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 .
DETAILED ACTION
Applicant’s amendment of 6 March 2026, in which claims 9-11 have been amended, and new claims 13-16 have been added, is acknowledged.
Claims 8-16 are pending in the instant application.
Claim 12 is withdrawn, as being drawn to a non-elected invention.
Claims 8-11, 13-16 are being examined herein.
Response to arguments of 6 March 2026
In view of Applicant’s amendment of 6 March 2026, the objection to claims 9-11 is herein withdrawn. Applicant has corrected the language.
In view of Applicant’s amendment of 6 March 2026, the rejections of claims 8-11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, are herein withdrawn. Applicant has deleted the recitation a subject “suspected of having” amyloid-beta associated diseases from claims 9, 10. Applicant has provided a literature reference showing that many COX-2 inhibitors increased production of amyloid beta 42. New rejections are made below, based on Applicant’s amendment of 6 March 2026.
Applicant’s arguments (Remarks of 6 March 2026, page 5, third paragraph) against the rejection of claims 8-11 under 35 U.S.C. 112, first paragraph, scope of enablement for the claimed method of treating a subject having an amyloid-beta associated disease comprising administering to the subject propionic acid or derivative(s) thereof, have been considered.
Applicant argues that the Specification demonstrates potential activity of sodium salt of propionic acid to treat Alzheimer’s disease.
On 6 March 2026, Applicant has amended the claims to recite a method of treating a subject having an amyloid-beta associated disease by administering to the subject an alkali salt of propionic acid, specifically sodium salt of propionic acid (newly added claims 13, 14); newly added claims 15, 16 recite Alzheimer’s disease as the amyloid-beta associated disease.
The examiner acknowledges Applicant’s amendment and argument, yet maintains that the Specification is enabling for a method of reducing locomotory paralysis in transgenic C. elegans nematodes strain CL4176, or for a method of reducing beta-amyloid peptide cell toxicity, comprising contacting the nematodes with propionic acid sodium salt; yet, the data in the Specification does not reasonably provide enablement for the claimed scope of a method of treating a subject having an amyloid-beta associated disease comprising administering to the subject propionic acid sodium salt. As detailed in the rejection, Artal-Sanz teaches there are a number of pitfalls of the C. elegans model system, such as the fact that a particular C. elegans disease model might not completely recapitulate the pathophysiology of the human disease. Artal-Sanz teaches that hits identified in worms may need considerable optimization before being used in humans. Artal-Sanz teaches that invertebrate and nonmammalian models can only be useful at the early stages of research to provide quick answers and suggest putative new therapeutics, towards the identification of putative novel targets and drug leads. Artal-Sanz teaches that any discovery will need to be further tested and validated in mammalian systems in order to increase confidence to predict drug action and safety in humans. Artal-Sanz teaches that even though various assays have been validated, no drug exists yet that was identified explicitly in a worm-based assay.
Kanwar teaches the need to evaluate a therapeutic agent for its ability to penetrate the BBB in relevant animal models of disease, for use in treating a neurodegenerative disease, such as Alzheimer’s disease.
Thus, based on the combined teachings of Artal-Sanz, and Kanwar, there is a level of uncertainty in determining whether propionic acid sodium salt, which is effective to reduce locomotory paralysis in transgenic C. elegans nematodes strain CL4176, will have therapeutic utility in treating a neurodegenerative disease such as Alzheimer’s disease.
For this reason, the rejection is herein maintained, and a modified rejection is made below, based on Applicant’s amendment of 6 March 2026.
In view of Applicant’s amendment of 6 March 2026, the rejections of claims 8, 9 under 35 U.S.C. 102(a)(1) and 102(a)(2) over Pappolla; over Hobden, A. (US 2007/0232656); over
Hobden et al. (US 2005/0288375); over Wechter; and over Rahbar, are herein withdrawn. All cited prior art recites derivatives of propionic acid.
In view of Applicant’s amendment of 6 March 2026, the rejection of claims 10, 11 under 35 U.S.C. 103 over Hobden, A. (US 2007/0232656), is herein withdrawn. Hobden recites derivatives of propionic acid.
Applicant’s amendment of 6 March 2026 necessitated the following new/modified objection and rejections.
Claim objection
Claims 9, 10 recite on line 1 “having, having a possible [….] diagnosis of having”. The repetition of the verb “having” is unnecessary.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8-11, 13-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Independent claims 9 and 10 recite a method of treating a subject having a possible or probable diagnosis of having or being at risk of developing an amyloid-beta disease. It is unclear what “a possible or probable diagnosis of having a disease” means. Is the subject suffering from a disease or not? If the subject is not suffering from a disease, why is the subject treated? As such, there is lack of clarity regarding the metes and bounds of the claims, with respect to the patient population encompassed by the claims.
Appropriate clarification is required.
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.
The following is a quotation of the first paragraph of 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 8-11, 13-16 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of reducing locomotory paralysis in transgenic C. elegans nematodes strain CL4176, or for a method of reducing beta-amyloid peptide cell toxicity, comprising contacting the nematodes with propionic acid sodium salt,
does not reasonably provide enablement for the claimed scope of a method of treating a subject having an amyloid-beta associated disease comprising administering to the subject propionic acid sodium salt, as recited by claims 8-11, 13-16. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir.1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breath of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
Claims 9-10 are drawn to a method for treating a subject having, or being at risk of developing an amyloid-beta associated disease, comprising administering to the subject an effective amount of a composition (or a nutritional supplement or a functional food comprising a composition, in claim 10) comprising propionic acid sodium salt.
Claims 8 and 11 recite that the amyloid-beta associated disease is Alzheimer's disease, Down syndrome, hypercholesterolemia, brain traumata or an amyloid-beta associated disease due to drug side effects of COX-2 inhibitors and/or isoprenoids.
Thus, claims 8-11, 13, 14, taken together with the specification, imply that propionic acid sodium salt is effective to treat any amyloid-beta associated disease, including Alzheimer's disease, or Down syndrome, or hypercholesterolemia, or brain traumata or an amyloid-beta associated disease due to drug side effects of COX-2 inhibitors and/or isoprenoids in a subject in need thereof.
Claims 15, 16, taken together with the specification, imply that propionic acid sodium salt is effective to treat Alzheimer's disease in a subject in need thereof.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
Applicant has shown that propionic acid sodium salt is effective to reduce paralysis in nematode C. elegans.
Artal-Sanz et al . (Biotechnol. J. 2006, 1, 1405-1418, cited in PTO-892 of 10 September 2025) teach that the nematode worm Caenorhabditis elegans has emerged as a convenient and versatile tool that can be used as a platform for devising and streamlining efficient drug discovery and drug target identification methodologies (Abstract). Artal-Sanz teaches that, while among animal models, C.elegans is certainly the most cost effective choice for a target validation scheme (page 1416, left column, fourth paragraph, lines 7-9), there are a number of pitfalls of the C. elegans model system, such as the fact that a particular C. elegans disease model might not completely recapitulate the pathophysiology of the human disease (page 1416, left column, second paragraph). Importantly, Artal-Sanz teaches (page 1416, left column, third paragraph) that hits identified in worms may need considerable optimization before being used in humans.
Artal-Sanz teaches (page 1415, left column, second paragraph) that invertebrate and nonmammalian models can only be useful at the early stages of research to provide quick answers and suggest putative new therapeutics, towards the identification of putative novel targets and drug leads. Artal-Sanz teaches that any discovery will need to be further tested and validated in mammalian systems in order to increase confidence to predict drug action and safety in humans.
Artal-Sanz teaches (page 1415, right column, second paragraph) that even though various assays have been validated, no drug exists yet that was identified explicitly in a worm-based assay.
Thus, based on the teachings of Artal-Sanz, there is a level of uncertainty in determining whether a compound that reduces locomotory paralysis in C. elegans will have therapeutic utility in treating a disease in a human, or mammal.
Further, Kanwar et al. (International Journal of Nanomedicine 2012, 7, 3259-3278, cited in PTO-892 of 10 September 2025) teach that therapeutic agents have to penetrate the blood-brain barrier (BBB) in order to effectively treat neurodegenerative diseases, such as Alzheimer’s disease (page 3260, right column, lines 3-6). Kanwar teaches that a major limitation in the treatment of neurodegenerative disease, such as Alzheimer’s disease, is the inability to deliver drug molecules across the brain barrier (page 3267, right column, first paragraph). Thus, Kanwar teaches the need to evaluate a therapeutic agent for its ability to penetrate the BBB in relevant animal models of disease, for use in treating a neurodegenerative disease, such as Alzheimer’s disease.
Thus, based on the combined teachings of Artal-Sanz, and Kanwar, there is a level of uncertainty in determining whether propionic acid or its sodium salt will have therapeutic utility in treating a neurodegenerative disease such as Alzheimer’s disease.
Regarding the scope of claims 9, 10, Abyadeh et al. (Neural Regeneration research 2024, 19 (6), 1262-1276, published on line October 2, 2023, cited in PTO-892 of 10 September 2025) teach the connections between dysregulation of amyloid-beta proteins and a spectrum of disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, autism, Down syndrome, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration; additionally, dysregulation of amyloid-beta proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes (see also Figure 1).
Abyadeh teaches (page 1270, under Conclusion) that Aβ and tau protein are well-established pathogenic factors in several neurodegenerative diseases, particularly in AD; however, a growing body of evidence has indicated the presence of these factors in other diseases and provided molecular mechanisms underlying their aggregation and pathogenesis. Abyadeh teaches that research about the role of these pathological factors in other diseases is limited. The reasons for the alteration of protein expression and modification in these diseases are multifactorial and may vary depending on the specific condition. One possible explanation is that Aβ and tau proteins are involved in various cellular processes beyond their roles in neurodegeneration; they participate in signaling pathways, synaptic function, and neuronal plasticity, and their dysregulation can contribute to pathological processes in different diseases. For example, in cardiovascular diseases, Aβ and tau may be involved in vascular dysfunction and contribute to cerebrovascular pathology. In diabetes, these proteins may contribute to neuronal damage and cognitive impairment associated with the disease. The presence of Aβ and tau protein alterations in these diseases may indicate the potential involvement of neurodegenerative mechanisms, but their presence alone does not appear to be specific. However, these proteins may play a critical role in cellular dysfunction and contribute to the progression of pathology specific to each condition. Most studies are focused on altered levels of Aβ and tau protein and also phosphorylation of tau protein in disease; however, other PTMs such as acetylation and truncation also play a critical role. Moreover, conformational changes including trans and cis conformation may induce different levels of toxicity, which is not well investigated in these diseases. Regarding their potential as diagnostic and therapeutic biomarkers, further research is needed. While Aβ and tau have been extensively studied in the context of AD, their use as biomarkers in other diseases is still being explored. It is important to consider the specificity and sensitivity of these biomarkers in different conditions, as well as their correlation with disease progression and response to treatment.
Abyadeh teaches that the presence of Aβ and tau protein alterations in diseases beyond AD suggests shared mechanisms and potential contributions to pathogenesis, yet further research is necessary to unravel the specific roles of these proteins in different conditions, assess their diagnostic value, and explore their potential as therapeutic targets.
As such, Abyadeh teaches the unpredictability, the complexity of mechanisms involved, and the need for further research in order to assess the therapeutic value of targeting amyloid-beta proteins in diseases characterized by dysfunction of amyloid-beta proteins, beyond Alzheimer’s disease.
(5) The relative skill of those in the art:
The level of skill in the art is that of the authors of the references cited to support the examiner’s position (MDs, PhDs, or those with advanced degrees and the requisite experience in treatment of amyloid-beta diseases).
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
A disclosure should contain representative examples which provide reasonable assurance to one skilled in the art that the claimed method is effective in treating the full scope of diseases as claimed.
The Specification has provided guidance (Example 1, pages 18-19, Figure 1) for one compound of the instant invention, propionic acid sodium salt, being able to reduce locomotory paralysis in transgenic C. elegans strain CL4176 expressing amyloid-beta peptide in muscle cells. The Specification teaches (page 18, last paragraph) that this model is useful to view the ability of the compound tested to reduce beta-amyloid peptide cell toxicity.
However, the Specification provides no data showing that propionic acid sodium salt is effective to treat Alzheimer’s disease.
However, the Specification provides no data showing that propionic acid sodium salt is effective to treat any other diseases, beyond Alzheimer’s disease, characterized by dysfunction of the amyloid-beta protein, or any disease listed in claims 8, 11.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in scope with instant claims 8-11, 13-16.
Claim Rejections - 35 USC § 103
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.
Claim interpretation: the term “amyloid-beta associated diseases” in claims 8-11 is interpreted to be (Specification, page 1, lines 11-12) neurodegenerative diseases characterized by accumulation of amyloid-beta peptides in the brain.
Claims 8-11, 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Govindarajan et al. (Journal of Alzheimer’s disease 2011, 26, 187-197, cited in PTO-892).
Govindarajan teaches (Abstract) a method of treating Alzheimer’s disease in a patient in need thereof, comprising orally (Fig. 2) administering to the patient a therapeutically effective amount of HDAC inhibitor sodium butyrate.
Govindarajan does not teach a method of treating Alzheimer’s disease with sodium propionate, as in instant claims, where sodium propionate is a nutritional supplement or a functional food, as in instant claim 10, 11, 14, 16.
It would have been obvious to a person of ordinary skill in the art to administer sodium propionate, which is a direct homolog of sodium butyrate, to a subject suffering from Alzheimer’s disease, with a reasonable expectation of achieving therapeutic effect. In the absence of unexpected results, stereoisomers are considered obvious variants of each other. "Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties". In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Regarding claims 10, 11, 14, 16, it would have been obvious to a person of ordinary skill in the art to mix the sodium propionate with food upon administration, to arrive at the instant invention.
As such, claims 8-11, 13-16 are rejected as prima facie obvious.
Conclusion
Claims 8-11, 13-16 are rejected.
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 IRINA NEAGU whose telephone number is (571)270-5908. The examiner can normally be reached Mon-Fri 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S. LUNDGREN can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629
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