DETAILED ACTION
This Office Action is in response to Applicant’s Amendment and Remarks filed on 22 December 2025 in which claims 2, 5, 7, 12, 15 and 17 were canceled, and claims 1, 3, 11, 13 and 21 were amended to change the scope and breadth of the claims.
Claims 1, 3, 4, 6, 8-11, 13, 14 and 18-21 are pending in the current application, and are examined on the merits herein.
The Declaration of Dr. Suchismita Acharya, submitted by Applicant on 28 July 2025 under 37 CFR §1.132 are acknowledged and will be further discussed below.
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 .
Withdrawn Rejections
Applicant’s amendment, filed 22 December 2025, with respect to the rejection of claims 1-4, 11-14 and 17-20, under 35 U.S.C. § 112, second paragraph, for indefiniteness, has been fully considered and is persuasive.
Claim 1 has been amended to recite “administering to the patient in need thereof…”;
Claims 2, 5, 7, 12, 15 and 17 have been canceled;
Claim 3 has been amended to recite “wherein the acute interstitial nephritis…is characterized by at least one of: a serum creatinine level of at least 1.5 times baseline, wherein the baseline is a serum creatinine level of a subject without an acute kidney injury…”
Claim 11 has been amended as suggested in the Office Action mailed 22 September 2025.
The rejection is hereby withdrawn.
Modified Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on 22 December 2025, where the limitations in pending claims 1, 3, 11, 13 and 21 as amended now have been changed. Therefore, rejections from the previous Office Action, dated 22 September 2025, have been modified and are listed below.
Response to Arguments
Applicant's arguments filed 12 December 2025 and Declaration filed 28 July 2025 have been fully considered but they are not persuasive.
Applicant contends the claims have been amended to recite treating amongst others acute glomerular renal disease.
The above argument is not found persuasive, because the Office Action has already provided a prima facie case of obviousness for administering the compound of Formula I to treat acute glomerular renal disease.
Applicant contends evidence presented in the Declaration demonstrate the presently claimed compound of claim 1 (also known as AVR-48) acts as an TLR4 agonist, and functions by a different mechanism than a canonical TLR4 antagonist. Applicant contends “the compounds” promote effective innate response in CBMCs. Applicant contends CBMCs treated with AVR-48 do not initiate any overt innate immune response or increased cytokines compared to LPS, which is the basis of the combination of Acharya, Li and Jalan.
It is not clear which compounds promote an innate response, since the only compound tested was AVR-48. Even if Applicant discovered a different mechanism of action from administering AVR-48, the prior art as a whole teach, suggest and provide motivation for performing the positively recited steps. However, as discussed previously, the prior art recognized the same TLR4 activities of AVR-48 as Applicant.
Applicant previously argued “the skilled artisan would understand that the compounds claimed herein help enhance an immune response and mitigate LPS tolerance where, in principle, a TLR4 antagonist will suppress the immune system”.
The arguments are not found persuasive. As previously noted, Acharya et al. also teach the presently claimed compound acts as both a TLR4 and TLR2 activator and inhibitor. The ordinary artisan would have also known from Acharya et al., that these effects are concentration dependent. And, the ordinary artisan would have known the compound can be formulated at a concentration to inhibit TLR4 and increase the anti-inflammatory cytokine, IL-10. Acharya et al. teach this will reduce inflammation and treat acute lung injury.
Thus, the amendments, arguments and Declaration are not persuasive to overcome the rejection over Acharya et al., because one of ordinary skill in the art would have known the activation/inhibition of TLR4 and simultaneous increase in IL-10 is concentration dependent. It is well within the level of ordinary skill in the art to optimize the concentration of the claimed compound following the guidance of Acharya et al.
The rejection is hereby maintained.
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3, 4, 6, 8-11, 13, 14 and 18-21 are rejected under 35 U.S.C. 103 as being unpatentable over Acharya et al. (US Patent Application Publication No. 2020/0022995, cited in previous Office Action) in view of Li et al., (Chin. J. Integ. Med., 2019, vol. 25, no. 1, pp. 37-44, cited in previous Office Action) and further in view of Jalan et al. (WO2012/022939, cited in previous Office Action).
Acharya et al. teach a method of treating a subject in need of immunomodulation, comprising identifying a subject in need of immunomodulation; and providing the subject with an effective amount of a compound 8,
PNG
media_image1.png
124
318
media_image1.png
Greyscale
(claims 3 and 18). The compound inhibits a TLR4 and TLR2 at 1-10 µM, inhibits TLR2 at 75-100 µM, and activates TLR4 at 75-10 µM (claim 3). The compound also modulates IL-10 at a concentration dependent manner (see fig. 7 and 8). Acharya et al. teach “reducing inflammation via activation of the anti-inflammatory cytokine IL-10 will be therapeutic for acute lung injury (ALI)….” (para [0037]). Achayra et al. teach simultaneously inhibiting TLR2 and TLR4 pathways and up-regulating IL-10 (para [0065]; [0111]). Acharya et al. teach compound 8 stimulates IL-10 production at 0.1-1.0 µM (para [0167]). The compound is formulated to treat sepsis (claim 22). The compound is formulated into a pharmaceutical composition adapted for pulmonary, parenteral, intravenous, enteral, or oral administration (para [0061]).
Acharya et al. do not expressly disclose treating acute glomerular kidney disease (present claims 1, 11, 17 and 21).
Li et al. evaluated the efficacy of a tablet comprising a mixture of plant extracts (SHT tablet) on targeting multiple toll-like receptor (TLR) pathways to treat renal ischemia-reperfusion injury (IRI), (title, abstract). Li et al. teach the active ingredients of Chinese medicine produce “multi-targeted therapeutic effects”, making it a promising pathway for designing new treatments (p.43, second para). Acute kidney injury (AKI) often results from insults to ischemia, toxic substance and septicemia, wherein renal-IRI is one of the primary causes of AKI (p.42, Discussion). Increasing evidence demonstrates ischemia-induced inflammatory responses are primarily stimulated via TLRs, including TLR2 and TLR4 (Li et al., p.42). Li et al. further found protein and mRNA expression levels of TLR2 and TLR4 exhibited synchronized uptrend after surgery-induced ischemia in a rat-animal model (p.43, third para). High doses of SHT had a protective effect on renal-IRI, wherein TLR2 and TLR4 were much lower than the model group. Li et al. conclude SHT’s protective effect on renal function may relate to the regulation of renal TLR2 and TLR4 expression, for the clinical prevention and treatment of ischemic AKI (p.43-44, bridging para).
Jalan et al. teach the use of a TLR4 inhibitor for treating an individual suffering from kidney disease (claim 1). These patients include those suffering from acute kidney injury (examples 3 and 4). Jalan teaches treating an individual suffering from renal dysfunction and/or renal failure (claim 4). The patient suffering from kidney failure also has glomerular damage (p.28, line 17 to p.29). Jalan et al. teach a method of identifying a patient suitable for treatment of renal dysfunction and/or renal failure, the method comprising measuring and comparing the level of TLR4 in the patient’s urine with a control patient not suffering from the disease (claim 10).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer p-nitrophenyl-N-acetyl-β-D-glucosamine to treat a patient suffering from acute glomerular renal disease.
One having ordinary skill in the art would have been motivated to provide the compound in a therapeutically effective amount to treat the acute glomerular renal disease, wherein the compound simultaneously increases IL-10, with a reasonable expectation of success. Acharya et al. teach the presently claimed compound acts as both a TLR4 and TLR2 activator and inhibitor. The ordinary artisan would have also known from Acharya et al., that these effects are concentration dependent. And, the ordinary artisan would have known the compound can be formulated at a concentration to inhibit TLR4 and increase the anti-inflammatory cytokine, IL-10. Acharya et al. teach the compound will reduce inflammation and treat acute lung injury. It is well within the level of ordinary skill in the art to optimize the concentration of the claimed compound following the guidance of Acharya et al. to simultaneously inhibit TLR4 and treat an acute injury while increasing IL-10 and reduce inflammation.
One having ordinary skill in the art would have been motivated to administer p-nitrophenyl-N-acetyl-β-D-glucosamine to treat a patient suffering from acute glomerular renal disease because it inhibits TLR4 inhibitor, where Jalan et al. found TLR4 inhibitors are useful for the treatment of acute kidney injury including those suffering from glomerular damage. As discussed above, p-nitrophenyl-N-acetyl-β-D-glucosamine inhibits both TLR2 and TLR4. Furthermore, Li et al. teach targeting multiple receptors is expected to be advantageous. More specifically Li et al. found targeting TLR2 and TLR4 had a renal protective effect in an IRI-animal model, for the treatment of acute kidney injury.
The ordinary artisan would have had a reasonable expectation of success because p-nitrophenyl-N-acetyl-β-D-glucosamine is recognized as targeting both TLR2 and TLR4, wherein targeting both receptors was an effective means for treating renal-IRI for the treatment of kidney disease, and further supported by Jalan et al. which teach inhibiting TLR4 for treating kidney disease.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAHAR A CRAIGO whose telephone number is (571)270-1326. The examiner can normally be reached M-F: Noon-8pm ET.
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 use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699