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. Specification The disclosure is objected to because of the following informalities: The use of the terms Zeiss® Stemi ® and HYPERLINK "https://www.google.com/search?q=ProLong%E2%84%A2+Glass&safe=active&sca_esv=998a066a4e114733&ei=OCyoaY22CaGq5NoPiJ2tsAc&ved=2ahUKEwjWsYzkpoaTAxVSEGIAHZOcCPkQgK4QegQIARAC&uact=5&oq=is+prolong+glass+trade+mark%3F&gs_lp=Egxnd3Mtd2l6LXNlcnAiHGlzIHByb2xvbmcgZ2xhc3MgdHJhZGUgbWFyaz8yChAhGKABGMMEGApIy94IUK27CFiy1whwAngAkAEAmAFWoAH8BqoBAjE0uAEDyAEA-AEBmAIPoAKhB8ICChAAGLADGNYEGEfCAggQABgHGAgYHsICChAAGAcYCBgKGB7CAggQABiiBBiJBcICBRAAGO8FwgIIEAAYgAQYogSYAwCIBgGQBgWSBwIxNaAHwk6yBwIxM7gHlQfCBwUwLjguN8gHMIAIAA&sc lient=gws-wiz-serp&mstk=AUtExfAZ0gMuyjYorsU27gkudg94bq6UidYcEbHL9CJc6y89Ol_F250kpOFJArseBmVnFSDyuc4z4lZLtEykSHFAQGctwSBKcbGgUwX0XemowvjOUuY2BkCRhnY0u9UU7wgmEfQ&csui=3" ProLong ™ which are a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required. The disclosure is objected to because of the following informalities: In page 17, the structural formula of L 1 , L 2 , L 3 , and L 4 includes a small dot or period , as indicated by the gray arrow , without any explanation of its meaning or purpose . Appropriate correction is required. Claim Rejections - 35 USC § 112 Indefiniteness 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. Claims 1, 3- 12, and 14- 2 2 are 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. Claims 1, 12, and 19 define a chemical compound using one or more Markush groups, and th e claim s encompass a massive number of distinct alternative members . For example, EDG can be R 1 -substituted or unsubstituted alkyl/cycloalkyl/ heteroalkyl / heterocycloalkyl /aryl /heteroaryl, OR 2 NR 4 C(O)R 3 , —NR 4 R 5 , —SR 6 , or PR 7 R 8 . R 1 can be halogen or unsubstituted alkyl/ heteroalkyl /cycloalkyl/ heterocycloalky l /aryl/heteroaryl . R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , a nd R 8 can be hydrogen, R 12 -substituted or unsubstituted alkyl/heteroalkyl/cycloalkyl/heterocycloalky l /aryl/heteroaryl . R 12 can be R 1 6 -substituted or unsubstituted alkyl/heteroalkyl/cycloalkyl/heterocycloalky l /aryl/heteroaryl. R 16 can be unsubstituted alkyl/ heteroalkyl /cycloalkyl/ heterocycloalky l /aryl/heteroaryl . For example, if a claim defines a chemical compound using one or more Markush groups, and that claim encompasses a massive number of distinct alternative members, the claim may be indefinite under 35 U.S.C. 112(b) if one skilled in the art cannot determine its metes and bounds due to an inability to envision all of the compounds defined by the Markush group(s). See MPEP § 2173.05(h). In such a circumstance, a rejection of the claim for indefiniteness under 35 U.S.C. 112(b) is appropriate. The recitations of “( ATTRv or ATTRm )” and “(SSA or ATTRwt )” in claim 14 are indefinite because they appear to possibly be preferred embodiments, similar to a “such as” recitation. While the use of parenthesis is usually clear for the use of acronyms, in the situations above, these do not appear to be complete or clear acronyms and it is not clear why these embodiments are contained in parenthesis. The dependent claims fall therewith. Claims 1, 3- 12, and 14- 2 2 are 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. C laims 1, 12, and 19 recite limitation “R 11 . ” The claims do not define the variables that “R 11 ” may represent. The dependent claims fall therewith. Clarification and/or amendment is required. Claims 1, 3- 12, and 14- 2 2 are 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. In c laims 1, 12, and 19 , the structural formula of L 1 , L 2 , L 3 , and L 4 includes a small period or dot, as indicated by the gray arrow. Because the claims do not clearly define the meaning or purpose of this period or dot, the scope of the claims cannot be determined with reasonable certainty by a person of ordinary skill in the art. Accordingly, the claims fail to inform a person of ordinary skill in the art of the metes and bounds of the invention with reasonable certainty. The dependent claims fall therewith. Clarification and/or amendment is required. Claim 21 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 21 recites the limitation “the misfolded or aggregated protein.” The claim lacks an antecedent basis for this limitation. Claim 20 recites “a misfolded or aggregated protein.” It is suggested that claim 21 be amended to depend from claim 20 to correct this issue. Clarification and/or amendment is required. 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 -22 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 2018 0327373 ; cited on IDS filed May 7, 2024) in view of Yang et al. ( US 9,551,722, 2017 ; cited on PTO-892 ). Regarding claims 1 , 3, 12, and 19-21, Yang ‘3 73 discloses a method of detecting an amyloid or amyloid like protein comprising ( i ) contacting a compound of Formula Ic with a sample potentially comprising the amyloid or amyloid like protein, wherein in presence of an amyloid or amyloid like protein the compound forms a detectable complex; and (ii) detecting the formation of the detectable complex such that the presence or absence of the detectable complex correlates with the presence or absence of the amyloid or amyloid like protein (claim 20). Yang ‘3 73 discloses that the compound can be administered to the eye ( ¶ 435 ). Yang ‘3 73 discloses the method can be used in the detect ion , diag nosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding ( ¶ 199 ), and the protein can be transthyretin ( TTR or t ransthyretin amyloidosis , ATTR) ( ¶ 504 ). Regarding claims 4 and 14, Yang ‘3 73 discloses that the disease can be systemic amyloidosis such as familial amyloid polyneuropathy (FAP) ( ¶ 501 ). Regarding claims 5-7, 15-18, and 22, Yang ‘3 73 discloses that the compounds can be administered topically to the eye as an eye drop and delivered to the conjunctiva of the eye ( ¶ 435 ) , which reads on topical administration to a surface of the eye without injection or direct administration to the interior of the eye of instant claims . Regarding claims 8 and 9, Yang ‘3 73 discloses that the compound can form a detectable complex in presence of an amyloid or amyloid-like protein , and that the detectable complex can have a fluorescent excitation peak upon irradiation with an appropriate wavelength of light ( ¶¶ 200-201 ). Regarding claims 10 and 11, Yang ‘3 73 discloses that the disease can be senile systemic amyloidosis (SAA) ( ¶ 501 ), which reads on a disease caused by misfolded or aggregated wild type transthyretin protein ( ATTRwt ) (instant claim 4), and the disease can be FAP ( ¶ 501) , which reads on a disease caused by mutations in the transthyretin gene (page 1, Background of instant specification as filed) . Regarding claims 1, 2, 12, 13, and 19, Yang ‘3 73 dose not discloses the compound of formula I in instant claim 1 or the compound in instant claim 2. Instead, Yang ‘345 discloses the compound of formula Ic (claim 1) and compound of formula in claim 18. The structural distinction lies in the linkage between the carbonyl group and the WSG. In the instant claims, the c arbonyl group is connected to an oxygen atom and the WSG is attached via an ester bond . In Yang ‘345 , the carbonyl group is connected to an NH group and the WSG is attached via an amide bond . Yang ‘722 discloses a method of detecting amyloid peptide comprising ( i ) contacting an amyloid peptide with a compound having the structure of formula (I) ; and (ii) detecting said detectable amyloid complex (claim 1). Yang ‘722 discloses t he compound of formula I in claim 1 and the compound in claim 15 , which correspond to the compound s of instant claims. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yang ‘3 73 by using the compound of Yang ‘722 to detect systemic amyloidosis efficiently . A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Yang ‘722 teaches that its compound s can be use d for detecting amyloid peptide s . Further, a person of ordinary skill in the art would have been motivated to use the compound of Yang ‘722 to improve permeability and cleavability of the compound . Accordingly, applying the compound of Yang ‘722 to the method of Yang ‘3 73 constitutes no more than the predictable use of prior art elements according to their established functions. Claims 1-22 are rejected under 35 U.S.C. 103 as being unpatentable over Sarraf (US 201 7 0 248616 ; cited on IDS filed May 7, 2024) in view of Yang et al. (US 9,551,722, 2017; cited on PTO-892) and Yang et al. (US 2018 0327373 ; cited on IDS filed May 7, 2024) . Regarding claims 1, 3, 5-7, 12, 15, and 17 -21, Sarraf discloses methods of detecting an amyloid or amyloid like protein in a sample, such as a human sample, in contact with a compound used in the detection of amyloid in the sample (¶ 71) . Sarraf discloses that the compound can be topically administered to the eye (¶ 74 ). Sarraf discloses the compounds can be used for determining the presence or absence of one or more disease or condition characterized by protein aggregation or protein misfolding (¶ 311), and the protein can be TTR (¶ 333 ). Regarding claims 4 and 14, Sarraf discloses that the disease can be systemic amyloidosis such as FAP ( ¶ 330 ). Regarding claims 8 and 9, Sarraf discloses that the compound can form a detectable complex in presence of an amyloid or amyloid-like protein , and that the detectable complex can have a fluorescent excitation peak upon irradiation with an appropriate wavelength of light (¶¶ 122-123 ). Regarding claims 10 and 11, Yang ‘3 73 discloses that the disease can be S S A (¶ 330 ), which reads on a disease caused by ATTRwt (instant claim 4), and the disease can be FAP ( ¶ 330 ) , which reads on a disease caused by mutations in the transthyretin gene (page 1, Background of instant specification as filed). Regarding claims 1, 2, 12, 13, and 19, Sarraf doe s not disclose the compound of formula I in instant claim 1 or the compound in instant claim 2. Instead, Yang ‘345 discloses the compound of formula Ic (claim 1) and compound of formula in claim 18. The structural distinction lies in the linkage between the carbonyl group and the WSG. In the instant claims, the carbonyl group is connected to an oxygen atom and the WSG is attached via an ester bond. In Yang ‘345 , the carbonyl group is connected to an NH group and the WSG is attached via an amide bond in. As discussed above, Yang ‘722 discloses a method of detecting amyloid peptide comprising ( i ) contacting an amyloid peptide with a compound having the structure of formula (I) ; and (ii) detecting said detectable amyloid complex (claim 1). Yang ‘722 discloses the compound of formula I in claim 1 and the compound in claim 15, which correspond to the compounds of instant claims. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Sarraf by using the compound of Yang ‘722 to detect systemic amyloidosis efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Yang ‘722 teaches that its compounds can be use d for detecting amyloid peptides. Further, a person of ordinary skill in the art would have been motivated to use the compound of Yang ‘722 to improve permeability and cleavability of the compound . Accordingly, applying the compound of Yang ‘722 to the method of Sarraf constitutes no more than the predictable use of prior art elements according to their established functions. Regarding claims 16 and 22, Sarraf does not disclose the compound is delivered to conjunctiva of the eye. As discussed above, Yang ‘722 discloses the compound can be delivered to the conjunctiva of the eye ( ¶ 435 ) . It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Sarraf to deliver the compound to conjunctiva of the eye. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Yang ‘373 teaches the compounds can be administered topically to the eye and the compounds can be delivered to the conjunctiva of the eye for detecting systemic amyloidosis. Further, a person of ordinary skill in the art would have been motivated to use topical administration to the eye conjunctiva for easy, self-administered, and rapid clinical application. Accordingly, applying the teachings of Yang ‘373 to the method of Sarraf constitutes no more than the predictable use of prior art elements according to their established functions. Claims 1-22 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 9,551,722, 2017; cited on PTO-892) in view of Yang et al. (US 2018 0327373 ; cited on IDS filed May 7, 2024) . Regarding claims 1-3, 12, 13, and 19-21, as discussed above, Yang ‘ 722 discloses a method o f detecting an amyloid peptide comprising ( i ) contacting an amyloid peptide with a compound having the structure of formula (I), thereby forming a detectable amyloid complex; and (ii) detecting said detectable amyloid complex (claim 1). Yang ‘722 discloses the compound of formula (I) in claim 1 and the compound in claim 15, which read on the compound of instant claims 1, 12, and 19, and the compound in instant claims 2 and 13. Yang ‘722 does not disclose topical administration of the compound to an eye and detection of a misfolded or aggregated protein such as ATTR. As discussed above, Yang ‘3 73 discloses a method of detecting an amyloid or amyloid like protein (claim 20). Yang ‘3 73 discloses that the compound can be administered to the eye (¶ 435). Yang ‘3 73 discloses the method can be used in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding (¶ 199), and the protein can be TTR (¶ 504). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yang ‘ 722 by administering the product to an eye and detecting a misfolded or aggregated protein such as ATT R to detect systemic amyloidosis efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Yang ‘373 teaches that misfolded or aggregated protein such as ATT R can be detected by administering the compound to an eye. Accordingly, applying the compound of Yang ‘ 373 to the method of Yang ‘ 722 constitutes no more than the predictable use of prior art elements according to their established functions. Regarding claims 4 and 14, Yang ‘722 does not disclose a type of systemic amyloidosis. As discussed above, Yang ‘ 373 discloses that the disease can be systemic amyloidosis such as FAP (¶ 501). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of Yang ‘722 to detecting systemic amyloidosis such as FAP as taught by Yang ‘3 73. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Yang ‘373 teaches systemic amyloidosis such as FAP can be detected by the method. Regarding claims 5-7, 15-18, and 22, Yang ‘722 does not disclose topical administration of the compound to an eye and the delivery of the compound to conjunctiva . As discussed above, Yang ‘373 discloses that the compounds can be administered topically to the eye as an eye drop and the compounds can be delivered to the conjunctiva of the eye (¶ 435). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yang ‘722 for topically administering the compound to an eye and delivering the compound to conjunctiva. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Yang ‘373 teaches the compounds can be administered topically to the eye and the compounds can be delivered to the conjunctiva of the eye for detecting systemic amyloidosis. Further, a person of ordinary skill in the art would have been motivated to use topical administration to the eye conjunctiva for easy, self-administered, and rapid clinical application. Accordingly, applying the teachings of Yang ‘373 to the method of Yang ‘722 constitutes no more than the predictable use of prior art elements according to their established functions. Regarding claims 8 and 9, Yang ‘ 722 do es not disclose detection by fluorescent signal. As discussed above, Yang ‘ 373 discloses that the compound can form a detectable complex in presence of an amyloid or amyloid-like protein and the detectable complex can have a fluorescent excitation peak upon irradiation with an appropriate wavelength of light (¶¶ 200-201). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yang ‘ 722 by using fluorescent signal for detecting the complex. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Yang ‘373 teaches the compound, when bound to a misfolded or aggregated protein, can be detected through its emitted fluorescent signal, upon activation by a laser light. Further, a person of ordinary skill in the art would have been motivated to use this fluorescence -based imaging technique for efficient, real-time, and specific detection of misfolded or aggregated proteins. Accordingly, applying the teachings of Yang ‘373 to the method of Yang ‘ 722 constitutes no more than the predictable use of prior art elements according to their established functions. Regarding claims 10 and 11, Yang ‘722 do es not disclose the protein is wild type or mutated. As discussed above, Yang ‘ 373 discloses that the disease can be SAA (¶ 501), which reads on a disease caused by ATTRwt (instant claim 4), and the disease can be FAP (¶ 501), which reads on a disease caused by mutations in the transthyretin gene (page 1, Background of instant specification as filed). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of Yang ‘722 for detecting the wild type or mutated misfolded or aggregated ATTR protein. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Yang ‘373 teaches wild type or mutated ATTR can be detected using the method. Further, a person of ordinary skill in the art would have been motivated to apply the detection method to wild type and mutated ATTR for broad diagnostic applications. Accordingly, applying the teachings of Yang ‘373 to the method of Yang ‘ 722 constitutes no more than the predictable use of prior art elements according to their established functions. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 1-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 19 of U.S. Patent No. US 10,370,345 ( 2019; cited on IDS filed May 7, 2024) in view of Yang et al. (US 2018 0327373 ; cited on IDS filed May 7, 2024) and Yang et al. (US 9,551,722, 2017; cited on PTO-892). Regarding claims 1- 3, 5-7 , 12, 13, and 1 5 -2 2 , claim 19 of the ‘345 recites a method for detecting an amyloid or amyloid like protein comprising ( i ) contacting a compound of formula Ic with a body part or a body area of a patient potentially comprising the amyloid or amyloid like protein; (ii) forming a detectable complex of the amyloid or amyloid like protein; and (iii) detecting the detectable complex such that the presence or absence of the detectable complex correlates with the presence or absence of the amyloid or amyloid like protein. Claims of the ‘345 do not disclose topical administ ration of the compound to an eye and detecti on a misfolded or aggregated protein such as ATTR. As discussed above, Yang ‘ 373 discloses that the compounds can be administered topically to the eye as an eye drop and the compounds can be delivered to the conjunctiva of the eye (¶ 435). As discussed above, Yang ‘3 73 discloses the method can be used in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding ( ¶ 199 ), and the protein can be TTR ( ¶ 504 ). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘345 by administering the compound to an eye and detecting a misfolded or aggregated protein such as ATTR as taught by Yang ‘3 73. Claims of the ‘345 do not disclose the identical compounds of instant claims. As discussed above, Yang ‘722 discloses the identical compounds for detecting amyloid peptides (claims 1 and 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘345 by using the compound of Yang ‘722 to detect systemic amyloidosis efficiently. Regarding claims 4 and 14, claims of the ‘345 do not disclose a type of systemic amyloidosis. As discussed above, Yang ‘ 373 discloses that the disease can be systemic amyloidosis such as FAP ( ¶ 501 ). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘345 for detecting systemic amyloidosis such as FAP as taught by Yang ‘3 73. Regarding claims 8 and 9, claims of the ‘345 do not disclose detection by fluorescent signal. As discussed above, Yang ‘ 373 discloses that the compound can form a detectable complex in presence of an amyloid or amyloid-like protein and the detectable complex can have a fluorescent excitation peak upon irradiation with an appropriate wavelength of light ( ¶¶ 200-201 ). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘345 for using fluorescent signal as taught by Yang ‘3 73. Regarding claims 10 and 11, claims of the ‘345 do not disclose the protein is wild type or mutated. As discussed above , Yang ‘ 373 discloses that the disease can be SA A ( ¶ 501 ), which reads on a disease caused by ATTRwt (instant claim 4), and the disease can be FAP (¶ 501) , which reads on a disease caused by mutations in the transthyretin gene (page 1, Background of instant specification as filed). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘345 for detecting the wild type or mutated misfolded or aggregated ATTR protein as taught by Yang ‘3 73. Claims 1-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of U.S. Patent No. US 10, 934 , 264 ( 20 21 ; cited on IDS filed May 7, 2024) in view of Yang et al. (US 2018 0327373 ; cited on IDS filed May 7, 2024) and Yang et al. (US 9,551,722, 2017; cited on PTO-892). Regarding claims 1-3, 5-7, 12, 13, and 1 5 -2 2 , claim 12 of the ‘ 264 recites a method for monitoring response to a treatment of a patient having a disease or condition characterized by amyloid deposit in a body part or a body area of the patient, the method comprising ( i ) forming a detectable complex in the body part or the body area following the treatment by contacting an effective amount of the compound with the amyloid deposit; and (ii) detecting the detectable complex, wherein a decrease of detectable complex as compared to before treatment indicates that the patient is responsive to treatment. C laims of the ‘264 do not disclose topical administration of the compound to an eye and detection a misfolded or aggregated protein such as ATTR . As discussed above, Yang ‘ 373 discloses that the compounds can be administered topically to the eye as an eye drop and the compounds can be delivered to the conjunctiva of the eye (¶ 435). As discussed above, Yang ‘3 73 discloses the method can be used in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding (¶ 199), and the protein can be TTR (¶ 504). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘264 by administering the compound to an eye and detecting a misfolded or aggregated protein such as ATTR as taught by Yang ‘3 73. Claims of the ‘264 do not disclose the identical compounds of instant claims. As discussed above, Yang ‘722 discloses the identical compounds for detecting amyloid peptides (claims 1 and 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘ 264 by using the compound of Yang ‘722 to detect systemic amyloidosis efficiently. Regarding claims 4 and 14, claims of the ‘264 do not disclose a type of systemic amyloidosis. As discussed above, Yang ‘ 373 discloses that the disease can be systemic amyloidosis such FAP (¶ 501). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘264 for detecting systemic amyloidosis such as FAP as taught by Yang ‘3 73. Regarding claims 8 and 9, claims of the ‘264 do not disclose detection by fluorescent signal. As discussed above, Yang ‘ 373 discloses that the compound can form a detectable complex in presence of an amyloid or amyloid-like protein and the detectable complex can have a fluorescent excitation peak upon irradiation with an appropriate wavelength of light (¶¶ 200-201). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘264 for using fluorescent signal as taught by Yang ‘3 73. Regarding claims 10 and 11, claims of the ‘264 do not disclose the protein is wild type or mutated. As discussed above, Yang ‘ 373 discloses that the disease can be SAA (¶ 501), which reads on a disease caused by ATTRwt (instant claim 4), and the disease can be FAP (¶ 501), which reads on a disease caused by mutations in the transthyretin gene (page 1, Background of instant specification as filed). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘264 for detecting the wild type or mutated misfolded or aggregated ATTR protein as taught by Yang ‘3 73. Claims 1-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1 and 15 of U.S. Patent No. US 9,551,722 ( 2017; cited on PTO-892 ( 20 21 ; cited on IDS filed May 7, 2024) in view of Yang et al. (US 2018 0327373 ; cited on IDS filed May 7, 2024). Regarding claims 1-3, 5-7, 12, 13, and 1 5 -2 2 , claim 1 of the ‘ 722 recites a method o f detecting an amyloid peptide, the method comprising ( i ) contacting an amyloid peptide with a compound having the structure of formula (I), thereby forming a detectable amyloid complex; and (ii) detecting said detectable amyloid complex . Claims 1 and 15 of the ‘722 recite identical compounds of instant claims. C laims of the ‘722 do not disclose topical administration of the compound to an eye and detection a misfolded or aggregated protein such as ATTR . As discussed above, Yang ‘ 373 discloses that the compounds can be administered topically to the eye as an eye drop and the compounds can be delivered to the conjunctiva of the eye (¶ 435). As discussed above, Yang ‘3 73 discloses the method can be used in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding (¶ 199), and the protein can be TTR (¶ 504). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘ 722 by administering the compound to an eye and detecting a misfolded or aggregated protein such as ATTR as taught by Yang ‘3 73. Regarding claims 4 and 14, claims of the ‘722 do not disclose a type of systemic amyloidosis. As discussed above, Yang ‘ 373 discloses that the disease can be systemic amyloidosis such as FAP (¶ 501). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘722 for detecting systemic amyloidosis such as FAP as taught by Yang ‘3 73. Regarding claims 8 and 9, claims of the ‘722 do not disclose detection by fluorescent signal. As discussed above, Yang ‘ 373 discloses that the compound can form a detectable complex in presence of an amyloid or amyloid-like protein and the detectable complex can have a fluorescent excitation peak upon irradiation with an appropriate wavelength of light (¶¶ 200-201). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘722 for using fluorescent signal as taught by Yang ‘3 73. Regarding claims 10 and 11, claims of the ‘722 do not disclose the protein is wild type or mutated. As discussed above, Yang ‘ 373 discloses that the disease can be SAA (¶ 501), which reads on a disease caused by ATTRwt (instant claim 4), and the disease can be FAP (¶ 501), which reads on a disease caused by mutations in the transthyretin gene (page 1, Background of instant specification as filed). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘722 for detecting the wild type or mutated misfolded or aggregated ATTR protein as taught by Yang ‘3 73. Claims 1-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of copending Application No. 18/214,841 (US 2024 0208916; cited on PTO-892) in view of Yang et al. (US 2018 0327373; cited on IDS filed May 7, 2024) and Yang et al. (US 9,551,722, 2017; cited on PTO-892). Regarding claims 1 -3, 12, 13, and 19-2 1 , claim 2 of the ‘841 recites a method for determining whether a subject is afflicted with systemic amyloidosis associated with misfolded or aggregated transthyretin comprising ( i ) administering to an eye of the subject a compound of Formula ( Ic ) ; and (ii) detecting the presence or absence of a complex of the misfolded or aggregated transthyretin with the compound, wherein the complex, if present, generates a detectible signal indicating that the subject is positive for the systemic amyloidosis . Claims of the ‘841 do not disclose the identical compounds of instant claims. As discussed above, Yang ‘722 discloses the identical compounds for detecting amyloid peptides (claims 1 and 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘ 841 by using the compound of Yang ‘722 to detect systemic amyloidosis efficiently. Regarding claims 4 and 14, claims of the ‘ 841 do not disclose a type of systemic amyloidosis. As discussed above, Yang ‘ 373 discloses that the disease can be systemic amyloidosis such as FAP (¶ 501). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘ 841 for detecting systemic amyloidosis such as FAP as taught by Yang ‘3 73. Regarding claims 5-7 , 15-18, and 22, claims of the ‘841 do not disclose topical administration of the compound to an eye and the compound deliver y to conjunctiva of the eye. As discussed above, Yang ‘ 373 discloses that the compounds can be administered topically to the eye as an eye drop and the compounds can be delivered to the conjunctiva of the eye (¶ 435). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘841 for topically administering the compound to an eye and delivering the compound to conjunctiva as taught by Yang ‘3 73. Regarding claims 8 and 9, claims of the ‘ 841 do not disclose detection by fluorescent signal. As discussed above, Yang ‘ 373 discloses that the compound can form a detectable complex in presence of an amyloid or amyloid-like protein and the detectable complex can have a fluorescent excitation peak upon irradiation with an appropriate wavelength of light (¶¶ 200-201). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘ 841 for using fluorescent signal as taught by Yang ‘3 73. Regarding claims 10 and 11, claims of the ‘ 841 do not disclose the protein is wild type or mutated. As discussed above, Yang ‘ 373 discloses that the disease can be SAA (¶ 501), which reads on a disease caused by misfolded or aggregated ATTRwt (instant claim 4), and the disease can be FAP (¶ 501), which reads on a disease caused by mutations in the transthyretin gene (page 1, Background of instant specification as filed). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘ 841 for detecting the wild type or mutated misfolded or aggregated ATTR protein as taught by Yang ‘3 73. This is a provisional nonstatutory double patenting rejection. Claims 1-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 2 2 and 24-27 of copending Application No. 18/579,251 (US 2024 0325572; cited on PTO-892) in view of Yang et al. (US 2018 0327373; cited on IDS filed May 7, 2024) and Yang et al. (US 9,551,722, 2017; cited on PTO-892). Regarding claims 1-3, 5-7, 12, 13, and 15-22 , claim 2 2 of the ‘ 251 recites a method for determining whether a patient has a neurological disease or disorder, comprising administering to the patient a compound . Claim 24 of the ‘ 251 recites the compound is administered to the eye of the patient. Claim 25 of the ‘ 251 recites detecting the presence or absence of binding of the compound or its parent compound with a detectable target protein . Claims of the ‘251 do not disclose topical administration of the compound to an eye and detection a misfolded or aggregated protein such as ATTR. As discussed above, Yang ‘ 373 discloses that the compounds can be administered topically to the eye as an eye drop and the compounds can be delivered to the conjunctiva of the eye (¶ 435). As discussed above, Yang ‘3 73 discloses the method can be used in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding (¶ 199), and the protein can be TTR (¶ 504). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘251 by administering the compound to an eye and detecting a misfolded or aggregated protein such as ATTR as taught by Yang ‘3 73. Claims of the ‘251 do not disclose the identical compounds of instant claims. As discussed above, Yang ‘722 discloses the identical compounds for detecting amyloid peptides (claims 1 and 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘ 251 by using the compound of Yang ‘722 to detect systemic amyloidosis efficiently. Regarding claims 4 and 14, claims of the ‘ 25 1 do not disclose a type of systemic amyloidosis. As discussed above, Yang ‘ 373 discloses that the disease can be systemic amyloidosis such as FAP (¶ 501). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘ 251 for detecting systemic amyloidosis such as FAP as taught by Yang ‘3 73. Regarding claims 8 and 9, claims 26 and 27 of the ‘ 25 1 recite the detection comprises activation of a tissue of the patient to be examined by a light thereby producing emission of a detectable signal, and detecting the detectable signal , and the detectable signal is a fluorescent signal. Regarding claims 10 and 11, claims of the ‘ 251 do not disclose the protein is wild type or mutated. As discussed above, Yang ‘ 373 discloses that the disease can be SAA (¶ 501), which reads on a disease caused by ATTRw t (instant claim 4), and the disease can be FAP (¶ 501), which reads on a disease caused by mutations in the transthyretin gene (page 1, Background of instant specification as filed). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘ 251 for detecting the wild type or mutated misfolded or aggregated ATTR protein as taught by Yang ‘3 73. This is a provisional nonstatutory double patenting rejection. Claims 1-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 28, 30, 32, and 33 of copending Application No. 19/146,892 in view of Yang et al. (US 2018 0327373; cited on IDS filed May 7, 2024) and Yang et al. (US 9,551,722, 2017; cited on PTO-892). Regarding claims 1-3, 5-7, 12, 13, and 15-22, claim 28 of the ‘892 recites a method for determining whether a patient has a neurological disease or disorder, comprising administering to the patient a compound . Claim 30 of the ‘ 892 recites the compound is administered to the eye of the patient. Claims of the ‘892 do not disclose topical administration of the compound to an eye and detection a misfolded or aggregated protein such as ATTR. As discussed above, Yang ‘ 373 discloses that the compounds can be administered topically to the eye as an eye drop and the compounds can be delivered to the conjunctiva of the eye (¶ 435). As discussed above, Yang ‘3 73 discloses the method can be used in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding (¶ 199), and the protein can be TTR (¶ 504). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘892 by administering the compound to an eye and detecting a misfolded or aggregated protein such as ATTR as taught by Yang ‘3 73. Claims of the ‘892 do not disclose the identical compounds of instant claims. As discussed above, Yang ‘722 discloses the identical compounds for detecting amyloid peptides (claims 1 and 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘ 892 by using the compound of Yang ‘722 to detect systemic amyloidosis efficiently. Regarding claims 4 and 14, claims of the ‘251 do not disclose a type of systemic amyloidosis. As discussed above, Yang ‘ 373 discloses that the disease can be systemic amyloidosis such as FAP (¶ 501). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘892 for detecting systemic amyloidosis such as FAP as taught by Yang ‘3 73. Regarding claims 8 and 9, claims 32 and 33 of the ‘892 recite t he detection comprises activation of a tissue of the patient to be examined by a light thereby producing emission of a detectable signal, and detecting the detectable signal , and the detectable signal is a fluorescent signal. Regarding claims 10 and 11, claims of the ‘251 do not disclose the protein is wild type or mutated. As discussed above, Yang ‘ 373 discloses that the disease can be SAA (¶ 501), which reads on a disease caused by ATTRwt (instant claim 4), and the disease can be FAP (¶ 501), which reads on a disease caused by mutations in the transthyretin gene (page 1, Background of instant specification as filed). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the method of the ‘251 for detecting the wild type or mutated misfolded or aggregated ATTR protein as taught by Yang ‘3 73. This is a provisional nonstatutory double patenting rejection. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JONG HWAN BAEK whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-0670 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon - Thu, 9 am - 3 pm ET . 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, FILLIN "SPE Name?" \* MERGEFORMAT Michael G Hartley can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-0616 . 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. /JONG HWAN BAEK/ Examiner, Art Unit 1618 /Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618