DETAILED ACTION
A non-final Office action was mailed 16 January 2026 (“Office Action”).
Applicant’s reply to the Office Action was received 16 April 2026 (“Reply”).
Status of the Claims
The listing of claims filed with the Reply has been examined.
Claims 1, 59, 60, 106, 108, 110, 112, and 115 are pending.
Claims 1 and 115 are amended.
Claims 106, 108, 110, and 112 are withdrawn.
Claims 2–58, 61–105, 107, 109, 111, 113, 114, and 116–234 are canceled.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 16 April 2026 is acknowledged and has been considered.
Status of Rejections and Objections
The text of those sections of Title 35, U.S. Code and/or text providing the basis for non-statutory double patenting rejections not included in this action are set forth in the Office Action.
Unless repeated herein, any objection or rejection in the Office Action is withdrawn.
Claim Interpretation
Claim 1 includes variables A2, A3, and A4, which are defined as aryl, cycloalkyl, heteroaryl, and heterocyclyl. Those terms are defined in the specification. (Spec., pp.8–11). By contrast, the variable A5 in claim 1 is defined as arylene, cycloalkylene, heteroarylene, and heterocyclylene. Those terms are not defined in the specification. The variable A5 terms are interpreted as synonyms of aryl, cycloalkyl, heteroaryl, and heterocyclyl, respectively, because the suffix “ene” is understood to mean the functional group is divalent and each of variables A2, A3, A4, and A5 is divalent in Formulae (Ib), (Ic), (Id), and (Ie).
Objections to the Specification
The specification is objected to because it contains a typographical error.
The paragraph defining “alkyl” on page 6, line 19, begins with “i.e.i.e.e.g.”
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
Claims 1, 59, 60, and 115 are rejected under 35 U.S.C. § 112(a) because the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with the claims.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The breadth of the claim extends to treating or preventing an unknown number of disorders for an unidentified patient population. Dependent claims 59 and 60 recite a list of diseases and types of disorders, including, e.g., auto-immune disorders, bacterial and viral infections, cancer. The claim therefore encompasses, inter alia, a method of preventing auto-immune disorders, bacterial and viral infections, and cancer. The breadth of the claims is broad.
The nature of the invention generally relates to the pharmaceutical art and more specifically to a “NEK7 small molecule inhibitor compound,” pharmaceutical compositions thereof, methods of making the compound, and methods of administering the compound to a subject. The claim encompasses a method of preventing auto-immune disorders, bacterial and viral infections, cancer, etc. The nature of the invention is sophisticated.
The state of the prior art is discussed in the instant specification, which states: “the exact mechanism of the NLRP3-NEK7 interaction is not well understood. Accordingly, there is a need to develop inhibitors that will directly target NEK7 to affect the inflammatory response modulated by the NLRP3 inflammasome in several pathological diseases . . ..” (Id., 1:27–2:6). Accordingly, the state of the art is not very advanced.
Generally, in order to treat a disease, one of skill in the art must identify a biological target for affecting the disease, demonstrate a first drug candidate some way modulates the normal processes of the biological target, and demonstrate that a subject would benefit from such modulation without detrimental side effects. Typically, the process includes in vitro laboratory screening, in vivo testing, and clinical testing. Once that process has been successfully completed by the first drug candidate, subsequent drug candidates can benefit from the established proof of concept if a substantial correlation can be established between the first drug candidate and the subsequent drug candidates. In order to prevent a disease, one of skill in the art would need to identify the subjects likely to acquire such as disease, carry out the claimed invention (e.g., administer the claimed compound/composition), and demonstrate the subject did not have any cells infected by the pathogen and/or demonstrate the subject did not develop the disease as a result of the administration of the compound/composition.
Examiner is unaware of evidence from the specification or prior art that supports a claim for preventing the claimed classes of diseases or any specific diseases by administering a NEK7 small molecule inhibitor. Thus, the state of the prior art is in its infancy for preventing diseases.
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art is generally unpredictable. The relevant art requires each potential drug candidate to be assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18, 24 (CCPA 1970). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical or veterinary medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor is limited to in vitro assays of representative compounds to assess their respective activity against NEK7 and IL-1b. (Spec., 213:4–213:7; 484:1–500:12). There is no guidance for preventing the claimed classes of diseases or any specific diseases by administering to a subject a NEK7 small molecule inhibitor.
The existence of working examples relate to in vitro assays of representative compounds to assess activity against NEK7 and IL-1b. Biological Example 1 (NEK7 enzymatic assay) utilizes a casein substrate and full-length recombinant human NEK7 in a buffer. Biological Example 2 (IL-1b) utilizes THP-1 cells and a treatment protocol to ascertain the amount of cleaved IL-1b. Biological Example 3 provides the results for certain compounds of structures (Ia), (Ib), (Ic), (Id), and (Ie) in Tables 2a–e. Biological Example 4 shows comparative data for type 1.5 binding. There are no examples demonstrating in vivo activity against a specific disease with any compounds. And the specification does not explain whether the assays in Biological Examples 1 and 2 are established in the art or how the assays correlate to a known method of treating a disease. There are no examples demonstrating the prevention of the claimed classes of diseases or any specific disease by administering to a subject a NEK7 small molecule inhibitor prior to the subject becoming diagnosed with a disease or disorder.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure is extensive, as it includes in vitro and in vivo screening for each specific disease or disorder encompassed by the claims. As claimed, the scope of such diseases is essentially unbound. Therefore, experimentation would include screening a representative number of the claimed compounds against an assay known to be correlative for each of specific diseases encompassed by the claimed classes of diseases (e.g., auto-immune disorders, bacterial and viral infections, cancer) and each of the specific diseases.
Scope of Enablement Conclusion
In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a person having ordinary skill in the art to use the full scope of the claimed invention. The breadth of the claims is broad in scope; the nature of the invention is sophisticated; the state of the prior art is in its infancy for treating or preventing a disease or disorder; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor and existence of examples are limited to in vitro assays of certain compounds to assess activity against NEK7 and IL-1b; there are no working examples demonstrating in vivo activity against a specific disease with such compounds and there is no evidence of correlation between the in vitro assays in established methods of treatment; and, the quantify of experimentation needed to practice the claimed invention is extensive. Thus, when the evidence is considered as a whole, undue experimentation would be required to practice the full scope of the claimed invention.
Of particular note is the lack of information correlating the in vitro activity against NEK7 and IL-1b to existing technologies. As such, the disclosure does not indicate which, if any, specific diseases may be treated using the claimed compounds. Furthermore, there is no evidence that the disclosed compounds can prevent any disease according the claimed method.
Examiner recommends amending the claims to recite specific diseases that have been screened for with the claimed compounds and/or for which there is a correlation to the activity against NEK7 and IL-1b in the specification. Classes of diseases like auto-immune disorders, bacterial and viral infections, cancer, etc. are unlikely to pass muster due to the limited examples in the specification.
Response to Arguments
Applicant’s arguments submitted with the Reply have been fully considered but are not persuasive. Applicant’s comments focus on the scope of the compounds in amended claim 1 as opposed to: (i) the scope of diseases encompassed by the claims, and (ii) the lack of evidence to support a claim to preventing a NLRP3-mediated disorder (such as Alzheimer’s disease).
Double Patenting
Claims 1, 59, and 60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 63–65 of copending Application No. 18/262,787 (reference claims filed 27 February 2026).
17/998,135
18/262,787
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Instant claims 1, 59, and 60 are directed to a method of treating classes of diseases (e.g., auto-immune, inflammatory, and cardiovascular disorders) and specific diseases (e.g., type II diabetes, atherosclerosis, Alzheimer’s disease) comprising administering a compound of formula (Ib) to a subject in need thereof.
Reference claims 1 and 63–65 are directed to a compound of formula (I) and methods of treating classes of diseases (e.g., auto-immune, inflammatory, and cardiovascular disorders) and specific diseases (e.g., type II diabetes, atherosclerosis, Alzheimer’s disease) comprising administering the compound of formula (I) to a subject in need thereof.
The variables in the instant formula (Ib) and the reference claims formula (I) overlap. For example, A2 and A both include aryl, cycloalkyl, heteroaryl, and heterocycle. The formulae in the conflicting claims, therefore, cover the same compounds while the methods in the conflicting claims cover treating the same diseases with those compounds.
Although the claims at issue are not identical, they are not patentably distinct from each other because they cover the invention, as explained above. As such, an infringer of a patent granted based on the claims of one of the instant application or the reference application would also be an infringer of the other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 C.F.R. § 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 C.F.R. § 1.17(a)) pursuant to 37 C.F.R. § 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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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 submit an Automated Interview Request: http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached on 571-270-7674.
/J.M.N./Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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