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 .
Priority
This application is a 371 of PCT/US20/53787 (10/01/2020)
PCT/US20/53787 has PRO 62/908,937 (10/01/2019).
Election/Restrictions
Applicant previously elected Group I (claims 1-11) without traverse in the reply filed on April 22, 2025.
Status
Claims 1-11, 19-26 are pending. Claims 19-26 were newly presented.
Any rejection not reiterated in this action is withdrawn.
Claim Rejections - 35 USC § 112
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.
Claims 1-11, 19-26 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
Applicant amended the claims to include language such as the following:
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Applicant has not pointed to support for the new claim language, there does not appear to be support for the language in the original filing, one of skill in the art would not recognize that such a scope was possessed based on the original filing. In particular, nothing is disclosed about how “imputing” and “measuring” is to be conducted such that one of skill in the art would know what Applicant intends to claim with such language in this context. A claim containing a limitation which does not have a basis in the original disclosure is properly rejected under 35 U.S.C. 112 as failing to comply with the written description requirement. Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff’d. mem., 738 F. 2d 453 (Fed. Cir. 1984). The examiner could not locate support for such a new limitation and there does not appear to be a written description of the limitation in the application. See Hyatt v. Dudas, 492 F.3d 1365, 1370, 83 USPQ2d 1373, 1376 (Fed. Cir. 2007) (holding that "[MPEP] § 2163.04 (I)(B) as written is a lawful formulation of the prima facie standard for a lack of written description rejection."). Thus, the independent claims and those that depend therefrom are rejected.
As per MPEP 2163 II A: With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure.").
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Despa et al. J. Am. Heart Assoc. 2014, 3:e001015.
Despa et al. treated animals with the sEH inhibitor 1-(1-acetypiperidin-4-yl)-3-adamantanylurea (APAU) to elevate blood levels of epoxyeicosatrienoic acids (EETs) and reduce aggregated amylin in the heart:
“Because EETs reduce proteinaceous deposition on blood vessels and have antiaggregation properties, we hypothesized that increasing the EETs level in the blood may limit the infiltration of aggregated amylin in the heart. To elevate blood levels of EETs, HIP rats were treated with the sEH inhibitor APAU33 for 13 weeks (HIP-T group). [] sEH inhibition increased plasma levels of EETs in treated HIP rats (Figure 4A and Table 1)... Thus, APAU efficiently increases EETs level.” Page 8 left column (citations omitted).
Despa also teaches measurement of amylin levels in the blood - “EETs reduce the level of amylin oligomers circulating in the blood” (p. 10, Figure 6). These teachings anticipate the claimed method of reducing amylin by administering an effective amount of a soluble epoxide hydrolase inhibitor to increase epoxyeicosatrienoic acids.
Response to Applicant Remarks 35 USC 102
Applicant argues that Despa does not teach the claims as amended. This is not persuasive as detailed above, Despa teaches measuring and implicitly imputing the levels of amylin in the same manner as claimed.
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.
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.
Claims 1-11, 19-20, 22-24, 26 are rejected under 35 U.S.C. 103 as being unpatentable over Liang et al. ACS Chem. Neurosci. 2019, 10, 4018-4030 in view of Jackson et al. Ann. Neurol. 2013, 74, 517-526 and in further view of Liu et al. Eur. J. Pharm. Sci. 2013, 48, 619-627.
Liang et al. teaches treating Alzheimer’s disease by administering TPPU, “a potent inhibitor of soluble epoxide hydrolase (sEH),” which “can increase the endogenous concentration of EETs, leading to mitigation of inflammation.” See Abstract and p. 4019 left column. “TPPU intervenes in the canonical amyloid cascade of AD, offering multiple benefits in alleviating neuroinflammation, mitochondrial dysfunction, tau hyperphosphorylation, and eventual death of neurons.” Liang 4026 left column.
In summary, Liang teaches administering an effective amount of the sEH inhibitor TPPU to increase epoxyeicosatrienoic acids (EETs); however, Liang is silent regarding imputing or measuring amylin.
According to Jackson, Alzheimer’s patients are inherently in need of amylin reduction:
“Our data suggest that hyperamylinemia and accumulation of oligomerized amylin in the brain are intrinsic components of the pathological mechanisms linking age-related metabolic disorders with both diabetic brain injury and AD.” Jackson 524.
“[A]mylin amyloid formation in the wall of cerebral blood vessels (see Figs 1, 4A,
and 5) may induce failure of elimination of Aβ from the brain, thus contributing to the etiology of AD.” Jackson 525.
Jackson’s teachings—that amylin accumulation is “intrinsic” to AD and “drugs that prevent amylin oligomerization and/or increase clearance of amylin oligomers from the circulation may reduce the amylin deposition toxic effect on the brain”—imply that Alzheimer’s patients would have benefited from amylin reduction, leading a PHOSITA to conclude that those patients would have been in need of amylin reduction. Jackson also teaches measurement of brain amylin levels (p. 518-22). Consequently, Lian in view of Jackson render obvious the claimed method of administering the sEH inhibitor TPPU to patients in need of amylin reduction according to claims 1-2.
Although Liang and Jackson do not teach the claimed dosage (claim 5) or the oral/i.v. route of administration (claim 4), these limitations are obvious in view of Liu.
Liu et al. teaches the sEH inhibitor TPPU is “the most promising compound among the five tested compounds in murine models” in terms of pharmacokinetics and anti-inflammatory effects. Liu 621 (left column). Liu administered 0.01 mg/kg TPPU via i.v. or 0.1 mg/kg to 3.0 mg/kg orally. See, e.g., p. 623, Table 2 and Fig. 2.
Since Liu teaches TPPU is an effective sEH inhibitor with promising PK and anti-inflammatory effects, a PHOSITA would have found it obvious to select TPPU as the sEH inhibitor to use in Liang’s method of treating Alzheimer’s. The PHOSITA would have had a reasonable expectation of success because Liang teaches sEH inhibitors are effective at treating Alzheimer’s by increasing EET and because Liu teaches TPPU is an effective sEH inhibitor. Furthermore, the claimed administration route (oral or i.v. per claim 4) and dosage amount (20 μg/kg per claim 5) would have been obvious in view of Liu’s disclosure of administering TPPU via both oral and i.v. routes. The intravenous route involved 10 μg/kg, which a PHOSITA would have been motivated to optimize by increasing the dosage in order to improve sEH inhibition and/or EET concentration; thereby arriving at the claimed invention.
Regarding the limitation of claim 6 of “identifying a subject diagnosed with a neurological disease” is a mental step (i.e., an observation or evaluation performed in the human mind) and is inherent in Liang’s teachings, since administering TPPU to an Alzheimer’s patient inherently requires recognition of an Alzheimer’s diagnosis; thereby rendering obvious claims 6-8 and 11.
Although Liang does not teach the claimed dosage (claim 9) or the oral/i.v. route of administration (claim 10), these limitations are obvious in view of Liu.
Liu et al. teaches the sEH inhibitor TPPU is “the most promising compound among the five tested compounds in murine models” in terms of pharmacokinetics and anti-inflammatory effects. Liu 621 (left column). Liu administered 0.01 mg/kg TPPU via i.v. or 0.1 mg/kg to 3.0 mg/kg orally. See, e.g., p. 623, Table 2 and Fig. 2.
Since Liu teaches TPPU is an effective sEH inhibitor with promising PK and anti-inflammatory effects, a PHOSITA would have found it obvious to select TPPU as the sEH inhibitor to use in Liang’s method of treating Alzheimer’s. The PHOSITA would have had a reasonable expectation of success because Liang teaches sEH inhibitors are effective at treating Alzheimer’s by increasing EET and because Liu teaches TPPU is an effective sEH inhibitor. Furthermore, the claimed administration route (oral or i.v. per claim 10) and dosage amount (20 μg/kg per claim 9) would have been obvious in view of Liu’s disclosure of administering TPPU via both oral and i.v. routes. The intravenous route involved 10 μg/kg, which a PHOSITA would have been motivated to optimize by increasing the dosage in order to improve sEH inhibition and/or EET concentration; thereby arriving at the claimed invention.
Regarding claims 19-20, administration of TPPU would inherently result in reducing amylin deposition in brain capillaries and increasing expression of LRP1 in brain cells in the same manner as instantly claimed.
Regarding claims 22 and 26, Liang teaches the administration of TPPU affects mitochondrial function, thus one of ordinary skill in the art would monitor mitochondrial activity and DNA content and arrive at the claimed invention.
Regarding claims 23-24, as with claim 22, administration of TPPU would inherently result in reducing amylin deposition in brain capillaries and increasing expression of LRP1 in brain cells in the same manner as instantly claimed.
With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Claims are rejected under 35 U.S.C. 103 as being unpatentable over Liang et al. ACS Chem. Neurosci. 2019, 10, 4018-4030 in view of Jackson et al. Ann. Neurol. 2013, 74, 517-526 and in further view of Liu et al. Eur. J. Pharm. Sci. 2013, 48, 619-627 as applied to claims 1-11, 19-20, 22-24, 26 above and further in view of Karnati et al. (Journal of Alzheimer’s Disease 48 (2015) 563–580).
Regarding claims 21 and 25, modified Liang does not teach administering an agent to modulated miR-103 and/or miR-107. However, Karnati teaches modulation of miR-103/107 as key to Alzheimer’s progression and are promising in “development of novel therapeutic strategies” (p. 566, 573-574, Table 1). One of ordinary skill in the art would have considered combining therapeutics for the same purpose and arrive at the claimed invention. MPEP 2133.06; “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Response to Applicant Remarks 35 USC 103
Applicant argues that neither Liang nor Jackson teach the claims as amended. This is not persuasive as detailed above, Jackson teaches measuring and implicitly imputing the levels of amylin in the same manner as claimed.
Conclusion
No claims allowed.
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 ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
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