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 .
Election/Restrictions
Applicant’s election of species in the reply filed on 3/12/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
In response to the species election, applicant elected
(1) exenatide for Genus G,
(2) molecular change of the brain for Genus BFI(iv), reading on claim 10 and withdrawal of claims 8-9, and
(3) Genus Addition election reads on claims 11-12 and 18-19 and withdrawal of claims 13-17.
Claim Status
Claims 1-19 are pending.
Claims 8-9 and 13-17 are withdrawn as being directed to a non-elected species, the election having been made on 3/12/2026.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 10/28/2013 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Objections
Claims 1, 12, and 18 are objected to because of the following informalities
Claim 1 contains the acronym “GLP-1R”, and an acronym in the first instance of claims should be expanded upon/spelled out as “glucagon-like peptide-1 receptor” with the acronym indicated in parentheses as GLP-1R. The abbreviations can be used thereafter.
Claim 12 contains the acronym “TAR DNA-binding protein 43”, and an acronym in the first instance of claims should be expanded upon/spelled out as “Transactive response DNA binding protein 43 kDa” with the acronym indicated in parentheses as (TAR DNA-binding protein 43). The abbreviations can be used thereafter.
Claim 18 contains the acronyms “DNA” and “RNA”, and an acronym in the first instance of claims should be expanded upon/spelled out as “Deoxyribonucleic acid” and “Ribonucleic acid” with the acronyms indicated in parentheses as (DNA) and (RNA). The abbreviations can be used thereafter.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 2 is drawn to administer a list of GLP-1R agonists or any other molecule that activates GLP-1R not in the list, but claim 2 failing to further limit the subject matter of “a GLP-1R agonist” in claim 1 (the sum of a list of GLP-1R agonists and any other molecule that activates GLP-1R not in the list in claim 2).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-4, 10, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bomba et al. (Neurobiol Aging. 2018 Apr:64:33-43, cited in IDS).
Claim 1 is drawn to a method of treating aging-associated brain functional impairment in a subject comprising administering an effective amount of a GLP-1R agonist to the subject.
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Bomba et al. teach Exenatide exerts cognitive effects by modulating the BDNF-TrkB neurotrophic axis in adult mice (Title). In the abstract, Bomba et al. teach altered brain insulin signaling participates in the cognitive decline seen in Alzheimer’s disease patients and the aging brain (reading on a human patient) and glucagon-like peptide-1 (GLP-1) regulates insulin secretion and, along with GLP-1 analogues, enhances neurotrophic signaling and counteracts cognitive deficits in preclinical models of neurodegeneration. Bomba et al. further teach exenatide promotes the enhancement of long-term memory performances. Bomba et al. teach 2-month treatment with exenatide in adult mice enrolled at 10 months of age (m.o.a.). The time frame of the intervention (10-12 m.o.a.) was chosen because, in mice, this age bracket is comparable to the mid-life stage of humans, a period that is crucial for the onset of either age-related cognitive decline or dementia (p34, col 1, para 2). In legend of figure 6, Bomba et al. teach exenatide activating the transcription factor CREB and CREB increases BDNF protein levels, thereby promoting the enhanced activation of the neurotrophic BDNF-TrkB axis leading to activation of ERK5 (a prosurvival kinase) and PSD95 (a protein highly involved in synaptic potentiation). Exenatide also promotes anti-apoptotic effects by reducing the proBDNF-p75NTR-mediated signaling cascade. Reduction in proBDNF-p75NTR signaling results in decreased activation of a set of kinases, ERK1,2 and JNK, that participate in neuronal demise. See Bomba et al. (p37, col 1, Sec 3.4-Sec 3.5) and figure 6 shown above in details.
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With respect to claims 1-2 and 4, Bomba et al. teach a method of administering exenatide (a GLP-1R agonist) to adult mice at 10 months of age, comparable to the mid-life stage of humans, a period that is crucial for the onset of either age-related cognitive decline or dementia (p34, col 1, para 2). Bomba et al. teach exenatide treated mice performed significantly better in parameters related to long-term memory (LTM) activities, showed reduced time spent to reach the platform location, and time spent in the opposite quadrant (p35, col 2, Sec 3.1, para 2; p36, Fig 1).
With respect to claim 3, Bomba et al. teach animals receiving daily injections of exenatide (p34, col 1, Sec 2.1). Figure 1A at page 36 shows exenatide in a formulation comprising an inherent carrier mixed with exenatide suitable for the injection.
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With respect to claims 10 and 18, Bomba et al. teach exenatide activating the transcription factor CREB and CREB increases BDNF protein levels, reading on aging-associated measurable molecular change in gene expression (p39, Fig 6, legend) and Bomba’s western blot shows change of protein levels as follows (p38, Fig 4A).
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.
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 1-7, 10-12, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Bomba et al. (Neurobiol Aging. 2018 Apr:64:33-43) as applied to claims 1-4, 10, and 18, and further in view of NCT01255163 (2018-02-22) and Bloom (JAMANeurol.2014;71(4):505-508).
Claim 5 is drawn to administration of a GLP-1R agonist to a primate.
Bomba et al. teach (a) defective glucose metabolism and utilization in subjects affected by mild cognitive impairment, (b) insulin resistance along with altered insulin-related signaling found in the brain of AD patients, (c) brain aging associated with decreased insulin sensitivity (p33, col 2, para 1) and (d) Exenatide exerts cognitive effects by modulating the BDNF-TrkB neurotrophic axis in adult mice (Title).
Bomba et al. do not teach administration of Exenatide to a human patient.
Similarly, NCT01255163 teaches Exendin-4 (or Exenatide) has shown promising results in animal and cellular models of Alzheimer's disease (p8, Brief Summary). NCT01255163 teaches the treated patients are human with age > 60 (p14, Inclusion Criteria), reading on claims 5-7.
With respect to claims 19, NCT01255163 teaches the effects of Exendin-4 on cognitive performance by measuring molecular change of chemicals in blood and cerebrospinal fluid (p9, para 1) including CSF and plasma biomarkers, such as CSF A42, tau, p181-tau and plasma A42/A40.
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Bloom is cited to show soluble toxic aggregates of both amyloid-β (Aβ) and tau can self-propagate and spread throughout the brain by prionlike mechanisms, successful therapeutic intervention for AD would benefit from detecting these species known in the art (Abstract and the figure shown as follows (p506)). Thus, it would be obvious to measure the structural change for aggregation of amyloid-β (Aβ) and tau to evaluate Exenatide’s treatment effect of NCT01255163, further reading on claims 11-12.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Bomba et al. with NCT01255163 and Bloom because (A) Bomba et al. teach (i) defective glucose metabolism and utilization in subjects affected by mild cognitive impairment, (ii) insulin resistance along with altered insulin-related signaling found in the brain of AD patients, (iii) brain aging associated with decreased insulin sensitivity (p33, col 2, para 1) and (iv) Exenatide exerts cognitive effects by modulating the BDNF-TrkB neurotrophic axis in adult mice (Title), and (B) NCT01255163 teaches (i) Exendin-4 (or Exenatide) has shown promising results in animal and cellular models of Alzheimer's disease (p8, Brief Summary) consistent with Bomba et al. and (ii) Exenatide can be beneficially administered to treat human patients with age > 60 (p14, Inclusion Criteria) having early-stage Alzheimer's disease or mild cognitive impairment (p9, Eligibility). Bloom is cited to show soluble toxic aggregates of both amyloid-β (Aβ) and tau can self-propagate and spread throughout the brain by prionlike mechanisms known in the art (Abstract; p506, Figure). The combination would have reasonable expectation of success because both references of Bomba et al. and NCT01255163 teach a method of administering Exenatide to treat animals to improve cognitive effects.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7, 10-12, and 18-19 are provisionally rejected 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. (Neurobiol Aging. 2018 Apr:64:33-43), NCT01255163 (2018-02-22) and Bloom (JAMANeurol.2014;71(4):505-508).
Claim 1 of the ‘745 application disclosed a method comprising administering a GLP-1R agonist for decreasing an aging-associated functional change in a subject.
Claim 2 of the ‘745 application disclosed the subject is a mammal.
Claims 1-2 of the ‘745 application do not disclose administering a GLP-1R agonist to treat aging-associated brain functional impairment in a subject in human.
The relevancy of Bomba et al. in view of NCT01255163 and Bloom is described above not repeated here.
Because Bomba et al. in view of NCT01255163 and Bloom teach beneficially administering exenatide taught by claims 1-2 of the ‘745 application to treat age-related cognitive decline in both mammal and human, one of ordinary skill in the art would have found it obvious to combine claims 1-2 of the ‘745 application in view of Bomba et al. and NCT01255163 and Bloom.
Thus, claims 1-2 of the ‘745 application in view of Bomba et al., NCT01255163, and Bloom are obvious to the instant claims 1-7, 10-12, and 18-19.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
30-March-2026
/LI N KOMATSU/ Primary Examiner, Art Unit 1658
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