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 § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 28 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Erickson et al (US 20180104244).
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
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-2, 4-6, 8, 11-14 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) and further in view of Turner (US 2020/0339639).
Regarding claims 1, 2, 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 a FXS treatment of mGluR modulator but is silent to the administering to the FXS patient identified in step (c) an effective amount of a GABAA modulator; wherein the FXS treatment comprises a GABAA receptor modulator, a muscle relaxer, and/or a gene therapy; 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.
Gomez-Mancilla/Erickson teach EEG abnormalities as a symptom of FXS (Erickson: Para. 0023), 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 Gomez-Mancilla/Erickson to provide the above advantage of recording an observable symptom such as the EEG in real time to see if the treatment is working.
Regarding claim 4, Gomez-Mancilla/Erickson/Turner 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/Erickson/Turner 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/Erickson/Turner 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/Erickson/Turner 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)
Regarding claim 11, Gomez-Mancilla/Erickson/Turner teach the FXS patient is administered the GABAA modulator, which optionally is AZD7325. (Para. 0004-0007).
Regarding claims 12-14, Gomez-Mancilla/Erickson/Turner 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) 15-20, 22, 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Erickson et al (US 20180104244) in view of Turner (US 2020/0339639).
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) that is measured in a biological sample or a level of peripheral FMRP no greater than a predetermined value (Para. 0016: FXS patient has transcriptionally silenced FMRP). Erickson teach EEG abnormalities as a symptom of FXS (Para. 0023), 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.
Regarding claims 16-17, Erickson/Turner 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/Turner 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/Turner teach the FXS patient is a male patient (Para. 0045: human patient includes male patients).
Regarding claim 24, Erickson/Turner teach taking a biological sample is a blood sample, a plasma sample, or a serum sample. (Para. 0028: blood sample)
Claim(s) 25, 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Erickson/Turner in view of Gomez-Mancilla et al (US 2013/0052644).
Regarding claims 25 and 27, Erickson/Turner 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/Turner to provide the above advantage of ensuring the patient is a likely candidate for FXS treatment.
Response to Arguments
Applicant’s arguments, see p. 6, filed 4/14/2026, with respect to rejection under 35 USC 112b have been fully considered and are persuasive. The 35 USC 112b rejection of claims 24, 25, and 27 has been withdrawn.
Applicant’s arguments with respect to claim(s) 1-2, 4-6, 8, 11-20, 22, 24-25, 27-28 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicants argue that the Gomez-Mancilla measures particular biomarkers to select those individuals having FXS who are likely to respond to treatment with an mGluR5 antagonist. Applicants argue that the there are no actual administration step and further monitoring prior to the determination that a patient is a candidate for a mGluR5 antagonist. This is not convincing because the new rejection incorporates the administration of the GABA(A) modulator of Erickson.
Applicants argue that Erickson is relied on to teach that a GABA(A) modulator can be administered to treat FXS. Erickson does not teach any method of identifying patients that would be good candidates for a GABA(A) modulator. This is not convincing because the Gomez-Mancilla teaches this step. Applicants argue that from the disease or condition being FXS, there is nothing else in common between the references. This is not convincing because the substitution for the GABA(A) modulator of Erickson is for the purpose of following the treatment of different FXS conditions .
Applicants argue that Turner does not teach a correlation or equivalency between a GABA(A) modulator and an mGluR5 modulator. This is not convincing because the EEG monitoring is within the nexus of the treatments (See Erickson Para. 0023: EEG abnormalities are a sign and symptom to be monitored). Thus the treatments to be monitored before, during, and after as it Turner is within the scope of the treatments monitored by symptoms of FXS.
Regarding claim 28, no amendments or arguments have been put forth for the rejection of this claim and therefore the rejection is maintained.
Conclusion
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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/Dennis White/Primary Examiner, Art Unit 1758
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