NON-FINAL REJECTION
Receipt is acknowledged of Applicants' Amendments and Remarks, filed Feb. 23, 2026.
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The rejections and/or objections set forth below are either maintained or newly applied, and constitute the complete set presently applied to the instant claims.
STATUS OF THE CLAIMS
Claims 1-21 and 36 have been canceled.
Claims 22 and 23 have been amended and incorporate no new matter.
No new claims have been added.
Claims 24-33 stand withdrawn as drawn to nonelected inventions and/or species.
Thus, claims 22, 23, 34, and 35 now represent all claims currently pending and under consideration.
INFORMATION DISCLOSURE STATEMENT
The information disclosure statement (IDS) submitted on Feb. 23, 2026 was filed after the mailing date of the non-final action on Oct. 22, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
RESPONSE TO ARGUMENTS & EVIDENCE
Applicant’s arguments and evidence, filed Feb. 23, 2026, with respect to the rejection of claims 22, 23, and 34 under 35 U.S.C. § 102 over Smrcka et al. have been fully considered and are persuasive. Therefore, the rejection has been withdrawn.
However, upon further consideration, new grounds of rejection are set forth below. Specification paragraph numbers refer to the published application, US Pub. 2024/0277658.
NEW REJECTIONS
Claim Rejections - 35 U.S.C. § 112(b) – Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 34 is 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 pre-AIA the applicant regards as the invention.
Specifically, claim 34 contains a period before Table 1:
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In addition, claim 34 fails to end with a period.
As recognized by MPEP § 608.01(m), each claim must end with a period.
Claims 22, 23, 34, and 35 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 pre-AIA the applicant regards as the invention.
As recognized by MPEP § 2173.05(c)(III), the common phrase "an effective amount" may or may not be indefinite. The proper test is whether or not one skilled in the art could determine specific values for the amount based on the disclosure. See In re Mattison, 509 F.2d 563, 184 USPQ 484 (CCPA 1975).
Here, independent claim 22 is drawn to a method of treating a disease selected from infectious diseases or cancer by activating NLRP3 inflammasome, comprising administering to a patient in need thereof an "effective amount" of a compound of formula (I).
However, the specification fails to define or quantify the "effective amount" of a compound of formula (I) that activates NLRP3 inflammasome, or treats infectious diseases or cancer; nor does it provide any objective criteria, dose ranges, blood-level targets, minimum efficacy thresholds, or other boundaries that would allow a skilled artisan to determine what amounts fall within or outside the claim scope.
The specification discloses only in vitro data, with no accompanying dose-response data or other guidance, which is insufficient to clearly define the metes and bounds of the dosage range that constitutes an "effective amount."
Furthermore, the claims recite various biochemical and cellular effects that administering "an effective amount" of a compound of formula (I) allegedly achieves:
activating NLRP3 inflammasome, as recited by claim 22; and
boosting immune responses or breaking immune evasion in cancer or infectious diseases in a subject, or boosting specific immune responses by activating the NLRP3 inflammasome, as recited by claim 35.
It is unclear (1) which of these effects must be achieved; (2) to what degree each must occur; or (3) whether all of them or some combination define the term "effective amount."
Because the specification fails to define or quantify an "effective amount" of a compound of formula (I), one of ordinary skill in the art would be unable to clearly determine the specific amount of a compound of formula (I) to administer to achieve the above-listed effects. Accordingly, the term "effective amount" renders the metes and bounds of the claims indefinite.
In addition, MPEP § 2111.04 recognizes that claim scope is not limited by claim language that does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. Here, the active method step to be carried out is administering a compound of formula (I) to a patient with an infectious disease or cancer, which may in turn achieve the recited results or effects. However, these recitations simply describe what the active step of administering a compound of formula (I) is supposed to accomplish, and thus fail to further limit the scope of the claims.
Thus, for examination purposes, the claimed results and/or effects of administering a compound of formula (I) to a patient with an infectious disease or cancer are construed as intended use limitations and are given no patentable weight.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
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.
Claims 22, 23, 34, and 35 are 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 methods of treating infectious diseases, does not reasonably provide enablement for methods of treating cancer. The specification does not enable a 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.
MPEP § 2164.01(a), citing In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), sets out the factors to consider whether experimentation is undue, which are addressed below.
(A) The breadth of the claims. The claims are broadly drawn to methods for treating any infectious disease or any cancer by activating NLRP3 inflammasome, comprising administering an effective amount of a compound of formula (I) to a patient in need thereof.
The instant specification defines the term "patient" to be used interchangeably with the term "subject," which "refers to an animal, including, but not limited to, a primate (e.g., human), monkey, cow, pig, sheep, goat, horse, dog, cat, rabbit, rat, or mouse" (para. [0258]). Thus, the claimed patient population encompasses any mammalian subject, and is not limited to humans.
The instant specification defines "cancer" by way of example and in non-limiting terms to include a laundry list of different types of cancers, including, e.g., hematologic cancers such as acute myeloid leukemia, as well as solid tumors such as head and neck cancer (paras. [0538]-[0541]; [0581]).
Similarly, the specification defines "infectious disease" by way of example and in non-limiting terms to include any infectious disease caused by a bacterium, virus, fungus, or a parasite, accompanied by a laundry list of examples of infectious diseases (paras. [0542]-[0543]).
Compounds of formula (I) encompass a broad genus of urea and thiourea compounds having the structural formula,
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wherein B is O or S; X and X' are each C1-5-alkyl, -CH(CH2OH), or absent; and A and A' each encompass substituted or unsubstituted benzene, pyridine, quinoline, naphthyridine, oxadiazole, thiadiazole, isothiazole, or thiophene groups.
Thus, the claims are exceptionally broad, in every respect: the patient population, the diseases to be treated, and the compounds for administration.
(B) The nature of the invention. The claims are drawn to methods of treating cancer or infectious disease in a patient by activating NLRP3 inflammasome, comprising the active step of administering a compound of formula (I) to the patient. However, the specification fails to demonstrate that any compound of formula (I) actually treats cancer or infectious disease in a living patient. Rather, the focus of the disclosure is identification of compounds which activate NLRP3 inflammasome in vitro, with no evidence that the tested compounds, in turn, treat any disease in vivo. Thus, the nature of the invention is the activity of compounds of formula (I) as NLRP3 inflammasome activators.
(C) The level of predictability in the art. It is widely understood in the art of medicinal chemistry that the treatment of cancer with any compound is highly unpredictable, even when supported by substantial in vitro and in vivo data. Despite the high level of skill in the art, structure-activity relationships are not always linear, and small modifications to a lead compound can have dramatic effects on pharmacokinetic properties, bioavailability, and/or clinical efficacy.
For example, Smrcka et al. (WO 2009/020677, of record) claim methods for treating a disease or condition, e.g., cancer, by administering to a patient an effective amount of an agent that interacts with at least one amino acid residue of the interaction site of the G protein β subunit, wherein the agent is the elected compound, 1,3-di(quinoline-6-yl)urea (claims 9 and 35).
However, Surve et al. (cited on PTO-892) disclose that compound NSC-12155 binds to G-βγ, while the elected compound, NSC-71881, does not (p. 17794, left col.; Table 1), despite their close structural similarity:
NSC-12155
Binds to G-βγ
NSC-71881
Weak/no binding to G-βγ
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Because Surve et al. show that NSC-71881 does not possess the biological activity proposed by Smrcka et al. (G-βγ binding), one of ordinary skill in the art would not expect NSC-71811 to treat the diseases disclosed by Smrcka et al.
In addition, Cell Miner (cited on PTO-892) discloses National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) NCI-60 human tumor cell line screening data for NSC-71881, which showed no meaningful activity against any tumor type.
Across all 60 cell lines (representing nine types of cancers: leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney), NSC-71881 showed flat dose-response curves with little to no growth inhibition: all drug activity values = 4, i.e., all GI50 values were above 10-4 M (> 100 μM), which did not pass the minimum activity range threshold for further investigation or development.
Thus, there is no expectation that the elected compound would actually function to treat any cancer, regardless of its purported mechanism of action.
(D) The amount of direction provided by the inventor. The specification discloses that "targeted activation of NLRP3 can induce an inflammasome-dependent anti-cancer immune response, e.g. by increasing the activity of cytotoxic cells against tumor cells. Thus, NLRP3 activators may be used for the treatment of malignancies" (para. [0005]). While this may be the case in principle, no evidence is cited which establishes a link between this mechanism of action in vitro and the treatment of disease in vivo.
While the specification presents evidence that certain compounds of formula (I) are NLRP3 inflammasome activators in vitro, there are no working examples or embodiments demonstrating that compounds of formula (I) in fact treat any disease in any subject. Because there is no expectation that the claimed methods of treating cancer would be operative in a living patient, predicting and/or determining which embodiments would function in the claimed methods would require undue experimentation.
(E) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In view of the unpredictability in the art of small molecule cancer therapeutics; experimental evidence that the elected compound species failed to inhibit growth across all 60 cancer cell lines tested; and the lack of guidance and direction provided by the instant disclosure, one of ordinary skill in the art would be unable to practice the invention commensurate with the scope of the claims without undue experimentation.
Claim Rejections - 35 USC § 102
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 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 22, 23, and 34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mallick et al. (Indian Vet. Med. J., Vol. 5, No. 2, pp. 90-91 (1981), cited on PTO-892).
Mallick et al. exemplify a case of equine babesiosis in a pony aged about 8 years with initial symptoms of anorexia, dullness, depression, stiffness in the gait, and 103°F body temperature. Following initial treatment, the pony's conditioned worsened, with a fever of 106°F, increased respiration, and petechiae in the conjunctival mucous membranes. The examination of blood smear revealed rare infection of the parasite Babesia equi (p. 90).
The animal was then given 2 ml of babesan 5% solution subcutaneously. When
examined on the third day of babesan treatment, the fever had subsided to 102.4°F and it appeared to be improving, and following additional treatment, the pony recovered (p. 90).
As evidenced by the CAS Registry record for NSC-71881, babesan is the elected compound species of formula (I), 1,3-di(quinolin-6-yl)urea) (EN-23).
As evidenced by the instant specification (para. [0256]),
"treating" or "treatment" of any condition, disease or disorder refers to ameliorating the condition, disease or disorder (i.e., arresting or reducing the development of the condition, disease or disorder or at least one of the clinical symptoms thereof).
As further evidenced by the instant specification (para. [0258]),
"subject" refers to an animal, including, but not limited to, a primate (e.g., human), monkey, cow, pig, sheep, goat, horse, dog, cat, rabbit, rat, or mouse. The terms “subject” and “patient” are used interchangeably herein in reference, for example, to a mammalian subject, such as a human.
As further evidenced by the instant specification (paras. [0542]-[0543]),
In any of the methods described herein, the subject can have an infectious disease. In some examples of any of the methods described herein, the subject has been identified as having an infectious disease, or has been diagnosed as having an infectious disease. For example, an infectious disease can be caused by a bacterium, virus, fungus, or a parasite. Non-limiting examples of infectious disease include . . . babesiosis.
Thus, Mallick et al. disclose a method for treating an infectious disease comprising administering an effective amount of the elected compound, 1,3-di(quinolin-6-yl)urea, which is a compound of formula (Ic) as recited by claim 22; a compound of formula (Ic5) as recited by claim 23; and compound 3 as recited by claim 34.
While Mallick et al. do not explicitly disclose that administering an effective amount of 1,3-di(quinoline-6-yl)urea to treat an infectious disease activates the NLRP3 inflammasome, as recited by claim 22, this limitation is given no patentable weight, for the reasons set forth above.
CONCLUSION
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 10:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA E. TOWNSLEY/Examiner, Art Unit 1629
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