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 .
Claim Status
Claims 1-9, 11-17, and 19 are pending.
Claims 1-2, 7, and 12 are currently amended.
Claims 10 and 18 are cancelled.
Claims 8-9 and 13-17 are withdrawn as being directed to a non-elected species, the election having been made on 3/12/2026.
Claims 1-7, 10-12, and 18-19 have been examined.
Priority
This application is a 371 of PCT/CN2021/138827 12/16/2021
PCT/CN2021/138827 has PRO 63/126,122 12/16/2020
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/21/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Terminal Disclaimer
The terminal disclaimer filed on 6/29/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of application # 18394367 has been reviewed and accepted.
Withdrawn Rejection
The objection of claims 1, 12, and 18 is withdrawn because of the amendment to claims 1 and 12 together with cancellation of claim 18 overcome the objection.
The rejection of Claim 2 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, is withdrawn because the amendment to claim 2 overcomes the rejection.
The rejection of claims 1-4, 10, and 18 under 35 U.S.C. 102(a)(1) as being anticipated by Bomba et al. is withdrawn because a more relevant prior art reference of Mullins et al. (Curr Alzheimer Res. 2019; 16(8): 741–752.) is currently used as new ground or rejection.
The rejection of claims 1-7, 10-12, and 18-19 under 35 U.S.C. 103 as being unpatentable over Bomba et al. in view of NCT01255163 and Bloom is withdrawn is withdrawn because more relevant references of Mullins et al. in view of Kim et al. are currently used as new ground or rejection.
The provisional rejection of claims 1-7, 10-12, and 18-19 on the ground of nonstatutory double patenting as being unpatentable over claim of copending Application No. 18/394,367 (the ‘367 application) in view of Bomba et al., NCT01255163 (2018-02-22) and Bloom is withdrawn because the approved TD of record overcomes the provisional ODP rejection.
Because of the new ground of rejections by citing new references not previously presented, the affidavit and arguments do NOT apply to the new ground of rejections as shown in the following.
New Ground of Objection and Rejection
Claim 1 is objected to because of the following informalities:
Applicant amends claim 1 by adding “glucagon-like peptide-1 receptor” with the acronym indicated in parentheses as GLP-1R to overcome the prior objection. However, applicant also adds multiple genes with acronyms without their full names. For instance, the acronym of “C1qa” should be revised to be “A-chain polypeptide of complement component C1q (C1qa)”. Similarly, the laundry list of acronym of multiple genes should be spelled out by their full names followed by acronym indicated in parentheses.
Appropriate correction is required.
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.
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.
Claim 2 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is NEW MATTER rejection.
Claim 2 adds a new limitation “exenatide is administered about 0.0017 mg/kg, wherein the subject is a human” without support by the specification of record. The specification disclosed dose (GLP-1R including the elected species of exenatide) will range from about 0.001 mg/kg body weight to about 1 g/kg body weight (p14, para 2, line 3-18). The wild range of dose is not supported by a specific dose “about 0.0017 mg/kg for human in claim 2. Thus, claim 2 is rejected as NEW MATTER without support.
The introduction of claim changes which involve narrowing the claims by introducing elements or limitations which are not supported by the as-filed disclosure is a violation of the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety for every possible position does not constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species); and Regents of the Univ. of Minnesota v. Gilead Scis., Inc., 61 F.4th 1350, 1356-58, 2023 USQ2d 269 (Fed. Cir. 2023). See MPEP 2163.05 (II).
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.
Claim 2 is 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.
Claim 2 is unclear with respect to a GLP-1R administered at about 0.0017 mg/kg to a human subject. The meters and bounds of the administered dose are unclear because (i) the administered GLP-1R at 0.0017 mg/kg can be interpreted as a daily dose or weekly dose and (ii) alternatively, the administered GLP-1R at 0.0017 mg/kg can also be interpreted as a dose of a single administration and a patient receives more than one times of administration each day. MPEP 2173.02 (I) states “During examination, after applying the broadest reasonable interpretation to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected. Zletz, 893 F.2d at 322, 13 USPQ2d at 1322. For example, if the language of a claim, given its broadest reasonable interpretation, is such that a person of ordinary skill in the relevant art would read it with more than one reasonable interpretation, then a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph is appropriate.”
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, 11-12, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mullins et al. (Curr Alzheimer Res. 2019; 16(8): 741–752.).
Claim 1 is drawn to a method of treating a subject with aging-associated brain functional impairment, comprising administering to the subject an effective amount of GLP-1R agonist; wherein aging-associated brain functional impairment comprises any of aging-associated measurable structural, functional or molecular change of the brain.
Mullins et al. teach exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist used for treating type 2 diabetes, is neuroprotective and disease-modifying in Alzheimer’s Disease (AD). Mullins et al. teach analysis of exenatide treatment for clinical, cognitive, and biomarker outcomes in early AD (p1, Background and Objective). Mullins et al. teach GLP-1 agonists including exenatide have shown reductions in Aβ plaques alongside improvements in synaptic function and behavior in multiple transgenic mouse models of AD (p3, para 3, line 9-11) and exenatide was recently found to have beneficial effects on motor function in a randomized, placebo-controlled double-blind Phase II trial in PD (p3, para 3, last 3 lines). Mullins’s teachings are consistent with applicant’s admission of GLP-1R agonist such as Exenatide able to treat aging-associated brain functional impairment comprising Alzheimer’s Disease (AD) and Parkinson's disease (PD) in diabetic patients in the specification (p1, last two lines to p3, line 1-14). Mullins et al. teach baseline of each patient is obtained according to neurological examination, a Lumbar Puncture (LP) for Collection of Cerebrospinal Fluid (CSF), blood draws for clinical laboratory tests and biomarkers, and brain MRI/Magnetic Resonance Spectroscopy (p4, 2nd last para). Mullins et al. teach the use of MRI to analyze the structural imagines of Gray matter and White Matter (p5, 2.2. MRI Acquisitions and Data Processing to p6, para 1) and further show structural MRI results in Fig 3. Mullins et al. further teach analysis of blood and CSF biomarkers of AD patients including Aβ42 and Aβ40 in the soluble phase of plasma (p6, 2.4. Blood and CSF Biomarkers of AD) and many other bioactive molecules listed in Table 1 (page 21), reading on the limitation of secretion or release of proteins into blood fluids.
With respect to claim 3, Mullins et al. teach Exendin-4 is manufactured for human use as exenatide and it is delivered via subcutaneous (SC) injection (p3, para 2), reading on GLP-1R agonist (e.g., exenatide) administered with a liquid pharmaceutically acceptable carrier suitable for subcutaneous injection.
With respect to claims 4-7, Mullins et al. teach exenatide administered to a patient at age of 59 ± 9 years (p10, 4. Discussion) or 71.7 ± 6.9 years (p21, Table 1).
With respect to claim 11, Mullins et al. teach anatomical MRI imaging revealed that progression of GM atrophy and cortical thinning in the canonical AD pattern (p11, 2nd last para; Fig 3), reading on co1iical atrophy.
With respect to claims 12 and 19, Mullins et al. show the measured protein is amyloid-beta or tau protein in CSF (p4, 2nd last para; p18, Fig 1, legend).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-7, 11-12, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Mullins et al. as applied to claims 1, 3-7, 11-12, and 19 and further in view of Kim et al. (WO 2018.075901 A1).
Claim 2 is drawn to the dose of GLP-1R agonist.
Mullins et al. teach a method comprising administering GLP-1R agonist of exenatide to treat a subject for aging-associated brain functional impairment.
Mullins et al. do not specify a dosage of exenatide.
Kim et al. teach a method of delivering a neuroprotective polypeptide to the central nervous system (Title). Kim et al. teach the dosage of the active ingredient can be optimized from about 0.01 to about 100 µg/kg/day in a sustained release formulation. Kim et al. teach an appropriate amount may be determined by one of ordinary skill in the art using only routine experimentation [0250]. Kim et al. further teach the active ingredient is Exenatide [0260]. Kim et al. also teach the treated CNS diseases including Parkinson's disease (PD) and Alzheimer's disease (AD) [0045-0046]. Kim et al. suggest the dosage of Exenatide as a result-effective variable and one of ordinary skill in the art using only routine experimentation to optimize the effective dosage of Exenatide ranged from about 0.01 to about 100 µg/kg/day in a sustained release formulation [0250], reading on claim 2. 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05(I).
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Mullins et al. and Kim et al. because (a) Mullins et al. teach a method of administering Exenatide to treat Alzheimer’s Disease (p1, Background and Objective) and (b) Kim et al. suggest the dosage of Exenatide to treat CNS diseases including Parkinson's disease (PD) and Alzheimer's disease (AD) [0045-0046] ranged from about 0.01 to about 100 µg/kg/day in a sustained release formulation [0250]. The combination would have reasonable expectation of success because both references teach administration of Exenatide to treat Alzheimer’s Disease.
Conclusion
No claim is 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.
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/J.L/Examiner, Art Unit 1658
31-August-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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