DETAILED ACTION
Claims 14-17, 20-23, 37, 42, 44, 49, 61, 68, and 84 were pending; claims 16-17, 23, 42, and 49 were withdrawn. Per Applicant’s response on 11/20/2025 claims 14, 44, 49 were amended and claims 20-21 and 37 were canceled.
Claims 14-17, 22-23, 42, 44, 49, 61, 68, and 84 are pending. Claims 16-17, 23, 42, and 49 stand withdrawn as not be directed to the elected species, Y677N. Claims 14-15, 22, 44, 61, 68, and 84 are the subject of the Office Action below
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 .
Priority
The instant application filed 12/23/2021 Claims Priority from Provisional Application 63/185111, filed 5/6/2021, and from Provisional Application 63/130438, filed 12/24/2020.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 10/7/2025 and 11/20/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statements are being considered by the Examiner.
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.
Claims 14-15, 20, 21, 22, 37, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over The Orphazyme Company Report, Company announcement No. 01/2019 published 1/20/2019; Millat et al. “Niemann-Pick C1 Disease: Correlations between NPC1 Mutations, Levels of NPC1 Protein, and Phenotypes Emphasize the Functional Significance of the Putative Sterol-Sensing Domain and of the Cysteine-Rich Luminal Loop,” Am. J. Hum. Genet. 68:1373–1385, 2001; and Pavan US 20160025712 A1 published 1/28/2016.
NOTE: The claims were amended by removing A1054T as a mutation, therefore art directed to other known mutations is added to the rejection. Independent claim 14 was also amended to require the limitations of claim 37, now canceled.
Instant claim 14 is directed towards a method of treating or preventing Niemann Pick disease, type C (NPC) in a subject in need thereof, the method comprising administering a therapeutically effective amount of arimoclomol to the subject, wherein the subject is identified as having at least one missense mutation in at least one of the two alleles in an NPC gene, wherein the at least one missense mutation in at least one of the two alleles in an NPC gene are selected from the group consisting of I1061T, P1007A, S940L, R1186H, T1205K, G886V, R978C, P1007L, L472P, R518W, G910S, A927V, S954L, G992W, S1004P, T1036M, N1156S, V1165M, N222S, G248V, S357L, R404W, E451K, Y677N, E718D, S734I, G765V, H8970, A926V, N968S, P981L, M1001V, P1007R, H1016L, T1036A, R1059Q, V1078, F1079L, F1087L, V1141G, M1142T, A 151T, V1155G, and T1205K.
Instant claim 14 is obvious by the following logic, arimoclomol is a known treatment for Niemann Pick disease, type C (NPC), the drug was first patented in 2009 for this indication.
NPC is diagnosed via multiple biomarker/symptom tests and/or genome sequencing, thereby “identifying” a genetic mutation indicative of NPC in combination with biomarkers of the disease.
A diagnosed patient with NPC regardless of genetic profile will be given arimoclomol based on the fact that there are few effective treatments for NPC and no cures. As such, patients in need of treatment (those diagnosed with NPC) will be treated with arimoclomol as to mitigate the disease to both check efficacy and hopefully improve the patient’s life.
Orphazyme Company Report teaches the treatment of NPC with standard care, miglustat (meeting the limitation of instant claim 15 and 21) and arimoclomol, a known two drug combination. The Phase II/III study showed positive results in the patients treated, indicating the drug combination was a potential efficacious treatment for NPC. The Report states, “A responder rate of more than 50% in the placebo control group impeded the ability to show an overall effect on this endpoint. However, when considering patients who severely progressed during the trial, only 10.7% of the arimoclomol-treated patients got ‘much worse’ or ‘very much worse’ compared to 26.7% in the placebo control group.” This again indicated that the drug combination will be tried in all patients with any genetic mutation causing the disease in order to improve patient quality of life.
The Orphazyme Company Report doesn’t teach a specific genetic profile of the patients (specifically a missense mutation) and its identification, however the Report states, “Post-hoc analyses are on-going to further the understanding of these results.”
Moreover, The Orphazyme Company Report states:
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Clearly this indicated the known cause of the disease. The disease is “genetic.” The disease “is caused by mutations in the NPC gene leading to defective NPC protein.” Therefore NPC is able to be identified by the genetic mutations that lead to defective NPC protein in the patient in combination with biomarkers and symptoms.
Instant claim 14 requires the patient is identified as having at least one missense mutation in at least one of the two alleles in the NPC gene, this limitation is not taught by The Orphazyme Company Report, though clearly implied by the known cause of the disease.
Millat teaches some known correlations in 2001 between NPC1 mutations and levels of NPC1 protein and function of the protein, i.e. the correlation between mutation and defective NPC protein. Millat teaches missense mutations in the sterol-sensing domain (SSD) that lead to infantile neurological onset, and missense mutations in the cysteine-rich luminal loop resulted in a wide array of clinical and biochemical phenotypes. Given that some missense mutations lead to classic phenotypes of the disease one would use this known mutation to identify a patient with NPC, and then treat them with arimoclomol after identification. One would be motivated to know the genetic mutation causing the disease as to inform the doctor of the outcome potential in future patients, therefore it would be obvious to try arimoclomol in these patients.
Instant claim 44 requires an NPC1 genotype selected from the group consisting of G886V/R978C, Y677N/R1059Q, E718D/P1007L,G765V/P1007A, I1061T/I962fs, V1165M/F1199sp1, and N1156S/F1199sp2. Millat teaches I1061T as a known mutation but is silent on I962fs. However there are two problems with this genotype towards patentability. One, the mutations seem to be irrelevant to the use of the drug combination of arimoclomol/miglustat in patients diagnosed with NPC as the disease is poorly managed and has few options for patients making this known drug combination an obvious choice for all patients with NPC including I1061T/I962fs patients. Two, Applicant has not shown any significance to this patient population in the Specification that would lend to patentability. As such it is obvious to treat all NPC patients with the arimoclomol/miglustat and expect some efficacy. Therefore this claim is rejected as well.
RESPONSE to Applicant’s Arguments: Applicant argues that the amendment to remove the A1054T missense mutation overcomes the rejection. However, the art teaches other mutations claimed, as such the art still meets the limitations as claimed. Therefore this argument is not persuasive.
Claim Rejections - 35 USC § 103
Claims 14-15, 22, 44, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over The Orphazyme Company Report, Company announcement No. 01/2019 published 1/20/2019; and Millat et al. “Niemann-Pick C1 Disease: Correlations between NPC1 Mutations, Levels of NPC1 Protein, and Phenotypes Emphasize the Functional Significance of the Putative Sterol-Sensing Domain and of the Cysteine-Rich Luminal Loop,” Am. J. Hum. Genet. 68:1373–1385, 2001 as applied to claims 14-15, 22, and 44 above in further view of Morkeberg WO2016041561A1.
Instant claim 61 requires arimoclomol is the arimoclomol citrate salt administered at about 100 mg/day to about 700 mg/day; and instant claim 68 wherein arimoclomol is administered in a dosage adjusted by patient body weight. Instant claim 84 requires wherein arimoclomol is the citrate salt.
WO teaches the citrate salt of arimoclomol, see claim 43.
WO teaches, “The target dosage for the API is in one embodiment within a range of 0.1 to 100 mg/kg bodyweight, such as 0.1 to 0.5 mg/kg, for example 0.5 to 1 .0 mg/kg, such as 1 to 2 mg/kg, for example 2 to 5 mg/kg, such as 5 to 10 mg/kg, for example 10 to 15 mg/kg, such as 15 to 20 mg/kg, for example 20 to 30 mg/kg, such as 30 to 40 mg/kg, for example 40 to 50 mg/kg, such as 50 to 75 mg/kg, for example 75 to 100 mg/kg bodyweight.”
Wo also teaches dosing of, “ wherein said formulation is administered as 75 to 1000 mg/day, such as 75-100, 100-150, 150-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900 or 900- 1000 mg/day,” in claim 45.
It would be obvious to a PHOSITA to dose the known drug in its known forms and dosages in order to provide efficacy for the patient. A PHOSITA would reasonably expect the drug to have efficacy based on its mode of action. As such these claims are obvious.
RESPONSE to Applicant’s Arguments: Applicant argues that the amendment to remove the A1054T missense mutation overcomes the rejection. However, the art teaches other mutations claimed, as such the art still meets the limitations as claimed. Therefore this argument is not persuasive.
Conclusion
No claims allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629