Anti-Amyloidogenic Curcumin Analogues

§102 §103 §112

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 . Status of the Claims Claims 1-22 are pending. Claims 6 and 11-20 are withdrawn. Claims 1-5, 7-10 and 21-22 are rejected. Election/Restrictions Restriction to one of the following inventions is required under 35 U.S.C. 121: Group I. Claims 1-10, 21 and 22, drawn to a compound of formula (I), (II), (III), (IV), or (V), classified in CPC C07C or C07D. Group II. Claims 11-20, drawn to a method of treating Alzheimer’s disease or preventing amyloid plaque formation using a compound of claim 1, classified in CPC A61K. The inventions are independent or distinct, each from the other because: Inventions I and II are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case, the process of Group II as claimed can be practiced with materially different products. For example, Alzheimer’s disease can be treated with antibodies such as gantenerumab and aducanumab. Restriction for examination purposes as indicated is proper because all these inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because at least the following reason(s) apply: The inventions have acquired a separate status in the art in view of their different classification (C07C vs A61K); The inventions have acquired a separate status in the art due to their recognized divergent subject matter (organic compounds vs biological treatment methods); and The inventions require a different field of search (e.g., searching different classes /subclasses and employing different search strategies). Traversal of Restriction Requirement The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention. Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103(a) of the other invention. Election of Species This application contains claims directed to the following patentably distinct species: Compounds of formula (I), (II), (III), (IV) and (V). See species claims 3, 4 and 6. The species are independent or distinct because the species as claimed have a materially different design which imparts to each compound a different chemical reactivity and pharmacokinetic profile, resulting in different in vitro and in vivo effects. In addition, these species are not obvious variants of each other based on the current record. Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. There is a search and/or examination burden for the patentably distinct species as set forth above because the species require a different field of search (e.g., searching different classes /subclasses, such CPC C07C and C07D, and employing different search strategies based on the different structures). Traversal of Election Requirement The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species or grouping of patentably indistinct species. Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103(a) of the other species. Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141. Rejoinder The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined. In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01. Telephonic Election During a telephone conversation with Mr. Lin J Hymel on 9/16/2026 a provisional election was made to prosecute the invention of Group I (claims 1-10, 21 and 22), with a species election of compound 25. Affirmation of this election (with or without traverse) must be made by applicant in replying to this Office action. Claims 1-5, 7-10, 21 and 22 read on the formula (I), PNG media_image1.png 169 417 media_image1.png Greyscale , species election of compound 25, PNG media_image2.png 121 131 media_image2.png Greyscale PNG media_image3.png 129 255 media_image3.png Greyscale , wherein R1 is 3,5-dichloro, R2 through R5 are H, and R6 is p-NMe2. Examination of the elected invention was conducted in accordance with the MPEP 803.02. The elected species appears allowable in view of the prior art; therefore, examination of the Markush-type claim has been extended until prior art was found. Since art was found on a nonelected species, subject matter not embraced by the elected embodiment or the rejected species is therefore withdrawn from further consideration. Claims 6 and 11-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be amended in compliance with 37 CFR 1.48(b) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. Any amendment of inventorship must be accompanied by a request under 37 CFR 1.48(b) and by the fee required under 37 CFR 1.17(i). Priority This application was filed on 02/07/2025 and claims benefit of provisional application no. 63/550,985, filed on 02/07/2024. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application. The disclosure of the invention in the prior application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a), except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed application, Application No. 63/550,985, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) for one or more claims of this application. The ‘985 application discloses compounds of formula I, PNG media_image4.png 194 472 media_image4.png Greyscale , wherein “R1-R6 can be independently H or any substituent”, including 32 examples thereof. See p. 3 ll. 4-5 and Figures 1A, 4A, 4B, 4C, 4D and 5A. The examples represent a genus having the structure PNG media_image5.png 178 430 media_image5.png Greyscale , wherein X is H, p-CH3, p-Cl, p-Et, p-Pr, p-iPr, p-iBu, p-cyclohexyl, p-Br, p-I, p-CF3, p-NO2, p-CN, p-C(O)Me, p-OMe, p-OEt, 3,4-dioxinyl, p-SMe, p-imidazolyl, m-CF3, m-Cl, o-CF3, o-CH3, o-Cl, 3,5-diCl, 2,4-diCl, and 2-Cl-5-CF3, 3,5-diMe; and also represent the following compounds: PNG media_image6.png 228 541 media_image6.png Greyscale PNG media_image7.png 218 587 media_image7.png Greyscale PNG media_image8.png 215 586 media_image8.png Greyscale PNG media_image9.png 223 591 media_image9.png Greyscale . The ‘985 application does not disclose or provide blazemarks for the genus of claim 1 (formula 1) wherein “R6 is dialkylamino with each alkyl portion having C1-C5, or the alkyl portions fused to form a 5- or 6-membered saturated ring”. It also fails to provide support for the genus of compounds of formula (I) wherein R6 is NMe2 and “R1 is one or two halogens at the para, meta, or di-meta position,” m-CH3, “one or two halomethyl, dihalomethyl, or trihalomethyl groups at the para, meta, or di-meta position”, o-CN, m-CN, o-NO2, m-NO2, o-C1-C5 alkyloxy, m-C1-C5 alkoxy, p-C3-C5 alkoxy, C1-C5 keto (except for p-acyl), C1-C5 thioether (except for p-SMe), C1-C6 alkyl (except for p-C1-4 alkyl), cycloalkyl (except p-cyclohexyl), “or any combination thereof”. Furthermore, there is no support for compounds with the aforementioned R1 groups and a different R6 group. Therefore, the claimed formula (I) contains subject matter not supported by the ‘985 application. The ’985 application discloses compounds of formula III, PNG media_image10.png 241 447 media_image10.png Greyscale , (“wherein any position not indicated with H can be independently any substituent”), which represent a portion of the formula (II), PNG media_image11.png 150 375 media_image11.png Greyscale , compounds instantly claimed. ‘985 p. 3 ll. 15-16. According to claim 1, the compounds of formula (II) require that R6 is H or “dialkylamino with each alkyl portion having C1-C5, or the alkyl portions fused to form a 5- or 6-membered saturated ring.” This subgenus is not supported by the formula (III) structures disclosed in the ‘985 application. The same analogy applies to instant formula (III), PNG media_image12.png 175 410 media_image12.png Greyscale , which is not supported by the genus circumscribed by formula (IV), PNG media_image13.png 240 438 media_image13.png Greyscale , of the ‘985 application. See p. 3-4. Lastly, formula (V), PNG media_image14.png 168 317 media_image14.png Greyscale , wherein R1 and R6 are as claimed in claim 1 (and n is 0-3), is not fully supported by the ‘985 application, which discloses compounds 25-25 PNG media_image15.png 201 371 media_image15.png Greyscale , but does not disclose the Markush groups R1 and R6 as recited in claim 1. See, e.g., ‘985 Scheme 3 in the drawings. In addition to claim 1, claim 2 is also not fully supported by the ‘985 application. Claim 2 is drawn to compounds of formula (VI), PNG media_image16.png 189 404 media_image16.png Greyscale , wherein R1 is an “aromatic ring…” The ‘985 application does not dislcose “aromatic ring” as a genus for R1. The only aromatic ring disclosed is phenyl. Claims 3-5 are drawn to species disclosed in the ‘985 application and, therefore, are entitled to the earlier priority date. Claims 7-10 and 21-22 depend from claim 1 and refer back to the same structures in claim 1 that lack support in the ‘985 application. Therefore, claims 1-2, 7-10 and 21-22 have an effective filing date of 02/07/2025. Claims 3-5 have an effective filing date of 02/07/2024. Information Disclosure Statement The information disclosure statement (IDS) submitted on 5/13/2025 is in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. Accordingly, the IDS has been considered by the examiner and a signed copy is enclosed herewith. Claim Rejections – 35 USC 112 (enablement) Claim 21 is rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a kit comprising an antibody selected from the group consisting of aducanumab, lecanemab and donancinab, does not reasonably provide enablement for a kit comprising all antibodies “having a binding specificity for an epitope found in amyloid plaque.” The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with the claim. As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described. They are: 1. The nature of the invention 2. The state of the prior art 3. The predictability or lack thereof in the art 4. The amount of direction or guidance present 5. The presence or absence of working examples 6. The breadth of the claims 7. The quantity of experimentation needed, and 8. The level of skill in the art The Nature of the Invention The nature of the invention is a kit comprising a compound of claim 1, which are amyloid plaque inhibitors, and an antibody with binding specificity to amyloid plaque. The purpose of preparing kits of pharmaceutically active compounds is to facilitate the transport, storage and/or administration of the compound. In this case, the administration is intended to occur with the antibody administration for treating conditions such as Alzheimer’s disease, where amyloid plaque is implicated in disease progression. The State of the Prior Art and the Predictability or lack thereof in the art The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and the physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). With respect to antibodies “having a binding specificity for an epitope found in amyloid plaque,” the prior art recognizes that there is “no specific epitope that was predictive as to the success of an antibody-antigen pairing” for Aβ peptides found in amyloid plaques. See, e.g., Sci. Rep. 2023, 13, 12387 (at p. 3). Many antibodies have failed “in clinical trials occurring after AD has progressed too much.” (Id at 6) Indicating that there is a reasonable level of unpredictability in the art with respect to effective antibodies against amyloid plaque and their Aβ peptides. There is no disclosure in the prior art regarding a predictable structure required of the antibodies that would provide a PHOSITA with a reasonable expectation that the antibodies would have the claimed function of having a binding specificity for an epitope found in amyloid plaque. The Amount of Direction/Guidance Present and Presence or Absence of Working Examples The specification discloses three antibodies as examples: aducanumab, lecanemab, and donancinab. See, e.g., claim 22. The specification does not provide sufficient guidance for how to discover or prepare other antibodies having the claimed function. The Quantity of Experimentation Needed and the Level of Skill in the Art A PHOSITA would need to conduct a burdensome quantity of experimentation in order to determine which antibodies exhibit the desired activity. The quantity of experimentation would be undue when faced with the task of testing all presently known antibodies and synthesizing new ones in attempt to discover the antibodies that encompass the breadth of the claimed scope. The specification must teach how to make and use the claimed invention, not how to figure out for oneself how to make and use invention. Considering that the instant invention potentially contains new subject matter (i.e., new antibodies) not previously disclosed in the prior art, the lack of a predictable structure-function correlation, the prior art and the specification do not provide the necessary guidance to enable the skilled to prepare the full scope of the claimed antibodies without undue experimentation. 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. Claims 3-5 and 7-8 are rejected under 35 U.S.C. 112(b) being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. Claims 3-5 refer to the specification for the structural limitations of specific compounds. Consequently, one must refer back to the specification to find the structure of those compounds. Claims must, under modern claim practice, stand alone to define an invention, and incorporation into claims by express reference to the specification is not permitted. According to MPEP 2173.05(s), incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ 2d 1608 (1993). Since this case does not qualify for the incorporation-by-reference exception, it is improper to refer to the specification for the structure of the claimed compounds, leaving a PHOSITA without the information required to ascertain the scope of the claimed compounds. Therefore, claims 3-5 are indefinite. This rejection may be overcome by adding the structures of the recited compounds to the claims. Claims 7-8 each present a broad limitation together with a narrower limitation. A broad limitation together with a narrow limitation that falls within the broad limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 7 recites the broad recitation “amyloid precursor” and also recites “such as Aβ 1-42”, which is the narrower statement of the limitation. Claim 8 recites the broad recitation “mammalian brain” and also recites “such as in a human brain”, which is the narrower statement of the limitation. Claims 7-8 are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. This rejection may be overcome by deleting the narrower limitation, or by deleting the broader limitation. Claim Rejections - 35 USC § 112(d) 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. Claim 2 is rejected under 35 U.S.C. 112(d) 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. Claim 2 encompasses compounds of Formula (VI), PNG media_image17.png 140 304 media_image17.png Greyscale , wherein “R1 is an aromatic ring…”. This R1 Markush grouping of aromatic rings is broader than the R1 Markush grouping of phenyl rings pertaining to Formula (I), PNG media_image18.png 137 317 media_image18.png Greyscale , of claim 1, from which claim 2 depends. Therefore, claim 2 fails to further limit claim 1. 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. (1 of 3) Claims 1-3, 5 and 7-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Faudzi et al. Med. Chem. Commun. 2015, 6, 1069-1080. Faudzi teaches several NO-inhibiting compounds of the structure PNG media_image19.png 126 332 media_image19.png Greyscale , such as compound 4a, wherein Ar is phenyl and R1 is 4-NMe2, and compound 4b, wherein Ar is 4-methoxyphenyl and R1 is 4-NMe2. See, e.g., Table 1. Compounds 4a and 4b anticipate the instant compounds of formula (I), PNG media_image20.png 133 313 media_image20.png Greyscale , wherein R1 is p-OMe or H; R2 through R5 are H; and R6 is NMe2, which compounds are embraced by claim 1. Claim 2 reads on compound 4b, which has a structure of instant formula (VI), PNG media_image21.png 127 289 media_image21.png Greyscale , wherein R1 is an aromatic ring with H or p-C1 alkyloxy. Claim 3 reads on compound 4b, which is identical to instant compound 15 (Fig. 4B). Compound 4a meet the requirements of claim 5. Claims 7-9 recite inherent properties of the compounds of claim 1, which properties are necessarily inherent in the prior art compounds, because the compounds have the same structures and the claimed compounds. See In re Papesch, 315 F.2d 381,391, 137 USPQ 43, 51 (CCPA 1963)(“a chemical compound and its properties are inseparable”). See also In re Spada, 911 F. 2d 705, 709, 15 USPQd 1655, 1658 (Fed. Cir. 1990)(“[p]roducts of identical chemical composition cannot have mutually exclusive properties”). See MPEP 2112 (“Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). ‘When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.’ ”) Claim 10, drawn to a pharmaceutical composition comprising the compound of claim 1 and an excipient, is anticipated by Faudzi’s teaching of testing the compounds as solutions in DMSO in a MTT assay. Faudzi p. 1079 (right column). (2 of 3) Claims 1-2, 5 and 7-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jaipuria et al. Chemistry 2024, 6, 1477-1494 (pub. 11/22/2024). Jaipuria teaches compounds having “anti-amyloidogenic activity on Aβ1-42 peptides”. Compounds 4-9 (Table 1) are identical to instant compounds 4-9 (Fig. 4A). Jaipuria’s compounds 11-16 (Table 1) are identical to instant compounds 11-16 (Fig. 4A). Additionally, compounds 17-28 (Table 1) are identical to instant compounds 17-28 (Fig. 4A). Jaipuria’s compounds anticipate the claimed compounds of formula (I), PNG media_image20.png 133 313 media_image20.png Greyscale , according to claims 1-2. Claims 7-9 recite inherent properties of the compounds of claim 1, which properties are necessarily inherent in the prior art compounds. For example, regarding claim 7, Jaipuria teaches that the compounds inhibit Aβ42 peptides, based on the ThT assay results of Table 1. See, e.g., p. 1480-1481. The properties recited by claims 8 and 9, pertaining to inhibiting amyloid plaque in a mammalian brain and crossing a blood-brain barrier, these properties are also necessarily inherent in the prior art compounds, because the compounds have the same structures and the claimed compounds. See In re Papesch, 315 F.2d 381,391, 137 USPQ 43, 51 (CCPA 1963)(“a chemical compound and its properties are inseparable”). See also In re Spada, 911 F. 2d 705, 709, 15 USPQd 1655, 1658 (Fed. Cir. 1990)(“[p]roducts of identical chemical composition cannot have mutually exclusive properties”). See MPEP 2112 (“Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). ‘When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.’ ”) Claim 10, drawn to a pharmaceutical composition comprising the compound of claim 1 and an excipient, is anticipated by Jaipuria’s teaching of assaying the compounds as solutions in DMSO. See section 4.2.1. (3 of 3) Claims 1-2, 5 and 7-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Quiroz et al. Chemistry 2023, 5, 223-241 (pub. 2/7/2023). PNG media_image22.png 285 379 media_image22.png Greyscale Quiroz teaches several anticipatory compounds that “inhibited Aβ peptide aggregation”, such as compounds 25, 26, 27, 28 and 31. See Table 2 and p. 227. PNG media_image23.png 94 360 media_image23.png Greyscale PNG media_image24.png 84 369 media_image24.png Greyscale These compounds anticipate the claimed compounds of formula (I), PNG media_image20.png 133 313 media_image20.png Greyscale , wherein R1 is p-Cl, p-Me, p-OMe or p-NO2; R2 through R5 are H; and R6 is H, NMe2 or Cl, which compounds are embraced by claim 1. Claim 2 reads on compounds 26 and 27, which have a structure of instant formula (VI), PNG media_image21.png 127 289 media_image21.png Greyscale , wherein R1 is an aromatic ring with one p-halogen or one p-C1 alkyloxy. Compounds 25, 28 and 31 meet the requirements of claim 5. Claims 7-9 recite inherent properties of the compounds of claim 1, which properties are necessarily inherent in the prior art compounds. For example, regarding claim 7, Quiroz teaches that the compounds inhibit Aβ42 peptide aggregation, based on the ThT Assay results of Table 2. See, e.g., p. 227-228 and 240. The properties recited by claims 8 and 9, pertaining to inhibiting amyloid plaque in a mammalian brain and crossing a blood-brain barrier, these properties are also necessarily inherent in the prior art compounds, because the compounds have the same structures and the claimed compounds. See In re Papesch, 315 F.2d 381,391, 137 USPQ 43, 51 (CCPA 1963)(“a chemical compound and its properties are inseparable”). See also In re Spada, 911 F. 2d 705, 709, 15 USPQd 1655, 1658 (Fed. Cir. 1990)(“[p]roducts of identical chemical composition cannot have mutually exclusive properties”). See MPEP 2112 (“Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). ‘When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.’ ”) Claim 10, drawn to a pharmaceutical composition comprising the compound of claim 1 and an excipient, is anticipated by Quiroz’s teaching of assaying the compounds as solutions in DMSO. See Quiroz section 4.2.1. 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. 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 1-5, 7-10 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Quiroz et al. Chemistry 2023, 5, 223-241 (pub. 2/7/2023). Quiroz teaches several compounds that “inhibited Aβ peptide aggregation”, some compounds having a single double bond bridge and others having a diene bridge. Compare, for example, compound 16 with 26, and compound 17 with 27. See Table 2 and p. 227. PNG media_image25.png 243 518 media_image25.png Greyscale PNG media_image26.png 246 563 media_image26.png Greyscale Quiroz’s assay data show that elongating the double bond bridge (from one double bond to two double bonds) results in drastically improved Aβ peptide aggregation inhibition. Compared to instant claim 4, Quiroz teaches compound 18, PNG media_image27.png 106 241 media_image27.png Greyscale , with a single double bond bridge, but does not teach the diene analog corresponding to instant compound 20, PNG media_image28.png 113 222 media_image28.png Greyscale , wherein R is PNG media_image29.png 71 118 media_image29.png Greyscale . A PHOSITA desiring to make new Aβ peptide aggregation inhibitors would have been motivated to select compound 18 as a lead compound, because Quiroz singles it out as one of “four chalcones… with IC50 values in the micromolar range (Table 2)” (p. 227). Since Quiroz shows that elongating the double bond bridge results in improved Aβ peptide aggregation inhibition, a PHOSITA would have been motivated to modify compound 18 by elongating the bridge to a diene bridge. Thereby arriving at the diene-containing analog of instant compound 20, which compound a PHOSITA would have predicted would have improved inhibition properties. The diene analog of compound 18 has the same structure of instant compound 20, which is that of formula (I), PNG media_image20.png 133 313 media_image20.png Greyscale , wherein R1 is m-CF3; R2 through R5 are H; and R6 is NMe2. This compound is embraced by claims 1, 3-5. Claim 2 reads on the diene analog, which has a structure of instant formula (VI), PNG media_image21.png 127 289 media_image21.png Greyscale , wherein R1 is an aromatic ring with one m-trihalomethyl group. Claims 7-9 recite inherent properties of the compounds of claim 1, which properties are necessarily inherent in the prior art compounds. For example, regarding claim 7, Quiroz teaches that the compounds inhibit Aβ42 peptide aggregation, based on the ThT Assay results of Table 2. See, e.g., p. 227-228 and 240. The properties recited by claims 8 and 9, pertaining to inhibiting amyloid plaque in a mammalian brain and crossing a blood-brain barrier, these properties are also necessarily inherent in the prior art compounds, because the compounds have the same structures and the claimed compounds. See In re Papesch, 315 F.2d 381,391, 137 USPQ 43, 51 (CCPA 1963)(“a chemical compound and its properties are inseparable”). See also In re Spada, 911 F. 2d 705, 709, 15 USPQd 1655, 1658 (Fed. Cir. 1990)(“[p]roducts of identical chemical composition cannot have mutually exclusive properties”). See MPEP 2112 (“Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). ‘When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.’ ”) Claim 10, drawn to a pharmaceutical composition comprising the compound of claim 1 and an excipient. Quiroz’s teaching of assaying the compounds as solutions in DMSO renders obvious the diene analog in DMSO, because a PHOSITA would have been motivated to test the inhibition using the same assay procedure as Quiroz. See Quiroz section 4.2.1. Claims 21-22, drawn to a kit comprising the compound of claim 1 and an antibody such as aducanumab, are rendered obvious in view of Quiroz’s teaching that “aducanumab, a monoclonal antibody developed by Biogen which targets the Aβ aggregates, was approved by the FDA and became the first drug to treat AD.” See p. 223 (Introduction). A PHOSITA would have found it obvious to combine aducanumab with a compound of claim 1, namely the diene analog of compound 18 (i.e., instant compound 20) or Quiroz’s compounds 26 or 27, because these compounds were all expected to inhibit Aβ aggregates. See MPEP 2144.06 (“"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) (citations omitted).) Therefore, a PHOSITA would have been motivated to prepare a kit comprising one of Quiroz’s compounds and aducanumab to facilitate their transport and co-administration. Contact Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA L AGUIRRE whose telephone number is (571)272-5592. The examiner can normally be reached 10 am-6 pm MST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY H MURRAY can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AMANDA L. AGUIRRE/ Primary Examiner, Art Unit 1626