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.
Current Status of 17/274,948
This Office Action is responsive to the arguments and amendments received 18 November 2025.
Claims 1-4, 6-11, 20-21, 23, 25-26, 29-31, 34, 62, and 114-117 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group I, being claims 1-4, 6-11, 14-15, 20-21, 23, 25-26, and 29-34 in the reply received 21 June 2024 is acknowledged.
Applicant has also elected the following species:
5-Chloro-2-{[(2-{[3-(furan-3-yl)phenyl]amino}-2-oxoethoxy)acetyl]amino}benzoic acid.
The elected group and species have been determined to read on current claims 1-4, 6-11, 20-21, 23, 25-26, 29-31, 34, and 114-117.
Claims 62 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
A search for Applicant’s elected species retrieved applicable prior art or double patent art. Therefore, the provisional election of species is given effect, the examination is restricted to the elected species only, and claims not reading on the elected species are held withdrawn. MPEP 803.02; Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (Bd. Pat. App. lnt. 1987).
Priority
Applicant’s claim for the benefit of the prior-filed patent applications PCT/US2019/50849 (filed 12 September 2019) and US 62/731,074 (filed 13 September 2018) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Response to Amendments
The objections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The 35 U.S.C. 112 rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The 35 U.S.C. 102(a)(1) rejections to the claims, present in the previous office action, are maintained herein.
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are maintained herein, but altered as necessitated by Applicant’s amendments.
The double patenting rejections to the claims, present in the previous office action, are maintained herein, but altered as necessitated by Applicant’s amendments.
Response to Arguments
Applicant's arguments received 18 November 2025 have been fully considered, but they are not persuasive.
Applicant argues that BOE is not directed toward a method of treating hair graying through administration of TM5441. Applicant argues that new uses for old products are patentable subject matter.
The Examiner agrees that BOE is not directed toward a method of treating hair graying. Of course, the Examiner agrees that new uses for old products can be patentable. Applicant discusses an important point, that the selection of a particular patient population (usually afflicted by a particular disorder) is often a limitation within a method claim, and that type of limitation must be addressed by an Examiner to properly reject the claim. If there was less overlap between the patient population taught by BOE (elderly individuals) and the instantly claimed population (individuals having hair greying), the Examiner may be swayed by this argument. The selection of an elderly individual, following the method taught by BOE, always or nearly always meets the criterion of the patient required by instant claim 1, being a subject having hair greying.
Applicant argues that Tuan does not teach or suggest the treatment of hair graying through the administration of PAI-1 inhibitors. Applicant argues that the Examiner is focusing on the wrong questions and should consider specifically “whether TUAN teaches or suggests administration of a PAI-1 inhibitor to treat hair graying”. Applicant states that TUAN does not teach or suggest this.
The Examiner has adjusted the arguments within the 35 USC 103 rejections below, as necessitated by Applicant’s amendments. The Examiner now states within those rejections that TUAN renders the administration of the compounds therein to the patient population of 47-year-old humans to be obvious, due to the teaching of TUAN that a PAI-1 inhibitor was administered to cells from a 47-year-old patient. Because the combination of TUAN and PLACENCIO renders obvious a method of administering a PAI-1 inhibitor as instantly claimed, this method would have functioned in the manner instantly claimed to treat hair greying. The Examiner is not aware of any teachings of TUAN or PLACENCIO that would disrupt this function of the TM5441 compound. The Examiner does not agree with Applicant’s assertion that a proper rejection would require the Examiner to find the intention to treat hair graying within a reference or combination of references. Intentions are not method steps that can be practiced by an artisan.
Applicant then argues that the Examiner has not pointed out that TUAN teaches topical administration of a PAI-1 inhibitor to a site on the skin surface as is now present in instant claim 2.
TUAN appears to teach general epidermal administration of the PAI-1 inhibitors therein in claim 7. The Examiner agrees that TUAN is generally directed to the treatment of keloids. The Examiner’s interpretation of paragraph [0060] of TUAN aligns with the general teachings of TUAN: TUAN teaches the application of a therapeutic composition to keloid scars. TUAN does not appear to teach that the therapeutic composition cannot contact surrounding tissue. One of ordinary skill in the art would reasonably have read the teachings of TUAN, including the administration of PAI-1 inhibitors in the form of lotions to keloid scars, and understood that some of the lotion would contact the surrounding epidermis, having hairs therein.
Applicant requests that the double patenting rejections below be held in abeyance. These rejections will not be held in abeyance.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 6, and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
BOE (Boe, A.E.; Eren, M.; Murphy, S.B.; et al. “Plasminogen Activator Inhibitor-1 Antagonist TM5441 Attenuates Nω-Nitro-l-Arginine Methyl Ester–Induced Hypertension and Vascular Senescence” Circulation, Volume 128, Issue 21, 2318-2324)
as evidenced by:
SASHIN (Sashin, D. “Premature graying: Reasons, options” WebMD; https://www.webmd.com/beauty/features/abcs-premature-graying; 25-August 2024).
BOE teaches the use of TM5441, referred to in the instant application as 5-Chloro-2-{[(2-{[3-(furan-3-yl)phenyl]amino}-2-oxoethoxy)acetyl]amino} benzoic acid, to decrease hypertension and cardiac hypertrophy in mice (abstract). BOE also teaches that the same compound is a promising therapeutic agent for elderly humans, due to the prevalence of arteriosclerosis in that population (discussion section). Therefore, BOE teaches the administration of 5-Chloro-2-{[(2-{[3-(furan-3-yl)phenyl]amino}-2-oxoethoxy)acetyl]amino} benzoic acid to elderly humans. The table at the bottom right of page 2320 of BOE teaches the oral dosage of TM5441 provided to subjects therein. The Experimental Animals section of BOE teaches that the mice therein were fed the compound TM5441, in other words oral administration, each day for 8 weeks.
SASHIN provides general information about the age at which humans are affected by greying hair. SASHIN states that humans generally “start going gray” in their mid-30s to their mid-40s. One of ordinary skill in the art would understand that a population of elderly humans, referred to by BOE, would be affected by greying hair. Therefore, one of ordinary skill in the art would have read BOE to teach the oral administration of 5-Chloro-2-{[(2-{[3-(furan-3-yl)phenyl]amino}-2-oxoethoxy)acetyl]amino} benzoic acid to humans having greying hair.
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.
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 1-4, 6-11, 20-21, 25-26, 29-31, 34, and 114-117 are rejected under 35 U.S.C. 103 as being unpatentable over:
TUAN (US 2004/043026 A1, Publication Date 4 March 2004, Cited by Applicant in IDS of 16 June 2021)
in view of:
PLACENCIO (Placencio, V.R.; Ichimura, A.; et al. “Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti-Angiogenic Activity” PLoS ONE 10(7): e0133786. (2015)., Cited by Applicant in IDS of 31 January 2024)
as evidenced by:
SASHIN (Sashin, D. “Premature graying: Reasons, options” WebMD; https://www.webmd.com/beauty/features/abcs-premature-graying; 25-August 2024).
TUAN teaches a method of “reducing an excessive accumulation of collagen in a wound healing process comprising the step of reducing PAI-1 activity” (claim 1), and also teaches that this can be accomplished using a PAI-1 inhibitor (claims 2-3). TUAN teaches that the experiments therein were performed on samples from patients aged 4-47 (Table 1, Pg. 14-15). A short list of diseases mediated by “an excessive accumulation of collagen” are taught in TUAN claim 8, wherein the list includes keloids. The Figures and examples of TUAN exclusively focus on the treatment of the condition of keloid scars. Paragraph [0113] of TUAN teaches that PAI-1-neutralizing antibodies were able to reduce “collagen accumulation of keloid fibroblasts” in experiments reported therein. A short list of PAI-1 inhibitors, including several small molecules, is taught in claim 4 of TUAN. TUAN also teaches that the PAI-1 inhibitor is administered to a subject (claim 6). TUAN teaches epidermal administration of the PAI-1 inhibitors therein in claim 7. TUAN teaches administration via transdermal patches bearing compositions therein in paragraph [0073]. It is clear without being explicitly stated that a transdermal patch will be removed by some process after some period of time (in other words, it is not expected to remain on the subject forever). TUAN teaches that compositions therein, which include PAI-1 inhibitors, are non-irritating in paragraph [0061]. TUAN teaches administration via injection at the end of paragraph [0060]. TUAN teaches oral administration within paragraph [0064]. TUAN teaches the administration of compositions therein via lotions in paragraph [0071].
Taken together, TUAN teaches the administration of PAI-1 inhibiting small molecules to at least the patient population of 47-year-old humans for the treatment of keloids.
SASHIN provides general information about the age at which humans are affected by greying hair. SASHIN states “Typically, White people start going gray in their mid-30s, Asian people in their late 30s, and Black people in their mid-40s”. Therefore, it would be understood by one of ordinary skill in the art that: the 47-year-old individual present in Table 1 of TUAN would most likely have had at least two greying hairs, and the 33-year-old individual in the same table may have had at least two greying hairs.
PLACENCIO teaches, within the abstract, that “TM5441” is a known, orally-bioavailable inhibitor of plasminogen activator inhibitor-1 (PAI-1). Fig. 1 of PLACENCIO teaches the structure and chemical name of “TM5441”, the chemical name being 5-chloro-2-{[(2-{[3-(furan-3-yl)phenyl]amino}-2-oxoethoxy)acetyl]amino}benzoic acid. PLACENCIO also teaches that TM5441 is superior with regard to its pharmacokinetics, relative to other known PAI-1 inhibitors (Introduction section, 3rd paragraph).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to combine the PAI-1 inhibiting compounds within the method of treating keloids in 47-year-old subjects having graying hair (taught by TUAN) with the TM5441 compound (taught by PLACENCIO), for the purpose of providing a composition with improved pharmacokinetic properties to the patient. The artisan would have expected success with this replacement because the TM5441 compound of PLACENCIO is a PAI-1 inhibitor and the method of treating keloids taught by TUAN requires a PAI-1 inhibitor. This method, rendered obvious as described above, would have functioned in the manner instantly claimed to treat hair greying, because the Examiner is not aware of any teachings of TUAN or PLACENCIO that would disrupt this function of the TM5441 compound.
Regarding claim 8: TUAN teaches the administration of compositions therein via lotions in paragraph [0071]. Lotions are commonly applied using the fingers. This reads on the massaging of a composition onto a skin site in instant claim 8.
Regarding claims 9-11, 29-30, and 114-115: TUAN teaches administration of compositions via transdermal patches, and this is understood to mean that the patches have a finite residence time on the skin. PLACENCIO teaches daily administration of a PAI-1 inhibitor (abstract), and it would be obvious to one of ordinary skill in the art to test once daily administration using the method rendered obvious by the combination of TUAN and PLACENCIO. It would be obvious to one of ordinary skill in the art to optimize this residence time and the number of applications of transdermal patches, for the purpose of providing an effective dosage of the composition to a subject at all times. See MPEP 2144.05(II)(A).
Regarding claims 25-26: The penetration time of the PAI-1 inhibitors, within instant claims 25-26, are defined by the limitations of the positive steps of instant claim 1. Those limitations have been found to be obvious, and so the penetration time of the inhibitors must also be obvious. In other words, the penetration time of the inhibitors of the instant methods are solely an outcome of the composition and the administration thereof. In other words, the method cannot be separated from the outcome of the method.
Regarding claim 31 and 116: It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to experiment with the application time of the compositions taught by TUAN. This routine experimentation would have resulted in some application times, and thereby the intervals between applications, longer than those specifically disclosed by TUAN. See MPEP 2144.05(II)(A).
Claims 1-4, 6-11, 20-21, 23, 25-26, 29-31, 34, and 114-117 are rejected under 35 U.S.C. 103 as being unpatentable over:
TUAN (US 2004/043026 A1, Publication Date 4 March 2004, Cited by Applicant in IDS of 16 June 2021)
in view of:
PLACENCIO (Placencio, V.R.; Ichimura, A.; et al. “Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti-Angiogenic Activity” PLoS ONE 10(7): e0133786. (2015)., Cited by Applicant in IDS of 31 January 2024)
and in view of:
LIU (Liu, S.; Yeo, D.C.; et al. “Peptide delivery with poly(ethylene glycol) diacrylate microneedles through swelling effect” Bioengineering & Translational Medicine 2017; 2: 258–267).
Teachings of TUAN and PLACENCIO are shown in the second 35 U.S.C. 103 rejection above.
Regarding claim 23: LIU teaches, within the Discussion section therein, the production of PEGDA microneedles loaded with a Gap 26 peptide. LIU teaches that the Gap 26 peptide was selected for the purpose of keloid scar reduction (Discussion section) and also teaches that the peptide-loaded microneedle system therein was able to reduce collagen expression in a keloid model system (Conclusions section).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application to combine the method of treating keloids via transdermal administration of compounds to 47-year-old subjects having graying hair (taught by TUAN) with the loaded microneedle administration system (taught by LIU), for the purpose of increasing the speed of transdermal delivery of therapeutic compounds. The artisan would have expected success in this combination because TUAN and LIU both teach the transdermal administration of compositions which are intended to decrease the amount of collagen present in keloid scars.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 6-8, 20-21, 23, 25-26, 29-31, 34 and 114-117 are provisionally rejected on the ground of anticipatory nonstatutory double patenting as being unpatentable over:
Claims 1-4, 6-8, 21-22, 24, 26-27, 30-32, and 34-35 of copending Application No. 17/274,937 (referred to below as the ‘937 application).
Although the claims at issue are not identical, they are not patentably distinct from each other because: Claim 1 of the ‘937 application teaches a method of treating senescent alopecia by administering one of the PAI-1 inhibitors present in instant claim 1 to a subject. A subject having senescent alopecia reasonably constitutes a subject having or having had a plurality of graying hairs. Claim 2-4 and 6-8 of the ‘937 application are identical to the instant claims of the same number. Claims 21-22, 24, 26-27, 30-32, and 35 of the ‘937 application are identical to claims 20-21, 23, 25-26, 29-31, and 34 of the instant application, respectively. Claims 30, 31, 32, and 35 of the ‘937 application anticipate instant claims 114-117 respectively.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are currently allowable.
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 JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625