DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. 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 18/577071
3. This Office Action is responsive to the amended claims of 5 January 2024.
4. Claims 1-6 have been examined on the merits.
Priority
5. This application is a 371 of PCT/KR2022/010751 filed on 22 July 2022, which claims the foreign priority date of 23 July 2021 of the Republic of Korea patent #: 10-2021- 0097163.
6. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
7. The information disclosure statements (IDS) submitted on 5 January 2024, 5 March 2024, 11 November 2024, 8 April 2025, 29 July 2025 and 1 December 2025, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification and/or prior art, while being enabling for treating systemic sclerosis, does not reasonably provide enablement for preventing systemic sclerosis of the instant claims, with a pharmaceutical composition comprising a compound of Chemical Formula 1 (hereinafter, referred as to “the instant compound”), or a pharmaceutically acceptable salt. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
10. The Wands Factors used in an (scope of) enablement rejection include (per
MPEP 2164.01(a)):
1. The breadth of the claims:
The broadest reasonable interpretation (BRI) of instant claim 1 is drawn to a
pharmaceutical composition comprising the instant compound for preventing or treating systemic fibrosis.
The definition of “prevention” in paragraph [0018] of the application is acknowledged. However, to avoid confusion, the BRI of claim interpretation is adopted, namely, “preventing” or “prevention” is given general public acceptable definition (keep something from happening, or stop an event or action from occurring).
2. The Nature of the Invention:
The invention belongs to medicinals, more specifically, the administration of
compound(s)/compositions to patients with systemic fibrosis.
3. The state of the prior art:
A review of the prior art shows that the instant compound is used to treat systemic sclerosis (see prior art rejections, below).
Systemic sclerosis is a rare multi-system autoimmune disease characterized by fibrosis, vasculopathy, and autoimmunity. Since the cause of systemic sclerosis has not yet been clarified (para [0002], Ln 4, this instant application), there is no therapy that can stop the progression of systemic sclerosis to date and some drugs can only alleviate certain symptoms and reduce organ damage (para [0008], Lns 1-2, this instant application).
Nothing in the prior art supports preventing systemic sclerosis by administration of composition of the instant compound, or any other drugs.
4. The Level of one of ordinary skill:
The level of one of ordinary skill includes the knowledge/skill to engage in a
reasonable amount of experimentation to make and use the compositions of underlying the instant method claims.
The level of one of ordinary skill also includes knowledge in using the instant compound to treat systemic sclerosis.
However, no one has skill to engage in the undue burdensome level of experimentation required to provide guidance/enablement for preventing systemic sclerosis of the instant composition claims 1, 5 and 6.
5. The level of predictability in the art:
The art is predictable to make the instantly claimed pharmaceutical compositions.
However, the art does not provide predictability as to systemic sclerosis can be prevented beyond those reported, above, as known in the prior art. To generate this level of guidance, one has to engage in undue burdensome experimentation (since no predictability in the art) to test the pharmaceutical composition against systemic sclerosis to determine if the pharmaceutical composition can treat and/or prevent said disease. This level of experimentation would be required to match the scope of instant claims 1-6.
6. The amount of direction provided by the inventor:
While the Specification provides data of skin thickness, fibrosis factors Collagen I, Collagen III, and aSMA of the skin tissue, and evaluation of lung function in the mouse model (Fig. 2 and Experimental Example 2, Fig. 3 and Experimental Example 2, and Fig. 7 and Experimental Example 3-3) for treating systemic sclerosis using compositions of the instant compound and another active ingredient Nintedanib.
The Specification does not provide direction for preventing systemic sclerosis per the BRI of instant claim 1.
7. The existence of working examples; and
While the Specification provides data of skin thickness, fibrosis factors Collagen I, Collagen III, and aSMA of the skin tissue, and evaluation of lung function in the mouse model (Fig. 2 and Experimental Example 2, Fig. 3 and Experimental Example 2, and Fig. 7 and Experimental Example 3-3) for treating systemic sclerosis using compositions of the instant compound and another active ingredient Nintedanib. The Specification does provide enablement/guidance for treating SSc-ILD of claim 2 (see Example 3 page 9); for treating claim 3 diseases (see Example 2 pages 8-9).
The Specification does not provide direction for preventing systemic sclerosis per the BRI of instant claim 1.
8. The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The word “preventing” per the BRI of instant claim 1 would require an undue amount of experimentation to use the invention as claimed to treat or prevent systemic fibrosis using compositions of the instant compound, absent evidence in the Specification or prior art.
Therefore, claims 1-6 are rejected under 35 USC 112(a) for lacking enablement for the scope of preventing systemic fibrosis (per BRI of instant claim 1).
Deleting “preventing or” in all the claims will render moot this scope of enablement rejection.
Claim Rejections - 35 USC § 102
11. 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.
12. Claims 1-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by LEE (US 10,981,917 B2, pub. April 20, 2021, provided by Applicants and referenced in IDS of 5 January 2024)
The prior art reference LEE teaches the compound
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(see Example 40, Lns. 33-53 on col. 36), with a hydrochloride pharmaceutically acceptable salt. LEE teaches its use in a pharmaceutical composition to treat fibrosis (see “Abstract”). The phrase “for preventing or treating systemic fibrosis” constitutes intended use. Nothing precludes the use as claimed. Thus, this anticipates “pharmaceutical composition” of instant claims 1-2 and 4.
Furthermore, claim 3 is interpreted as inherent property/function. See MPEP 2112.01(I) and (II). This anticipates instant claim 3.
Furthermore, LEE teaches “other active ingredient”/”adjuvant” (Lns. 58-60, col 16) therefore anticipating instant claim 5.
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)(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.
14. Claims 1, 2, 4 and 5 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by LEE (WO 2022240035, WIPO translate, pub. November 17, 2022, effectively filed May 13, 2021)
The applied reference has a common inventor and/or assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
The prior art reference LEE teaches a pharmaceutical composition for treating fibrosis comprising the instant compound, or a pharmaceutically acceptable salt thereof (paras [0018]-[0021]). Thus, claim 1 is anticipated by LEE.
LEE teaches the hydrochloride salt (para [27]) as the preferred pharmaceutically acceptable salt of the instant compound (paras [20-21]) therefore anticipating instant claim 4.
LEE teaches types of fibrosis include interstitial lung disease (ILD), … and interstitial lung diseases include idiopathic pulmonary fibrosis (IPF), systemic sclerosis associated interstitial lung disease (SSc-ILD), … (para [2]). Thus, instant claim 2 is also anticipated by LEE.
Furthermore, LEE teaches other active ingredients ([para 39]) therefore anticipating instant claim 5.
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.
16. Claims 1, 2 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over:
LEE (WO 2022240035, WIPO translate, pub. November 17, 2022, effectively filed May 13, 2021)
In view of
LEE2 (Lee at el. “Inhibition of Prolyl-tRNA Synthetase as a Novel Therapeutic Target for Systemic Sclerosis” [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9); October 21, 2018. https://acrabstracts.org/abstract/inhibition-of-prolyl-trna-synthetase-as-a-novel-therapeutic-target-for-systemic-sclerosis/ Accessed February 17, 2026. (provided by Applicants and referenced in IDS of 5 January 2024)
Determining the scope and contents of the prior art
LEE teaches a pharmaceutical composition of the instant compound to treat systemic fibrosis in general (anticipating claim 1). LEE teaches types of fibrosis include interstitial lung disease (ILD), … and interstitial lung diseases include idiopathic pulmonary fibrosis (IPF), systemic sclerosis associated interstitial lung disease (SSc-ILD) (anticipating claim 2). LEE teaches the effect of improving lung function by compositions of the instant compound in pulmonary fibrosis in an animal model (paras [70] and [71]).
Another prior art reference LEE2 discloses successful decreases in skin thickness, collagen 1, and alpha smooth muscle actin (αSMA) by a novel Prolyl-tRNA synthetase inhibitor DWN12088 (the HCl salt of the instant compound) in systemic sclerosis.
Ascertaining the differences between the prior art and the claims at issue
LEE’s teaches anticipate claim 1 as described above in Paragraph 12. LEE teaches the effect of improving lung function in pulmonary fibrosis, not in SSc-ILD as recited in claims 2 and 3. LEE does not teach the effect on alleviating skin hardening, either.
Another prior art reference LEE2 does not teach the effect of improving lung function.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has
sufficient background in the development of method useful for treatment of systemic fibrosis and possesses the technical knowledge necessary to make adjustments to the administered composition to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding different compositions and understands the solutions that are widely-known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant claims are prima facie obvious in light of the combination of
references LEE and LEE2.
LEE’s teach of the effect of improving lung function is in pulmonary fibrosis, not specified to SSc-ILD as recited in claims 2 and 3. It’s worth noting that SSc-ILD is a specific type of pulmonary disease and SSc-related lung issues include ILD (scarring), pulmonary arterial hypertension (PH/vascular damage), or both. Since SSc-ILD is a species of pulmonary fibrosis, and they are interconnected each other so much and interstitial lung disease (ILD) is the most frequent cause of systemic sclerosis-related death, that an artisan in the art would have applied knowledge from pulmonary fibrosis to SSc-ILD with a reasonable expectation of success before the effective filling date of the application to get optimization/enhancement of the treatment outcomes. Thus, instant Claim 2 is obvious in view of LEE.
The same argument regarding pulmonary fibrosis and SSc-ILD applies to another LEE2’s disclosure on alleviating skin hardening. Thus, instant claim 3 is obvious over LEE on lung function (discussed with claim 2 above) in view of another LEE2’s disclosure on alleviating skin hardening.
17. Claims 1, 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over:
LEE (WO 2022240035, WIPO translate, pub. November 17, 2022, effectively filed May 13, 2021)
in view of
DISTLER (Distler O, at el. “Nintedanib for Systemic Sclerosis–Associated Interstitial Lung Disease”, N Engl J Med 2019;380:2518-28. Provided by Applicants and referenced in IDS of 1 December 2025)
further in view of
KHANNA (Khanna D, et al. “Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)”, Ann Rheum Dis 2018;77:212–220).
The applied reference has a common inventor and/or assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Determining the scope and contents of the prior art
LEE teaches instant claim 1, supra.
DISTLER teaches the antifibrotic and anti-inflammatory effects of Nintedanib in preclinical models of systemic sclerosis and interstitial lung disease (ILD).
KHANNA teaches the efficacy and safety of Tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.
Ascertaining the differences between the prior art and the claims at issue
LEE only teaches a pharmaceutical composition of the instant compound to treat systemic fibrosis, not a second active agent. DISTLER only teaches the antifibrotic and anti-inflammatory effects of Nintedanib, not related to the instant compound or Tocilizumab. KHANNA only teaches the efficacy and safety of Tocilizumab in patients, not related to the instant compound or Nintedanib. None of the three cited references teaches combination of two active ingredients to treat systemic fibrosis.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has
sufficient knowledge in the development of method useful for treatment of systemic fibrosis and possesses the technical knowledge necessary to make adjustments to the administered composition to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding different compositions and understands the solutions that are widely-known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant claims 5 and 6 are prima facie obvious in light of the combination of references LEE, DISTLER and/or KHANNA.
LEE teaches instant claim 1 to treat systemic fibrosis (see citations, above). The artisan would be expected to use at least one of Nintedanib or Tocilizumab as adjuvants to treat systemic fibrosis with the instant compound of LEE since Nintedanib and Tocilizumab were approved by FDA for the treatment of systemic sclerosis-associated ILD. The artisan would be motivated to use at least one of any medications already known to be useful to treat system fibrosis and would also be motivated to combine adjuvants also known for this purpose (see DISTLER and KHANNA, the whole articles) to get synergistic effects of two components. The instant claim 5 is obvious over LEE in view of DISTLER or KHANNA. The instant claim 6 is obvious over the combination of LEE, DISTLER and KHANNA.
Double Patenting
18. 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.
19. Claim 1 and 4-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 10-12 of copending Application No. 18/288,296 (reference application, referred hereinafter to as “Ref1”). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Ref1 claim 7 is drawn to a method for preventing or treating fibrosis in a subject in need thereof, comprising administering … the instant compound or a pharmaceutically acceptable salt thereof, anticipating instant claim 1.
Ref1 claim 10 is drawn to the pharmaceutically acceptable salt of hydrochloride of the instant compound, anticipating instant claim 4.
Ref1 claim 11 is drawn to the pharmaceutical composition further comprises other active component used for the prevention or treatment of fibrosis, anticipating instant claim 5.
Ref1 claim 11 is drawn to the other active component used for the prevention or treatment of fibrosis is Pirfenidone or Nintedanib, anticipating instant claim 6.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
20. Claims 1, 5 and 6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of copending Application No. 18/288,275 (reference application, hereinafter referred to as “Ref2”). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Ref2 claim 12 is drawn to a method for preventing or treating fibrosis by administering to the subject a pharmaceutical composition comprising: 1) a first component of the instant compound, or a pharmaceutically acceptable salt thereof, and 2) a second component selecting from a compound of Chemical Formula 2 (Pirfenidone), a pharmaceutically acceptable salt thereof, and a compound of Chemical Formula 3 (Nintedanib), or a pharmaceutically acceptable salt thereof, anticipating instant claims 1, 5 and 6.
Conclusion
21. No claims of 1-6 are presently allowable as written.
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/BIN TAO/
Examiner, Art Unit 1625
/JOHN S KENYON/
Primary Patent Examiner, Art Unit 1625