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 Claims
Per Applicant’s amendment to the claims, submitted on 04/21/2026, claims 1, 14, and 28 are amended, and claim 34 is canceled. Currently, claims 1, 2, 4, 10-11, 13-15, 17, 19, 23, 26, 28-30, 32, 36, and 38-39 are pending in the instant application. Claims 2, 4, 13, 15, 17, 19, 23, 26, 28-30, 32, 36, and 38-39 are withdrawn from consideration in accordance with the previously presented Restriction requirement. Claims 1, 10-11, and 14 are pending examination.
Claim Rejections - 35 USC § 112 Second Paragraph – Withdrawn
Rejection of claim 14:
In light of Applicant’s amendment to the claims, the rejection is hereby withdrawn. The claim has been amended to specify the target PIKfyve enzyme.
Claim Rejections - 35 USC § 112 First Paragraph - Withdrawn
Rejection of claims 1, 10-11, 14, and 34:
In light of Applicant’s amendment to the claims, the rejections are hereby withdrawn. Claim 1 has been amended to specify a group of individual PIKfyve inhibitor compounds. Claim 34 has been canceled.
Claim Rejections - 35 USC § 102 – Withdrawn
Rejections of 1 and 10-11 over Rosen (previously referenced):
In light of Applicant’s amendment to the claims, the rejections over the Rosen prior art are hereby withdrawn. Claim 1 now recites specified compounds as PIKfyve inhibitors. Rosen does not teach or suggest the newly recited compounds.
Rejections of claims 1, 14, and 34 in view of Bhagwat (previously referenced):
In light of Applicant’s amendment to the claims, the rejections over the Rosen prior art are hereby withdrawn. Claim 1 now recites specified compounds as PIKfyve inhibitors. While Bhagwat teaches a compound of newly amended claim 1 and treatment of neurological disease, they do not explicitly teach the treatment of neurological diseases in patients not having the indicated c9orf72 mutation.
Claim Rejections - 35 USC § 102 – Necessitated by Amendment
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.
Claim(s) 1, 10-11, and 14 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ozboya (US 2023/0271965 A1).
Claim 1 recites a method of treating a neurological disorder in a human patient, the method comprising administering to the patient a therapeutically effective amount of a PIKfyve inhibitor, wherein the patient does not express a mutant form of c9orf72 comprising an expanded GGGGCC hexanucleotide repeat, and wherein the PIKfyve inhibitor is selected from:
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Ozboya teaches compounds as PIKfyve inhibitors and methods of use of such compounds for the treatment of neurological disorders. More specifically, the teachings of Ozboya are directed towards neurological disorders in patients having mutations in TDP-43 such as familial or sporadic ALS (specification [0003])1. Furthermore, Ozboya teaches that the disclosed compounds would be effective in treating neurological disorders associated with TDP-43 or C9orf72 (specification [0048])2, essentially indicating that said compounds would be useful for treatment in patient populations having mutations, individually, in TDP-43, C9orf72, or both. Among the compounds taught by Ozboya is the following (specification [0423]):
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The above compound is identical to the first compound recited in the instant claim. As Ozboya essentially teaches a method of treating neurological disorders by administering a compound of the instant claim, and further indicates a patient population having TDP-43 mutation, the teachings are considered as anticipating of the instant method.
Claim 10 further limits the method of claim 1 wherein the neurological disorder is neuromuscular disorder.
As iterated in the rejection of claim 1, Ozboya teaches the treatment of ALS, which would be considered as a neuromuscular disorder.
Claim 11 further limits the method of claim 10 wherein the neuromuscular disorder is selected from the group consisting of amyotrophic lateral sclerosis, congenital myasthenic syndrome, congenital myopathy, cramp fasciculation syndrome, Duchenne muscular dystrophy, glycogen storage disease type II, hereditary spastic paraplegia, inclusion body myositis, Isaac's Syndrome, Kearns-Sayre syndrome, Lambert-Eaton myasthenic syndrome, mitochondrial myopathy, muscular dystrophy, myasthenia gravis, myotonic dystrophy, peripheral neuropathy, spinal and bulbar muscular atrophy, spinal muscular atrophy, Stiff person syndrome, Troyer syndrome, and Guillain-Barré syndrome.
As indicated in the claim 1 rejections Ozboya teaches at least the treatment of amyotrophic lateral sclerosis (ALS).
Claim 14 further limits the method of claim 1 wherein the PIKfyve inhibitor binds to PIKfyve enzyme and/or inhibits PIKfyve enzymatic activity.
As indicated previously, Ozboya teaches compounds as PIKfyve inhibitors, wherein such inhibitors are defined as compounds which competitively bind to PIKfyve enzyme (specification [0153])3. Additionally, Ozboya provides that the disclosed compounds were tested in a PIKfyve kinase domain binding assay. The results for said assay on the compound indicated in the claim 1 rejection, provided an IC50 value of 0.003 uM (specification [0423]):
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Conclusion
Claims 1, 10-11, and 14 are rejected.
THIS ACTION IS MADE FINAL. 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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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “TDP-43 is a nuclear DNA/RNA binding protein involved in RNA splicing. Under pathological cell stress, TDP-43 translocates to the cytoplasm and aggregates into stress granules and related protein inclusions. These phenotypes are hallmarks of degenerating motor neurons and are found in 97% of all ALS cases. The highly penetrant nature of this pathology indicates that TDP-43 is broadly involved in both familial and sporadic ALS. Additionally, TDP-43 mutations that promote aggregation are linked to higher risk of developing ALS, suggesting protein misfolding and aggregation act as drivers of toxicity. TDP-43 toxicity can be recapitulated in yeast models, where the protein induces a viability deficit and localizes to stress granules.”
2 “In an aspect, the invention features a method of treating a TDP-43-associated disorder or C9orf72-associated disorder (e.g., FTLD-TDP, chronic traumatic encephalopathy, ALS, Alzheimer’s disease, LATE, or frontotemporal lobar degeneration) in a subject in need thereof.”
3 “Inhibitors of this type may, for example, competitively inhibit PIKfyve activity by specifically binding the PIKfyve enzyme (e.g., by virtue of the affinity of the inhibitor for the PIKfyve active site), thereby precluding, hindering, or halting the entry of one or more endogenous substrates of PIKfyve into the enzyme’s active site.”
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