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. 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. Priority The instant application is a 371 of PCT/EP2022/064534 filed on 05/30/202 2 and claims foreign priority to application no. IT102021000014333 filed on 06/01/2021. The certified copy of the foreign priority application filed on 11/28/2023 is acknowledged. Information Disclosure Statement The information disclosure statement (IDS) submitted on 11/28/2023 and 11/28/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement s are being considered by the examiner. Status of the Claims The preliminary claim amendments filed on 11/28/2023 is acknowledged. Claims 1-10 are cancelled . Claims 11-28 are newly added. Accordingly, claims 11-28 are pending and being examined on the merits herein. Claim Rejections - 35 USC § 102 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. Claim(s) 11-15, 17, 19-24, 26, and 28 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Yennurajalingam et al. (The Oncologist, 2016 in PTO-892) . Yennurajalingam disclose a clinical trial to study the effects of dexamethasone on cancer symptoms (see Abstract). Yennurajalingam discloses that pain, fatigue, sleep disturbance, drowsiness, dyspnea, anorexia/cachexia, and depression are the most common and debilitating symptoms in patients with advanced cancer and are associated with overall survival time (see second paragraph left column page 384). Yennurajalingam discloses that these symptoms usually co-occur and constitute clinically relevant clusters in advanced cancer patients, and that these symptom clusters are unfortunately inadequately treated in cases of advanced cancer (see second paragraph left column page 384). Yennurajalingam discloses that the clinical trial involved a total of 114 participants based on an inclusion criteria of a diagnosis of advanced cancer and the presence of at least three symptoms during the previous 24 hours (pain, fatigue, chronic nausea and anorexia/cachexia, sleep problems, depression, or poor appetite) with an average intensity of greater than or equal to 4 on the Edmonton Symptom Assessment Scale (ESAS; a 0–10 scale) (see Table 1 on page 386 and section Participants left column page 385). Yennurajalingam discloses that eligible participants were given 4 mg of dexamethasone or placebo orally, twice a day, for 14 days (see section Intervention left column on page 385) . Here, since the dexamethasone was administered orally to human patients, the dexamethasone disclosed in Yennurajalingam would necessarily be a pharmaceutical composition with at least an acceptable vehicle. As seen in Tables 2 and 3 on page 387, three symptom clusters ( fatigue/anorexia-cachexia/ depression (FAD), sleep/anxiety/drowsiness (SAD), and pain/dyspnea (PD) ) were identified, and patients who received dexamethasone resulted in significant improvement in severity of the FAD cluster at day 8 and 14 (see also Abstract). Yennurajalingam discloses that FAD and FAD cluster scores were significantly correlated with one another at all three time points (baseline, day 8, and day 15) (Table 2), and that median (interquartile range) improvement in the FAD cluster at day 15 and day 8 was significantly higher in the dexamethasone group than in the placebo group (0.22 [-0.04 to 0.45] vs. 0.06 [-0.30-0.20], p = .016, and 0.15 [ - 0.84 to 0.35] vs. - 0.095 [ - 0.35 to 0.16], p = .017), respectively (Table3). Yennurajalingam suggests that the symptoms of the FAD cluster (fatigue/anorexia-cachexia/ depression) may share a common pathophysiologic al basis , and that the beneficial effects of dexamethasone on the FAD cluster are probably due to the ability of the drug to inhibit these mediator s (see first paragraph left column page 388 and section “Conclusion” right column page 388). Here, Yennurajalingam discloses that the oral administration of dexamethasone resulted in significant improvements in FAD cluster symptoms (fatigue/anorexia-cachexia/ depression) in advanced cancer patients. Therefore, claims 11-15, 17, 19-24, 26, and 28 are anticipated. Claim(s) 11-12, 16, 18, 20-21, 25, and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al. ( US20150231161A1 in PTO-892). Lee discloses a composition for preventing, treating or alleviating atopic dermatitis comprising an immunosuppressant and a transglutaminase 2 inhibitor as active ingredients (see Abstract). Lee discloses that the immunosuppressant is at least one selected from the group consisting of cyclosporine, tacrolimus, dexamethasone, and pimecrolimus (claim 2). Lee discloses that their composition can be formulated into oral formulations such as tablets (paragraph 0047). Lee demonstrates in Example 1 the therapeutic effect of the immunosuppressant and a TG2 inhibitor administered alone or in combination for mice suffering atopic dermatitis (paragraphs 0061-0115). Here, as seen in Figs. 1 and 2, co-administration of tacrolimus (1 mg/kg/day) and glucosamine (500 mg/kg/day) alleviated the dermatitis compared to a control and the two compounds administered alone. Figs. 3-5 also shows that co-administration of cyclosporine (10, 45, and 100 mg/kg/day) and glucosamine (100 and 500 mg/kg/day) was also effective in reducing skin lesions as determined through the clinical skin score. Lee also demonstrates in Example 2 that co-administration of either tacrolimus and glucosamine or cyclosporine and glucosamine had therapeutic effects for human atopic dermatitis patients (paragraphs 0116-0136 and FIGS. 17-23). Lee demonstrates in FIGS. 24-26 that cyclosporine, tacrolimus (FK-506), and dexamethasone showed similar patterns and suppressed an immune response , and further discloses that d examethasone was also expected to have similar effects to one of the immunosuppressants for the purpose of preventing or treating atopic dermatitis when administered in combination with glucosamine according to the ir invention (paragraph 0147). Even though Lee does not provide in vivo data for the administration of dexamethasone to a dermatitis patient, an ordinary skilled artisan could “at once envisage” administering dexamethasone for treating dermatitis in a subject in need thereof because Lee recites that their immunosuppressant is selected from one of four options including dexamethasone for treating atopic dermatitis , and provides further support that d examethasone would have similar therapeutics effects against atopic dermatitis as demonstrated from the co-administration of tacrolimus or cyclosporine with glucosamine for mice or humans with atopic dermatitis as described above. MPEP 2131.02 states that “ A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[ oes ] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Furthermore, it is noted that the instant claims recite a method of treatment “comprising” administering an effective amount of a recited inhibitor compound. The transitional phrase “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps . See MPEP 2111.03 I. Therefore, the additional administration of glucosamine as disclosed in Lee is within scope of the instant claims. Claim Rejections - 35 USC § 103 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 . Claim(s) 20 -24, 26, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Yennurajalingam et al. (The Oncologist, 2016 in PTO-892). The teachings of Yennurajalingam are as described above . Even though the dexamethasone disclosed in Yennurajalingam would necessarily be a pharmaceutical composition with at least an acceptable vehicle as described above and would therefore anticipate claims 20-24, 26, and 28 as discussed above , as an alternative, it would have been prima facie obvious before the effective filing date of the claimed invention to have formulated the dexamethasone of Yennurajalingam into a pharmaceutical composition with an acceptable vehicle. One of ordinary skill in the art would have found it obvious to try with a reasonable expectation of success because Yennurajalingam demonstrates the oral administration of 4mg dexamethasone to human patients. Conclusion No claim is found allowable. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT DAVID H CHO whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0691 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8AM-5PM . 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. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /D.H.C./ Examiner, Art Unit 1693 /SCARLETT Y GOON/ Supervisory Patent Examiner, Art Unit 1693