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 .
Status of the Claims
Claims 1, 4, 5, 8 and 9 are currently pending. Claim 8 is withdrawn. Therefore, Claims 1, 4, 5 and 9 are presented for examination.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/20/2026 has been entered.
Response to Amendment/Arguments
The Amendment filed on 4/26/2026 is compliant with the requirements of 37 CFR 1.121(c), accordingly the amendment has been entered. Applicant’s arguments have been fully considered and are addressed below.
Withdrawn rejection
Claims 1, 5 and 9 were rejected under 35 U.S.C. 103 as being unpatentable over Shapiro (US PG-PUB 2011/0201587) in view of Agatsuma at al. (WO 2004/024141A1 – cited on 02/16/2023 PTO-892 form). Applicant’s amendment and corresponding reply pertaining to the newly added limitation have overcome the rejection made of record in the previous Office Action, specifically, the removal of the pancreatitis limitation to claim 1.
Claim Rejections - 35 USC § 103
New rejection, necessitated by amendment
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.
A. Claims 1, 5, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Lilja et al., (HSP90 inhibition suppresses lipopolysaccharide-induced lung inflammation in vivo. PLoS One. 2015 Jan 23;10(1):e0114975. doi: 10.1371/journal.pone.0114975. PMID: 25615645; PMCID: PMC4304786) in view of Agatsuma at al. (WO 2004/024141A1 – cited on 02/16/2023 PTO-892 form) and Shapiro (US PG-PUB 2011/0201587). NOTE: The new machine translation (previously submitted) will be referenced for the teachings of the WO- application.
Claimed invention
A method of treating an LPS-induced inflammatory disease in a subject in need thereof, comprising administering to the subject a composition comprising a curvularin-type metabolite selected from the group consisting of compounds of Formula 2a to 2c and 4 below as an active ingredient,
[Formula 2]
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wherein the inflammatory disease is selected from the group consisting of keratitis, gastritis, bronchitis, pleurisy, spondylitis, urethritis, cystitis, burn inflammation, periodontitis, and gingivitis, and
wherein the composition is a food stuff or a dietary supplement.
Prior art
Lilja teaches a method of treating an LPS-induced inflammatory disease in a subject by administering an Hsp90 inhibitor. Specifically, Lilja teaches that administering the Hsp90 inhibitor, ganetespib, to a subject strongly suppresses lipopolysaccharide (LPS)-induced inflammation in the lung and airway in vivo, including LPS-induced neutrophil and mononuclear cell infiltration and induction of inflammatory mediators (Lilja, abstract; Figs. 1-3.) Lilja further teaches that Hsp90 inhibitors are useful as therapies for inflammatory diseases, in particular inflammatory diseases of the lung and airway (Lilja, abstract; Discussion). LPS-induced inflammation of the airway corresponds to bronchitis.
While Lilja teaches treatment of LPS-induced bronchitis with an Hsp90 inhibitor, Lilja does not expressly teach that the administered Hsp90 inhibitor is a curvularin-type metabolite of instant formula 2a, 2b or 4 or the composition as a food or dietary supplement.
However, the compounds of the instant formulae were already known to possess inhibitory activity against Hsp90. For example, Agatsuma teaches compounds of general formula I that are Hsp90 family protein inhibitors. See title, abstract. Agatsuma also reported known compounds (e.g., geldanamycin) that “bind to the Hsp90 family protein and exhibit pharmacological activities such as antitumor activity by inhibiting the function of the Hsp90 family protein. Therefore, compounds that bind to the Hsp90 family protein are useful as therapeutic agents for diseases involving the Hsp90 family protein or the protein to which the Hsp90 family protein binds (Hsp90 client protein).” See p. 4. The compounds of formula (I) bind Hsp90 family protein and examples included Compounds 2a, 2b and 4:
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.
Reference Compound 2 (above) corresponds to instant Formula 4;
Reference Compound 4 (above) corresponds to instant Formula 2b or Formula 2a.
See p. 7; see also Table 1 at p. 7.
The Hsp90 inhibitors of Agatsuma are useful for treating diseases involving the Hsp90 family protein or the protein to which the Hsp90 family protein binds, the diseases include inflammatory diseases such as asthma, Bechet’s disease, Periarteritis, and ulcerative colitis. See p. 8.
A person of ordinary skill in the art (POSA) would have found it obvious to treat an inflammatory disease such as bronchitis (i.e., an LPS inflammatory disease) in a subject in need thereof by administering to the subject a composition comprising Reference compounds 2 or 4 (i.e., Formulae 2a, 2b or 4). The POSA would have found it obvious because Lilja teaches that an Hsp90 inhibitor can be used to treat bronchitis, while Agatsuma teaches that compounds of instant Formulae 2a, 2b and 4 were already known Hsp90 inhibitors. The POSA would have had a reasonable expectation of success that compounds of instant Formulae 2a, 2b and 4 would be useful for treating bronchitis given that they are Hsp90 inhibitors and the use of inhibitors of Hsp90 was disclosed as an effective strategy for treating bronchitis.
Shapiro teaches that Hsp90 inhibitors are useful for treating inflammatory diseases and further teaches formulations of such compounds that include a food or dietary supplement forms and further comprise carriers and excipients. (Shapiro, title; abstract; 0004; 0060; 0064; Claim 17.) Shapiro, thus, discloses that anti-inflammatory Hsp90-inhibiting compounds are conventionally formulated as foodstuffs or dietary supplements. The POSA would have found it obvious to formulate the Hsp90 inhibitor as a food or dietary supplement for delivery. The POSA would have had a reasonable expectation of success of providing the inhibitor in a food or dietary supplement for suitable delivery of the compounds.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Claim 5, wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier, excipient or diluent. Shapiro teaches formulations include food and further disclose the addition of excipients or carriers. See 0060.
Claim 9 is drawn to the limitation “wherein the curvularin-type metabolite is isolated from marine fungus Penicillium sp. SF-5859 Accession No. KCTC 13354BP.” This is a product-by-process limitation that is analyzed according to MPEP 2113. The product of the isolation process is the curvularin-type metabolite. The source of the metabolite (i.e., the marine fungus) does not impart any additional structural limitations to the metabolite. Therefore, the structure of curvularin metabolites is unchanged by the marine fungus from which it was isolated. Consequently, this limitation is not given patentable weight because the fungus does not carry any structural implications for the metabolite product. Since the reference compounds have the same structure as instant Formulae 2a, 2b and 4, the limitations of claim 9 are met in the same way as claim 1.
B. Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Lilja et al., (HSP90 inhibition suppresses lipopolysaccharide-induced lung inflammation in vivo. PLoS One. 2015 Jan 23;10(1):e0114975. doi: 10.1371/journal.pone.0114975. PMID: 25615645; PMCID: PMC4304786) in view of Agatsuma at al. (WO 2004/024141A1 – cited on 02/16/2023 PTO-892 form) and Shapiro (US PG-PUB 2011/0201587), as applied to Claims 1, 5 and 9 above, taken further in view Tianjin Medical University General Hospital (CN103417529A, “TMU”).
Claimed invention
Claim 4 limits claim 1, wherein the composition inherently inhibits expression of iNOS and COX-2.
Prior art
Lilja, Agatsuma and Shapiro suggest the limitations claimed in Claim 1 as outlined above. Specifically, the references suggest treating bronchitis by administering a composition containing compounds of Formulae 2a, 2b and 4. However, the references do not expressly teach the composition possessing the feature of inhibiting expression of iNOS and COX-2. However, TMU teaches that effective treatment includes inhibiting expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). See abstract.
A POSA would have found it obvious to adapt the composition such that it also provides inhibitory activity against the expression of iNOS and COX-2 because TMU teaches that effective treatment includes inhibiting the expression of iNOS and COX-2. The POSA would have had a reasonable expectation of success that imparting inhibitory efficacy against COX-2 and iNOS as a function of the composition would benefit the treatment.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Response to Applicant’s arguments
Applicant argues that the claims are allowable because the newly amended claims no longer encompass pancreatitis and the prior art fails to teach or suggest any of the other inflammatory diseases. This, however, is not persuasive because the rejection contains a newly cited prior art that teaches Hsp90 inhibitors are useful for treating LPS-induced bronchitis. Therefore, the rejection is deemed to still be proper and is, therefore, maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached on (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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