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 .
Priority
Acknowledgment is made of applicant’s claim for priority. The certified copy has been filed in parent Application No. 63/288,998, filed on 12/13/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/13/2024, 02/02/2026, and 02/02/2026 are being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: while one of ordinary skill in the art would likely know the given proteins without the common names it is generally preferred that the first time a protein is mention the full name or common name be given.
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink (see page 21, http://www.cbs.dtu.dk/services/NetPhos) and GPS (http://gps.biocuckoo.org/ online.php), and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1-3, 5, 8-9, 11-12, 15-17 and 19, 22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kakraba (Kakraba et al., A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer's Disease. Front Mol Neurosci. 2019 Dec 12;12:310, IDS) as evidenced by Ganne (Ganne et al., Glial Fibrillary Acidic Protein: A Biomarker and Drug Target for Alzheimer’s Disease, Pharmaceutics 2022, 14, 1354, IDS) and evidenced by Reis(Reis et al., US 12552763 B2, 2026-02-17).
The reference Kakraba teaches “PNR502, a novel drug, opposes protein aggregation in a wide variety of AD-model systems, including 4 human cell types, and both C. elegans and mouse models of Aβ1–42 amyloidopathy. In mouse cerebra and in nematodes, it appears to reverse aggregation that had occurred previously. Further studies of this compound, and of subsequent-generation drugs that target GFAP, tubulin, and their interface, might provide even more effective therapeutic agents for the prevention or reversal of neurological disorders such as AD” (conclusion, page 12) and “One such analog, PNR502, markedly reduced the quantity of Alzheimer-associated amyloid aggregates in the BRI-Aβ1–42 mouse model of AD, while blunting the ability of the pro-inflammatory cytokine IL-1β to raise levels of amyloid plaque and its protein precursors in a neuronal cell-culture model. In transgenic Caenorhabditis elegans (C. elegans) strains that express human Aβ1–42 in muscle or neurons, PNR502 rescued Aβ-induced disruption of motility (3.8-fold, P < 0.0001) or chemotaxis (1.8-fold, P < 0.05), respectively. Moreover, in C. elegans with neuronal expression of Aβ1–42, a single day of PNR502 exposure reverses the chemotaxis deficit by 54% (P < 0.01), actually exceeding the protection from longer exposure. Moreover, continuous PNR502 treatment extends nematode lifespan 23% (P ≤ 0.001). Given that PNR502 can slow, prevent, or reverse Alzheimer-like protein aggregation in human-cell-culture and animal models, and that its principal predicted and observed binding targets are proteins previously implicated in Alzheimer’s, we propose that PNR502 has therapeutic potential to inhibit cerebral Aβ1–42 aggregation and prevent or reverse neurodegeneration”(abstract, page 1).
The reference US 12552763 B2 provides evidence that “Computer modeling of the interactions of PNR-5-02 and potential targets including GFAP (ΔG=−8 and −7 kcal/mole for two top peptides”(154).
The reference Kakraba teaches “PNR502 binds tubulin, as reported previously for combretastatin A4 (Pettit et al., 1989), and it binds even more avidly to Glial Fibrillary Acidic Protein (GFAP), an intermediate-filament protein most notably expressed in astrocytes and supporting their interactions with neurons (Figueiredo et al., 2008; Suzumura, 2013; Tsuda and Inoue, 2016)”(page 2). This anticipates claims 9 and 11.
The reference Kakraba teaches “GFAP, tubulin and plectin were significantly enriched in aggregates from AD relative to AMC, isolated by immuno-pulldown(IP) with antibodies to Aβ1–42(amyloid-β) or tau, whereas only GFAP and plectin were also significantly enriched (although to a lesser extent) in total insoluble aggregates”(page 9 and figure 7). It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
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This anticipates claim 1-3 and 8.
The reference Ganne provides evidence that kinases that phosphorylate GFAP
are upregulated in AD”(abstract). Thus while not specified it is anticipated that the GFAP in Kakraba were phosphorylated. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).This anticipates claims 5 and 12.
Since the upregulation of CBX8, TSPYLS, CDK2, and KRT33B occurred either by MSR1 or by siRNA knock-down of GFAP it is likely the inactivity of GFAP that causes this increase and thus also caused in the case of PNR502 since the active step of the claim is taught. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). This anticipates claims 15-17, 19, 22.
Claim(s) 1-3, 5, 8-9, 11-12, 15-17 and 19, 22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Reis (Reis et al., US 20200024249 A1, 2020-01-23) as evidenced by Ganne (Ganne et al., Glial Fibrillary Acidic Protein: A Biomarker and Drug Target for Alzheimer’s Disease, Pharmaceutics 2022, 14, 1354, IDS) and evidenced by Reis(Reis et al., US 12552763 B2, 2026-02-17).
The reference Reis teaches “A method to prevent or reduce protein aggregates in the central nervous system of a subject, the method comprising administering to the subject a composition comprising a compound that binds glial fibrillary acidic protein (GFAP)” (reference claim 1) and “The C. elegans ortholog of each of these proteins was “knocked down” (suppressed by RNA interference, RNAi) in turn, and the results implicate GFAP, β-tubulin, and plectin (among the chief direct-binding targets of PNR-5-02 in Alzheimer Disease hippocampus) as mediators of its protective benefits in C. elegans aggregation models”[0166]. The reference US 12552763 B2 provides evidence that “Computer modeling of the interactions of PNR-5-02 and potential targets including GFAP (ΔG=−8 and −7 kcal/mole for two top peptides”(154). It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).This anticipates claim 1 and 8-9.
The reference Reis teaches “Developing effective treatments for neurodegenerative diseases is one of the greatest medical challenges of the 21st century. Although many of these clinical entities have been recognized for more than a hundred years, it is only during the past twenty years that the molecular events that precipitate disease have begun to be understood. Protein aggregation is a common feature of many neurodegenerative diseases, and it is assumed that the aggregation process plays a central role in pathogenesis. In this process, one molecule (monomer) of a soluble protein interacts with other monomers of the same protein to form dimers, oligomers, and polymers. Conformation changes in three-dimensional structure of the protein, especially the formation of beta-strands, often accompany the process. Eventually, as the size of the aggregates increases, they may precipitate as insoluble amyloid fibrils, in which the structure is stabilized by the beta-strands interacting within a beta-sheet. Extracellular fibrous amyloid deposits or intracellular inclusions containing abnormal protein fibrils characterize many neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, frontal temporal dementia, and the human prion diseases. Thus, there is a need in the art for ways to prevent and/or reduce protein aggregates that cause or contribute to neurodegenerative diseases”[0003-0004]. This anticipates claims 2-3, 11.
The reference Ganne provides evidence that kinases that phosphorylate GFAP
are upregulated in AD”(abstract). Thus while not specified it is anticipated that the GFAP in Kakraba were phosphorylated. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).This anticipates claims 5 and 12.
Since the upregulation of CBX8, TSPYLS, CDK2, and KRT33B occurred either by MSR1 or by siRNA knock-down of GFAP it is likely the inactivity of GFAP that causes this increase and thus also caused in the case of PNR502 since the active step of the claim is taught. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). This anticipates claims 15-17, 19, 22.
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 9 and 11 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12552763 B2 in view of by Reis (Reis et al., US 20200024249 A1, 2020-01-23) as evidenced by Ganne (Ganne et al., Glial Fibrillary Acidic Protein: A Biomarker and Drug Target for Alzheimer’s Disease, Pharmaceutics 2022, 14, 1354, IDS) and evidenced by Reis(Reis et al., US 12552763 B2, 2026-02-17).
The patent ‘763 claims:
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The patent ‘763 does not specifically teach a method for treating a neurodegenerative disorder (claims 9 and 11).
The secondary references teach that all needed changes would be obvious as outlined in the 102 rejection (which is incorporated herein by reference).
It would have been prima facie obvious to one of ordinary skill in the art to have modified patent ‘763 with the secondary references because both teach a method to prevent or reduce protein aggregates in the central nervous system of a subject, the method comprising administering to the subject a composition comprising a compound that binds glial fibrillary acidic protein (GFAP). One would be motivated to do so to treat neurodegenerative disorders. One would have a reasonable expectation of success since they describe the same active step.
Allowable Subject Matter
Claims 4, 6, 7, 10, 13-14, 18, 20-21 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-3, 5, 8-9, 11-12, 15-17 and 19, 22 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR HASTINGS whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/A.A.H./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627
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