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
This application is a continuation in part of PCT/US2022/046018, filed October 7, 2022, which claims benefit of provisional application 63/253992, filed October 8, 2021. Claims 1-20 are pending in this application and examined on the merits herein.
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, 5, 6, 8, 9, 13, and 15-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jia et al. (PCT international publication WO2018/157014, Reference included with PTO-892)
Independent claim 1 is directed to a method for normalizing one of a number of indicators in a subject, comprising administering an active agent to the subject. Independent claims 19 and 20 are directed to methods for inhibiting progression of Alzheimer’s disease in a subject diagnosed with AD, or preventing AD in a subject not diagnosed with AD, respectively.
Jia et al. discloses method for quantitating bile acids and treating a neurological disorder in a subject by administering to the subject a bile acid modulating agent. (p. 2 paragraphs 6-7) Indicators of the disorder that can be improved include various neuropsychiatric indicators of Alzheimer’s disease, as well as biochemical indicators such as amyloid beta levels and phosphorylated tau. (p. 3 paragraph 7) Such a method would anticipate present claim 1. In certain embodiments the biochemical alterations indicate a neurological disorder such as Alzheimer’s disease, or alternately early or late cognitive impairment. (p. 13 paragraph 41) Administering such a therapy to a subject suffering from AD would reasonably be considered to be a method of treating AD, while administering the treatment to a subject suffering from early or late MCI would reasonably be considered to be a method of preventing progression to AD. Furthermore this treatment results in normalizing the aforementioned biomarkers, thereby anticipating claims 2, 3, 8, and 19. (p. 15 paragraphs 46 and 47) Regarding independent claim 20 and dependent claims 15-18, p. 17 paragraph 54 of Jia suggests monitoring the aforementioned biomarkers in the subject.
Still further, Jia et al. suggests treatment with a bile acid modulating agent, which can include tauroursodeoxycholate, or TUDCA. (pp. 15-16 paragraph 49) Treatment with this particular therapeutic agent would infringe dependent claims 5, 6, and 9.
For these reasons Jia et anticipates the present claims.
Claims 1-6, 8, 9, and 11-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Crisby. (Foreign patent publication GB2568291, Reference included with PTO-892)
Independent claim 1 is directed to a method for normalizing one of a number of indicators in a subject, comprising administering an active agent to the subject. Independent claim 20 is directed to methods for preventing AD in a subject not diagnosed with AD, which would reasonably be considered to include preventing the progression of mild cognitive impairment (MCI) to AD.
Crisby discloses a method of using hydroxychloroquine (HCQ) for treating MCI, comprising administering HCQ to a patient in need thereof. (p. 3 line 36 – p. 4 line 3) Such patients are not currently diagnosed with AD. (p. 4 lines 27-29) Such a treatment can have the effect of preventing the onset of dementia form any cause. (p. 4 lines 31-37) HCQ is also specifically described as normalizing beta-amyloid protein in CSF. (p. 5 lines 29-36) Therefore Crisby anticipates present claim 1. Additionally, Crisby describes measuring biological markers including amyloid beta production and clearance, tau formation and phosphorylation, neurofilaments, and inflammatory cascade markers, for example. (p. 6 liens 4-19) A method incorporating such measurements is described (p. 6 line 31 – p. 7 line 21) which would anticipate independent claim 20, as well as dependent claims 2, 3, 8, and 15-18. Regarding claims 5, 6, 9, 11, 13, and 14, all of these claims are infringed by a method of administering HCQ.
Regarding claims 4 and 12, while Crisby does not specifically mention the effect of HCQ on neuroinflammation, Varma et al. (Molecular Psychiatry 2023, vol. 28 pp. 1312-1326, Reference included with PTO-1449) is cited as an evidentiary reference to elucidate the mechanism by which the treatment described by Crisby functions. Specifically, Varma describes a study of the effect on HCQ treatment on both the risk of AD and markers of AD pathology. (p. 1313 left column second paragraph) HCQ is described as reducing tau phosphorylation, increasing phagocytosis of amyloid beta, and reducing LPS-induced neuroinflammation by reducing IL-1β and TNF-α. (p. 1314 figure 1, p. 1319 right column last paragraph – p. 1320 left column sixth paragraph) Therefore it is reasonably concluded that carrying out the treatment described by Crisby would inherently result in the effects recited in claims 4 and 12.
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.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Jia et al. as applied to claims 1-3, 5, 6, 8, 9, 13, and 15-20 above, and further in view of by Crisby. (Foreign patent publication GB2568291, Reference included with PTO-892)
The disclosure of Jia et al. is discussed above. While Jia et al. does not specifically describe coadministering TUDCA with HCQ, as described above, Crisby discloses administering HCQ for reducing the risk of AD in patients having risk factors for AD. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to administer ACQ and TUDCA together to a subject having biomarkers of AD risk, for example aberrant extracellular Aβ concentration, based on a rationale of both agents being usable together for the same purpose.
Therefore the invention taken as a whole is prima facie obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Crisby as applied to claims 1-6, 8, 9, and 11-20 above, and further in view of Stevens et al. (Reference included with PTO-1449)
The disclosure of Crisby is discussed above. Crisby does not specifically disclose a method wherein the HCQ is administered as a nanoparticle formulation. However, Stevens et al. discloses using a nanoparticle formulation of HCQ to improve pharmacokinetics and toxicity. (p. 2 third paragraph, pp. 7-8 section 3, pp. 9-10 section 6) It would have been obvious to one of ordinary skill in the art at the time of the invention to formulate HCQ as a nanoparticle for use in the method of Crisby. One of ordinary skill in the art would have been motivated to use this drug formulation in the hope of improving the solubility, pharmacokinetics, and toxicity of HCQ.
Therefore the invention taken as a whole is prima facie obvious.
Conclusion
No claims are allowed in this action.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 7/21/2026
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