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 .
DETAILED ACTION
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on 04/03/2026, wherein claim 1 is amended, claims 3, 7, 9-20, 22-28, 30 are cancelled and new claims 31-32 are added.
Election/Restriction
Applicant elected without traverse of Group I and species : 1) Sumatriptan as the specific triptan; 2) SSRI to be combined with the triptans; 3) Fragile X Syndrome (FXS) as the FMR1 mediated autism species or disease, 4) Fluvoxam as the specific SSRI, on 10/23/2025.
Claims 1-2, 4, 8 , 29, 31-32 read on the elected invention and species.
Claims 5-6 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention.
Status of Claims
Claims 1-2, 4-6, 8, 29, 31-32 are pending in the instant application.
Claims 5-6 remain withdrawn.
Claims 1-2, 4, 8 , 29 and 31-32 are currently under examination.
Priority
This application 18/249,229 filed on 04/14/2023 is a 371 of PCT/EP2021/078720 filed 10/15/2021,which claims benefit to GB patent Application No. 2016493.5 filed 10/16/2020 and GB patent Application No. 2111346.9 filed 08/05/2021.
The certified copy of GB patent Application Nos. 2016493.5 and 2111346.9 are filed on 04/14/2023.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/27/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
The information disclosure statement filed 04/26/2026 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Action Summary/ Response to Arguments
Applicant's remarks filed 04/03/2026 have been fully considered. Any objection and rejection found in the previous Office Action and not repeated herein has been withdrawn in view of amendment and Applicant’s persuasive remarks .The text of those sections of Title 35 U.S. code not included in this action can be found in a prior Office action.
Applicant's arguments filed 04/03/2026 have been fully considered, but NOT persuasive to overcome rejections under 35 U.S.C. $ 112, and 35 U.S.C. $ 102 anticipated by Wood and Hollander. Please note the biological/pharmacological activity of treating/ameliorating autism symptoms is the property of sumatriptan. Applicant can’t simultaneously assert that instantly claimed method of administering sumatriptan works for FMR1-mediated autism and prior art does not anticipate, unless Applicant can demonstrate, by way of objective evidence, that sumatriptan behaves materially differently in FMR1-mediated autism versus autism not mediated by FMR1. No such showing has been made.
Claim 30 reciting SSRI is cancelled, claims 1- 4, 8 , 29-30 rejected under 35 U.S.C. 103 as being unpatentable over Wood (WO 2021081376 A1) in view of McDougle et al. (Arch Gen Psychiatry, 1996, 53:1001-1008) is withdrawn. Claims 1-2, 4, 8 , 29 rejected under 35 U.S.C. 103 as being unpatentable over Wood (WO 2021081376 A1) in view of Uutela et al. (Front. Cell. Neurosci., 2014, Vol. 8 Article 150, page 1-9) is maintained and reiterated.
New claims 31 and 32 are directed to mutation of FMR1 gene. As necessitated by amendment, claims 1-2, 4, 8 , 29 and 31-32 are now rejected under 35 U.S.C. 103 as being unpatentable over Wood (WO 2021081376 A1) in view of Gürkan et al. ( Research in Autism Spectrum Disorders, 2012 Oct 1;6(4):1311–1320. doi: 10.1016/j.rasd.2012.05.007, Targeted Treatments In Autism And Fragile X Syndrome).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1, 2, 4, 8 , 29 and 31-32 are rejected under 35 U.S.C. 112(a) first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The specification, while being enabling for a method of ameliorating symptoms of FMR1 mediated autism with certain triptan (e.g. sumatriptan) at certain treatment regimen, does not reasonably provide enablement for treating FMR1 mediated autism with the recited triptans. This is a scope of enablement rejection.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). The determination that "undue experimentation" would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The Breadth of The Claims/ Nature of The Invention
Instant claims are directed to a method for the treatment, management or amelioration of FMR1 mediated autism comprising, administering a therapeutically effective amount of a medicament comprising one or more triptans to an individual in need of such treatment, management or amelioration. As disclosed by instant specification (See Page 5) : the terms "treatment", "treating", “treat” and the like, refer to obtaining a desired pharmacologic and/or physiologic effect. The effect can be prophylactic in terms of completely or partially preventing a disease or symptom thereof and/or can be therapeutic in terms of a partial or complete cure for a disease and/or adverse effect attributable to the disease. "Treatment" as used herein, covers any treatment of a disease in a mammal, particularly in a human, and includes: (a) preventing the disease from occurring in a subject which can be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting or slowing its development; and (c) relieving the disease, i.e., causing regression of the disease. As such, instantly claimed scope of “treatment” is extremely broad. Instant claims do not recite route of administration, treatment regimen(dose, frequency, duration, etc.) and measurement of therapeutic effect, etc. As such, the scope of instant claims are extremely broad in contrast with instant specification which only discloses a few working example of triptans (sumatriptan ) ameliorating certain behavior symptoms of FMR1-mediated autism model in mice.
The State of the Prior Art and the Predictability or Lack Thereof in the Art
It is well known in the art that autism is highly heterogenous and variety of genes have been implicated as related to autism, wherein FMR1 is one of the possible cause as discussed in Dolen (2009, Applicant’s IDS dated 10/23/2025). Gürkan (2012, Applicant’s IDS dated 10/23/2025) reviews neurobiology of autism and teaches FXS caused by full mutation of the fragile X mental retardation 1 gene (FMR1) is the most common single-gene cause of the autism with 60% percentage of ASD in FXS (See page 4) . In general, the treatment for autism including FMR1-related autism is highly unpredictable due to highly individual nature of the condition. There is no cure for the underlying pathology of FMR1-related autism and/or Fragile X syndrome (FXS). FMR1-related autism and/or Fragile X Syndrome can’t be prevented because it is caused by inherited gene dysfunction. The FDA-approved medications for treating certain symptoms of autism are risperidone and aripiprazole for treating irritability, aggression, and self-injurious or explosive behaviors. Although there are many studies (e.g. mGluR5 antagonists, D-cycloserine, etc.) on treating secondary behavioral problems in autism, treatments targeting the core symptoms of autism are relatively few and are in need of study for evidence of clinical efficacy (See Gürkan 2012, page 6-8).
More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity (e.g., cancer prevention) is generally considered an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The Amount of Direction Present and Presence or Absence of Working Examples
The specification does not provide sufficient guidance/protocols for a skilled artisan to practice the claimed treatment or in its full scope. The disclosed examples are directed to evaluating two compounds ( sumatriptan, oxitriptan) on behavior symptoms of FMR1 knock-out mice model compared with wild- type mice (See Example 1). It’s noted the effectiveness of triptans sumatriptan vary in different assays (daily living , sociability) and is not significant in comparation with control as shown in Figures 1-6, Table 1-6 and 11, which shows unpredictability of symptomatic treatment of FMR-1 related autism. No direction or examples are provided for assay of other recited triptans, e.g. almotriptan, rizatriptan, etc..
The level of one of ordinary skill in the art
The level of skill required to make and/or use the instant invention would likely require many years of professional experience conducting research in the art (e.g., medicine, pharmaceutical science, biology, biochemistry, medicinal chemistry, and/or organic chemistry, etc.) as well as an advanced educational degree (e.g., M.D. and/or Ph.D.) commensurate in level with the advanced techniques involved in the preparation and/or use of the instant invention.
The quantity of experimentation needed
An unduly extensive amount of experimentation would be required for one of ordinary skill in the art to develop protocols for different triptans and derivatives in different subjects. Different triptans have different chemical structure, different biological activity, different pharmacokinetic profile, etc. Working examples would be needed to determine the therapeutic regimen for different triptans, respectively. The therapeutically effective amount may vary depending on many factors, e.g. the subjects being treated, the disease condition and intended result etc. Therefore, it would be a great burden for one of ordinary skill in the art to carry out undue experimentation to use the claimed invention for treating the claimed in full scope.
Conclusion
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562,27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here with respect to the claimed method for treatment, management or amelioration of FMR1 mediated autism with triptans in view of the analysis above pursuant to In re Wands. In other words, one skilled in the art could not practice the claimed invention without undue experimentation.
Response to Argument
Applicant argues about the activity of sumatriptan (Remarks, page 3) and “ the improvements described above can be readily extrapolated to the other specified triptans, as listed in amended claim 1, because they possess similar receptor binding activities. Specifically, each of the triptans listed above bind agonistically to at least the 5-HT1B, 5-HT1D and 5-HT1F receptors. This similar activity, and common structural features, would lead to the reliable assumption that each of the triptans, as listed to claim 1, would have substantially the same treatment effect”. (Remarks, page 4).
RESPONSE: Applicant’s argument is fully considered, but NOT persuasive. Please note this is scope of enablement rejection. Instantly claimed “treatment" is very broad including preventing the disease from occurring in a subject which can be predisposed to the disease but has not yet been diagnosed as disclosed by instant specification. FMR1-related autism and/or Fragile X Syndrome can’t be prevented because it is caused by inherited gene dysfunction.
Instant specification disclosed assay of sumatriptan on behavior symptoms of FMR1 knock-out mice model compared with wild- type mice (See Example 1). It’s noted the efficacy of sumatriptan vary in different assays (daily living , sociability) and is not significant in comparation with control as shown in Figures 1-6, Table 1-6 and 11, which shows unpredictability of symptomatic treatment of FMR-1 related autism. As for other triptans recited in amended claim 1, almotriptan, frovatriptan, rizatriptan, naratriptan, etc., these different triptans have different chemical structures, different chemical/physical property, different pharmacological activity, efficacy and different toxicological profile. No direction or examples are provided for assay of other recited triptans, e.g. almotriptan, rizatriptan, etc.. In absence of sufficient evidence/data, a skilled artisan would not know if the other triptans would be effective for treating FMR1 medicated autism, due to the highly unpredictability for treating FMR1 medicated autism. Thus, 112(a) scope of enablement rejection is maintained.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-2, 4, 8 , 29 and 31-32 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is amended to recite “a method for the treatment, management or amelioration of FMR1 mediated autism comprising, administering a therapeutically effective amount of a medicament comprising one or more triptans selected from almotriptan, almotriptan malate, sumatriptan, sumatriptan succinate, frovatriptan, rizatriptan, naratriptan, zolmitriptan or mixtures thereof to an individual in need of such treatment, management or amelioration”. The term “management” is vague which might refer to general maintenance, not necessarily therapeutic improvement. The limitation “amelioration” is relative and subjective term. Instant specification does not disclose quantifiable degree or to what extent by what measurement would be considered as “amelioration” of FMR1 mediated autism. There are no objective standard to determine what’s the scope of instantly claimed method for management and amelioration of FMR1-mediated autism. The lack of clarity renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
MPEP 2173.05(b) IV states “ A claim that requires the exercise of subjective judgment without restriction may render the claim indefinite. In re Musgrave, 431 F.2d 882, 893, 167 USPQ 280, 289 (CCPA 1970). Claim scope cannot depend solely on the unrestrained, subjective opinion of a particular individual purported to be practicing the invention. Datamize LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1350, 75 USPQ2d 1801, 1807 (Fed. Cir. 2005)); see also Interval Licensing LLC v. AOL, Inc., 766 F.3d 1364, 1373, 112 USPQ2d 1188 (Fed. Cir. 2014)”.
Claims 2, 4, 8 , 29 and 31-32 are rejected due to dependency from claim 1.
Response to argument: Although claim 1 is amended to recite specific triptans, claim 1 still recites limitation “ management” and “amelioration” that are vague and unclear. The scope of claim 1 and its depending claims are indefinite.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hollander et al. (Neuropsychopharmacology 2000, 22, 163–167, Applicant’s IDS dated 10/23/2025, “The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder”).
Hollander teaches autism is heterogeneous disease related with variety of neurobiological biomarkers and clinical symptoms, e.g. unique behavioral dimensions: social impairment, communication difficulties and rigid, restricted interests, and repetitive behaviors (See abstract, page 163, left column). Hollander and incorporated reference teach pharmacological treatment studies support a role of 5-HT in autistic disorders (See page 163, right column; page 164, left column, para 1-4). Hollander teaches sumatriptan, originally marketed as an anti-migraine medication, is primarily a 5-HT1d receptor agonist but may also bind to 5-HT1b, and evaluate the repetitive behavior dimension response to sumatriptan in adult autistic patients (See page 164, left column; Method, Result)
Hollander teaches the severity of repetitive behaviors (as measured by the YBOCS-compulsion subscale), but not other behavioral dimensions (communication and social deficits as measured by ADI-R algorithm subscales), parallels sumatriptan-elicited growth hormone response, indicating specific component of the 5HT system (the 5HT 1d receptor) may play a role in mediating one specific behavioral component of autistic disorder (repetitive behavior) (See page 165, left column).
Hollander is silent about sumatriptan treating or ameliorating FMR1 mediated autism or the FMRI related autism is related to FXS. However, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. Therefore, the functional effects would be inherent/direct result of sumatriptan based upon the fact that Hollander medicament contains the instantly claimed sumatriptan administered to subjects with autism as in instant application. As such, Hollander anticipates instant claimed invention.
Applicant argues “repetitive behaviour was the only symptom that improved in the treatments disclosed therein. The full range of behaviours implicated in FMR1 mediated autism/FXS, including hyperactivity, stereotypy, sociability, cognitive performance and anxiety (see Example 1 of the present application) were not assessed or reported on. Also, there is no disclosure in Hollander of any of the patients treated in the study discussed therein had FMR1 mediated autism/FXS. Moreover, Hollander teaches that the improvement observed in the repetitive behaviors of the ASD patients is exerted through regulation of growth hormone levels, which has been documented in ASD but not through modification of the FMR1 pathway. Therefore Hollander cannot be considered to disclose or teach the effectiveness of triptans in FMR1 mediated autism/FXS”
RESPONSE: Applicant’s argument has been fully considered, but NOT persuasive. Please note the biological/pharmacological activity of treating/ameliorating autism symptoms is the property of sumatriptan, whether it’s exerted through regulation of growth hormone levels or through modification of FMR1 pathway. As stated in MPEP 2112 II, “INHERENT FEATURE NEED NOT BE RECOGNIZED AT THE TIME OF THE INVENTION: There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)”. Hollander explicitly teaches sumatriptan ameliorating autism symptoms which are related with FMR1-autism. Applicant can’t simultaneously assert that instantly claimed method of administering sumatriptan works for FMR1-mediated autism and Hollander does not anticipate, unless Applicant can demonstrate, by way of objective evidence, that sumatriptan behaves materially differently in FMR1-mediated autism versus autism not mediated by FMR1. No such showing has been made.
Further, a skilled artisan would have known FMR1 mutation/ is the most common single-gene cause of autism/FXS. Even though Hollander is silent about FMR1-mediated autism, by practicing the method of administering sumatriptan for ameliorating autism symptoms, one would probably be treating/ameliorating FMR1-mediated autism even though the prior art was not aware of it.
Claims 1-2, 4, 8 and 29 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WOOD (WO2021081376 A1, Applicant’s IDS dated 10/23/2025).
Wood disclosed a method of treating symptoms associated with autism spectrum disorder ASD comprising administering a therapeutically effective amount of a triptan (e.g. zolmitriptan, sumatriptan, etc.) to a patient in need thereof (See abstract, [0003]-[0007], claims 1-32). Wood and incorporated reference teaches serotonin system has been implicated in the pathophysiology of autism since an abnormal blood 5-HT level was discovered as the first biomarker of the disorder and FMR1 is related with ASD (See [0028]). Wood teaches triptans have selective activity on the 5-HT1B, 5-HT1D, and 5-HTlF receptors, which belong to the serotonin (5-HT) system (See [0027]). Wood teaches reduction of the symptoms/amelioration of autism in patients with ASD by triptans can be determined by various evaluation/measurement, e.g. OSU Autism Rating Scale (OARS-5), sociability, behaviors, etc. (See [0049]-[0053], [0192], Examples 1-4, Figure 1-4).
Regarding claim 2, Wood explicitly disclosed sumatriptan (See[0005], [0030]-[0031], [0054], claim 13, 20-32).
Regarding claim 8, Wood teaches the dosing regimen and variety of dose amount of sumatriptan for treating autism comprise administering a therapeutically effective amount of sumatriptan or a pharmaceutically acceptable salt thereof from about 1mg, to 50 mg to about 100mg (See [0054]-[0066], claim 20-32)
Regarding claim 29, Wood teaches medicament/formulation of sumatriptan comprise pharmaceutical carrier/excipient (See [0026], [0039]-[0042]).
Wood is silent about FMR1 mediated autism is related to Fragile X Syndrome (FXS) as recited in instant claim 4. It’s well-known that Fragile X Syndrome (FXS) is genetic disorder associated with mutation of FMR1 as disclosed prior art and by instant specification (See page 1). A skilled artisan would know FMR1 mediated autism is related to Fragile X Syndrome (FXS). Please note the subjects diagnosed as having or suspected of having autism spectrum disorder in need thereof taught by Wood is considered to encompass subjects with FMR-1 mediated autism related to FXS in the absence of evidence to the contrary. The functional effects of treating FMR-1 related autism and Fragile X Syndrome (FXS) would be inherent/direct result of triptans based upon the fact that Wood medicament contains the instantly claimed ingredients (triptans, sumatriptan) administered to subjects with autism as in instant application.
Wood collectively teaches a method for treatment and management of autism comprising administering triptans (e.g. sumatriptan, etc.) in a subject in need thereof. As such, Wood anticipates instantly claimed invention.
Applicant argues Wood presents findings using a chemically induced model compared to a wild-type. This model is very different to the FMR1 knockout mouse model used in the present invention. One having ordinary skill in the art would find the model of Wood does not accurately reflect the causation of FMR1 mediated autism and does not model all the behaviours known to be symptomatic in FMR1 mediated autism. Therefore, Wood cannot be considered to disclose or teach the effectiveness of triptans in FMR1 mediated autism/FXS (page 5).
RESPONSE: Applicant’s argument has been fully considered, but NOT persuasive. The animal model is not a limitation on the therapeutic property of triptan compound. The pharmacological activity of treating/ameliorating autism symptoms is the property of triptan/sumatriptan and does not change based on the model in which it’s tested. Wood discloses the same triptan compound for the same use of treating autism/ameliorating autism symptoms. A skilled artisan would have known mutations in the FMR1 gene are the most common single-gene cause of autism and FMR1 knockout mice are widely used model in assay for FXS/ FMR1 autism. If sumatriptan effectively treats/ameliorates autism symptom as instantly claimed, then Wood anticipates instantly claimed method of treating autism. Applicant can’t simultaneously assert that instantly claimed method works for FMR1 mediated autism and that Wood does not anticipate, unless Applicant can demonstrate, by way of objective evidence, that sumatriptan behaves materially differently in FMR1- autism versus no-FMR1 mediated autism. No such showing has been made. Thus, the 102(a) rejection is maintained.
MPEP 2112 I states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art' s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).” Please also note inherent feature need not be recognized at the relevant time. See MPEP 2112 II.
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 non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4, 8 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over WOOD (WO 2021081376 A1, Applicant’s IDS dated 10/23/2025), as applied to 102 rejection above, and further in view of Uutela et al. (Front. Cell. Neurosci., 2014, Vol. 8 Article 150, page 1-9, https://doi.org/10.3389/fncel.2014.00150, Distinctive behavioral and cellular responses to fluoxetine in the mouse model for Fragile X syndrome)(reiterated as necessitated by amendment).
The collective teaching of Wood is elaborated in preceding 102 rejection and applied as before. Wood collectively teaches a method for the treatment and management of autism comprising administering triptans (e.g. sumatriptan, etc.) to a patient in need thereof.
Wood is silent about FMR-1/FXS related autism. The functional effects of treating FMR-1 related autism and Fragile X Syndrome (FXS) is considered as direct result of triptans based upon the fact that Wood teaches treating autism with triptans (e.g. sumatriptan) as in instantly claimed.
Uutela teaches fluoxetine, a SSRI, is a therapeutic agent for treating symptoms of autism spectrum disorder (ASD), including Fragile X syndrome (See whole article). Uutela teaches Fragile X syndrome (FXS) caused by FMR1 mutation, is a well characterized form of autism spectrum disease (ASD), and treatment with fluoxetine has been shown to benefit FXS individuals with autism, social anxiety, or selective mutism (See Introduction, page 1). Uutela further teaches evaluation of behavioral and cellular effects of fluoxetine on adult Fmr1 knockout (KO) mice, a mouse model for FXS wherein fluoxetine reduced anxiety-like behavior of both wild-type and Fmr1 KO mice(See abstract, Results from page 3, Figure 1-3).
It would be obvious and logical for a skilled artisan to further explore triptans taught by Wood in patients with FMR1/FXS related autism for targeted treatment based on the combined teachings of Wood and Uutela, together with experimentation and optimization based on general knowledge of treatment for FMR-1 autism. The skilled artisan would be motivated to combine the teachings of Wood and Uutela because both triptans taught by Wood and fluoxetine taught by Uutela are 5-HT inhibitor that show efficacy in symptomatic treatment of autism. The FMR1 knockout mouse model is a well-established animal model for studying autism, including those associated with FXS as taught by Uutela. A POSA would have been motivated to evaluate triptans (e.g. sumatriptan), taught by Wood in FMR1 knockout mouse model and reasonably expected triptans (e.g. sumatriptan) ameliorate autism symptom in mice model.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and general knowledge of treatment/management of autism. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Applicant argues: Office action argues that Uutela teaches that the SSRI fluoxetine can treat symptoms of ASD, including FXS, and that this would motivate the skilled person to explore triptans in patients with FMR1/FXS related autism. However, one having ordinary skill in the art would understand Uutela relates to a different class of pharmaceutical compounds–the SSRIs. Wood cannot be modified by Uutela to teach or make obvious claim 1 because it would render Wood inoperable (See MPEP 2143.01.V). The structure of the SSRIs of Uutela, such as fluoxetine, is very different to the triptan family of Wood.
RESPONSE: Please note this 103 rejection does NOT rely on Uutela for teaching triptans for treating autism. Wood already teaches a method for the treatment and management of autism comprising administering triptans (e.g. sumatriptan, zolmitriptan etc.) as elaborated in 102 rejection. Uutela is a teaching reference that is directed to combination of SSRI with triptan as recited in cancelled claim 30. Further, Uutela teaches Fragile X syndrome (FXS) caused by FMR1 mutation and association with autism spectrum disease (ASD), and fluoxetine evaluated on adult Fmr1 knockout (KO) mice, a mouse model for FXS. The FMR1 knockout mouse model is a well-established animal model for studying autism, including those associated with FXS as illustrated and validated by Uutela. A POSA would have been motivated to evaluate triptans (e.g. sumatriptan) taught by Wood in FMR1 knockout mouse model and reasonably expected triptans (e.g. sumatriptan) ameliorate autism symptom in mice model in absence of evidence to the contrary. The Applicant does not provide any unexpected result that sumatriptan works differently in FMR1-mediated autism. Thus, 1-2, 4, 8 and 29 remain rejected over Wood in view of Uutela.
Claims 1- 2, 4, 8 , 29 and 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over WOOD (WO 2021081376 A1, Applicant’s IDS dated 10/23/2025), as applied to 102 rejection above, and further in view of Gürkan et al. ( Research in Autism Spectrum Disorders, 2012 Oct 1;6(4):1311–1320, Applicant’s IDS dated 10/23/2025, doi: 10.1016/j.rasd.2012.05.007, Targeted Treatments In Autism And Fragile X Syndrome) (newly applied as necessitated by amendment).
The collective teaching of Wood is elaborated in preceding 102 and 103 rejection and applied as before. Wood collectively teaches a method for the treatment and management of autism comprising administering triptans (e.g. sumatriptan, zolmitriptan etc.) to a patient in need thereof.
Wood is silent of FMR-1/FXS related autism as recited in claim 4 and mutation recited in new claims 31 and 32. Please note the functional effects of treating FMR-1 related autism and Fragile X Syndrome (FXS) is considered as properties of triptans based upon the fact that Wood teaches sumatriptan administered to subjects with autism.
Gürkan teaches targeted treatment in autism and Fragile X syndrome (See whole article). Gürkan and incorporated reference teach FXS is the most common single-gene cause of the autism and approximately 30% have full autism, but when Pervasive Developmental Disorder-Not Otherwise Specified (PDD NOS) which occurs in an additional 30%, is also included, the total percentage with an ASD is 60% (Harris et al., 2008). FXS is caused by a full mutation (>200 CGG repeats) in the 5′untranslated region of the fragile X mental retardation 1 gene (FMR1) which is near the distal arm of the long end of the X chromosome. This mutation causes hypermethylation at the FMR1 promoter region and transcriptional silencing, which in turn lead to a deficit of the FMR1 protein (FMRP). The overlap between autism and FXS relates to the many functions of FMRP that is absent or deficient in FXS (page 4, 3rd para. Fragile X Syndrome Section). Gürkan and incorporated reference also teach KO mouse model pf FXS in variety study of autism/FXS (See page 5, 2nd para and last para).
Wood collectively teaches a method for the treatment and management of autism comprising administering triptans (e.g. sumatriptan, etc.) to a patient in need thereof. A skilled artisan would have known mutations in the FMR1 gene is the most common single-gene cause of autism that can be evaluated in KO mice model as illustrated by Gürkan and incorporated reference. A skilled artisan would be motivated to evaluate sumatriptan in recognized KO mice model and reasonably expect sumatriptan would ameliorate autism symptom in mice model.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and general knowledge of treatment/management of autism. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is 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.
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/L.M./Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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