state of the art with regard to adverse effects and toxicity of molindone administration.
Applicant argues that the package insert and scientific literature associated with molindone cautions that treatment with molindone causes motor symptoms or extrapyramidal symptoms. Consequently, the fact that pre-gastric mucosal administration of molindone reduces or eliminates motor abnormalities is contrary to the effect of oral administration of molindone. Applicant continues to argue that Dr. Kovacs provides significant and unexpected improvements in bioavailability of the claimed molindone formulation.
This is not persuasive because this improvement in bioavailability is not considered significant or unexpected. Applicant has shown that various motor and/or aberrant symptoms are associated with oral administration of molindone. However, Mekonnen et al. clearly teaches that molindone can be administered in ways other than orally, for example topically, buccally, sublingually, or nasally. Regardless, one of ordinary skill in the art would know how to optimize the route of administration through routine experimentation so as to reduce or minimize these symptoms.
Regarding the establishment of unexpected results or synergism, a few notable principles are well settled. The Applicant has the initial burden to explain any proffered data and establish how any results therein should be taken to be unexpected and significant. See MPEP 716.02 (b). It is applicant’s burden to present clear and convincing factual evidence of nonobviousness or unexpected results, i.e., side-by-side comparison with the closest prior art in support of nonobviousness for the instant claimed invention over the prior art. The claims must be commensurate in the scope with any evidence of unexpected results. See MPEP 716.02 (d). With regard to synergism, a prima facie case of synergism has not been established if the data or result is not obvious. The synergism should be sufficient to overcome the obviousness, but must also be commensurate with the scope of the claims. Further, if the Applicant provides a DECLARATION UNDER 37 CFR 1.132, it must compare the claimed subject matter with the closest prior art in order to be effective to rebut a prima facie case of obviousness. See MPEP 716.02 (e).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam 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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/Yong S. Chong/Primary Examiner, Art Unit 1623