DETAILED ACTION
Applicant’s response filed 2/19/2026 has been received and entered into the application file. All arguments have been fully considered. Claims 1-17 are currently pending. Claims 5-10 and 12 are withdrawn. Claims 1, 11, 13 and 17 are currently amended.
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 .
Drawings
The corrected drawing sheets submitted 2/19/2026 are in compliance with 37 CFR 1.121(d) therefore, the objection to the drawings is withdrawn.
Nucleotide and/or Amino Acid Sequence Disclosures-Updated
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification at paragraph [0154] are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification-Objection Withdrawn
Applicant’s amendment submitted 2/19/2026 has corrected the indicated trade names and removed the previously indicated embedded hyperlink, thus obviating the previous objection.
Claim Objection-Withdrawn
Applicant’s amendment submitted 2/19/2026 has amended claim 1 to spell out the acronym NEK6, i.e., NIMA-related kinase 6, thus obviating the previous objection.
REJECTION(S) WITHDRAWN
Claim Rejections - 35 USC § 112
RE: Rejection of Claims 1-4, 11 and 13-17 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement:
Applicant’s amendment to claim 1 is sufficiently described in the specification. Therefore, the previous rejection is withdrawn.
RE: Rejection of Claims 13 and 17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite:
Applicant’s amendment submitted 2/19/2026 provides appropriate clarification. Therefore, the previous rejection of claims 13 and 17 is withdrawn.
REJECTION MAINTAINED/UPDATED
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) 1 and 3-4 remain rejected under 35 U.S.C. 103 as being unpatentable over Gray et al., (WO 2019/126696; previously cited) (“Gray”).
Claim 11 is no longer included in view of Applicant’s amendment submitted 2/19/2026.
Regarding claims 1 and 3-4, Gray is directed to NEK inhibitors represented by Formula I (page 1 and Table 1) and methods of treating diseases in which NEK plays a role wherein levels of NEK are inhibited by administering therapeutically effective amounts of the disclosed NEK inhibitors (Abstract and page 2, second full paragraph, page 4, lines 7-10; page 42, lines 25-26). Gray teaches the treated diseases include proliferative diseases (e.g., cancer), and neurodegenerative diseases (page 31, lines 20-22), wherein neurodegenerative diseases include amyotrophic lateral sclerosis and frontotemporal lobar degeneration (page 33, lines 19 and 22). Gray further teaches the pharmaceutical compositions of the application may be administered to humans as pharmaceutical compositions in the form of injectable solutions or suspensions (page 24, lines 14-17; page 25, lines 12-13 and 25-27) and by any conventional route, including intracisternally (i.e., direct injection into the brain) (page 26, lines 12-13).
It is further noted that Gray’s Table 2 illustrates that compounds I-1 thru I-23 inhibited NEK6 and compounds I-1 and I-3 were the most potent inhibitors of NEK6, having IC50 values ranging from 50 nM to 250 nM, and compound I-18 had an IC50 value ranging from 250 nM to 1000 nM, i.e., directly inhibits the activity of the NEK6 enzyme.
Thus, regarding claims 1 and 3, Gray’s disclosed method administers, via direct injection into the brain, a NEK6 inhibitor that directly inhibits the activity of the NEK6 enzyme, e.g., compounds I-1, I-3 or I-18, for treating diseases that include proliferative diseases (e.g., cancer), and neurodegenerative diseases (page 31, lines 20-22), wherein neurodegenerative diseases include amyotrophic lateral sclerosis and frontotemporal lobar degeneration (page 33, lines 19 and 22).
Gray’s compounds I-1, I-3 and I-18 are copied below for convenience:
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Thus, given Gray teaches administering the identical NEK 6 inhibitors as disclosed in the instant specification ([0083]), and the instant specification discloses treatment with compound I-3 provided statistically significant axonal transport defect rescue, it is noted that although Gray does not comment on reducing axonal transport defects, the fact that Gray teaches administering the identical NEK6 inhibitors (e.g., directly into the brain) to patients suffering from amyotrophic lateral sclerosis and frontotemporal dementia means that any and all results of the method of Gray, whether recognized at the time of publication or not, were inherently achieved by the reference method. MPEP 2112.01
Thus, Gray’s teaching encompasses the subject matter of instant claims 1 and 3. The only difference between Gray and the instant claim is that Gray does not teach the disclosed method with sufficient specificity to be anticipatory for a subject that suffers from amyotrophic lateral sclerosis and frontotemporal dementia. The neurodegenerative diseases of amyotrophic lateral sclerosis and frontotemporal dementia are disclosed within the teachings of Gray, but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). Where, as here, the reference does not provide any explicit motivation to select the specific neurodegenerative diseases, anticipation cannot be found. However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been obvious to have selected various combinations of various disclosed neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia, from within Wolfinbarger's disclosure, to arrive at methods “yielding no more than one would expect from such an arrangement.”
Regarding claim 4 and the limitation “wherein the NEK6 inhibitor statistically significantly reduces the expression of NEK6 in the neurons of the subject”, it is noted, as set forth above, Gray teaches administering the same NEK6 inhibitors for treating amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), as disclosed in the instant specification. Thus, the fact that Gray teaches administering the identical NEK6 inhibitors (e.g., directly into the brain) to patients suffering from amyotrophic lateral sclerosis and frontotemporal dementia means that any and all results of the method of Gray, whether recognized at the time of publication or not, were inherently achieved by the reference method. MPEP 2112.01
Claim 2 remains rejected under 35 U.S.C. 103 as being unpatentable over Gray, as applied to claims 1 and 3-4 above, and further in view of DeJesus-Hernandez et al., (Neuron 72, 245-256, October 20, 2011; previously cited) (“DeJesus”) and Byrne et al., (Lancet Neurol 2012; 11:232-40, published online February 3, 2012; previously cited) (“Byrne”).
The teaching of Gray is set forth above.
Regarding claim 2 and the limitation “the subject suffers from a dipeptide repeat toxicity disease”, it is noted that although Gray teaches the treated subject suffers from ALS or FTD, Gray does not further comment on the ALS/FTD subjects being identified with dipeptide repeat toxicity disease. However, DeJesus teaches the C9ORF72 mutation, which causes repeat expansion of non-coding GGGGCC hexanucleotide (i.e., dipeptide repeat), is the most common genetic abnormality in both familial FTD and familial ALS and was identified in the majority of families with a combined ALS/FTD phenotype (Summary, pages 245-246).
Additionally, Byrne teaches that patients carrying the C9ORF72 repeat expansion phenotype had disease onset at a much earlier age and had significantly more co-morbid FTD than patients without the repeat, thus the presence of the dipeptide repeat toxicity resulted in reduced survival (Summary, page 232).
Therefore, taking into hand the teachings of DeJesus and Byrne, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include treating subjects suffering from a dipeptide repeat toxicity disease, thus meeting the limitation of claim 2.
The person of ordinary skill in the art would have been motivated to modify the method of Gray to include subjects having the C9ORF72 mutation (the most common genetic abnormality in both ALS and FTD), which causes repeat expansion of non-coding GGGGCC hexanucleotide (i.e., dipeptide repeat) and results in earlier disease onset and reduced survival, as taught by DeJesus and Byrne, for the predictable result of reducing disease onset and improving patient survival, thus meeting the limitation of claim 2.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Gray with DeJesus and Byrne because each of these teachings are directed at ALS and FTD therapies.
Claims 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Gray, as applied to claim 2 above, and further in view of He et al., (Pathology-Research and Practice 214 (2018) 1648-1654; previously cited) (“He”) and Glant et al., (Arthritis & Rheumatism, Vol. 65, No. 7, July 2013, pp. 1725-1735; previously cited) (“Glant”).
The teaching of Gray, in view of DeJesus and Byrne, is set forth above.
Regarding claims 13-14, it is noted the combined prior art renders obvious administering an NEK6 inhibitor (i.e., applying an ALS treatment to the subject) and renders obvious treating a subject suffering from ALS/FTD associated with the C9ORF72 dipeptide repeat toxicity (C9FTD/ALS).
Further regarding claims 13, 15 and 16 and the limitations regarding determining statistically significantly increased expression levels of NEK6 and/or NEK1 in a sample obtained from the subject as compared to a subject not suffering from C9FTD/ALS, it is noted that Gray does not further teach conducting such an assay regarding expression levels of NEK6 and/or NEK1 in subjects to be treated. However, as set forth above the combined prior art renders obvious treating subjects suffering from ALS/FTD associated with the C9ORF72 dipeptide repeat toxicity (C9FTD/ALS), and per the specification at [0139], patients suffering from ALS/FTD associated with the C9ORF72 dipeptide repeat toxicity necessarily have increased expression of NEK6 and NEK1.
He further teaches methods of interfering (inhibiting) NEK6 as a promising therapeutic target for breast cancer patients given that NEK6 was overexpressed in a majority of breast cancer specimens, as compared to the expression levels in healthy non-tumorous tissue. He teaches interference of NEK6 diminished oncospheroid-forming capacity of breast cancer cells (Abstract).
Thus, He has established it was well-known to determine NEK6 expression levels in subjects needing inhibition treatment, i.e., prior to treatment. He further taught determining healthy and non-healthy expression levels.
Additionally, although He determined the expression levels from tissue samples, and not from peripheral blood mononuclear cell (PBMC) samples, Glant is directed to
methods of inhibiting arthritis-specific upregulated genes (e.g., NEK6) in rheumatoid arthritis (RA) patients and teaches known methods for determining NEK6 expression levels from PBMCs (Results, page 1725; left col, 2nd paragraph, page 1728; DISCUSSION, right col, page 1732; Figure 2A; Supplementary Figure 1). Glant is directed to exploring the therapeutic potential of targeted inhibition of epigenetic factors implicated in rheumatoid arthritis (RA) (Objective and Results, page 1725).
Glant teaches the peripheral blood mononuclear cells (PBMCs) were separated on a Ficoll gradient within 1 hour from blood samples obtained from consenting, healthy individuals and from RA patients naive to treatment with disease-modifying antirheumatic drugs (DMARDs) (RNA isolation, complementary DNA (cDNA) synthesis, and quantitative reverse transcription–polymerase chain reaction (qRT-PCR), page 1726).
Thus, Glant has established it was well-known in enzyme-inhibition therapeutic methods to determine the expression levels of the target enzyme. Glant specifically teaches determining NEK6 expression levels in healthy subjects and subjects needing inhibition treatment. Glant clearly teaches NEK6 expression levels can be determined by obtaining PBMCs from a blood sample from the subject.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include determining NEK6 expression levels by obtaining PBMCs from a blood samples of healthy subjects and subjects needing inhibition treatment (i.e., prior to treatment), thus meeting the limitation of claim 13.
The person of ordinary skill in the art would have been motivated to modify the method of Gray to include determining NEK6 expression levels by obtaining PBMCs from a blood samples, as taught by Glant, for the predictable result of determining the severity of a patient’s disease state and establishing a baseline of enzyme activity, thus permitting development of a more effective and personalized treatment, thus meeting the limitation of claim 13.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Gray with He and Glant because each of these teachings are directed at kinase inhibition therapies targeting NEK6.
Claim 17 remains rejected under 35 U.S.C. 103 as being unpatentable over Gray, in view of He and Glant, as applied to claims 13-16 above, and further in view of Hinchcliffe et al., (Degenerative Neurological and Neuromuscular Disease 2017:7 61-70; previously cited) (“Hinchcliffe”).
The teaching of Gray, in view of He and Glant, is set forth above.
Regarding claim 17, and the limitation directed to further administering medicaments recited in claim 17, it is noted that Gray further teaches the NEK inhibitor may be administered in combination with additional pharmaceutical agents, e.g. adjunctive therapeutic agents (page 35, lines 27-29).
Gray differs from the instant claim in that, Gray does not further comment on the applied ALS treatment comprising administering edaravone, riluzole, dextromethorphan hydrobromide and quinidine sulfate, or a sodium phenylbutyrate - taurursodiol formulation, as recited in claim 17. However, Hinchcliffe teaches Riluzole (i.e. rilutek) is a well-known medicament for treating amyotrophic lateral sclerosis (ALS) and has been shown to slow the course of the disease and extend patient survival (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include further administering a well-known ALS medicament, such as riluzole (i.e., rilutek).
The person of ordinary skill in the art would have been motivated to modify the ALS treatment method of Gray to include further administering of riluzole (i.e., rilutek), a well-known ALS medicament, as taught by Hinchcliffe, for the predictable result of slowing the advancement of the disease and extending patient survival, thus meeting the limitation of claim 17.
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Gray with Hinchcliffe because each of these teachings are directed at ALS therapies.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Allowable Subject Matter
Claim 11 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claim is 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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to E. YVONNE PYLA whose telephone number is (571)270-7366. The examiner can normally be reached M-F 9am - 6pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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E. YVONNE PYLA
Primary Examiner
Art Unit 1633
/EVELYN Y PYLA/ Primary Examiner, Art Unit 1633