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 .
DETAILED ACTION
The Non final action dated 05/27/2026 is vacated and this new action is filed . This was to correct for the wrong expiry term of 2 months entered in the PTO-326. It has been corrected to 3 months in this action.
Claims 1-20 are pending
Claims 4-5, 7, 9-13 and 15-20 are withdrawn from examination as being drawn to a nonelected specie.
Claims 1-3, 6, 8 and 14 are under consideration in the instant office action.
Election/Restrictions
Applicant’s election without traverse of the following species in their response dated 04/15/2026 is acknowledged.
Species 1: two agents to include an anti-hypertensive agent (minoxidil) and an HDAC inhibitor (vorinostat)
Species 2: keloid
Species 3: radiation is not administered
Species 4: surgical resection is not performed
Species 5: steroid is administered (triamcinolone acetonide)
Upon further consideration, Specie 1 of anti hypertensive agent minoxidil has been expanded to include Losartan and the HDAC inhibitors are expanded to include valproic acid, trichostatin A and phenylbutyrate.
Examination of the claims are conducted to the extent they read on the elected species and the expanded species. Claims 4-5, 7, 9-13 and 15-20 withdrawn from examination as being drawn to a nonelected specie.
Claims 1-3, 6, 8 and 14 are under examination and the requirement for restriction is made final.
Priority
This application claims the benefit of U.S. Provisional Application No. 63/435,626 filed on December 28, 2022
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-3, 6, 8 and 14 are rejected under 35 U.S.C. 103(a) as being unpatentable over by Priestley et al (British Journal of Dermatology, 1991, 125, 217-221) and Hedayatyanfard et al. Wound repair and Regeneration, volume 26, issue 4, pages 340-343, 2018, Abstract) in view of Chung (US 2005/0272644) (refences are already of record)
Instant claims are drawn to a method for treating or delaying the onset, progression, or relapse of a fibrotic disorder in a subject, the method comprising administering to the subject combination of a histone deacetylase (HDAC) inhibitor, and an anti-hypertensive agent.
Priestley et al. discloses that Minoxidil had a range of inhibitory effects on both normal and abnormal skin fibroblasts and would be useful in the treatment of Keloids and other fibroses (abstract). They disclose that 75% inhibition at 1 mM Minoxidil of fibroblast GAG secretion compares with the effect of 10µg/ml clobetasol propionate (a potent corticosteroid) (page 221, col. 1, 1st para). They further disclose that Minoxidil has the right range of activities and is not cytotoxic and further studies have to be done to see if it works in vivo at this range (page 221, col.2, 1st para).
Hedayatyanfard et al. disclose that Keloid and hypertrophic scars are two types of fibrosis caused by extracellular matrix overexpression, and angiotensin II via AT1 receptor is known to play a key role in stimulation of fibrosis. They further disclose that treatment of patients with hypertrophic scars and keloids with Losartan 5% resulted in reduction of vascularity and pliability and concluded that losartan potassium ointment (5%) can alleviate the keloid and hypertrophic scar (see the entire abstract)
While Priestley disclose the utility of minoxidil and a steroid in treatment of fibrosis including keloids and Hedayatyanfard et al. discloses use of Losartan in treatment of keloids they do not disclose the combination therapy with HDAC inhibitors.
However, Chung et al. discloses a method of increased therapeutic gain in chemotherapy and/or radiotherapy nonmalignant disease such as Keloids to produce high probability of cure with low frequency of sequelae of therapy, comprising administrating a composition of a HDAC inhibitor such as valproic acid, trichostatin A , trichostatin C, phenylbutyrate, SAHA (Vorinostat), etc. and a pharmaceutically acceptable carrier or a pharmaceutically acceptable salt thereof to a subject in need (Claims 1, 3 and 6, [0028- [0036]). They disclose that the HDAC inhibitors valproic acid, trichostatin A and phenylbutyrate were discovered to have strong effects on not only decreasing skin swelling, promotion of desquamation healing in mucositis and dermatitis, reduction of fibrosis [0036] and teach that these agents are structurally unrelated histone deacetylase inhibitors, and all have similar effects on suppressing the radiation-induced skin damage including acute dermatitis and desquamation, and late fibrosis, ulceration and necrosis [0075]. Chung discloses that he compounds of the present invention can be administered intravenously, enterally, parentally, intramuscularly, intranasally, subcutaneously, topically or orally.[0010].They also disclose that the application of steroidal or nonsteroidal anti-inflammatories is the most common treatment for radiation and chemotherapy-induced tissue injury such as corticosteroids [0005-0006] and disclose their method further comprising a second agent such as corticosteroid (claims 17 and 19).
As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by the combined teachings of Priestley et al. Hedayatyanfard et al. and Chung An ordinarily skilled artisan would be motivated from Priestley et al. Hedayatyanfard et al. to utilize Minoxidil , losartan and other anti-hypertensive agents in the treatment of fibrosis and keloids . Chung provides motivation to utilize HDAC inhibitors in the treatment fibroids and . discloses specific HDAC inhibitors useful in the treatment. Accordingly both Minoxidil and HDAC inhibitors are individually known in the art as agents for treating fibrosis, whose efficacy when administered alone is well established for fibrosis and keloids. It is generally obvious to combine two compositions, each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. In re Kerkhoven, 205 U.S.P.Q. 1069 (CCPA 1980). The idea for combining said compositions flows logically from their having been individually taught in the prior art. In re Crockett, 126 U.S.P.Q. 186, 188 (CCPA 1960).Accordingly, to establish obviousness in such fact situations it is NOT necessarythat the motivation come explicitly from the reference itself (although the Examiner believes it does, as discussed supra). The natural presumption that two individually known anticancer agents would, when combined, provide a third composition also useful for treating cancer flows logically from each having been individually taught in the prior art. Applicant has presented no evidence (e.g. unexpected results) to rebut this natural presumption.. One skilled in the art would have been imbued with at least a reasonable expectation that Minoxidil and the HDAC inhibitors would potentially act synergistically and boost the activity of each other as they both act with different mechanism for the same ultimate purpose of decreasing fibrosis.
With regards to the use of the elected HDAC inhibitor Vorinostat (also called as SAHA), Chung teaches Vorinostat as HDAC inhibitor useful in their method along with Valproic acid and trichostatin and as such it would have been obvious to utilize Vorinostat (SAHA) in place of trichostatin or valproic acid as they all are HDAC inhibitors. Substituting equivalents, namely HDAC inhibitors, motivated by the reasonable expectation that the respective species will behave in a comparable manner or even provide comparable results in related circumstances, see In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) is prima facie obvious. Moreover, the express suggestion to substitute one equivalent for another need not be present to render the substitution obvious, see In re Font 213 USPQ 532.
With regards to administration of a steroid along with the combination claimed in instant claim 14, Steroids, Both Priestley et al. and Chung discloses the utility of steroids in the treatment of fibrosis of keloids. Chung et al. further discloses using corticosteroids in addition to the HDAC inhibitors in their method to treat fibrotic conditions and as such it would have been obvious to a person of ordinary skill in the art to administer a steroid such as those recited in instant claims with the combination of minoxidil and HDAC inhibitors, absence of evidence to the contrary.
.
Conclusion
Claims 1-3, 6, 8 and 14 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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