DETAILED ACTION
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
Claims 1 and 37 are pending and examined.
NOTE: This application has been transferred to Primary Examiner Barsky. The examiner makes Newell et al., “N-methyl antitumour agents,” Cancer Chemother Pharmacol (1987) 19:91-102 of record as it relates to the state of the art and the Examiner’s search.
Claim of Foreign Priority
This is a correction. The examiner notes that the claimed to foreign priority was not made in an Application Data Sheet provided by Applicant.
Response to Amendments
Applicant’s amendments to the claims of June 1, 2026, in response to the Office Action of March 4, 2026, are acknowledged.
Response to Arguments
A suggestion for allowance is set forth below.
Applicant argues that the claims are enabled to treat cancer. Applicant provides data for dose-dependent treatment of HCC cells, pancreatic cells, and glioblastoma cells for 911-Me, 912-Me, or 913-Me.
Even if Applicant’s claimed compounds can treat cells of these forms, this does not enable treating the hundreds of types of cancers. Moreover, treating a cell does not show pharmacokinetics for crossing the BBB to treat tumors of the CNS, including glioblastoma. Glioblastoma is one of the few cancer types Applicant argues the claimed agent are able to treat with data provided in Applicant’s most recent Remarks.
Further, the Specification does not refer to any specific form of cancer other than hepatocellular carcinoma (HCC). The lack of pharmacokinetic data includes dosages, routes of administration, and ability to penetrate the BBB.
The instant claims are not enabled for the treatment of all forms of cancer.
According to City of Hope, “Busting myths: Cancer is not just one disease,” October 31, 2023, https://www.cancercenter.com/community/blog/2023/10/cancer-is-not-one-disease- date accessed October 14, 2026, quoting Dr. Ahn:
Sometimes, drugs overlap and can work for different cancer types, but that’s something that has to be proven through clinical research, because it’s certainly not safe or reasonable to assume that one drug is going to work for every cancer type just because it works for one.
According to Upton et al., “Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy,” Theranostics 2022; 12(10):4734-4752, “The BBB is a unique and complex structure that is a significant impediment to effective drug delivery to the brain for the treatment of brain tumors.” P4748, 1st par. “The discovery of a safe and efficacious approach to bypassing the BBB for clinical use for the treatment of brain tumors is urgently needed and has the potential to change the course of brain tumor therapy greatly.” Id.
In short, there is no presumption that cancers can be treated with a particular agent nor can it be taken for granted that cancers of the CNS can be treated by administering a drug that is shown to treat a type of cancer in an in vitro assay.
Suggestions for Allowance:
Applicant can limit claim 1 to the specific compounds shown. Applicant can limit claim 37 to administering a compound of claim 1 (once amended) to treat HCC in a subject in need thereof.
Claim Objections
Claims 1 and 37 are objected to for including structures that are illegible. The examiner can only decipher the claimed compounds because the same structures appear to be those included in the Specification. The amendments to the claims appear to have been input in grayscale. This did not delay substantive examination on the merits.
Claims 1 and 37 do not end in a period.
Claim Rejections - 35 USC § 112
Claims 1 and 37 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant provides a Formula (I) with various substituents. At the end of the claim, Applicant defines the compound to be among a specific limit list wherein many of the optional variables provided above are no longer relevant. Thus, Applicant claims the breadth of what the compound can be defined as and then indicates that it cannot actually be defined in many of those ways. This is indefinite. For example, R1 and R2 can only be a 5-membered ring with 2-3 nitrogen atoms. R1 and R2 are defined to include many other compounds. Further, L is defined as optionally interrupted and substituted with a number of moieties. However, the specific compounds claimed do not include any of this. So, if the compound is selected from one defined at the end of claims 1 and 37, all of the language defining L, R1 and R2, among others are meaningless and inconsistent with the limitations that truly define the claim.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claim 37 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the select species of compounds of formula (I): ST-910, ST-920, 932-iso, 932, 922, 923, 924, 911-Me, 912-Me, 914-Me, 913-Me,
as well as a method of treating liver cancer by administering the disclosed 932-Iso compound to a subject in need thereof, does not reasonably provide enablement for the full scope of compounds of formula (I), or treating the full scope of conditions set forth in claim 37. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the Invention: The nature of the invention is complex in that the claims are drawn to many species of compounds of formula (I), but only show synthesis steps for select species ST-910, ST-920, 932-iso, 932, 922, 923, 924, 911-Me, 912-Me, 914-Me, 913-Me. Additionally, prevention, as claimed, is undeterminable and not a guaranteed outcome, and efficacy of the full scope of claimed compounds of formula (I) in the context of the full scope of conditions in the claimed method is not demonstrated. The Applicant only demonstrates efficacy of 932-iso in treating human liver cancer cells.
Breadth of the Claims: The claims are broad in that the claims recite a broad range of compounds of formula (I), and a method for treating a broad range of cancers as set forth in claim 37, including cancers of the CNS such as glioblastoma. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the Specification and Existence of Working Examples: The specification describes synthesis steps for select compounds of formula (I): ST-910, ST-920, 932-iso, 932, 922, 923, 924, 911-Me, 912-Me, 914-Me, 913-Me, as well as data for activity against HCC line HUH7 using the Applicant’s disclosed compound, 932-Iso. However, no working examples are given for the full scope of compounds of formula (I), or a method of treating conditions set forth in claim 37. While it is noted that the applicant has shown synthesis steps for select compounds of formula(I), as well as data for activity against relevant cell lines with a single compound of formula(I), the applicant is not enabled for the full scope of treating all claimed cancers, including those of the CNS and there is no pharmacokinetic provided in any respect.
Predictability and State of the Art: The state of the art at the time the invention was made was unpredictable and underdeveloped. It is known in the art that the development of conditions such as liver cancer and other conditions claimed by the Applicant, is highly dependent on multiple unpredictable factors including individual genetic disposition, demographic, environmental exposures, etc., and that prevention of such compounds is not able to be determined or guaranteed. It is also known that enablement of a species of compound within a genus, does not provide enablement of the genus as a whole. Kunal teaches that even small changes in the chemical structure of a compound can lead to unpredictable effects on activity (Roy, Kunal, and Arkaprava Banerjee. Activity Cliffs. SpringerBriefs in Molecular Science, Cham, Springer Nature Switzerland, 2025. Accessed 18 Feb. 2026).The Applicant claims disparate disease states to be treated by the claimed compound. These include Alzheimer’s, congestive heart failure, osteoporosis, and fibrosis, among others. This list emphasizes the unrelated nature of the diseases claimed, as they are all known in the art to have different mechanisms in unrelated organ systems.
Mayo Clinic. (Cancer - Symptoms and Causes) Mayo Clinic, 7 Dec. 2022, www.mayoclinic.org/diseases-conditions/cancer/symptoms-causes/syc-20370588. Accessed 27 Feb. 2026). – explains the mechanism of cancer development, involving uncontrollable replication of cells.
Gordan, J.D. (Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update), Journal of Clinical Oncology, Vol. 42, no. 15, pp. 1830-1850 (Year: 2024) – teaches the first-line treatment for hepatocellular carcinoma, including tyrosine kinase inhibitor, atezolizumab, and VEGF inhibitor, bevacizumab.
Grossberg, G.T. (Present Algorithms and Future Treatments for Alzheimer’s Disease), Journal of Alzheimer's Disease, Vol. 67, pp. 1157-1171 (Year: 2019) – teaches that Alzheimer’s disease is a neurodegenerative disorder and that cholinesterase inhibitors are primarily used to treat cognitive impairment linked to Alzheimer’s.
These references highlight that the conditions claimed by the Applicant are not expected by one skilled in the art to be treated by related compounds, as they progress through unrelated mechanisms.
While the specific cancer cell line (HCC line HUH7) described by the applicant is known in the art to be that of liver cancer and the applicant shows activity against it using 932-iso, due to the unpredictable nature of the conditions claimed, the applicant does not disclose a method for treating the full scope of the claimed conditions.
Amount of Experimentation Necessary: The quantity of experimentation necessary to carry out the claimed invention is high, as the skilled artisan could not rely on the prior art or instant specification to teach how to make all of the compounds of formula (I), or treat all of the conditions set forth in claim 37, by administering to a subject in need thereof. In order to carry out the claimed invention, one of ordinary skill in the art would have to determine through trial and error, how to arrive at each and every species of cancer claimed, a POSA would need to test different dosages and routes of administration for each of those cancers. This would require extensive experimentation and testing.
Additionally, one of ordinary skill in the art would need to determine treatment, as claimed, in all the conditions set forth by administering all the compounds set forth, in relevant cell lines or subject groups in controlled experiments.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claim 37 is not considered to be fully enabled by the instant specification.
As such, no claim is allowed.
Conclusion
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 extension fee 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 JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
