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 OFFICE ACTION
This Office Action is in response to the papers filed on 03 march 2026.
CLAIMS UNDER EXAMINATION
Claims 12-16 have been examined on their merits.
PRIORITY
Provisional Application 62/943,005 filed on 03 December 2019, is acknowledged.
REJECTIONS
Claim 12 has been amended to recite over 180 possible compounds. The compounds recited in claim 13 have been amended. The rejections have been modified to address the amended claims.
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 12-16 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.
Regarding claim 12: The Markush group recited in claim 12 is improper because the alternatives defined by the Markush grouping do not share a substantial structural feature and a common use that flows from the substantial structural feature. Claim 12 recites xylazine, haloperidol and harmine among the expansive list of chemical compounds. The chemical structure of xylazine features a dihydrothiazine ring linked to a 2,6-dimethylphenyl group, with the molecular formula C₁₂H₁₆N₂S. The chemical structure of haloperidol features a core piperidine ring linked to a p-chlorophenyl group and a hydroxy group at one side, and a p-fluorobutyrophenone chain on the nitrogen, with the chemical formula C21H23ClFNO2. Harmine is a β-carboline alkaloid, featuring a fused indole and pyridine ring system (β-carboline core) with a methoxy group at position 7 and a methyl group at position 1, giving it the systematic name 7-methoxy-1-methyl-β-carboline and the chemical formula C13H14N2O.
The claim also includes hycanthone, cyclopamine and thiothixene as possible alternatives. Hycanthone is a thioxanthen-9-one compound having a hydroxymethyl substituent at the 1-position and a 2-[(diethylamino)ethyl]amino substituent at the 4-position, with the molecular formula C20H24N2O2S. Cyclopamine is a naturally occurring steroidal alkaloid with a unique six-ring structure, featuring a C-nor-D-homosteroid backbone fused to an octahydrofuro[2-b]pyridine system via a spirocenter, containing 10 chiral centers, with the molecular formula C27H41NO2. Thiothixene features a central thioxanthene ring system (a tricyclic structure with sulfur replacing the oxygen in xanthene), substituted at the 9-position with a propylidene side chain that connects to a 4-methylpiperazin-1-yl group, and a dimethylsulfonamide attached to the 2-position of the thioxanthene core, forming a molecule with E/Z isomers. The list of alternatives recited in claim 12 is so expansive that a person of ordinary skill cannot determine the metes and bounds of the claimed invention. Appropriate correction is required. All dependent claims are included in this rejection.
Claim 12 recites improper Markush language. The claim has been amended to recite administering a compound, wherein the compound “comprises” one or more of the recited compounds, salts thereof or a combination thereof. A Markush grouping is a closed group of alternatives. The claim language is indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. Appropriate correction is required. All dependent claims are included in this rejection.
Claim 12 recites administering a therapeutically effective amount of a “compound”, wherein the compound comprises…”. The claim recites over 180 compounds. While the last line of the claim recites “or a combination of any of the foregoing”, the claim language is unclear. It is unclear if the claim means “a compound” can comprise all of the compounds listed. Appropriate correction is required. All dependent claims are included in this rejection.
Regarding claim 13: The Markush group recited in claim 13 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the alternatives do not share a substantial structural feature and a common use that flows from the substantial structural feature. Harmine (a hallucinogen) is structurally unrelated to genistein (a plant-derived isoflavone in soybeans) and celecoxib (a nonsteroidal anti-inflammatory drug).
Claim 13 recites improper Markush language. A Markush grouping is a closed group of alternatives. The claim language is indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. Appropriate correction is required.
Claim 13 recites administering a therapeutically effective amount of a “compound”, wherein the compound comprises…”. While the last line of the claim recites “or a combination of any of the foregoing”, the claim language is unclear. It is unclear if the claim means “a compound” can comprise all of the compounds listed. Appropriate correction is required.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 06 March 2026 are acknowledged.
Argument: The Applicant states the tables have been removed, and the claims no longer recite an improper Markush group.
Response to Argument : Claims 12-13 recite a list of alternatives. The claims are interpreted to be a Markush group. The Markush groups recited in the claims are improper because the alternatives do not share a substantial structural feature and a common use that flows from the substantial structural feature.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 12 and 14-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Apgar et al. (previously cited; Use of Haloperidol in Alzheimer’s Disease. Am Fam Physician. 1999; 59(7): 1974-1975) as evidenced by Panda et al. (Mitostasis in age-associated neurodegeneration. Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease. Volume 1871, Issue 1, January 2025, 167547) and Bhatia et al. (previously cited; Mitochondrial Dysfunction in Alzheimer’s Disease: Opportunities for Drug Development. Curr Neuropharmacol. 2022 Mar 28;20(4):675–692).
Apgar et al. determine the optimal dosage of haloperidol to treat patients who have Alzheimer's disease (page 1, first paragraph). Outpatients with Alzheimer's disease received haloperidol (page 1, second paragraph). Apgar teaches the standard dosage has a therapeutic effect (same cited section).
The specification does not define “dysfunction of neuronal mitostasis”. As evidenced by Panda et al., mitostasis is the process of maintaining cellular mitochondrial function (see Abstract). As evidenced by Panda, Alzheimer's Disease (AD), is a neurodegenerative disorder “characterized by a defined set of hallmarks”, including “neuronal network dysfunction” (page 6, left column, second paragraph). Table 1 of Panda discloses “the specific mitochondrial functions impaired” in AD. Impaired mitochondria are interpreted to be dysfunctional. Therefore a subject with AD has dysfunction of neuronal mitostasis.
As evidenced by Bhatia, “mitochondrial dysfunctional and altered mitochondrial bioenergetics play a vital role in the development of AD. It is one of prominent and earliest features of AD” (page 2, right column, first paragraph). As evidenced by the specification, toxic Aβ species are reported to accumulate intraneuronally, and within mitochondria, during the development of Alzheimer's disease, impairing energy metabolism, increasing ROS and decreasing ATP production ([0003]). Therefore a subject with AD has dysfunction neuronal mitostasis.
Because Apgar administers a therapeutically effective amount of haloperidol to a patient with Alzheimer’s disease, it would treat dysfunctional neuronal mitostasis. Therefore claim 12 is anticipated.
As evidenced by the specification, Alzheimer’s disease is a neurodegenerative disorder (PG Pub [0005]). Therefore claim 14 is included in this rejection. Alzheimer’s disease reads on claims 15-16.
Therefore Applicant’s Invention is anticipated as claimed.
Claim 13 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (previously recited; Carvedilol as a potential novel agent for the treatment of Alzheimer’s disease. Neurobiol Aging. 2011 December ; 32(12): 2321.e1–2321.e12) as evidenced by Panda and Bhatia et al.
Wang teaches chronic oral administration of carvedilol to mice (patients) with Alzheimer’s Disease (AD) (Abstract; see page 2, third paragraph). Wang teaches carvedilol treatment improves cognitive function (see page 7, last paragraph). Administration of 1.5 mg/kg/day (last paragraph of page 2) led to significant improvements in cognitive function (last paragraph of page 7). Therefore the art administers a therapeutically effective amount.
The specification does not define “dysfunction of neuronal mitostasis”. As evidenced by Panda et al., mitostasis is the process of maintaining cellular mitochondrial function (see Abstract). As evidenced by Panda, Alzheimer's Disease (AD), is a neurodegenerative disorder “characterized by a defined set of hallmarks”, including “neuronal network dysfunction” (page 6, left column, second paragraph). Table 1 of Panda discloses “the specific mitochondrial functions impaired” in AD. Therefore a subject with AD has dysfunction of neuronal mitostasis.
As evidenced by Bhatia, “mitochondrial dysfunctional and altered mitochondrial bioenergetics play a vital role in the development of AD. It is one of prominent and earliest features of AD” (page 2, right column, first paragraph). As evidenced by the specification, toxic Aβ species are reported to accumulate intraneuronally, and within mitochondria, during the development of Alzheimer's disease, impairing energy metabolism, increasing ROS and decreasing ATP production ([003]). Therefore a subject with AD has dysfunction of neuronal mitostasis.
Because Wang administers a therapeutically effective amount of haloperidol to a patient with Alzheimer’s disease, it would treat dysfunction of neuronal mitostasis. Therefore claim 13 is anticipated.
Therefore Applicant’s Invention is anticipated as claimed.
37 CFR 1.132 Declaration
The Declaration filed under 37 CFR 1.132 by Ronald Davis, Ph.D. in the response filed on 06 March 2026 is acknowledged. The Declaration addresses “how the person of ordinary skill in the art would have interpreted certain statements in the present application and cited art”. The Declarant argues not all patients with Alzheimer’s Disease have the claimed dysfunctions. The Declaration acknowledges the specification identifies AD, Parkinson’s disease, amylotrophic lateral sclerosis, mood disorders and schizophrenia as exemplary disorders exhibiting the claimed dysfunctions, but argues this does not mean they have the claimed dysfunctions.
The Declaration under 37 CFR 1.132 filed 06 March 2026 insufficient to overcome the rejection of the claims under 35 USC 102(a) as set forth in the last Office action because:
The preamble of the claims 12 and 13 is directed to a method of treating “dysfunction of neuronal mitostasis” or “dysfunction of ATP generation”. The specification does not define these terms. “Mitostasis” is defined as the process of maintaining cellular mitochondrial function (see Abstract of Panda et al.). Table 1 of Panda discloses the following:
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As evidenced by Panda, Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (ALS), are neurodegenerative disorders charactered by a defined set of hallmarks, including “neuronal network dysfunction” (page 6, left column, second paragraph).
Therefore a subject with AD has dysfunction of neuronal mitostasis.
As evidenced by Bhatia, “mitochondrial dysfunctional and altered mitochondrial bioenergetics play a vital role in the development of AD. It is one of prominent and earliest features of AD” (page 2, right column, first paragraph). Therefore, as evidenced by Bhatia, dysfunction of neuronal mitostasis is a characteristic of Alzheimer’s disease.
As evidenced by the specification, toxic Aβ species accumulate intraneuronally, and within mitochondria, during the development of Alzheimer's disease, impairing energy metabolism, increasing ROS and decreasing ATP production ([0003]).
The Declaration does not provide evidence AD occurs without dysfunction of neuronal mitostasis. The Declaration has not provided evidence the prior art references do not teach the claimed method.
Affidavits or declarations are provided as evidence and must set forth facts, not merely conclusions. In re Pike and Morris, 84 USPQ 235 (CCPA 1949). Upon consideration of the facts taught by the prior art and the information submitted by the Affiant, the balance of evidence indicates that the prior art teaches the instantly claimed inventions.
RESONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 24 November 2025 are acknowledged.
Argument 1: The Applicant argues Bhatia et al. is not prior art.
Response to Argument 1: Bhatia is not cited as prior art. The rejections cite Bhatia as a post-filing evidentiary reference. Therefore the argument is not persuasive.
Argument 2: The Applicant argues the prior art does not teach or suggest the listed compounds for treating dysfunction or neuronal mitostasis or dysfunction of ATP generation in a patient. The Applicant argues the references treat Alzheimer’s disease. The Applicant argues Alzheimer’s disease is a heterogenous disorder. The Applicant argues it can not be said all patients have dysfunction of neuronal mitostasis or dysfunction of ATP generation.
Response to Argument 2: The specification does not define “dysfunction of neuronal mitostasis” or “dysfunction of ATP generation”. As evidenced by the cited evidentiary references, impaired mitochondrial function is a feature of AD.
The prior art references treat subjects with Alzheimer’s disease. The references administer a therapeutically effective amount of recited drugs. Therefore they would inherently treat dysfunction of neuronal mitostasis. The arguments are not persuasive.
CONCLUSION
No Claims Are Allowed
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653