FINAL REJECTION
Receipt is acknowledged of Applicants' Amendments and Remarks, filed Jul. 27, 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Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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 3-8 and 11-20 have been canceled.
No claims have been amended, and no new claims have been added.
Thus, claims 1, 2, 9, 10 now represent all claims currently pending and under consideration.
INFORMATION DISCLOSURE STATEMENT
No new Information Disclosure Statements (IDS) have been submitted.
MAINTAINED REJECTIONS
The following rejections are maintained from the previous Office Action dated Apr. 30, 2026, on the ground that the references cited therein continue to read on the limitations of the amended claims.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
Claims 1, 2, 9, and 10 stand 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 inflammatory pulmonary diseases, does not reasonably provide enablement for prevention of inflammatory pulmonary diseases. 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 the claims.
The claims are directed to methods of treating or preventing an inflammatory pulmonary disease or disorder, which is not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention without undue experimentation.
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.
(A) The breadth of the claims & the nature of the invention.
The claims are narrowly drawn to methods of preventing or treating an inflammatory pulmonary disease comprising administering a pharmaceutical composition comprising an effective amount of a compound of formula (I), a compound species known as FJU-C28 (5,6-dihydro-1-(1-oxo-2-propen-1-yl)-4-(phenylthio)-6-(2-propen-1-yl)-2(1H)-pyridinone).
However, the specification does not set forth a definition of the terms "prevent," "preventing," or "prevention." While Figs. 11A to 11F illustrate “the effect of FJU-C28 on preventing endotoxin-induced lung function decrease in mice with systemic inflammation” (p. 6, lines 18-19), the term "prevention" is unsupported, because administration of the claimed compound mitigates LPS endotoxin-induced lung damage, but does not prevent LPS-induced lung damage from occurring.
(B) The level of predictability in the art.
"Prevention" connotes the absolute absence of a condition which cannot reasonably be achieved with regard to the claimed conditions, or in medicine generally. In addition, there is no definitive method by which to determine whether a patient will develop the claimed conditions in the future, and thus, be in need of preventive therapy. Even if a patient can be identified as having known risk factors for a disease, there is no way to predict that a patient will, in fact, later develop that disease. Further, the failure of a condition to develop cannot reliably be attributed to the active agent; for example, the condition may reverse or resolve due to lifestyle factors or spontaneous remission. Thus, the term "preventing” is unsupported by the disclosure.
(C) The amount of direction provided by the inventor.
Example 7 discloses the effect of FJU-C28 on lung function in mice with LPS-induced systemic inflammation, in which mice were administered the endotoxin LPS (7.5 mg/kg) and treated with or without FJU-C28 (5 mg/kg) for 24 hours. Untreated mice with LPS-induced systemic inflammation had significantly decreased lung function. However, treatment with FJU-C28 restored the LPS-induced decreases in lung function (FIG. 11), reduced the neutrophil infiltration in the interstitium, and sustained most of the alveolar structure (FIG. 12A). The results indicate that FJU-C28 could attenuate lung injury by suppressing the secretion of proinflammatory cytokines, including IL-6 and RANTES, in LPS-induced systemic inflammation (p. 23, line 17 to p. 24, line 17).
While this is sufficient to support methods of treating inflammatory pulmonary disease, no examples of the prevention of any disease are disclosed or tested.
(D) 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, coupled with a lack of guidance, direction, and/or a working embodiment provided by the instant disclosure, one of ordinary skill in the art would be required to engage in undue experimentation in order to prevent inflammatory pulmonary disease, i.e., to practice the invention commensurate with the scope of the claims.
Claim Rejections - 35 U.S.C. § 103
Claims 1, 2, 9, and 10 stand rejected under 35 U.S.C. 103 as being unpatentable over Jow et al. (TWI 531368 B).
Jow et al. disclose that acute lung injury caused by sepsis is a common risk factor in the clinic. Because patient mortality remains high, strategies are needed to improve the survival rate of patients with sepsis and acute lung injury with anti-inflammatory effects (para. [0001]).
To that end, Jow et al. disclose and claim a pharmaceutical composition for inhibiting activation of immune cells and inhibiting systemic inflammatory responses, comprising a compound of formula (I) or a salt thereof and a pharmaceutically acceptable excipient (claim 2).
The compound of formula (I) of Jow et al. is also known as FJU-C4 (5,6-dihydro-1-(2-methyl-1-oxo-2-propen-1-yl)-4-(phenylthio)-6-(2-propen-1-yl)-2(1H)-pyridinone) (see Examples 1-5), which is shown below for comparison with the claimed compound, FJU-C28:
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Jow et al. disclose that the pharmaceutical composition inhibits inducible nitric oxide synthase (iNOS); inhibits cyclooxygenase 2 (COX2); and inhibits the expression of pro-inflammatory cytokines, including TNFα, IL-1β, and IL-6 (claims 4-8).
Thus, Jow et al. disclose, teach, and suggest the treatment of acute lung injury by administering to a subject in need thereof an effective amount of FJU-C4.
As evidenced by the instant specification (Example 7), acute lung injury (ALI) is an inflammatory pulmonary disease, as recited by claim 1. The instant specification further evidences that acute lung injury results in an excessive inflammatory response that underlies acute respiratory distress syndrome (ARDS) and lung fibrosis, as recited by claim 2.
Jow et al. disclose that the concentration of the compound of formula (I) is greater than 0.1 μM (claims 1-3), which encompasses the range of 0.1 to 10 μM, as recited by claim 9.
Jow et al. exemplify the treatment of mice with acute lung injury by administering FJU-C4 at concentrations between 1 mg/kg and 5mg/kg, as well as more than 5 mg/kg (Example 5), which reads on the range of 5 to 50 mg/kg, as recited by claim 10.
Jow et al. differs from the claimed methods only in that the prior art compound, FJU-C4, has an allyl methyl substituent, which has been replaced with hydrogen in the claimed compound, FJU-C28, as shown above.
However, it would have been predictable to one of ordinary skill in the art as of the filing date to modify the compound of Jow et al. (FJU-C4) by replacing the allyl methyl group with hydrogen to arrive at the claimed compound (FJU-C28) with a reasonable expectation of success, because FJU-C4 was known to treat the identical diseases via the same mechanism of action, resulting in the identical molecular and cellular effects.
As recognized by MPEP § 2144.08 (II)(A)(4), where a prior art compound shares the same utility as those claimed, one of ordinary skill in the art would have a reasonable expectation that modifying the compound by the interchange of hydrogen and alkyl would yield compounds having similar properties. Hydrogen and methyl substitutions are known in the art and have been held to be obvious variants of each other. See MPEP § 2144.09; In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990); and In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring).
Further, MPEP § 2144.09 recognizes that a prima facie case of obviousness may be made when chemical compounds have (1) very close structural similarities and (2) similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
A prima facie case of obviousness based on structural similarity is rebuttable by proof that the claimed compounds possess unexpectedly advantageous or superior properties. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963).
RESPONSE TO ARGUMENTS
Applicant's arguments filed Jul. 27, 2026 have been fully considered but they are not persuasive.
With respect to the rejection of claims 1, 2, 9, and 10 under 35 U.S.C. § 112(a) for lack of an enabling disclosure commensurate with the scope of the claims, Applicant contends that paragraph "(8) Animal Model" in the "Materials and Methods" section of the specification states that "The mice were injected with/without FJU-C28 (5 mg/kg) dissolved in DMSO/PBS buffer, and after one hour the mice were stimulated with an intraperitoneal injection of LPS (7.5 mg/kg) in PBS buffer " That is, the claimed compound was administered to the animal prior to the administration of LPS. Example 7 shows that under these conditions, the pre-administered FJU-C28 could restore the LPS-induced decreases in lung function and reduce lung injuries. Therefore, the Examples demonstrate that the compound of formula (I) recited in claim 1 can
prevent an inflammatory pulmonary disease or disorder (Remarks, p. 5).
However, the disclosed examples demonstrate that administration of the claimed compound can mitigate, reduce, or attenuate LPS-induced inflammation, not prevent it. Specifically, Figs. 11A-11F (shown below) show that compared to control, mice with LPS-induced systemic inflammation had significantly decreased lung inspiratory capacity (IC), vital capacity (VC), lung compliance (C chord), forced expiratory volume at 100 ms (FEV100), and forced vital capacity (FVC). Treatment with FJU-C28 restored the LPS-induced decreases in lung function including VC (p<0.05), C chord, FEV100 (p<0.05), and FVC (p<0.05), compared to those of LPS-treated mice (spec. p. 23, line 19 to p. 24, line 4).
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“LPS + C28” indicates administration of the claimed compound, FJU-C28 (5 mg/kg) prior to induction of inflammation via intraperitoneal injection of LPS (7.5 mg/kg). However, as shown in Figs. 11A-11F (above), lung function in this pre-treated group, while improved over LPS alone, remains diminished as compared to control. Further, partially restoring LPS-induced decreases in lung function is not the same as preventing decreased lung function from occurring at all. The data presented in the specification establishes that pre-treatment with the claimed compound mitigates, attenuates, or reduces lung injury, but does not prevent decreased lung function induced by LPS, which still causes lung injury.
Similarly, Fig. 12A demonstrates that, in LPS-stimulated mice, neutrophils infiltrate and accumulate in the interstitium of the lungs, and the alveolar structure was destroyed and became thickened and irregular, compared to mice in the control group. Treatment with FJU-C28 reduced the neutrophil infiltration in the interstitium and sustained most of the alveolar structure in mouse lung tissue in the LPS+FJU-C28 treatment group compared to the LPS group (spec p. 24, lines 4-17; emphasis added). Again, this is evidence that administration of the claimed compound mitigates, attenuates, or reduces lung injury, but does not prevent LPS-induced lung injury and decreased lung function from occurring.
Thus, the data presented in the specification supports treating pulmonary inflammation, regardless of whether the claimed compound is administered prior to or subsequent to the lung injury. However, it does not support prevention of lung injury, which would result in measurements identical to the control group.
For the foregoing reasons, the rejection of claims 1, 2, 9, and 10 under 35 U.S.C. § 112(a) is maintained.
With respect to the rejection of claims 1, 2, 9, and 10 under 35 U.S.C. § 103 as unpatentable over Jow et al. (TW I531368 B), Applicant contends that the test results of Example 1 show that, as compared with FJU-C4, the claimed compound FJU-C28 protected macrophages from LPS-induced cell death and exhibited lower cytotoxicity than FJU-C4 at higher concentrations (FIG. 1B). In addition, Applicant contends that Examples 3 and 4 show that FJU-C28 not only suppressed the expression of TIMP1, IL-6, and IL-10, but also inhibited the expression of RANTES, which was not suppressed by FJU-C4.
Thus, Applicant contends that the claimed compound, FJU-C28, has two advantages over FJU-C4: lower cytotoxicity, and the ability to suppress RANTES, neither of which could have been predicted or reasonably expected from the disclosure of Jow et al. (Remarks, pp. 6-7).
First, the data presented in Fig. 1B compares the cytotoxicity of the prior art compound, FJU-C4, with the claimed compound, FJU-C28, in RAW264.7 macrophages, which were pretreated with various concentrations for 30 min and then stimulated with or without LPS for 24 hours. Because LPS-induced inflammation reduces cell viability for both C4 and C28, cell viability for each compound alone is the relevant measure.
Fig. 1B (below) shows that FJU-C28 alone had lower cell viability (i.e., is more cytotoxic) than FJU-C4 alone at all concentrations except one (10 μM):
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This single data point suggests experimental variability rather than evidence of lower cytotoxicity across a range of therapeutic concentrations. The comparative data presented in Fig. 1B does not show a reliably consistent dose-response curve, and thus is of little probative value.
Second, it is acknowledged that Table 2 and Examples 3-4 establish that the claimed compound, FJU-C28, inhibits RANTES (CCL5), while the prior art compound, FJU-C4, does not. However, the specification provides no clinical data demonstrating that this mechanistic difference improves patient outcomes. Because RANTES is not always pro-inflammatory, inhibition could have mixed or even counterproductive effects when administered to treat an inflammatory pulmonary disease in vivo, depending on the disease stage and etiology. Thus, the theoretical benefit of RANTES inhibition is uncertain, and any advantage remains speculative.
For the foregoing reasons, the rejection of claims 1, 2, 9, and 10 under 35 U.S.C. § 103 is maintained.
CONCLUSION
No claims are 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.
CORRESPONDENCE
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
