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 12 May 2026.
Claims 1-4, 6-11, 20-21, 23, 25-26, 29-31, 34, 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. No claims are currently withdrawn due to Applicant’s elections.
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.
Information Disclosure Statement
The information disclosure statement (IDS) received on 12 May 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, this information disclosure statement is being considered by the examiner.
Response to Amendments
New rejections under 35 U.S.C. 112 are presented herein.
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 partially 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 have been converted from provisional rejections to rejections due to the reference application becoming a patent. New double patenting rejections are presented herein.
Response to Arguments
Applicant's arguments received 12 May 2026 have been fully considered.
Applicant argues against the instant rejections under 35 USC 102 by stating that claim 1 describes administering the composition to a subject, wherein the subject’s scalp has gray hairs, for the treatment of hair graying. Applicant argues that the patient population of BOE, supposedly all subjects with hypertension or cardiac hypertrophy, is different from the instantly claimed population, subjects with graying hair. Applicant admits that BOE specifically calls out the population of elderly humans as a particularly promising group to be treated by the methods therein. Applicant argues that the Examiner has not provided sufficient showing that elderly subjects “always or nearly always have gray hair”. Again, Applicant argues that the Examiner should focus on whether or not the TM5441 is taught by BOE to be administered to treat hair graying.
It is important to note that instant claim 1 does not require topical administration of the drug, which claim 2 does. Applicant’s arguments related to the rejections under 35 USC 102 (BOE and SASHIN references) have not changed, and neither has the Examiner’s thoughts about these rejections. BOE teaches the administration of 5-Chloro-2-{[(2-{[3-(furan-3-yl)phenyl]amino}-2-oxoethoxy)acetyl]amino} benzoic acid to elderly humans, and a population of elderly humans entirely or nearly entirely overlaps with the instantly claimed population. The Examiner has provided a reference (SASHIN) discussing the age at which humans generally experience graying hair, which is much earlier than the stage at which humans would be called “elderly”. The population being treated is a required limitation within instant claim 1, and this limitation is taught by BOE. Applicant is telling the Examiner to focus on the purpose for the administration of the drug, which is not a required claim limitation.
Applicant argues that TUAN does not teach a treatment for hair graying. Applicant argues that only two of the patients of TUAN were over 30 years of age. Applicant argues that TUAN does not teach the treatment of any tissue samples from the scalp. Applicant argues that claim 2 requires topical application of the drug onto a subject’s scalp.
As noted above, the Examiner has provided a reference describing the age that humans begin to have gray hair, and this age range includes patients discussed with TUAN. The population taught by TUAN does not entirely overlap with the claimed population, but the Examiner believes that there is sufficient overlap to uphold the rejections below. TUAN appears to teach general epidermal administration of the PAI-1 inhibitors therein in claim 7. 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. The Examiner has withdrawn the rejections of instant claim 2 and all dependent claims thereof under 35 USC 103, due to Applicant’s new requirement that the topical application be performed on the scalp.
Applicant argues that the patient population of the ‘937 application, previously serving as the reference application within a double patenting rejection, is not the same as the instant patient population, because subjects having senescent alopecia may not have gray hairs.
The ‘937 application, which is now the ‘804 patent, states that the subject has gray hair in claim 34.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 31 and 116 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in making this determination include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number for a prima facie case are discussed below.
Claims 31 and 116 each limit the instant method to include a specific time period that is longer than the same time period within “a reference treatment regimen for graying hair”. The Examiner has not found any reference treatment regimens within the instant claims or specification. Therefore, the inventor has provided insufficient direction to one of ordinary skill in the art. One of ordinary skill in the art would not know how to perform a method that falls within the scope of claims 31 or 116. The level of predictability in the pharmaceutical arts is low, and one of ordinary skill in the art would not have known, at the time of filing, how to complete this partial information given by the inventor.
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, 29-31, and 34 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 claims 29-30: 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 claim 31: 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).
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, 6-11, 20-21, 23, 25-26, 29-30, 34, 114-115, and 117 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-4, 6-8, 21-22, 24, 26-27, 30, 34-35, and 94-99 of U.S. Patent No. 12,653,804 (referred to below as the ‘804 patent).
Although the claims at issue are not identical, they are not patentably distinct from each other because: Claim 1 of the ‘804 patent teaches a method of treating senescent alopecia by administering both of the PAI-1 inhibitors present in instant claim 1 to a subject. Claim 34 of the ‘804 patent specifies that the hair of claim 1 is gray. A subject having senescent alopecia with gray hairs would be read by one of ordinary skill in the art to constitute a subject having or having had a plurality of graying hairs on their scalp. Therefore, claims 1 and 34 of the ‘804 patent anticipate instant claims 1 and 2 of the instant application. Claim 2 of the ‘804 patent teaches topical application of compounds of claim 1 therein to the skin surface. Claims 3-4, 6-8, 21-22, 24, 26, 35, and 35 (the duplicate is not in error) of the ‘804 patent anticipate instant claim 3-4, 6-8, 20-21, 23, 25, 34, and 117 respectively. Claim 3 of the ‘804 patent anticipates instant claims 9-10. Claim 26 of the ‘804 patent anticipates instant claim 11. Claims 27 and 94-99 of the ‘804 patent anticipate instant claim 26. Claim 30 of the ‘804 patent anticipates instant claims 29-30 and 114-115.
Claims 1-4, 6-11, 20-21, 23, 25-26, 29-30, 34, 114-115, and 117 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1, 2-5, 6-11, 15, 21-22, 24, 26-31, and 35 of copending Application No. 19-665,900 (referred to below as the ‘900 application).
Although the claims at issue are not identical, they are not patentably distinct from each other because: Claims 1 and 5 of the ‘900 application teach the administration of a PAI-1 inhibitor, wherein the subject has senescent alopecia. Claim 34 of the ‘900 application teaches that the hair on the subject is gray. A subject having senescent alopecia with gray hairs would be read by one of ordinary skill in the art to constitute a subject having or having had a plurality of graying hairs on their scalp. Claim 2 of the ‘900 application teaches topical application of the PAI-1 inhibitor. Claim 15 of the ‘900 application teaches that the PAI-1 inhibitor is 5-Chloro-2-{[(2-{[3-(furan-3-yl)phenyl]amino}-2-oxoethoxy)acetyl]amino} benzoic acid. Therefore, claims 1, 2, 5, and 15 of the ‘900 application anticipate instant claims 1 and 2 of the instant application. Claims 3-4, 6-11, 21-22, 24, 30-31, 35, 30-31, and 35 (the duplicates are not in error) of the ‘900 application anticipate claims 3-4, 6-11, 20-21, 23, 29-30, 34, 114-115, and 117 of the instant application. Claims 26 and 28 of the ‘900 application anticipate claim 25 of the instant application. Claims 27 and 29 of the ‘900 application anticipate claim 26 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 8-11, 20-21, 23, 25-26, 29-30, 34, 114-115, and 117 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-2, 39, 41, 56, 67, 69-72, 77-78, 80, 82-85, and 102 of copending Application No. 19-520,395 (referred to below as the ‘395 application).
Although the claims at issue are not identical, they are not patentably distinct from each other because: Claims 1 and 2 of the ‘395 application teach topical application of a PAI-1 inhibitor, wherein the topical application is administered to the skin. Claim 39 of the ‘395 application teaches that the PAI-1 inhibitor is 5-Chloro-2-{[(2-{[3-(furan-3-yl)phenyl]amino}-2-oxoethoxy)acetyl]amino} benzoic acid. Claim 41 of the ‘395 application teaches that the PAI-1 inhibitor is delivered to reduce graying of hairs. One of ordinary skill in the art would understand topically applying a composition to reduce graying of hairs to indicate topical application to the scalp. Therefore, claims 1-2, 39, and 41 of the ‘395 application anticipate instant claims 1-2. Claims 56 of the ‘395 application anticipates claims 29-30 and 114-115 of the instant application. Claims 67, 69-72, 77-78, and 80 of the ‘395 application anticipates claims 3, 8-11, 20-21, and 23 of the instant application. Claims 82 and 84 of the ‘395 application anticipate claim 25 of the instant application. Claims 83 and 85 of the ‘395 application anticipate claim 26 of the instant application. Claim 102 of the ‘395 application anticipates claims 34 and 117 of the instant application.
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.
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
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