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 .
Election/Restrictions
Claims 1, 3-7 and 17-18 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/1/25.
Moceintostat, quisinostat, scriptaid, and LMK-235 in claim 11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/1/25.
Drawings
The drawings were received on 11/17/25. These drawings are acceptable.
Specification
The amendment to the specification filed on 11/17/25 has been entered and the sequence listed in the specification are now in compliance with 37 CFR 1.821-1.825.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 10-11 and 20-21 remain rejected under 35 U.S.C. 103 as being unpatentable over Varasi et al. (WO 2011/045265A2, ‘265) and Belinostat, PubChem CID 6918638, National Library of Medicine NCBI, 2006, https://pubche.nobi.nm.nih.gov/compourd/Belifoslat retrieved on the line 7/22/25, pages 1-52.
'265 teaches using a histone deacetylase (HDAC) inhibitor (substituted spirocyclic derivatives) to treat atopic dermatitis (page 16). The inhibitor can be combined with additional agents, including PXD101.
'265 does not specifically teach administering PXD101 to cell or a subject having atopic dermatitis, and that PXD101 is also known as Belinostat (PubChem CID: 6918638).
However, one of ordinary skill in the art would possess the knowledge that the designated PubChem CID for Belinostat is 6918638. See MPEP 2141(II)(C). Rationales to support rejections under 35 U.S.C. 103 recites, "Prior art is not limited to the references being applied, but includes the understanding of one of ordinary skill in the art." See also MPEP 2141. FACTORS TO CONSIDER IN DETERMINING LEVEL OF ORDINARY SKILL. Thus, Belinostat is also known as PXD101 and Beleodaq.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to use PXD101 (also known as Belinostat, PubChem CID 69186385) in the method of treating atopic dermatitis in a patient comprising administering a certain substituted spirocyclic substituted derivative taught by ‘265, namely to arrive at the claimed invention. Since Belinostat and the HDAC inhibitors taught by ‘265 are HDAC inhibitors, one of ordinary skill in the art would have been motivated as a simple substitution to use PXD101 in place of the histone inhibitor taught by '265 to treat the skin condition. See MPEP 2143(I)B. In addition, ‘265 teaches the compounds of formula (I) can also be used in combination with additional agents, in particular anti-tumor and differentiating agents, either by separate administrations, or by including the two active principles in the same pharmaceutical formulation. Suitable additional agents include: other histone deacetylase inhibitors (for example SAHA, PXD101, JNJ- a) 16241199, JNJ-26481585, SB939, ITF-2357, LBH589, PCI-24781, resminostat, CHR- 3996, AR-42, valproic acid, butyric acid, MS-275, MGCD0103, chidamide or FK-228). Since Belinostat and the HDAC inhibitors taught by ‘265 are HDAC inhibitors, one of ordinary skill in the art can use Belinostat with the histone deacetylase inhibitor taught by ‘265 to try to an observe an additive effect. The limitation in the pre-amble of claim 10 (up-regulating the expression of miR-335 in a cell) is considered an inherent function of administering the HDAC inhibitor and PXD101 to the subject. The pre-amble of instant claim 21 (a method for restoring skin barrier function) is considered an inherent function of administering PXD101 with a spirocyclic derivative as set forth in ‘265 to a patient having atopic dermatitis.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Response to Arguments
Applicant's arguments filed 11/17/25 have been fully considered but they are not persuasive. It appears that the same argument is cited against the 103 rejection for each pending claim.
Applicant argues that it would not have been a simple substitution to use Belinostat for a spirocyclic derivate as taught in Varasi (‘265) to treat atopic dermatitis (another name for eczema) because the HDAC inhibitors taught by Varasi et al. are structurally different and have different properties than PDX101 and page 2 of Varasi et al disclose that clinical benefits HDAC inhibitors are limited by toxicity problems, poor pharmacokinetic properties, poor potency and lack of selectively (see MPEP 2143(II)(B)).
NOTE: only instant claims 11 and 21 embrace a therapeutic method. While it is acknowledged that Belinostat is not considered a spirocyclic inhibitor and embraced by the HDAC inhibitors taught by Varasi; Belinostat and the spirocyclic compounds taught by ‘265 are HDAC inhibitors. Both HDAC inhibitors are species of large-capped hydroxamic-based inhibitors. See pages 2589-2590 of Elaut et al. Current Pharmaceutical Design 2007, 13, 2584-2620. The HDAC inhibitors both share the following structure:
Page 2 of ‘265:
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In addition to the teaching in ‘265 that both are considered HDAC inhibitors, the compounds of ‘265 and Belinostat are both hydroxamic-based inhibitors and there is a reasonable expectation of success that they can be both be used as HDAC inhibitors. See MPEP 2143.02 II. AT LEAST SOME DEGREE OF PREDICTABILITY IS REQUIRED; APPLICANTS MAY PRESENT EVIDENCE SHOWING THERE WAS NO REASONABLE EXPECTATION OF SUCCESS. Obviousness does not require absolute predictability, but at least some degree of predictability is required.
With respect to the argument that the citation of Page 2 of Varasi et al. for support that it was not a simple substitution that would yield predictable results, the argument is not found persuasive because ‘clinical benefit’ is different than treating atopic dermatitis or administering Belinostat to a cell. Treating or alleviating atopic dermatitis in a subject recited in the instant claims embrace administering Belinostat to a subject, whereas a clinical benefit includes therapeutic effect and other effects (side effects, cost, etc.). The claims do not recite achieving a clinical benefit. Since the inhibitors taught in ‘265 and Belinostat are HDAC inhibitors and HDAC inhibitors have been found to have potent and specific activities in pre-clinical studies (indicating a reasonable expectation of success for use in a non-human subject). See page 2 of Varasi. In addition, both inhibitors are hydroxamic-acid based HDAC inhibitors and ‘265 suggest that HDAC inhibitors can be used to treat atopic dermatitis, there is a reasonable expectation that they can both be used as an HDAC inhibitor to treat or alleviate atopic dermatitis in an individual.
In response to applicant’s argument that Varasi publication is directed to spirocyclic derivatives as histone deacetylase (HD) inhibitors and Varasi only teaches that these types of derivatives are useful for treating various diseases/disorders (atopic dermatitis) and there is no teaching in the publication for other HD inhibitors, including Belinostat (which is not a spirocyclic derivative) can be used to treat atopic dermatitis, the argument is not found persuasive because the compounds of ‘265 and Belinostat are hydroxamic-based HDAC inhibitors and there is a reasonable expectation of success that they can be both be used as HDAC inhibitors.
In addition, the phrase “comprising” recited the claimed method does not limit the method step to only administering Belinostat to a subject to treat atopic dermatitis Applicant’s arguments do not appear the address the additional reason for the 103 rejection embracing administering a spirocyclic HD inhibitor and Belinostat to a cell or a subject. The additional motivation applies because of the phrase “comprising” recited in the claimed methods, which does not limit the method step to only administering Belinostat to treat or alleviate atopic dermatitis in a subject. Varasi teaches combining spirocyclic derivatives with additional agents, including Belinostat (pages 16-18). Even though using Belinostat (PubChem CID 6918638) for treating or alleviating atopic dermatitis was not specifically taught in the prior art, Varasi suggests combining a spirocyclic with PXD101 (also known as Belinostat) to treat several conditions, including atopic dermatitis.
Applicant argues that the examiner provides no evidence that miR-335 would be up-regulated when Belinostat is administered to a cell, the argument is not found persuasive because the only step required in the method of upregulating miR-335 in a cell in instant claim 10 is a method step comprising administering Belinostat to the cell. Applicant appears to have recognized that miR-335 is upregulated in a cell when Belinostat is administered to the cell. “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979)”. See MPEP 2145(II). Thus, the limitation is considered an inherent property of administering Belinostat to a cell. Administering the inhibitor of ‘265 with an additional agent (Belinostat) to a cell would read on this limitation. The same reasoning can applied to the pre-amble (restoring a skin barrier function in an individual with atopic dermatitis) of instant claim 21 because the only method step embraces comprising administering Belinostat to a subject with atopic dermatitis.
Conclusion
See attached PTO-326 for disposition of claims.
The art made of record and not relied upon is considered pertinent to applicant's disclosure. US 11826325 claims a method of treating a skin infection caused by a species of bacteria comprising using Belinostat. However, the foreign priority date (4/25/21) of ‘325 is after the effective filing date of the instant application, which is 12/26/19.
Licw et al. (J Allergy Clin Immunol. Feb. 2020, cited on an IDS) teaches the claimed invention, but is considered a post-filed reference because the foreign priority document, Singapore 1020191318P (12/26/2019), for the instant application is in English.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636