Prosecution Insights
Last updated: April 19, 2026
Application No. 18/252,813

REFINED USES OF GABA A RECEPTOR MODULATORS IN TREATMENT OF FRAGILE X SYNDROME

Non-Final OA §102§103§112
Filed
May 12, 2023
Examiner
WHITE, DENNIS MICHAEL
Art Unit
1758
Tech Center
1700 — Chemical & Materials Engineering
Assignee
Children'S Hospital Medical Center
OA Round
1 (Non-Final)
58%
Grant Probability
Moderate
1-2
OA Rounds
3y 1m
To Grant
99%
With Interview

Examiner Intelligence

Grants 58% of resolved cases
58%
Career Allow Rate
470 granted / 817 resolved
-7.5% vs TC avg
Strong +48% interview lift
Without
With
+48.5%
Interview Lift
resolved cases with interview
Typical timeline
3y 1m
Avg Prosecution
20 currently pending
Career history
837
Total Applications
across all art units

Statute-Specific Performance

§101
1.5%
-38.5% vs TC avg
§103
44.7%
+4.7% vs TC avg
§102
31.3%
-8.7% vs TC avg
§112
15.0%
-25.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 817 resolved cases

Office Action

§102 §103 §112
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 . Claim Rejections - 35 USC § 112 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. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claims 24-25, 27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, 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 24 recites the limitation "the biological sample" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 25 recites the limitation "claim 23" in line 1. There is insufficient antecedent basis for this limitation in the claim. The claim is cancelled. Claim 27 is rejected as being dependent on claim 25. 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 (i.e., changing from AIA to pre-AIA ) 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. Claim(s) 1, 4-6, 8 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Gomez-Mancilla et al (US 2013/0052644). Regarding claim 1, Gomez-Mancilla et al teach a method for identifying a Fragile X Syndrome (FXS) patient who is likely to respond to a treatment for FXS (FXS treatment), the method comprising: (a) providing a biological sample of a FXS patient (Para 0005; claim 3: sample having FXS); (b) detecting Fragile X mental retardation protein (FMRP) in the biological sample (Para. 0005; claim 3: detect amount of FMRP) ; and (c) identifying the FXS patient for the FXS treatment, wherein the FMRP is undetectable in the biological sample or has a level no greater than a predetermined value (Para. 0005; claim 3: reduced amount of FMRP compared to a control). Regarding claim 4, Gomez-Mancilla et al teach the biological sample is a blood sample, a plasma sample, or a serum sample (Para. 0462: serum, para. 0420: blood). Regarding claim 5, Gomez-Mancilla et al teach the FXS patient is a male human patient (Para. 0002: FXS in 1/4000 males and 1/8000 females). Regarding claim 6, Gomez-Mancilla et al teach step (b) is performed by an immunoassay comprising at least one antibody specific to human FMRP. (Para. 0016, 00467: FMRP specific antibodies) Regarding claim 8, Gomez-Mancilla et al teach the immunoassay comprises two antibodies specific to the human FMRP, the two antibodies binding to different epitopes of the human FMRP. (para. 0467: FMRP specific antibodies used in combination at Para. 0487) Claim(s) 15-20, 22, 24, 28 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Erickson et al (US 20180104244). Regarding claim 15, Erickson teach a method for treating Fragile X syndrome (FXS), comprising subjecting an FXS patient to a treatment for FXS (FXS treatment) (Para. 0017,0025-0027 : GABA(A) modulator for drug therapy of FXS), wherein the FXS patient has undetectable peripheral Fragile X mental retardation protein (FMRP) or a level of peripheral FMRP no greater than a predetermined value (Para. 0016: FXS patient has transcriptionally silenced FMRP). Regarding claims 16-17, Erickson teach the FXS treatment comprises an effective amount of a GABAA modulator, which optionally is a selective GABAA agonist, a muscle relaxer, which optionally is baclofen, and/or a gene therapy, which optionally comprises a vector that expresses a functional FMRP polypeptide; the FXS treatment comprises a GABAA modulator, which is AZD7325 (Para. 0004-0007). Regarding claims 18-20, Erickson teach the FXS patient is administered a low dose of the GABAA modulator; the GABAA modulator is AZD7325, which is administered to the FXS patient at 5mg twice per day; GABAA modulator is administered orally. (Para 0039-0040, 0045: low dose, orally, one or more portions, the rate of administration is sufficiently broad to read on 5mg twice per day as the amounts of 100ug to 100mg per kg of the body weight covers the limitation of 5mg twice per day). Regarding claim 22, Erickson teach the FXS patient is a male patient (Para. 0045: human patient includes male patients). Regarding claim 24, Erickson teach taking a biological sample is a blood sample, a plasma sample, or a serum sample. (Para. 0028: blood sample) Regarding claim 28, Erickson teach a pharmaceutical composition for use in treating Fragile X syndrome (FXS) in a FXS patient, wherein the pharmaceutical composition comprises a GABAA modulator, a muscle relaxer, and/or a vector expressing a functional FMRP polypeptide (Para. 0004-0007: AZD7325), and wherein the FXS patient has undetectable peripheral Fragile X mental retardation protein (FMRP) or a level of peripheral FMRP no greater than a predetermined value (Para. 0016: FXS patient has transcriptionally silenced FMRP). 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 (i.e., changing from AIA to pre-AIA ) 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. 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 in order 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. Claim(s) 2, 10-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gomez-Mancilla et al in view of Erickson et al (US 20180104244). Regarding claims 2,10, Gomez-Mancilla et al teach a FXS treatment of mGluR modulator but is silent to the FXS treatment comprises a GABAA receptor modulator, a muscle relaxer, and/or a gene therapy, optionally wherein the FXS treatment comprises the GABAA receptor modulator; administering to the FXS patient identified in step (c) an effective amount of a GABAA modulator, which optionally is a selective GABAA agonist. Erickson et al teach treatment of FXS using therapeutically effective amounts of GABA (A) alpha 2 and/or 3 partial agonist (Para. 0017,0025-0027 : GABA(A) modulator for drug therapy of FXS). It is advantageous to provide GABA (A) alpha 2 and/or 3 partial agonist as FXS treatment for subsets of FXS patients and directed at different symptoms (Abstract). Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the GABA(A) modulator of Erickson et al to the treatment of Gomez-Mancilla to provide the above advantage of treating symptoms and patients with a subset of FXS patients. Regarding claim 11, Gomez-Mancilla/Erickson teach the FXS patient is administered the GABAA modulator, which optionally is AZD7325. (Para. 0004-0007). Regarding claims 12-14, Gomez-Mancilla/Erickson teach the FXS patient is administered a low dose of the GABAA modulator; the GABAA modulator is AZD7325, which is administered to the FXS patient at 5mg twice per day; GABAA modulator is administered orally. (Para 0039-0040, 0045: low dose, orally, one or more portions, the rate of administration is sufficiently broad to read on 5mg twice per day as the amounts of 100ug to 100mg per kg of the body weight covers the limitation of 5mg twice per day). Claim(s) 25, 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Erickson et al (US 20180104244) in view of Gomez-Mancilla et al (US 2013/0052644). Regarding claims 25 and 27, Erickson is silent to the peripheral FMRP level is measured by an immunoassay comprising at least one antibody specific to human FMRP; the immunoassay comprises two antibodies specific to the human FMRP, the two antibodies binding to different epitopes of the human FMRP. Gomez-Mancilla et al teach a method for identifying a Fragile X Syndrome (FXS) patient who is likely to respond to a treatment for FXS (FXS treatment), the method comprising: (a) providing a biological sample of a FXS patient (Para 0005; claim 3: sample having FXS); (b) detecting Fragile X mental retardation protein (FMRP) in the biological sample (Para. 0005; claim 3: detect amount of FMRP) ; and (c) identifying the FXS patient for the FXS treatment, wherein the FMRP is undetectable in the biological sample or has a level no greater than a predetermined value (Para. 0005; claim 3: reduced amount of FMRP compared to a control); Gomez-Mancilla et al teach step (b) is performed by an immunoassay comprising at least one antibody specific to human FMRP. (Para. 0016, 00467: FMRP specific antibodies); Gomez-Mancilla et al teach the immunoassay comprises two antibodies specific to the human FMRP, the two antibodies binding to different epitopes of the human FMRP. (para. 0467: FMRP specific antibodies used in combination at Para. 0487). It is desirable to measure the FMRP level to ensure the patient is a likely candidate for FXS treatment. Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the FMRP level measurements of Gomez-Mancilla to the method of Erickson to provide the above advantage of ensuring the patient is a likely candidate for FXS treatment. Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gomez-Mancilla et al in view of Turner (US 2020/0339639). Regarding claim 9, Gomez-Mancilla et al is silent to performing gamma electroencephalogram (EEG) on the FXS patient to measure electrical activity of the brain. Turner teach treatment of FXS is monitored using gamma EEG activity changes over time (Para. 0043 and 0148: Gamma EEG recordings reads on " before, during, and/or after the FXS treatment to monitor treatment efficacy") It is desirable to record an observable symptom such as the EEG in real time to see if the treatment is working. Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the Gamma EEG monitoring of Turner to the method of Gomez-Mancilla et al to provide the above advantage of recording an observable symptom such as the EEG in real time to see if the treatment is working. Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Erickson et al in view of Turner (US 2020/0339639). Regarding claim 21, Erickson teach using EEG abnormalities as symptoms for FXS, but is silent to performing gamma electroencephalogram (EEG) on the FXS patient before, during, and/or after the FXS treatment to monitor treatment efficacy. Turner teach treatment of FXS is monitored using gamma EEG activity changes over time (Para. 0043 and 0148: Gamma EEG recordings reads on " before, during, and/or after the FXS treatment to monitor treatment efficacy") It is desirable to record an observable symptom such as the EEG in real time to see if the treatment is working. Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the Gamma EEG monitoring of Turner to the method of Erickson et al to provide the above advantage of recording an observable symptom such as the EEG in real time to see if the treatment is working. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS MICHAEL WHITE whose telephone number is (571)270-3747. The examiner can normally be reached M-F 8:30am-5pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris R. Kessel can be reached at (571) 270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Dennis White/Primary Examiner, Art Unit 1758
Read full office action

Prosecution Timeline

May 12, 2023
Application Filed
Nov 07, 2025
Non-Final Rejection — §102, §103, §112 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
58%
Grant Probability
99%
With Interview (+48.5%)
3y 1m
Median Time to Grant
Low
PTA Risk
Based on 817 resolved cases by this examiner. Grant probability derived from career allow rate.

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