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
Claims 1 and 5-20 are pending in the instant application.
Priority
This application claims priority to the provisional application 63407106 filed on 9/15/2022.
Information Disclosure Statement
The information disclosure statement (IDS) dated 6/23/2026 complies with the provisions of 27 CFR 1.97, 1.98, and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits.
Withdrawn Rejections
The rejection of claims 1-20 under § 112(b) is withdrawn in light of the amendments; the claim now specifies what the determining step is referring to. Claims 2-4 were canceled.
The rejection of claim 2 under § 112(b) is withdrawn in light of the amendments; this claim was canceled.
The rejection of claim 3 under § 112(b) is withdrawn in light of the amendments; this claim was canceled.
The rejection of claim 3 under § 112(a) is withdrawn in light of the amendments; this claim was canceled.
The rejection of claims 1-2 and 4-6 under § 102/103 is withdrawn in light of the amendments; applicant incorporated the contents of claim 3 into the base claim, wherein the crystallographic parameters were not supplied by the references. Claims 2-4 were canceled.
Claim Rejections – 35 USC § 112(b)
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 20 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 20
Claim 20 is drawn to 18 pages of chemical names that cannot be meaningfully compared to the list of 821 chemicals provided in Fig 6 due to its excessive length, OCR errors, and absence of a delineated structure [e.g. a list beginning with (1)]. MPEP § 2173.05(m) recites “Claims are rejected as prolix when they contain long recitations that the metes and bounds of the claimed subject matter cannot be determined.” Claim 20 is thus rejected as prolix for being unreasonable for a person of skill in the art to reasonably pick out a given chemical name from the concatenated block of text. Because applicant already possesses the list of 821 compounds alongside their chemical structure in Fig 6 wherein each are assigned a unique number, to overcome this rejection, applicant should replace this claim with the language:
“A compound selected from the group consisting of compounds 1-821 and any salt, hydrate, or solvate thereof.”
Claim Rejections – 35 USC § 112(a)
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.
Claims 1 and 5-20 are 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.
Claim 1
Claim 1 is drawn to the genus of ‘molecules that bind multiple sites of a stacked protein associated with a neurological disease,’ wherein no structural criteria for these molecules or their targets has been provided. Given this description, one of skill in the art would not be able to envisage the members of this genus because it is not a well-known genus in the prior art. Applicant can meet the written description requirement by (i) describing a representative number of species or (ii) describing the core structure that is responsible for these properties. Regarding (i), applicant has provided a large number of chemical structures for treating Alzheimer’s disease (AD), Parkinson’s Disease (PD), and Multiple Systems Atrophy (MSA), each of which comprise a variety of protein targets (pg 76, para 00182). Applicant has not purported that any single species is capable of treating all of these disease. While Example 3 discloses that a screen was performed using HEK293 cells expressing YFP-tagged truncated a-syn (pg 95, para 00224), this example fails to describe the conclusions of that study (i.e. which of the compounds actually disrupted/detected the stacking of a-syn).
Secondly, it is known that binding is dependent on both the chemical identity of the molecule and the target. This is evidenced by Honer (doi: 10.2967/jnumed.117.196741), who describes several molecules that bind tau, but not alpha-synuclein, despite all of them being organic molecules (pg 677, col 2, para 4). Furthermore, while tau is implicated in Alzheimer’s disease, Blokhuis (doi: 10.1007/s00401-013-1125-6) teaches that other diseases such as ALS involve aggregates of different protein identities (e.g. FUS, TDP-43, OPTN, UBQLN2) (abstract). Thus from the list of diseases provided, one cannot presume a single protein as the target, even though this is presumed to be a-syn. Given the heterogeneity of the protein targets within these diseases and the structures represented, one of skill in the art would not be able to envisage other members of this genus. Regarding (ii), applicant has not provided the core structural feature(s) that a molecule must contain in order to possess the property of ‘binding multiple sites of a stacked protein associated with AD, PD, and MSA. In sum, because these different diseases exhibit different protein targets and applicant has not described any universally-targeting species, applicant has failed to meet the written description requirement of ‘molecules that bind multiple sites of a stacked protein.’ Dependent claims 5-20 fail to cure these deficiencies, thus also fail the written description requirement.
Combining the limitations of previous claim 3 into base claim 1 fails to address the written description issues described. Parts (a)-(g) are drawn to a genus of compounds with specific crystallographic parameters (e.g. stacking with planar cores of 3.3-3.5 Å and angles between perpendicular planes), wherein no chemical structural information is provided beyond comprising “one or two rings”. Given this description, one of skill in the art would not be able to envisage the members of this genus. Applicant can meet the written description requirement by (i) describing a representative number of species or (ii) describing the core structure that is responsible for these properties. Regarding (i), applicant has failed to provide crystallographic data regarding every compound described within the specification, thus it is unclear which of the described species even possess the claimed properties of (c)-(f). Furthermore, the precise stacking of said molecules within a crystallographic structure is variable depending on the conditions of the crystallization procedure (solvent, temperature, impurities, and crystal polymorphs), thus one of skill in the art would not be able to a priori predict the precise crystallographic stacking angles or distances simply by looking at a drawn chemical structure (See Dunitz doi: 10.1039/b211531j). Dunitz answers the question “Are crystal structures predictable? The one-word answer to the title question is still ‘No’, although at certain levels of discussion a ‘Maybe’, or even a conditional ‘Yes’, may be entertained as possible responses” (Abstract). Dunitz teaches
“Experts in the field have tried their skills in two blind tests and discussed their methods, together with their successes and failures, at two meetings organized by the Cambridge Crystallographic Data Centre in 1999 and 2001. Although some successes were reported, no method gave consistently reliable predictions” (545, col 1, para 1).
For example, Price (doi: 10.1039/c3cs60279f) teaches while computational methods exist to estimate crystal structure parameters, they fail to anticipate the crystal that is adopted in reality. Price teaches
“[Computation prediction methods] are based on the assumption that the crystal structure will be the thermodynamically most stable of all possible structures. However, polymorphism, the observation of different crystal structures containing only the same molecules, immediately shows that some crystal structures are not the thermodynamically most stable.”
“…the crystal energy landscape rarely contains only one crystal structure, i.e. it is relatively rare for a molecule to have one way of packing with itself that is significantly more favourable, than any other. The fields of crystal engineering and self-assembly are dominated by multicomponent systems because of the scarcity of molecules that can close pack with strong intermolecular interactions defining a unique packing in all three dimensions… Hence, the main use of CSP studies is to find the range of different packings that are thermodynamically plausible crystal structures.”
Corpinot (doi: 10.1021/acs.cgd.8b00972) echoes these statements, “the structures of bespoke molecular crystals are still impossible to predict solely on the basis of previous crystallographic knowledge and intuition” (pg 1427, col 1, para 3). Thus it is impossible for applicant to meet the written description requirements via providing a representative number of species, because these properties cannot be predicted a priori.
Regarding (ii), applicant has failed to provide the core structure necessary to preserve these specific crystallographic properties. Instant Fig 4 (shown below), suggests that only fused 5-membered aromatic cycles are capable of producing such an effect, however the claim is drawn to any chemical structure comprising “one or two rings” even those that are not fused.
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Applicant has claimed many compounds that do not feature the structural element shown in Fig. 4, thus applicant has failed to clearly provide what structural elements are responsible for this particular stacking. In sum, because applicant cannot meet the written description requirement via describing a representative number of species, applicant is limited to the group of chemical compounds where crystallographic studies have been completed which verify the existence of these properties. In sum, Applicant has failed to meet the written description requirement of compounds possessing the instantly claimed properties.
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.
18/468633
Claim 1, 6-17, 19-20
Claims 1, 6-17, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/468633 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other as described in the claim-by-claim analysis below. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
To avoid improperly treating what is disclosed in a reference patent or copending application as if it were prior art in the context of a nonstatutory double patenting analysis, the examiner must first properly construe the scope of the reference claims. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02. If claims to the compound’s use and the compound were subject to a restriction requirement, and the compound was elected, a nonstatutory double patenting rejection may not be appropriate in a divisional application claiming the restricted compound’s use. See MPEP § 804.01. However, subject matter disclosed in the reference patent or application that does not fall within the scope of a reference claim cannot be used to support a nonstatutory double patenting rejection as this would effectively be treating the reference patent or application as prior art. See MPEP § 804(B)(1).
The specification of this reference describes:
“The present disclosure also provides methods for detecting a neurological disease the method comprising contacting the brain tissue with a labeled molecule which binds to multiple sites of stacked proteins associated with neurological disease, determining the binding of the labeled molecule; and thereby determining a neurological disease associated with the brain tissue” (pg 68, para 00159).
“Detecting a neurological disease of the present disclosure involves contacting brain tissue with a labeled molecule. The labeled molecule may be any molecule that is both able to bind to multiple sites of stacked proteins of a neurodegenerative disease and has a detectable label. The detectable label may be any detectable label that is detectable using Positron emission tomography (PET). Detectable labels include, without limitation, [2H], [3H], [11C], [18F], [13N], etc” (pg 69, para 00163).
“In some embodiments, the labeled molecule is a molecule according to formula (I). In some embodiments, the labeled molecule is a molecule according to formula (II). In some embodiments, the labeled molecule is a molecule according to formula (Ill). In some embodiments, the labeled molecule is a molecule according to formula (IV). In some embodiments, the labeled molecule is a molecule according to formula (V). In some embodiments, the labeled molecule is a molecule according to formula (VI). In some embodiments, the labeled molecule is a molecule according to formula (VII). In some embodiments, the labeled molecule is a molecule according to formula (VIII). In some embodiments, the labeled molecule is a molecule according to formula (IX). In some embodiments, the labeled molecule is a molecule according to formula (X). In some embodiments, the labeled molecule is a molecule according to formula (XI). In some embodiments, the labeled molecule is a molecule according to formula (XII). In some embodiments, the labeled molecule is a molecule according to formula (XIll)(a)” (pg 70, para 00164).
At the time of filing, the method of detecting neurological disease comprising contacting instantly claimed compounds were a known use, thus rendering obvious the method of detecting a neurological disease in the instant application. The claim-by-claim analysis comparing the instant application with that of the reference is as follows:
Regarding instant claim 1, the reference teaches using the compounds to detect a neurological disease comprising contacting the molecules with brain tissue (pg 69, para 00163). The reference teaches using positron emission tomography (pg 69, para 00163). The reference teaches using the same labeled molecules as instantly claimed, thus these molecule inherently possess the features of (a)-(e). “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” See MPEP §2112.01(II). The reference teaches neurological disease is Alzheimer’s Disease (pg 15, para 0040).
Regarding instant claim 6, the reference teaches the instantly claimed molecules disrupt the stacking of the protein, tau (pg 69, para 00162).
Regarding instant claim 7, the reference claims the same chemical oxazolyl formula (I) (claim 1).
Regarding instant claim 8, the reference claims the identical naphthyridinone/dihydronaphthyridinone structure (claim 2).
Regarding instant claim 9, the reference claims the identical naphthyridinone and dihydronaphthyridinone structures for variable T (claim 3).
Regarding instant claim 10, the reference claims the identical naphthyridinone (claim 4).
Regarding instant claim 11, the reference claims the identical variables for X (claim 5).
Regarding instant claim 12, the reference claims the identical variables for X (claim 6).
Regarding instant claim 13, the reference claims the identical variables for Z (claim 7).
Regarding instant claim 14 the reference claims the identical variables for Z (claim 8).
Regarding instant claim 15, the reference claims the identical formulas (claim 9).
Regarding instant claim 16, the reference claims the identical species of formula (I) (claim 10).
Regarding instant claim 17, the reference claims the identical exemplary species of formula (I) shown below (claim 11).
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Regarding instant claim 19, the reference claims the identical formula (XVI) (claim 14).
Regarding instant claim 20, the reference claims the identical Fig 6 (claim 20).
Claim 5 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/468633 in view of Honer (doi: 10.2967/jnumed.117.196741). This is a provisional nonstatutory double patenting rejection.
Claim 5
Regarding instant claim 5, the reference does not claim isotopically labelled compounds.
Honer teaches isotopically labeling compounds (e.g. 18F, 3H) for the purpose of imaging tau aggregates using positron emission tomography (PET) (Abstract, Fig 1).
It would have been obvious to combine the teachings of the reference and Honer, because both methods are drawn to detecting tau using a radiolabeled molecule. One of skill in the art would have had a reasonable expectation of success because Honer teaches several radiolabeled tracers that bind tau aggregates, wherein the label is an isotopic label that is detectable by PET, and the reference teaches tau binding compounds that are amenable to having isotopic labels incorporated into their structures.
18/468657
Claim 1, 6-16, 19-20
Claims 1, 6-16, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/468657 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other as described in the claim-by-claim analysis below. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
To avoid improperly treating what is disclosed in a reference patent or copending application as if it were prior art in the context of a nonstatutory double patenting analysis, the examiner must first properly construe the scope of the reference claims. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02. If claims to the compound’s use and the compound were subject to a restriction requirement, and the compound was elected, a nonstatutory double patenting rejection may not be appropriate in a divisional application claiming the restricted compound’s use. See MPEP § 804.01. However, subject matter disclosed in the reference patent or application that does not fall within the scope of a reference claim cannot be used to support a nonstatutory double patenting rejection as this would effectively be treating the reference patent or application as prior art. See MPEP § 804(B)(1).
The specification of this reference describes:
“The present disclosure also provides methods for detecting a neurological disease the method comprising contacting the brain tissue with a labeled molecule which binds to multiple sites of stacked proteins associated with neurological disease, determining the binding of the labeled molecule; and thereby determining a neurological disease associated with the brain tissue” (pg 68, para 00159).
“Detecting a neurological disease of the present disclosure involves contacting brain tissue with a labeled molecule. The labeled molecule may be any molecule that is both able to bind to multiple sites of stacked proteins of a neurodegenerative disease and has a detectable label. The detectable label may be any detectable label that is detectable using Positron emission tomography (PET). Detectable labels include, without limitation, [2H], [3H], [11C], [18F], [13N], etc” (pg 69, para 00163).
“In some embodiments, the labeled molecule is a molecule according to formula (I). In some embodiments, the labeled molecule is a molecule according to formula (II). In some embodiments, the labeled molecule is a molecule according to formula (Ill). In some embodiments, the labeled molecule is a molecule according to formula (IV). In some embodiments, the labeled molecule is a molecule according to formula (V). In some embodiments, the labeled molecule is a molecule according to formula (VI). In some embodiments, the labeled molecule is a molecule according to formula (VII). In some embodiments, the labeled molecule is a molecule according to formula (VIII). In some embodiments, the labeled molecule is a molecule according to formula (IX). In some embodiments, the labeled molecule is a molecule according to formula (X). In some embodiments, the labeled molecule is a molecule according to formula (XI). In some embodiments, the labeled molecule is a molecule according to formula (XII). In some embodiments, the labeled molecule is a molecule according to formula (XIll)(a)” (pg 70, para 00164).
At the time of filing, the method of detecting neurological disease comprising contacting instantly claimed compounds were a known use, thus rendering obvious the method of detecting a neurological disease in the instant application. The claim-by-claim analysis comparing the instant application with that of the reference is as follows:
Regarding instant claim 1, the reference teaches using the compounds to detect a neurological disease comprising contacting the molecules with brain tissue (pg 69, para 00163). The reference teaches using positron emission tomography (pg 69, para 00163). The reference teaches using the same labeled molecules as instantly claimed, thus these molecule inherently possess the features of (a)-(e). “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” See MPEP §2112.01(II).The reference teaches neurological disease is Alzheimer’s Disease (pg 15, para 0040).
Regarding instant claim 6, the reference teaches the instantly claimed molecules disrupt the stacking of the protein, tau (pg 69, para 00162).
Regarding instant claim 7, the reference claims the same chemical oxazolyl formula (I) (claim 7).
Regarding instant claim 8, the reference claims the identical naphthyridinone/dihydronaphthyridinone structures (claim 8).
Regarding instant claim 9, the reference claims the identical naphthyridinone and dihydronaphthyridinone structures for variable T (claim 9).
Regarding instant claim 10, the reference claims the identical naphthyridinone (claim 10).
Regarding instant claim 11, the reference claims the identical variables for X (claim 11).
Regarding instant claim 12, the reference claims the identical variables for X (claim 12).
Regarding instant claim 13, the reference claims the identical variables for Z (claim 13).
Regarding instant claim 14 the reference claims the identical variables for Z (claim 14).
Regarding instant claim 15, the reference claims the identical formulas (claim 15).
Regarding instant claim 16, the reference claims the identical species of formula (I) (claim 16).
Regarding instant claim 19, the reference claims the identical formula (XVI) (claim 19).
Regarding instant claim 20, the reference claims the identical Fig 6 (claim 20).
Claim 5 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/468633 in view of Honer (doi: 10.2967/jnumed.117.196741). This is a provisional nonstatutory double patenting rejection.
Claim 5
Regarding instant claim 5, the reference does not claim isotopically labelled compounds.
Honer teaches isotopically labeling compounds (e.g. 18F, 3H) for the purpose of imaging tau aggregates using positron emission tomography (PET) (Abstract, Fig 1).
It would have been obvious to combine the teachings of the reference and Honer, because both methods are drawn to detecting tau using a radiolabeled molecule. One of skill in the art would have had a reasonable expectation of success because Honer teaches several radiolabeled tracers that bind tau aggregates, wherein the label is an isotopic label that is detectable by PET, and the reference teaches tau binding compounds that are amenable to having isotopic labels incorporated into their structures.
Allowable Subject Matter
Claim 7
The compounds of claim 7 were found allowable over the prior art. The closest prior art to the naphthyridinone/dihydronaphthyridinone substituted oxazolyl compounds of formula (I) are those of Duggan (US20100130540) who teaches naphthyridinone/dihydronaphthyridinone structures of formula (I) as a means of treating neurodegenerative diseases (pg 1, para 0003; pg 1, para 0007).
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Importantly, Duggan does not teach or suggest attaching the naphthyridinone/dihydronaphthyridinone unit to the 4-position of the oxazole as instantly claimed. Duggan teaches other 5-membered heterocycles such as imidazole (shown below) and triazole being separated by methylene linker (pg 1, para 0012).
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Absent a specific teaching to combine the naphthyridinone/dihydronaphthyridinone unit with a oxazole unit, whilst removing the methylene spacer, one of skill in the art would not have been motivated to generate the instantly claimed structures of formula (I). Dependent claims 5-13 and 19 which are drawn to more specific exemplary structures of Formula (I) and pharmaceutical compositions thereof are also rendered allowable.
Claim 19
The compounds of claim 19 were found allowable over the prior art. The closest prior art to the pyrrolopyrimidinone, pyrrolopyridinone, furopyrimidinone and furopyridinone structures of formula (XVI) are those of Tamagnan (US20100143253). Tamagnan teaches structure of the formula below as a means of treating neurodegenerative diseases (pg 15, para 0062-0063).
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Importantly, the structures of Tamagnan lack the 5-membered heterocycle affixed to the 3-position of pyrimidinone unit, which is analogous to the 5-position of the pyridinone unit (as shown below).
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Furthermore, of the fused heterocycles shown in Tamagnan’s formula above, all of them lack the carbonyl functionality of a pyrimidinone/pyridinone. Absent a specific teaching (i) to incorporate a carbonyl to generate a pyridinone or pyrimidinone species; and (i) to incorporate a 5-membered heterocycle at the 3 or 5 position, one of skill in the art would not have been motivated to generate the instantly claimed compounds. Dependent claims 15-18 which are drawn to more specific exemplary structures of Formula (XVI) are also rendered allowable.
Claim 20
Claim 20 is drawn to 812 distinctive species largely composed of the following structures (G1)-(G6), shown below. Structures of (G4) represented species of formula (I), discussed previously. Note: the short-hand structures drawn below depict greater breadth than what is claimed. Examiner does not assert that the genera of (G1)-(G6) shown below are also allowable. Examiner is merely using this as a means of organizing the discrete instantly claimed species. In other words, only the discretely claimed species described within Fig 6 were found allowable.
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These distinct chemical species of (G1)-(G6) were not found in the prior art. The closest prior art to (G1) is that of Inoue (US20090131413). Inoue teaches compounds of formula (I), shown below (pg 2, para 0014).
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At best Inoue teaches the following structure, which lacks the 4-fluoro group on the benzyl unit and attaches an N-linked (2,4-di-4-morpholinylphenyl)group that was not featured in any of the compounds in Fig 6.
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Absent a specific teaching to remove the dimorpholine unit and fluorinate the benzyl unit, one of skill in the art would not have been motivated to modify the structure of Inoue.
The closest prior art to (G2)-(G3) is that of Molette (US20190071450), who teaches a structures of formula (I), shown below (pg 3, para 0025).
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However, Molette fails to teach any exemplary species comprising the same heterocycle unit as (G2) and (G3), shown below (pg 5, para 0053).
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Given the teachings of Molette, one of skill in the art would not have been motivated to select a heterocycle that was not specifically taught in the reference. See also the structures of Honer (doi: 10.2967/jnumed.117.196741), who teaches the following structures shown below (Fig 1), none of which were claimed in Fig 6.
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The closest prior art to (G5)-(G6) is that of Chatzopoulou (doi: 10.1039/c3cc45410j) who teaches a method of generating 3-indole containing oxazoles (Table 2, shown below).
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Because none of the compounds within Fig 6 featured an indole at 6-position of the oxazole, one of skill in the art would not have been motivated to remove this element, as it is critical for the synthesis to function (Table 2, shown below).
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Absent a specific teaching to generate each of the specific species described in Fig 6, one of skill in the art would not have been motivated to synthesize said species.
MPEP §2144.09 sets forth various considerations when considering compounds of close chemical structure, e.g., that successive addition of the same chemical group, such as additional CH2 groups, are generally expected to be so close that they possess the same or similar properties.
However, while structural similarity is one consideration for obviousness, the evidence as a whole must be considered. In this case, there are large disparities between the chemical structures claimed and those in the prior art (e.g. completely different heterocycles and functional groups). As discussed above, absent a motivation to generate the instantly claimed compounds, one of skill in the art would not have found it obvious to generate them.
Response to Arguments
Applicant’s arguments filed on 6/23/2026 have been fully considered but they are not persuasive.
NSDP; pg 41
Applicant requests that the double patenting rejection over U.S. Patent No. 18/468657 and 18/468633 be held in abeyance.
A request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see 37 CFR 1.111(b) and MPEP §714.02). Thus, the double patenting rejections of record have been maintained as no response to these rejections has been filled by applicant at this time.
112(a), WD, pg 44, para 4
Applicant argues they have supplied a representative number of species. Applicant argues that the surface of the stacked proteins tends to be relatively flat, and that example compounds 17, 83, and 125, exhibit the propensity to form supramolecular polymer assemblies with a-synuclein aggregates. Applicant argues that compound GTP-1 exhibited a similar stacking a-syn. Applicant admits “lt was hypothesized that the tilt of the aromatic region of GTP-1 relative to the amyloid backbone is a geometric consequence of the optimal pi-pi stacking distance, as well as the 4.77 A repeat of the amyloid (and the helical twist, although this is negligible over short assemblies … commonality of heterocyclic aromatics in small molecules that bind amyloids and the constancy of the rise in amyloids, the adoption of a tilted heterocycle relative to the amyloid backbone, which allows for significant favorable pi-pi interactions between small molecules while maintaining the translational symmetry of the amyloid”. Applicant lists compound 22, 83, 143, 293-294, and 427 as alternative compounds that exhibit a planar core and presumed identical binding behavior.
Applicant lacks the data the show that any of the individual compounds described are capable of disrupting/detecting any stacked protein associated with AD, PD, and MSA (e.g. tau, a-syn, FUS, TDP-43, OPTN, UBQLN2). At issue is not the presence/absence of a planar core within the exemplary compounds, it’s whether one of skill in the art would envisage any of the claimed compounds given the description in claim 1. Firstly, of the example compounds shown, they all exhibit freely rotating aromatic rings and side groups (e.g. CF3) which can never exhibit planar geometry, thus while applicant asserts the importance of planarity in the compound design, it is clear from the examples that this is not the primary concern. If planarity were a design criteria, then one of skill in the art would envisage a compound such as naphthyridine which has no degrees of rotational freedom. However, none of the exhibited compounds are naphthyridine or naphthyridine-based, hence underlining the failure to meet the written description rejection. Applicant must supply the core chemical structure responsible for the function of disrupting/detecting stacked proteins to detect AD, PD, and/or MSA.
Secondly (as described in detail in the written description rejection), crystallographic parameters of a given compound cannot be assumed a priori, as a result, the rejection is maintained, despite applicant’s assertion that any compound with a heterocycle would adopt the rather specific binding geometry within a-syn. Examiner suggests supplying the structural information of the compounds (i.e. which has already been completed in application 18/468633) as a means of detecting AD, PD, and/or MSA and making the crystallographic parameters a dependent claim—of which a subset have been verified to adopt the geometries and angles claimed.
Conclusion
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 LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
