DETAILED ACTION This office action is in response to applicant’s filing dated September 2 , 202 5 . 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 Claims Claims 1 , 2, and 6 - 16 are pending in the instant application. Acknowledgement is made of Applicant's amendments filed September 2 , 202 5 . Acknowledgement is made of Applicant's amendment of claims 1, 2, 6, 9, and 14; and cancelation of claims 3-5 . Election/Restriction Applicant’s election without traverse of (i) 25-hydroxycholesterol-3-sulfate (25HC3S) as the elected compound species and (ii) idiopathic pulmonary disorder (IPD) as the elected inflammatory condition species in the reply filed on September 2, 2025 is acknowledged. Claims 1 , 2, and 6 - 16 are presently under examination as they relate to the elected species: 25-hydroxycholesterol-3-sulfate (25HC3S) and idiopathic pulmonary disorder. Priority The present application is a 371 of PCT/US21/39219 filed June 25, 2021, which claims benefit of priority to US Provisional Application Nos. 63/044,631 ; 63/127,905 ; and 63/141,382 filed on June 26, 2020; December 18, 2020; and January 25, 2021, respectively ; US Provisional Application Nos. 63/146,559 ; 63/146,568 ; 63/146,566 ; 63/146,563 ; and 63/146,565 filed on February 5, 2021 ; and US Provisional Application Nos. 63/149,977 and 63/149,993 filed on February 16, 2021. Information Disclosure Statement The information disclosure statements (IDS) submitted on January 17, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. Drawings The drawings are objected to because: Figure 1A, the structures are blurry and contain illegible components. Figure 1B is blurry. Figure 1C is blurry and the X and Y axis are illegible. Figure 1D is blurry and the X and Y axis are illegible. Figure 2B is blurry and illegible. Figure 2D is the bars are blurry. Figure 2E is blurry. The X axis and legend are illegible. Figure 2E is blurry and illegible. Figure 3A-D the legends are illegible. Figure 5 contains illegible text. Figure 6, the structures are blurry Figure 7 contains illegible text. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. 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. Claims 1, 2, and 6-16 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 a method of treating idiopathic pulmonary fibrosis comprising administering 25-hydroxycholesterol-3-sulfate (25HC3S), does not reasonably provide enablement for a method of treating any idiopathic pulmonary disorder. 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 these claims. This is a scope of enablement rejection . To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation . In re Wright , 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that: The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt , 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation". The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands , 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman , 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors: 1- the quantity of experimentation necessary, 2- the amount of direction or guidance provided, 3- the presence or absence of working examples, 4- the nature of the invention, 5- the state of the prior art, 6- the relative skill of those in the art, 7- the predictability of the art, and 8- the breadth of the claims These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher , 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons: 1. The nature of the invention and relative skill of those in the art The invention relates to a method of treating idiopathic pulmonary disorder (IPD) in a subject in need thereof comprising administering to the subject an effective amount of 25-hydroxycholesterol-3-sulfate (25HC3S) or salt thereof. The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience. The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher , 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al ., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain). 2. The breadth of the claims Claims 1, 2 and 6-16 are very broad in terms of the type of diseases being treated: any idiopathic pulmonary disorder are claimed to be treated with 25-hydroxycholesterol-3-sulfate (25HC3S) or a salt thereof . In medicine, a disorder is an abnormal condition that affects the body's function but may or may not have specific signs and symptoms ; a disorder may indicate that a specific disease is present, but there is usually not enough evidence to make a diagnosis as evidenced by NCI (National Cancer Institute, https://www.cancer.gov/publications/dictionaries/cancer-terms/def/disorder , obtained from the internet December 8, 2025) . Idiopathic means arising spontaneously from an obscure or unknown cause. By b roadest reasonable interpretation , the term idiopathic pulmonary disorder is any abnormal pulmonary condition with an unknown cause. Thus, the claims are extremely broad in terms of the type of diseases being treated. In a review of the state of the art, idiopathic pulmonary diseases may include i diopathic pulmonary fibrosis , n on - specific interstitial pneumonia , d esquamative interstitial pneumonia , r espiratory bronchiolitis/interstitial lung disease , a cute interstitial pneumonia , l ymphoid interstitial pneumonia , and c ryptogenic organising pneumonia . Idiopathic lung disease involves damage to the lung tissue resulting from scarring or inflammation without a clearly identifiable cause. There are likely to be several factors that play a role in the pathology, such as genetic and environmental factors, but these are not always clear as evidenced by Smith ( https://www.news-medical.net/health/Types-of-Interstitial-Lung-Disease-%28ILD%29.aspx , Internet Archive Wayback Machine date May 20, 2019, obtained from the internet on December 8, 2025) . McLean-Tooke et al (Clinical & Translational Immunology, 2019; 8:e1086 pp 1-15) , cited for evidentiary purposes, teaches i nterstitial lung disease (ILD) is an umbrella term for a large group of over 200 pulmonary disorders characterised by inflammation and/or fibrosis of the pulmonary interstitium with heterogeneous causes, clinical course and treatments ; w hile some ILDs have an identifiable trigger with occupational, environmental or medication exposure and others are strongly associated with systemic disease, in particular the connective tissue diseases (CTD), for many their origin is unknown and the term ‘idiopathic’ is applied ; th e largest group of these are the idiopathic interstitial pneumonias (IIP) (page 1, left, 1 st paragraph). McLean-Tooke teaches m ore recently, professional societies across the world have published joint position papers on disease classification and approach to treatment which continue to evolve with inclusion of new entities and evolving criteria for diagnosis ; h owever, despite these improvements in classification, there is still a substantial overlap in the clinical, radiological and pathological features across the different ILD entities, making an accurate diagnosis challenging ; t his particularly applies to the IIPs, CTD-ILDs and a group defined more recently as idiopathic pneumonia with autoimmune features (IPAF) which overlaps with, but appears separate to, both the idiopathic and CTD-associated ILDs (page 1, right) . McLean-Tooke teaches f or the idiopathic interstitial pneumonias (IIP), there are no identifiable triggers, although genetic predisposition is starting to be documented ; t he commonest radiological and pathological patterns are usual interstitial pneumonitis (UIP – giving a diagnosis of idiopathic pulmonary fibrosis (IPF)), non-specific interstitial pneumonitis (NSIP) and organising pneumonitis (OP) ; CTD-ILDs are commonly seen in a number of CTDs such as rheumatoid arthritis and systemic sclerosis where the radiological and pathological patterns similarly include UIP, NSIP and OP ; i n IPAF, patients may have a range of clinical (Raynauds, arthritis), serological (autoantibodies) and morphological (NSIP and OP) features which overlap with the idiopathic and CTD groups but do not meet the criteria for either of the conditions (page 2, left, 1 st paragraph). McLean-Tooke teaches t he antifibrotic era has been exciting, proving that rate of disease progression can be slowed and exacerbations can be reduced, although their use is currently limited to the IPF cohort ; t he question remains as to whether we should be characterising disease, and therefore choosing treatment, based on the clinical phenotype or the course of the disease (progressive vs nonprogressive) or the stage of the disease (inflammation in early stage in CTD-ILD, fibrosis with architectural distortion or honeycombing in the late phases) ; t he question of targeting process or disease pattern instead of specific disease entities is already being challenged and being explored in the progressive disease phenotype studies (page 12, right). Thus, the state of the art demonstrates that treatment of any idiopathic pulmonary disorder is highly unpredictable. Regarding idiopathic pulmonary disorders associated with Epstein-Barr virus, Marzouk et al ( Current Opinion in Pulmonary Medicine 2005, 11:456 - 460 ), cited for evidentiary purposes, teaches EBV (E p stein-Barr virus) , a DNA virus, is ubiquitous ; i t can cause latent and clinical infection by triggering dysregulated cellular activity in lymphocytes and mononuclear cells ; EBV has been associated with a number of diseases, including B-cell lymphoproliferative disease, Burkitt’s lymphoma, Hodgkin’s disease, nasopharyngeal carcinoma, sarcoidosis and other diseases ; a lthough normally associated with infection of the upper respiratory tract and B-lymphocytes, EBV can infect and replicate in the lower respiratory tract as well (page 457, left, 1 st paragraph); t hree types of pulmonary manifestation have been described: hilar/mediastinal lymphadenopathy, pleural effusion and interstitial pneumonitis ; t here are only limited reports indicating a pulmonary parenchymal involvement as a complication of an acute EBV infection in immunocompetent patients (page 457, left, last bridge paragraph). Marzouk teaches EBV antigens and DNA in the lower respiratory tract were significantly associated with a diagnosis of IPF also formalin fixation of samples can cause protein degradation and thus loss of detection in samples ; t he inability of Wangoo et al. to identify any EBV DNA in lung tissue is perhaps more surprising ; e ven if EBV were not associated with IPF, one would expect to find a low-level background of EBV DNA in lung tissue simply because of the blood volume in this organ ; i n general, EBV antigen staining needs to be interpreted with caution, as some antibodies are related to viral latency, whereas others are specific for productive replication (page 458, left, 2 nd paragraph). Marzouk teaches a n established therapy for EBV infection is not available ; t he published data do not support the use of acyclovir for treatment of acute EBV infection despite the antiviral activity of this drug ; a lthough prospective clinical studies in children are lacking, the first-line treatment for proven ILD is the application of systemic steroids ; t he inhalative steroid treatment appears to be an option with a topic immunosuppressive effect to treat the fibrosing process without a relevant systemic immunosuppressive effect (page 459, right, 3 rd paragraph). Marzouk teaches u sing monoclonal antibodies against viral antigen, EBV replication within type II alveolar cells was shown to occur in adult cryptogenic fibrosing alveolitis ; r ecent preliminary data suggest that EBV is associated with disease progression but did not increase the incidence of lung cancer in these patients, LMP1 is one of the EBV-associated proteins and is expressed on the surface of EBV infected cells in the latent and replicating LMP1 staining was found to be indicative of disease activity and may be a useful finding for the management of IPF ; r ecently EBV expression was confirmed in LCH using in-situ hybridization and indirect immunofluorescence; there was no association between EBV and sarcoidosis ; t hese findings indicate, however, the need for more studies and should be interpreted carefully ; t reatment for proven EBV-induced ILD is the application of systemic steroids ; t here is no data to support acyclovir for treatment of acute EBV infection (page 459, right, last paragraph) . Thus, the state of the art demonstrates that treatment of idiopathic pulmonary disorder associated with Epstein-Barr virus is highly unpredictable. 3. The amount of direction or guidance provided and the presence or absence of working examples The specification provides data for 25HC3S inactivating DNMT ( DNA methyltransferases ) activities in human hepatocytes and data (Example 1) . The specification provides additional data for the plasma pharmacokinetics of 25HC3S in Sprague Dawley rats (Examples 2 and 3). The specification provides n o examples of using 25HC3S for treating any idiopathic pulmonary disorder or for the treatment of any disorder. Thus, the examples provided do not constitute working examples. 4. The quantity of experimentation necessary Because of the known unpredictability of the art (as discussed supra ) and in the absence of experimental evidence commensurate in scope with the claims , the skilled artisan would not accept that 25HC3S could be predictably used as treatment of all idiopathic pulmonary disorders . Since there is no precedent in the literature for the treatment of any idiopathic pulmonary disorders with 25HC3S , how is the skilled physician supposed to know what type of dose regimen of 25HC3S to use for each of the pathologically different idiopathic pulmonary disorders ? Determining if 25HC3S will treat any particular idiopathic pulmonary disorders state would require subjecting 25HC3S into clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. This is undue experimentation given the limited guidance and direction provided by Applicants. Accordingly, the inventions of claims 1 , 2, and 6 -16 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success. 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. 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. 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. Claims 1 and 6-16 are rejected under 35 U.S.C. 103 as being unpatentable over Ren et al (US 2019/0269695 A1, cite in the IDS filed January 17, 2025) . Regarding claim 1 , Ren teaches a method of treating , in a subject in need thereof dysfunction or failure of at least one organ comprising administering to the subject a therapeutically effective amount of a composition comprising 5-cholesten-3, 25-diol, 3-sulfate (25HC3S) or a pharmaceutically acceptable salt thereof (claims 1 and 13); wherein the method comprises treating dysfunction or failure of lung (claim 14). Ren teaches dysfunction or failure of lung is lungs damaged by pulmonary fibrosis [0087]. 5-cholesten-3, 25-diol, 3-sulfate (25HC3S) is equivalent to 25-hydroxycholesterol-3-sulfate (25HC3S). Thus, Ren teaches a method of treating lung damaged by pulmonary fibrosis. Ren does not explicitly teach treating idiopathic pulmonary fibrosis. However, it would have been prima facie obvious to one of ordinary skill in the art to utilize the method of treating lung damaged by pulmonary fibrosis to treat lung damaged by idiopathic pulmonary fibrosis with a reasonable expectation of success since the art teaches treating lung damaged by pulmonary fibrosis generically. Regarding claim 6 , Ren teaches the exact dosage to be administered may vary depending on the age, gender, weight and overall health status of the individual patient, or on other treatments being received by the patient, as well as the extent or progression of the disease condition being treated and the precise etiology of the disease; however, in general for administration in mammals (e.g. humans), sufficient composition is administered to achieve 25HC3S or pharmaceutically acceptable salt thereof dosages in the range of from about 0.001 to about 100 mg or more per kg of body weight per 24 hr., and preferably about 0.01 to about 50 mg of compound per kg of body weight per 24 hr., and more preferably about 0.1 to about 10 mg of compound per kg of body weight per 24 hr. are effective [0174]. Regarding claim 7 , Ren teaches the time of day and the number of times per day that the pharmaceutical formulation is administered may vary and are best determined by a skilled practitioner such as a physician; the compound may be administered at least once a day (e.g., twice daily) before surgery for at least I month or at least 1 week, or at least 1 day before surgery, or even during surgery, e.g. surgery related to or associated with or which may cause organ failure [0178]. MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff , 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson , 65 USPQ2d 1379, 1382 (Fed. Cir. 2003). Regarding claim 8 , Ren teaches administration may be oral or parenteral, including intravenously, intramuscularly, subcutaneously, intradermal injection, intraperitoneal injection, etc., or by other routes (e.g. transdermal, sublingual, rectal and buccal delivery, inhalation of an aerosol, intravaginally, intranasally, topically, as eye drops, via sprays, by iontophoresis, by photoacoustic-guided drug delivery, microneedle delivery, etc. ; the route of administration typically depends on the nature of the condition that is treated and on e.g. whether the treatment is prophylactic or intended to effect a cure of disease that is present [0175]. Regarding claim 9 , Ren teaches the composition comprises at least one physiologically acceptable excipient [0017]. Regarding claims 10- 12 , Ren teaches the pharmaceutically acceptable formulations include solid, semi-solid, and liquid materials conventionally utilized to prepare solid, semi-solid and liquid dosage forms such as tablets, capsules, creams, lotions, ointments, gels, foams, pastes, aerosolized dosage forms, and various injectable forms (e.g. forms for intravenous administration) [0076]. Regarding claims 13-15 , examples of liquid carriers include but are not limited to various aqueous or oil based vehicles, saline, phosphate buffer and the like, or combinations thereof; water may be used as the carrier for the preparation of compositions which may also include conventional buffers and agents to render the composition isotonic; oral dosage forms may include various thickeners, flavorings, diluents, emulsifiers, dispersing aids [0077]. Regarding claim 16 , Ren teaches the compositions in a vial, approximately 30 to 50 mg of 25HC3S was weighed into a 20 mL vial (5 vials total, one vial for each vehicle) [0192]. Taken together, all this would result in the practice of the method of claims 1 and 6-16 with a reasonable expectation of success. Conclusion Claims 1, 2, and 6-16 are rejected. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT RAYNA B RODRIGUEZ whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-7088 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 8am-5:00pm, Monday - Thursday . 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, FILLIN "SPE Name?" \* MERGEFORMAT Amy L Clark can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-1310 . 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. /Rayna Rodriguez/ Primary Examiner, Art Unit 1628