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 .1
Status of Claims
Claims 1, 3, 7-8, 31, 36-37 and 42-50 are pending. Claims 1, 3, 7-8, 31, and 36-37 are under examination. Claims 42-50 are withdrawn.
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1, 3, 7-8, 31, and 36-37) and below species in the reply filed on Feb 17 2026 is acknowledged.
Applicant elected the following species, without traverse:
PNG
media_image1.png
184
260
media_image1.png
Greyscale
(4-(2-isothiocyanatoethyl)pyridine), identified in the specification as a PEITC analog at page 7, line 1. Claims 1, 3, 7-8, 31, and 36-37 read on the elected species.
Note that upon further search and consideration, the scope of PEITC analogs examined has been expanded to include the species of sulforaphane, as recited in examined claims 7 and 36.
Claims 42-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention II and specie, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 17, 2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 30 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: Page 48, lines 12-13 recites “high-throughout” rather than “high-throughput” when referring to the method of screening with MTT and Abeta uptake assays. Appropriate correction is required.
Claim Objections
Claim 3 is objected to because of the following informalities: between lines 1-2 of claim 3, the term “is” is missing between “neurodegenerative disorder” and “selected.”
Further, claim 3 is not in a proper claim format. Claim 3 contains two separate sentences, the second sentence starting as “In some embodiments… “
As required by MPEP 608.01(m), “[T]he Office practice is to insist that each claim must be the object of a sentence starting with . . . "The invention claimed is" (or the equivalent).” Not only is the form of the second sentence improper, but its presence as a second sentence in claim 3 is also improper. See also indefiniteness rejection of claim 3 for this second sentence as detailed below. Deletion of the second sentence will overcome this objection. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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, 3, 7-8, 31, and 36-37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a particular compound (sulforaphane for the treatment of AD, see novelty rejection below) for the treatment of a particular species of neurological disease, Alzheimer’s disease AD in a human subject, does not reasonably provide enablement for the of treatment and prevention of the full scope neurological disorders in a human subject, with the full scope of compounds claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
The predictability or unpredictability of the art:
The instant claimed invention is highly unpredictable since one skilled in the art recognizes the difficulties in treating the broad scope of neurological diseases in a human subject of claim 31, in the narrowest of embodiments, such as the elected species Alzheimer’s Disease AD, let alone any of the conditions characterized by neuronal cell death, dysfunctional energetic function, unregulated microglia phagocytic activity, and/or other related de-regulated biological functions (claim 1).
The basis of the claimed invention to treat AD is noted with the Detailed Description on page 18 of the specification. The Detailed Description notes the role of Aβ peptides, neurofibrillary tangles (NFTs) and neurite plaques as pathological hallmarks of the disease. Id.
Neurite plaques are aggregates of amyloid beta (Aβ) peptides composed of 40 (Aβ 40) or 42 (Aβ 42) amino acids. Id. Elevated brain levels of Aβ42 can cause neurotoxicity and neuron death as evidenced by impaired learning and recognition memory. Id.
Applicant’s approach of its claimed method to treat and prevent AD is noted at page 19, where the specification states in one particular AD in vivo mouse model (3xTg), said AD model mice treated with NAD+, NADH, PEITC individually showed significant reduction in the levels of neurotoxic Aβ42 and ratio of Aβ42 to Aβ40. See page 19, lines 30-31.
However, the art is unpredictable with anti- Aβ therapy as relied upon Applicant. Zhang et al.2 teaches “Although the [Aβ] aggregates have been considered to be toxic, soluble Aβ at physiological levels have been identified to have biological functions, including enhancement of long-term potentiation (LTP),… stimulation of neuronal differentiation,… improvement of the brain’s ability to recover from injuries,… inhibition of oxidative stress,… antimicrobial activity…and tumor suppression… (Fig. 4).” See page 11, column 2, last full paragraph
Further, as the invention relies upon Aβ mouse models, the art notes a lack of accurate Aβ animal models. See Zhang page 14, column 1. Zhang teaches in vivo mouse models of AD.
However, such mouse models only mimic the familial AD with an early onset of the disease. The late-onset sporadic AD is induced by a combination of genetic (e.g. Apolipoprotein E4 and TREM- 2),…. lifestyle and environmental factors…. Unfortunately, the current animal models are unable to exactly reflect this complexity, such as aging, which is the major risk factor of sporadic AD. The immune system has long been implicated as an important factor in Alzheimer’s development…. However, murine immune system is notably different from humans…. Furthermore, the extensive neuronal loss in AD patients has not been replicated in the murine models…. Thus, a lack of accurate disease models leads to a translational gap between animal research and the clinical setting. Design and exploration of patient-based research models will be required. . . . See page 14, column 1 bridge to column 2.
Therefore, the unpredictability of the art is Wands factor against the enablement of the full scope of the claimed invention.
The breadth of the claims
Claim 1 broadly claims treating a human patient suffering a condition characterized with neuronal cell death, dysfunctional energetic function, unregulated microglia phagocytic activity, and/or other related de-regulated biological functions, where the conditions are unduly and broadly defined as a neurodegenerative disorder, aging, systemic inflammation, neuroinflammation, cancer, and diabetes.
Claim 31 broadly treats, ameliorates and prevents ANY of AD, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, motor neuron disease, subjective memory complaints, and MI in a human patient.
Claim 1 is unduly broad by NOT reciting an effective amount of agent to treat the mammalian human patient suffering from the claimed conditions/diseases. In other words, any amount of claimed agent is purported to treat/prevent/ameliorate the claimed conditions. The claimed broad scope is a Wands factor weighing against enablement the full scope of the claimed invention.
The amount of direction or guidance presented, and the presence or absence of working examples
It has been established that “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
Claims 1 and 31 are unduly broadly directed to treating/preventing/ameliorating diseases and neurological disorders beyond the elected species, Alzheimer’s disease.
Pages 18-19 of the specification note the only experiments done by the inventors are directed to treatment of Alzheimer’s disease, in particular with computational modeling and in vitro and in vivo Aβ42 models of only 3 agents, NAD+, NADH and PEITC. See bottom of page 19 bridging to top of page 20. These experiments are described in further detail in Experimental Examples I and III starting at pages 39 and 49-50 of the specification. It is noted that there is a contradiction with regard to the in vivo mouse models, where page 19 states 3xTg mouse models were actually treated, while Example III says the 3xTg mouse model experiments will be conducted (i.e. a prophetic model, where no experiments were done by the time of the filing of this application).
Therefore, in view of the Wands factors as discussed above, Applicant fails to provide information sufficient to practice the full scope of the claimed invention.
Claim Rejections - 35 USC § 112(b)
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 1, 3, 7, 8, 31, and 36-37 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.
Claims 1, 3, 8, 31, and 37 are rejected for the recitation of the term “analog of PEITC” in claims 1 and 31, where claims 3, 8 and 37 depend from claims 1 and 31.
The common language usage/understanding for “analog” in the chemical/biological context is of similar chemical structures/substances/biological activity of such substances, in this case PEITC, phenyl isothiocyanate, below.
PNG
media_image2.png
118
210
media_image2.png
Greyscale
Other than the specific examples of PEITC analogs listed in claims 7 and 36, the specification only adds to the indefinite limitation of PEITC in the rejected claims.
Starting at page 48, last line, Example II describes the synthesis of PEITC analogs in scheme 1. Example II, at page 49, states a number of PEITC analogs, noting isothiocyanate and fused or unfused aromatic or heteroaromatic rings connected by CH2n (n= 0-12), where the rings are substituted by an undefined group of moieties (use of the term etc. to describe the substituents listed therein). The undefined nature of the various moieties of aromatic/heteroaromatic rings and undefined substituents in the specification do not provide definition to the rejected claims
Exacerbating the lack of definition of non-exemplified PEITC analogs are the prophetic statements of the specification where it states additional experiments will be conducted with these PEITC analogs using high-throughput screening (HTS) with MTT and Abeta uptake assays to assess the therapeutic efficacy of the PEITC analogs to treat neurodegenerative disorders described therein. See page 49, lines 12-14. This is a prophetic example, none of the assays have been done. Should any of these analogs prove to lack therapeutic activity, it draws into question whether such compounds are considered PEITC analogs in context of the claimed methods of treating, preventing and/or ameliorating a neurological disease/symptoms in a human patient.
Claim 3 is also indefinite on another basis, where it recites a second sentence, that further limits the broader scope of neurodegenerative disease, Alzheimer’s Disease (AD) recited in claim 3’s first sentence. The narrower second sentence limitation states, “In some embodiments, the AD is an early stage, prodromal phase of AD or late stage.”
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recites the broad recitation the first sentence claiming treating an Alzheimer’s disease (AD) patient, and the claim also recites a second sentence further limiting the AD patient claimed, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Deletion of the second sentence will overcome this objection.
Regarding claims 8 (line 12) and 37 (line 9), the phrase "but not limited to" renders the claims indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "but not limited to"), thereby rendering the scope of the claims unascertainable. See MPEP § 2173.05(d).
Claims 7 and 36 are indefinite for the recitation of the limitation where the therapeutic species of compounds include “any chemical moiety related to watercress and/or other cruciferous plant extraction.” The specification does not specifically define what chemical moiety “related” to watercress and other cruciferous plant extraction are included or excluded. It is unknown if “related” is defined as the extracted chemical themselves or include solvents, reagents, etc. used for the extraction process. See for example page 22, lines 15-16, which merely repeats the indefinite language.
The plain language meaning of “related” would include solvents, reagents, excipients related to such an extraction process, where these “related” ingredients would not have therapeutic value in treating neurological disease. Amendment of the claims to limit the chemical moieties to be limited to extracted plant extracts would overcome this rejection.
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.
Claims 1, 3, 7, 8, 31, 36 and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2002002190 A2 (WO 190). WO 190 is cited by Applicant on the IDS.
Regarding the method of claims 1, 3, 7, 31 and 36, WO 190 teaches a method of treating and ameliorating the elected species, Alzheimer’s disease (AD) in a subject, with an agent such as isothiocyanate, such as sulforaphane. See claims 1-3 and 6 of WO 190. Note that the WO 190 defines a subject treated to preferably a mammal such as a human. See page 5, lines 20-21.
Regarding claims 8 and 37, WO 190 does not expressly teach that sulforaphane3 is sourced from a plant extract or plant (i.e., cabbage as a member of brassica family).
However, the teaching of sulforaphane per se by WO 190, anticipates claims 8 and 37, because the source of the claimed compound sulforaphane by the application is irrelevant. Per MPEP 2112.0, citing to In re Spada, a chemical composition and its properties are inseparable. Because the prior art teaches the identical sulforaphane compound as claimed, despite further intended use limitations of sulforaphane being sourced from plant sources, the teaching of WO 190 of sulforaphane per se and the treatment/prevention of AD in subject, claims 8 and 37 are anticipated.
With regard to the prevention of claims 31, 36 and 37, WO 190 teaches the administration of sulforaphane to a human subject suffering in need of treatment of a neurodegenerative disease such as AD, see above discussion. As all human subjects are in need of the prevention of AD, WO 190 anticipates claims 31, 36 and 37.
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, 3, 7-8, 31, and 36-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18686950 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims and conflict reference claims 1-8 and 51-53 are all directed to methods to treat AD with a compound such as PEITC, NAD+, NADH and PEITC analogs, within the scope claimed.
Conflict claims 1-8 claim a method of treating a human patient, suffering from AD (neurodegenerative disorder) with a composition to protect neurons from cell death, etc., with PEITC, PEITC analogs, NAD+ and NADH. See conflict application claim 8 specifying some of the same PEITC analogs as claimed by claims 7 and 36. Also conflict claims 51-53 are directed compositions comprising the same PEITC analogs and NAD+, NADH.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion and Correspondence
In summary no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 CONTINUING DATA
This application is a CIP of PCT/US2021/048034 08/27/2021
PCT/US2021/048034 has PRO 63/071,032 08/27/2020
PCT/US2021/048034 has PRO 63/071,035 08/27/2020
2 Zhang et al. Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future Signal Transduction and Targeted Therapy ( 2023) 8:248 https://doi.org/10.1038/s41392-023-01484-7
3 As background, WO 190 notes brassica vegetable sources such as brussels sprouts and cabbage, when fed, are noted to modulate Phase I and II enzymes, that oxidize/reduce/detoxify xenobiotics. See page 1, line 20 bridging to page 2, line 6; and page 2, lines 12-13. Claim 1 of WO 190 notes its compounds, such as sulforaphane, elevate Phase II detoxification enzyme in diseased (Alzheimer’s) tissue of a subject.
Prosecution Insights