DETAILED ACTION
Claims 1-13 and 27-32 were pending. Claims 1, 3, 5, 7, 9, 11-12, 27, 29, and 31 have been amended, claims 4 and 10 have been canceled per the Reply of 12/10/2025.
Claims 1-3, 5-9, 11-13, and 27-32 are pending and the subject of the Office Action below.
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 .
Priority
The instant application, filed 6/16/2022 is a National Stage entry of PCT/US2020/065348, with an International Filing Date of 12/16/2020. PCT/US2020/065348 Claims Priority from Provisional Application 62/948521, filed 12/16/2019.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 12/10/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statement is being considered by the Examiner.
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 1-2, 5, 6-8, 11-13, 27-28, and 30-32 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Amended claims 1, 7, and 27 recite the genus of “an inhibitor of NADPH oxidase 4 (Nox4), wherein the inhibitor of Nox4 is not suramin.” Applicant has written description for the genus, an inhibitor of NADPH oxidase 4 (Nox4) as originally claimed and also for claims 3, 9, and 29 in which Applicant excludes suramin from a list of inhibitors positively recited, but Applicant does not have description for the genus of all Nox4 inhibitors while only excluding suramin.
Upon review of the instant specification, there seems to be no disclosure of what constitutes a “an inhibitor of NADPH oxidase 4 (Nox4), wherein the inhibitor of Nox4 is not suramin ." Moreover, while the instant specification cites “suramin” in the instant disclosure, the instant disclosure does not state anywhere the possession of a genus that excludes suramin. As Applicants have not contemplated the exclusion of any single particular species of the genus, specifically suramin, from the scope of the instant invention, and as such, proposes an issue of new matter and written description.
While it is recognized that adequate written description of a limitation is not required to be stated in haec verba in the specification or claims as originally filed, adequate written support for all claim limitations must arise from either an explicit or an implicit suggestion by the disclosure to show that such a concept as now claimed was actually in possession of the Applicant at the time of the invention.
As cited in In re Bimeda Research and Development Limited (No. 12-1420, Fed. Cir. July 25, 2013) the Federal Circuit cited inadequate written description for certain claims requiring the exclusion of a specific species, as “[C]laims to embodiments which exclude particular species are only supported if the disclosure offers some guidance or "blaze marks" to guide the skilled artisan toward excluding that particular species. (page 5 of the opinion). Moreover, in Santarus v, Par Pharma (Court of Appeals, Federal Circuit 2012 Nos. 2010-1360, 2010-1380) the court concluded that “[N]egative claim limitations are adequately supported when the specification describes a reason to exclude the relevant information” (page 12 of the opinion).
However, as there is no support in the instant disclosure of “blaze marks” to guide the skilled artisan toward excluding the art recognized suramin, nor has the instant disclosure cited ANY reason for the reason to exclude the art recognized suramin from the instantly claimed genus, such newly added negative claim limitation is not supported. Accordingly, the claims are considered to lack sufficient written description and are properly rejected under 35 U.S.C. 112, first paragraph.
Claim Rejections - 35 USC § 103
(NEW Rejection based on Amendment)
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.
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 1-2, 5-8, 11-13, 27-28, and 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Aissaoui et al. WO2016207785A1 published 12/29/2016 in further view of Spurney et al. “Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart,” Neuromuscular Disorders 18 (2008) 371–381.
Instant claim 1 requires a method of treating cardiomyopathy or heart failure in a subject who has a muscular dystrophy, the method comprising administering to a subject in need thereof a therapeutically effective amount of an inhibitor of NADPH oxidase 4 (Nox4), wherein the inhibitor of Nox4 is not suramin.
Aissaoui teaches NADPH oxidase 4 inhibitors (Nox4) of Formula (I) (not suramin) and their use as active ingredients in the preparation of pharmaceutical compositions. Aissaoui states, “Induction of NOX4 has been linked to the differentiation of mesenchymal cells such as myofibroblasts, adipocytes, smooth muscle cells and cardiac myocytes (Clempus, R.E., et al. NOX4 is required for maintenance of the differentiated vascular smooth muscle cell phenotype. Arterioscler Thromb Vase Biol 27, 42-48 (2007); Cucoranu, I., et al. NAD(P)H oxidase 4 mediates transforming growth factor-beta-induced differentiation of cardiac fibroblasts into myofibroblasts. Circ Res 97, 900-907 (2005); Li, J., et al. The NADPH oxidase NOX4 drives cardiac differentiation: Role in regulating cardiac transcription factors and MAP kinase activation. Mol Biol Cell 17, 3978-3988 (2006); Schroder, K. et al..NOX4 acts as a switch between differentiation and proliferation in preadipocytes. Arterioscler Thromb Vase Biol 29, 239-245 (2009)). Increased NOX4 activity has been implicated in a number of pathologies including fibrotic diseases and/or diseases or disorders associated with an impaired reactive oxygen species (ROS) production.”
Aissaoui in claim 14 states, “[a] compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, for use according to claim 13, wherein said fibrotic disease is pulmonary fibrosis; scleroderma; pancreatic fibrosis; liver fibrosis; chronic kidney disease; or cardiomyopathy.”
While Aissaoui dose teach treating cardiomyopathy Aissaoui doesn’t teach treating cardiomyopathy in a patient who has a muscular dystrophy.
Spurney teaches Duchenne muscular dystrophy (DMD; dystrophin-deficiency) causes dilated cardiomyopathy. Heart dysfunction was prominent at 9–10 months of age (as required by instant claim 12) and showed significantly increased LV internal diameter (end systole) and decreased posterior wall thickness (as required by instant claims 13 and 32). Spurney teaches, histologically, there was a 10-fold increase in connective tissue volume (fibrosis). mRNA profiling with RT-PCR validation showed activation of key pro-fibrotic genes, including Nox4 and Lox. Nox4 was specifically induced in heart, of the DMD model. Spurney concludes stating, Nox4 and Lox may specifically play an important role in the increased cardiac fibrosis seen in mdx mice.
A person of ordinary skill in the art looking to treat muscular dystrophy, would be aware of the role of Nox4 in cardiomyopathy in muscular dystrophy, and would look to use the Nox4 inhibitors of Aissaoui, as they are shown to treat cardiomyopathy with overexpressed/active Nox4. As such one would expect the inhibition of Nox4 (a known treatment for cardiomyopathy) to treat cardiomyopathy in in muscular dystrophy, as the disease has overexpressed/active Nox4 (Spurney). Therefore the claims were prima facie obvious at the time of filing.
Instant claim 2 requires wherein the inhibitor is administered daily. Aissaoui states, “In a preferred embodiment of the invention, the administered amount of such a compound of formula (I) as defined in any one of embodiments 1) to 17) is comprised between 1 mg and 1000 mg per day, particularly between 5 mg and 500 mg per day, more particularly between 10 mg and 400 mg per day.” Thereby teaching daily dosing.
Instant claim 5 requires (and claim 11), Duchenne muscular dystrophy (DMD) as taught by Spurney.
Instant claim 6 requires known symptoms of cardiomyopathy, these symtops would be present as found in the disease state, if Applicant has data to show that a specific symptom is significant for treatment this might lend to patentability. At present no data in the Specification points to this being a patentable distinction.
Instant claims 7 and 8 are similar to instant claims 1-2, they are directed to reducing the risk versus treating, given the discussion of Aissaoui to the increasing of risk as the disease progresses this method is also inherent as this is simply directed to treating the disease in an earlier state which is at once envisaged as fibrotic diseases are progressive in nature.
RESPONSE TO ARGUMENTS: The rejections are new based on amendment, and Applicant’s amendments are found obvious in view of the prior art.
Claim Rejections - 35 USC § 103
(NEW Rejection based on Amendment)
Claims 1-3, 5-9, 11-13, and 27-32 are rejected under 35 U.S.C. 103 as being unpatentable over Aissaoui et al. WO2016207785A1 published 12/29/2016 and Spurney et al. “Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart,” Neuromuscular Disorders 18 (2008) 371–381; as applied to claims 1-2, 5-8, 11-13, 27-28, and 30-32 above in further view of Teixeira et al. “Therapeutic potential of NADPH oxidase 1/4 inhibitors,” British Journal of Pharmacology (2017) 174 1647–1669 1647.
In regards to claims 3, 9 and 29 which require the Nox4 inhibitor is selected from a group consisting of several molecules including, GKT137831, a known Nox4 inhibitor.
Aissaoui and Spurney render obvious treating cardiomyopathy in a patient with muscular dystrophy with a Nox4 inhibitor. They don’t teach GKT137831, a known Nox4 inhibitor.
Teixeira teaches GKT137831 is a known Nox4 inhibitor. Teixeira teaches that GKT136901 and GKT137831 are two structurally related compounds demonstrating a preferential inhibition of NOX1 and 4 that have suitable properties for in vivo studies and have consequently been evaluated across a range of disease models and compared with gene deletion. Teixeira teaches GKT137831 has demonstrated excellent tolerability and reduction of various markers of chronic inflammation. NOX1/4 inhibition may provide a safe and effective therapeutic strategy for a range of inflammatory and fibrotic diseases.
A person of ordinary skill in the art would look to use GKT137831, a Nox4 inhibitor, in place of the Nox4 inhibitors of Aissaoui because GKT137831 has demonstrated excellent tolerability and efficacy in diseases mediated by Nox4. Therefore one would be inclined to use the molecule with a proven track record. Therefore the instant claims directed to GKT137831 are obvious.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/ Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/ Supervisory Patent Examiner, Art Unit 1629