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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/24/2026 has been entered.
Claim Status
Claims 17-31 were canceled in the response filed 9/24/2026. However, the claim set recites:
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The text corresponds to the first two lines of newly canceled claim 17. All text should be deleted from the canceled claims.
Claims 1, 3, 5-6, and 9-16 are pending.
Priority
The instant application was filed on 5/30/2024 and claims the benefit of priority to:
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See filing receipt dated 6/14/2024.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosures of the prior-filed applications, Application Nos. 18/094459; 17/366913; 16/818416; 16/137262; and 62/561129, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Claims 1, 3, 5, 6, and 9-16 only appear to be able to claim the benefit of the instant filing date (5/30/2024). The priority applications provide support for the production of NACA having the claimed impurities and being produced by the product-by-process limitations of claims 17, 26, and 29. However, none of the prior applications disclose a method for treating a disease or condition in an animal or human in need thereof comprising identifying that a subject has a disease or condition caused by oxidative stress and providing an effective amount of an N-acetylcysteine amide (NACA). The priority applications appear to be totally silent regarding any methods of treatment.
The Examiner invites the Applicant to point out where ALL of the limitations in claims 1, 3, 5, 6, and 9-16 can be found in the applications in the claimed priority chain to provide the Applicant with the priority date of one of the earlier filed applications. On p. 5of the response filed on 9/24/2026, the Applicant acknowledges the priority date of 5/30/2024 as the earliest date to which the instant application is entitled to.
Claim Interpretation
Impurities B1 and B2 are defined in [0196] of the specification as filed:
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Regarding claims 15 and 16, the term “diNACA” is defined as disulfide of N-acetyl-L-cysteine amide in [0005] of the specification as filed.
Maintained Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. See p. 5-13 of the OA dated 3/11/2026 regarding the rejection of record.
Claim(s) 1, 3, 5, 6, and 9-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wall (US 10590073B2, published 3/17/2020, of record) in combination with Goldstein (US2009/0234011, published on 9/17/2009, of record).
Applicant claims a method for treating a disease or condition in an animal or human in need thereof comprising:
identifying that the animal or human has a disease or condition caused by oxidative stress;
providing an effective amount of an N-acetylcysteine amide (NACA) composition to the animal or human sufficient to increase a concentration of NACA, and at least one of impurities B1 and B2, wherein impurity B1 is at a level greater than zero but less than 5% peak area percent (PA%) and impurity B2 is at a level greater than zero but less than 7 PA% as determined by HPLC peak area analysis.; and
treating the disease or condition with NACA that comprises at least one of impurities B1 or B2, wherein the disease or condition is selected from retinitis pigmentosa, retinitis pigmentosa associated with Usher syndrome, age-related macular degeneration, cystinosis, corneal endothelial loss, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, a liposomal storage disease, a gain of function mutation in ACOX1, or Hereditary cystatin C amyloid angiopathy (previously claim 7).
Wall discloses a process for preparing NACA. See claim 1. Wall further discloses that the NACA produced from said process contains impurities B1 and B2, though they are not fully characterized. Wall also explicitly teaches that B1 and B2 are detectable by HPLC and provides a chromatogram in Figure 13. See Fig. 13 and col. 16, line 62-col. 17, line 17. As the NACA comprising B1 and B2 in Wall is produced by an identical process to that claimed, it is presumed that the NACA, B1, and B2 composition of Wall is identical, or substantially identical, to those of instant claims 1 and 3. See MPEP 2112 and example 4 in [0202-0204] of the specification as filed. Wall further teaches that the disclosed process for preparing NACA can be used as an efficient method for the effective, large-scale synthesis of NACA that provides the product in high chemical yields, and high chemical and enantiomeric purity, without the need for chromatography. See col. 1, lines 45-50 and col. 5, lines 33-40.
Goldstein teaches methods and compositions comprising N-acetylcysteine amide (NACA/NAC amide) which are used in treatments and therapies for human and non-human mammalian disease, disorder, conditions, and pathologies. The compositions, alone or in combination with other suitable agents, are used to treated conditions and diseases caused by oxidative stress. See abstract and claims. Goldstein further teaches that the humans and non-human mammals in need of treatment are detected (identified) by means of physical examination, laboratory, or instrumental methods. See [0037-0042]. Goldstein teaches that the NACA compositions are provided in a therapeutically effective amount to treat the diseases and conditions caused by oxidative stress, including but not limited to traumatic brain injury and Alzheimer’s. See [0152]. The examples of Goldstein teach that administration of NACA to a subject increases the concentration of NACA in said subject, in order to treat the diseases and conditions caused by oxidative stress. See [0195-0254].
Wall does not explicitly teach using NACA to treat a disease or condition caused by oxidative stress. Goldstein does not explicitly teach NACA comprising impurities B1 and B2.
It would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Wall and Goldstein to arrive at the instantly claimed process with a reasonable expectation of success before the effective filing date of the claimed invention. A person of ordinary skill would have been motivated to combine the production process of Wall, which will necessarily produce NACA comprising B1 and B2 because it is identical to that claimed, with the treatment methods of Goldstein in order to predictably arrive at a method for effectively and efficiently producing NACA in high yield, chemical and enantiomeric purity for use in the treatment of diseases and conditions caused by oxidative stress in humans and non-human mammals. Also see MPEP 2143(I)(A).
Regarding claims 5, 6, and 9-13, Goldstein teaches that the NACA can be administered by several routes, including but not limited to oral, intramuscular, and topical administration. Goldstein teaches that the NACA can also be administered by injection or in the form of a topically administered gel, ointment, cream, suppository, lotion, drops, liquids, sprays and powders. See [0115-0117]. Goldstein also teaches that topical administration includes solutions of NACA. See [0117]. Goldstein teaches that dosages are depending upon the concentration of NACA, the mode of administration, and the condition or disease to be treated. See [0121], which recites: “as is appreciated by the skilled practitioner in the art, dosing is dependent on the severity and responsiveness of the condition to be treated, but will normally be one or more doses per day, with course of treatment lasting from several days to several months, or until a cure is effected or a diminution of disease state is achieved. Persons ordinarily skilled in the art can easily determine optimum dosages, dosing methodologies, and repetition rates”. In the same paragraph Goldstein further recites an exemplary oral dosage of at least 25-500 mg per dose, which overlaps with several of the claimed ranges. Also see MPEP 2144.05 regarding the obviousness of ranges and routine optimization.
Regarding claim 14, though this is a product-by-process type limitation to define the NACA composition, Wall does explicitly teach that the NACA can be purified by crystallization and that no chromatography is required. See col. 9, lines 33-40 and col. 1, lines 45-50.
Regarding claims 15 and 16, diNACA, or di-N-acetylcystine amide, is the immediate precursor to NACA in the process of Wall. As the NACA comprising B1 and B2 in Wall is produced by an identical process to that claimed, it is presumed that the NACA, B1, and B2 composition of Wall is identical, or substantially identical, to those claimed. See MPEP 2112. Further, Wall explicitly teaches that the NACA has a purity of ≥ 98.0%, which encompasses the ranges of impurities in the claim. See col. 9, lines 37-40 and col. 15, lines 5-16.
Response to Applicant Arguments on p. 6-7 of the response filed 9/24/2026
The Applicant argues that Wall (US 10590073B2) does not qualify as prior art because the present application claims priority to Application Serial No. 16/137262, now issued patent No. 10590073. This argument has been fully considered and is not persuasive for the reasons of record. See p. 10-16 of the OA dated 6/24/2026. Further, the Applicant acknowledges that the instant application is only entitled to the priority date of 5/30/2024 on p. 5 of the response.
Applicant argues that Goldstein falls to provide that which is missing from Wall, that is nothing in Goldstein teaches the treatment of any disease or condition with a NACA having the claimed impurities. Applicant argues the combination of Wall and Goldstein fails to teaches administering an effective amount of a NACA composition to an animal or human sufficient to increase the concentration of NACA, and at least one of impurities B1 and B2 in the concentrations claimed, for one of the diseases claimed. Applicant argues that Goldstein fails to teach any of the claimed diseases that can be treated by NACA. Applicant argues that “at best, the art of Goldstein is an invitation to experiment and fails to provide a reasonable expectation of success necessary to render the claimed invention obvious”. Applicant argues that the art of Goldstein fails to provide sufficient reduction to practice to demonstrate that the invention would work of its intended purpose, citing In re Omeprazole Patent Litigation, 536 F.3d 1361, 87 USPQ2d 1865 (Fed. Cir. 2008). Applicant summarizes the examples of Goldstein. Applicant argues that Goldstein provides no support or reasonable expectation of success given the limited results with an immortal cell line and two examples of radiation, which has multiple effects on cells and tissue. Applicants cite EPA and CDC websites regarding radiation health effects and argues that neither website mentions oxidative stress as being a factor in radiation sickness. Applicant argues that the skilled artisan would not look to a reference that teaches radiation sickness for the treatment of oxidative stress, given that radiation changes DNA. Thus, the skilled artisan in possession of Goldstein would not, and could not, have a reasonable expectation of success because Goldsten is limited to teaching the effects on glutamate toxicity and radiation toxicity.
These arguments have been fully considered but are not persuasive.
Regarding the levels of B1 and B2 in the NACA, example 4 in [0202-0204] of the specification as filed explicitly teaches that NACA used in the characterization experiment was prepared and quantified using methods described in Wall. Therefore, the claimed levels of B1 and B2 are inherent to the Wall publication. Also see MPEP 2112.
Regarding the arguments with respect to “reduction to practice”, this is a concept that is invoked with respect to pre-AIA 35 USC 102(g). The instant application does not have any claims which have a pre-AIA priority date, therefore “reduction to practice” is not relevant to the present rejection. See MPEP 2138.05.
Regarding in re Omeprazole Patent Litigation, 536 F.3d 1361, 87 USPQ2d 1865 (Fed. Cir. 2008), Example 3 of MPEP 2143(I)(A) summarizes the facts as follows:
“The case of In re Omeprazole Patent Litigation, 536 F.3d 1361, 87 USPQ2d 1865 (Fed. Cir. 2008), is one in which the claims in question were found to be nonobvious in the context of an argument to combine prior art elements. The invention involved applying enteric coatings to a drug in pill form for the purpose of ensuring that the drug did not disintegrate before reaching its intended site of action. The drug at issue was omeprazole, the generic name for gastric acid inhibitor marketed as Prilosec®. The claimed formulation included two layers of coatings over the active ingredient.
The district court found that Astra’s patent in suit was infringed by defendants Apotex and Impax. The district court rejected Apotex’s defense that the patents were invalid for obviousness. Apotex had argued that the claimed invention was obvious because coated omeprazole tablets were known from a prior art reference, and because secondary subcoatings in pharmaceutical preparations generally were also known. There was no evidence of unpredictability associated with applying two different enteric coatings to omeprazole. However, Astra’s reason for applying an intervening subcoating between the prior art coating and omeprazole had been that the prior art coating was actually interacting with omeprazole, thereby contributing to undesirable degradation of the active ingredient. This degradation of omeprazole by interaction with the prior art coating had not been recognized in the prior art. Therefore, the district court reasoned that based on the evidence available, a person of ordinary skill in the art would have had no reason to include a subcoating in an omeprazole pill formulation. [AltContent: rect]
The Federal Circuit affirmed the district court’s decision that the claimed invention was not obvious. Even though subcoatings for enteric drug formulation were known, and there was no evidence of undue technical hurdles or lack of a reasonable expectation of success, the formulation was nevertheless not obvious because the flaws in the prior art formulation that had prompted the modification had not been recognized. Thus there would have been no reason to modify the initial formulation, even though the modification could have been done. Moreover, a person of ordinary skill in the art likely would have chosen a different modification even if they had recognized the problem.[AltContent: rect]
Office personnel should note that in this case the modification of the prior art that had been presented as an argument for obviousness was an extra process step that added an additional component to a known, successfully marketed formulation. The proposed modification thus amounted to extra work and greater expense for no apparent reason. This is not the same as combining known prior art elements A and B when each would have been expected to contribute its own known properties to the final product. In the Omeprazole case, in view of the expectations of those of ordinary skill in the art, adding the subcoating would not have been expected to confer any particular desirable property on the final product. Rather, the final product obtained according to the proposed modifications would merely have been expected to have the same functional properties as the prior art product. [AltContent: rect]
The Omeprazole case can also be analyzed in view of the discovery of a previously unknown problem by the patentee. If the adverse interaction between active agent and coating had been known, it might well have been obvious to use a subcoating. However, since the problem had not been previously known, there would have been no reason to incur additional time and expense to add another layer, even though the addition would have been technologically possible. This is true because the prior art of record failed to mention any stability problem, despite the acknowledgment during testimony at trial that there was a known theoretical reason that omeprazole might be subject to degradation in the presence of the known coating material.”
As discussed in the rejection above:
“Goldstein teaches methods and compositions comprising N-acetylcysteine amide (NACA/NAC amide) which are used in treatments and therapies for human and non-human mammalian disease, disorder, conditions, and pathologies. The compositions, alone or in combination with other suitable agents, are used to treated conditions and diseases caused by oxidative stress. See abstract and claims. Goldstein further teaches that the humans and non-human mammals in need of treatment are detected (identified) by means of physical examination, laboratory, or instrumental methods. See [0037-0042]. Goldstein teaches that the NACA compositions are provided in a therapeutically effective amount to treat the diseases and conditions caused by oxidative stress, including but not limited to traumatic brain injury and Alzheimer’s (claim 1). See [0152]. The examples of Goldstein teach that administration of NACA to a subject increases the concentration of NACA in said subject, in order to treat the diseases and conditions caused by oxidative stress. See [0195-0254].”
Thus, the Omeprazole case does not share the same fact pattern as the instant 35 USC 103 rejection. Goldstein explicitly teaches compositions comprising NACA can be used to treat Alzheimer’s disease and prior art is presumed to be operable/enabling. See MPEP 2121. The impurities B1 and B2 in the instant composition, which are taught by Wall, are not shown to impart any criticality to the claimed NACA compositions other than as identifying markers. Therefore, there is no evidence that the NACA composition of Wall could not predictably be used in any of the methods of use of NACA of Goldstein. The rejection of record is maintained.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 AMY C BONAPARTE whose telephone number is (571)272-7307. The examiner can normally be reached 11-7.
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/AMY C BONAPARTE/ Primary Examiner, Art Unit 1692
