DETAILED ACTION
A Lack of Unity of Invention Restriction Requirement was mailed 20 August 2025.
Applicant’s Reply was received 16 October 2025 (“Reply”).
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA or pre-AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 and/or 103 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.
Status of the Claims
The listing of claims filed with the Reply has been examined.
Claims 1–4, 6–12, 14, 18, 19, 21–23, and 30–33 are pending. Claims 1, 6–12, 14, 18, 19, and 23 are amended. Claims 30–33 are new. Claims 5, 13, 15–17, 20, 24, and 29 are canceled.
Benefit of Earlier Filing Date
The instant application was filed 19 April 2023; is a national stage application of PCT/US2021/055651, filed 19 October 2021, and claims the benefit of U.S. Prov. Pat. App. Serial Nos. 63/093,705, filed 19 October 2020 and 63/253,404, filed 7 October 2021. Acknowledgment is made of Applicant’s claim.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 19 April 2023 and 16 October 2025 are acknowledged and have been considered.
Objections to the Specification
The abstract is objected to because it recites legal phraseology (“comprising”) and language that can be implied (“The invention relates to”; “The invention further relates to”).
Appropriate correction is required. For guidelines for the preparation of patent abstracts, see MPEP § 608.01(b) (Explaining: The abstract should be in narrative form and avoid legal phraseology (e.g., means, said), terms referring to purported merits of the invention (e.g., new, novel), and phrases that can be implied (e.g., The disclosure concerns, The disclosure defined by this invention,). The language should be clear and concise, and not repeat information given in the title. It should not compare the invention with the prior art. The abstract is generally limited to a single paragraph within the range of 50 to 150 words in length.).
Reply to Restriction Requirement and Election of Species
Applicant’s election without traverse of Group I in the Reply is acknowledged.
Claim 1 has been amended such that variable A is a heteroaryl selected from a list of 19 options and R1 is a 3- to 8-membered heterocycloalkyl.
Claims 2–4, 6–12, 14, 18, 19, 21–23, and 30–33 are consistent with claim 1.
Based on the amendments to claim 1, the restriction requirement between Groups I–III is hereby withdrawn.
Applicant’s election of species without traverse of
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is also acknowledged.
Scope of Search and Examination
A prior art search and examination will begin with the elected species. (MPEP § 803.02). If no prior art is found that would anticipate or render obvious the elected species, then the search will be extended to other species of the elected group. If no prior art is found that would anticipate or render obvious the elected group, then the search will be extended to non-elected species in non-elected groups. If prior art is found that anticipates or renders obvious a non-elected species or group, then the search will stop and the Markush-type claim will be rejected. The prior art search will not be extended unnecessarily to cover all non-elected species.
Should Applicant overcome the rejection by amending the Markush-type claim, then the claim will be reexamined. The prior art search will be extended to the extent necessary to determine the patentability of the Markush-type claim. If prior art is found during reexamination that anticipates or renders obvious the amended Markush-type claim, then the claim will be rejected, any claims to the nonelected species will be held withdrawn from further consideration, and the Office action will be final.
The elected species has been searched and prior art was found that renders the Markush-type claim 1 unpatentable. The prior art reference also renders claims 21 and 22 unpatentable.
Claim Rejections - 35 U.S.C. § 102
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)(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.
Claims 1, 21, and 22 are rejected under 35 U.S.C. § 102(a)(2) as being anticipated by WO2021/146192 (claiming the benefit of U.S. Prov. Pat. App. Serial Nos. 63/960,412, filed 13 January 2020, and 63/074,388, filed 3 September 2020) (“Rosen”) [IDS].
Rosen discloses compound RN 2668959-08-6 having the structure:
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. (Rosen, ¶75, compound 10).
Rosen discloses pharmaceutical compositions comprising the compound. (Id., ¶¶76–102).
Claim Rejections - 35 U.S.C. § 103
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.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966); MPEP § 2141(II).
Claim 1 is rejected under 35 U.S.C. § 103 as being unpatentable over Rosen in view of Mfuh et al., Current Medicinal Chemistry (2015), 22, 2819–2857 (“Mfuh”) and Patterson, L.H., Cancer and Metastasis Reviews (1993), 12, 119–134 (“Patterson”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
Rosen discloses compound RN 2668959-08-6. (Rosen, ¶75, compound 10). The compounds can exist in different forms, including a prodrug. (Id., ¶¶37–48).
Mfuh discloses a review of heterocyclic N-oxides. Mfuh states: “Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and precognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects.” (Mfuh, Abstract). Mfuh discloses pyridine N-oxides as potential drugs. (Id., pp.2829–2833).
Patterson discloses a rationale for using N-oxides as prodrugs for certain nitrogen-containing heterocycles. (Patterson, p.119). Patterson states a hypoxic tumor environment can reduce N-oxides. (Id.).
Ascertaining the differences between the prior art and the claims at issue
The elected species is an N-oxide. Compound RN 2668959-08-6 is not.
Resolving the level of ordinary skill in the pertinent art
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.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application discloses compound RN 2668959-08-6 as Example 17 and the elected species as Example 19. The instant application does not include evidence showing an unexpected result for Example 19 compared to Example 17.
The question of obviousness
Based on the above factors, it would have been obvious for a person having ordinary skill in the art prior to the filing of the instant application to combine the teachings of Rosen, Mfuh, and Patterson to arrive at the elected species because Rosen discloses the underlying compound RN 2668959-08-6 and states the compound can exist as a prodrug, Mfuh discloses N-oxides as being a useful alternative to underlying compounds, and Patterson discloses N-oxides can function as prodrugs. One of ordinary skill in the art would have been motivated to modify Rosen because it was known at the time of filing, based on Mfuh, and Patterson, that N-oxide prodrugs can improve one or more properties of the underlying compound. There would have been a reasonable expectation of success at arriving at the claimed invention because N-oxide forms of underlying compounds have been utilized in the art for decades and one of ordinary skill in the art has a high level of skill.
Claim Rejections - 35 U.S.C. § 112
The following is a quotation of 35 U.S.C. § 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claim 23 is 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.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” . . . These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The breadth of the claims extends to the prophylaxis of a hyperproliferative disease, diabetes, Francois-Neetens corneal fleck dystrophy, viral infection, or coronavirus that is “characterized by dysregulation of phosphoinositide-mediated signal transduction pathways or which may be ameliorated by modulating PIKFYVE-dependent signaling pathways, or by modulating endosome formation or trafficking.” The term prophylaxis is synonymous with preventing. Thus, the breadth of the claims is broad in scope.
The nature of the invention generally relates to the pharmaceutical art and more specifically to a method for the treatment or prophylaxis of a hyperproliferative disease, diabetes, Francois-Neetens corneal fleck dystrophy, viral infections, or coronavirus by administering a compound of claim 1 to a patient. Thus, the nature of the invention is sophisticated.
The state of the prior art is reflected by the discussion in the instant specification, which states: “Several small molecule inhibitors of PIKFYVE have recently been reported, including Apilimod.” (Spec., 3:24–25) (page:lines). The specification stats PIKFYVE inhibitors have shown promise as cancer therapies, MLS, FTD, and viral infection. (Id., 3:29–4:10). The specification states, “There continues to be a need for new, selected inhibitors of PIKFYVE.” (Id., 4:27–28).
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 that supports a claim for a method of preventing a disease by administering a compound of claim 1 to a patient.
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 that test the PIKFYVE inhibitory activity of the claimed compounds. (Spec., pp.113–121). The examples do not extend to a method of preventing a disease by administering a compound of claim 1 to a patient.
The existence of working examples relate to in vitro experiments. There are no examples demonstrating in vivo prevention of a disease in a patient.
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 and for each compound encompassed by the claims. As claimed, the scope of such diseases/claims is indeterminant and would require extensive experimentation.
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 preventing a disease with a compound of claim 1; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor is limited to in vitro assays that test the PIKFYVE inhibitory activity of the claimed compounds; there are no working examples demonstrating in vivo prevention of a disease in a patient; 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.
Examiner recommends amending the claims to the treatment of specific diseases.
Conclusion
The elected species is unpatentable and claims 1 and 21 are rejected.
The corresponding method of using the elected species in claim 23 is rejected.
Claims 2–4, 6–12, 14, 18, 19, and 30–33 are withdrawn.
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.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached on 571-270-7674.
The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JASON M. NOLAN/Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623