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 .
Response to Amendments
Applicant’s amendments to the claims of February 27, 2026, in response to the Office Action of January 29, 2026, are acknowledged.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The examiner acknowledges a Petition for Color Drawings has been filed.
Response to Arguments
The examiner notes, as reiterated above, that the list in the Specification does not constitute an IDS.
The 112(b) rejection and 112(a) rejection are each withdrawn in view of the amendments to the claims. The arguments with respect to the 102(a) rejection is persuasive. The 103 rejection in view of Steiner has also been withdrawn in view of the Amendments to the claims that remove a subject with Alzheimer’s disease from the claims.
With respect to the traversal of the 103 rejections, the examiner responds. The examiner acknowledges that Hopper does not teach voriconazole as a CYP46A1 inhibitor. However, Pikuleva establishes this. Hopper establishes that the claimed subject population can be treated with an agent that effectuates the mechanism of action of inhibiting CYP46A1. As such, a prima facie showing is made because there is a motivation to administer agents, including voriconazole, to the claimed subject population. The remaining limitations are taught and/or are rendered obvious as explained in more detail below.
Hopper teaches intrathecal, oral, and other claims routes of administration. Hopper also teaches administration in combination with other active agents. See par. 62. Examples of additional drugs that can be used include memantine, aspirin, heparin, warfarin, and others. See par.’s 44 and 84. Hopper also indicates that concomitant drug treatment may be administered simultaneously or staggered in their administration to a subject. They can also be administered as separate compositions with active agents or administered as one single preparation. See par. 100. Sequential, concurrent, and alternating administrations are all contemplated. See par. 62. The route of administration for the concomitant drug will be appropriately determined based on the clinical situation . See par. 101.
The examiner cites: Adachi et al., (US2008/0039500). Adachi teaches treating cerebral infarction by administering thioperamide. See prior art claim 2. The form and route of administration is not limited. An injection, such as IV injection is preferred. It can be adjusted with water, saline, and a solvent may be used. See par. 29. It can be administered shortly after reperfusion. See par. 28. A cerebral infarction is defined as an acute brain injury.
A rejection is set forth below.
Status of the Claims
Claims 16-27 are pending and examined.
Claim Rejections - 35 USC § 103
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.
Claims 16-27 are rejected under 35 U.S.C. 103 as being unpatentable over Pikuleva et al., (US20100075991), in view of Hopper et al., (US20220332699) (filed May 24, 2020), and in view of Henry et al., “Quantification of Brain Voriconazole Levels in Healthy Adults Using Fluorine Magnetic Resonance Spectroscopy,” Antimicrobial Agents and Chemotherapy p. 5271–5276 November 2013, and in further view of Adachi et al., (US2008/0039500).
Pikuleva teaches compounds and methods for regulating CYP46A1 activity in the brain and retina. Such compounds can be used to treat pathoneurological conditions associated with increased cholesterol levels. See Abstract. Voriconazole is a compound that inhibits CYP46A1 in the mouse brain. See Figures 6A-6D. Dosages were administered via IP injection. See par. 25. Conditions that are associated with an increased level of cholesterol in the brain are Alzheimer’s disease, among others. See par. 50. Voriconazole is taught to be an efficient inhibitor of brain cholesterol. See par. 74.
Absent evidence to the contrary, the forms are titratable. As described a suitable dosage level will depend on a variety of factors and can be determined by the person administering. See par. 53.
Hopper teaches a methods of treating or preventing disorders by administering compounds that inhibit CYP46A1. See Abstract. Findings have suggested that CYP46A1 inhibitors may be promising treatments for diseases including Alzheimer’s disease, traumatic brain injury, and cerebral infarction. See par. 2. Compounds can be administered orally, intranasally, parenterally, and through other routes. See par. 41. Further, the form can be a liquid solution or suspension, pill, tablet, and other solid form. See par. 45. Further, compounds can be administered in combination with other active agents and the combination can proceed by any technique apparent to those in the art, including separate, sequential, and concurrent administration. See par. 62. Secondary therapeutic agents include NSAIDs including aspiring (par. 82) and platelet aggregation inhibitor (par. 92), among many others. Hopper teaches intrathecal, oral, and other claims routes of administration.
Hopper also teaches administration in combination with other active agents. See par. 62. Examples of additional drugs that can be used include memantine, aspirin, heparin, warfarin, and others. See par.’s 44 and 84. Hopper also indicates that concomitant drug treatment may be administered simultaneously or staggered in their administration to a subject. They can also be administered as separate compositions with active agents or administered as one single preparation. See par. 100. Sequential, concurrent, and alternating administrations are all contemplated. See par. 62. The route of administration for the concomitant drug will be appropriately determined based on the clinical situation . See par. 101.
Henry is cited merely to show that voriconazole is known to cross the blood-brain barrier even when administered orally. See Abstract.
Adachi teaches treating cerebral infarction by administering thioperamide. See prior art claim 2. The form and route of administration is not limited. An injection, such as IV injection is preferred. It can be adjusted with water, saline, and a solvent may be used. See par. 29. It can be administered shortly after reperfusion. See par. 28. A cerebral infarction is defined as an acute brain injury.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to combine the teachings of Pikuleva, Hopper, Henry, and Adachi to arrive at the claimed methods. One would be motivated to do so because voriconazole is a known CYP46A1 inhibitor that has such effect in the brain of a subject and can treat Alzheimer’s disease among other conditions, as taught by Pikuleva. Further, this can occur through various routes of administration with numerous carriers and/or excipients. Even further, Hopper teaches treating conditions including Alzheimer’s disease, traumatic brain injury, and cerebral infarction by administering an agent that inhibits CYP46A1. Combination therapy is contemplated and the route of administration and form of drug is not particularly determinative to treatment. Moreover, Henry is cited merely to show that voriconazole effectively crosses the blood brain barrier. Even further, Adachi teaches administration of thioperamide following a stroke, as explained above. Overall, the administration of claimed API is known to effectuate a mechanism of action that will treat the claimed conditions and administration can be in combination with various secondary agents through various routes of administration. The particular dosing regimen would be routinely optimizable in view of the known APIs and the routes of administration as well as mechanism of action by which treatment is expected to occur.
As such, no claim is allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
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