DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority The present application, filed December 5, 2023, is a national stage application of PCT/US2022/033610, filed June 15, 2022, and claims the benefit of U.S. provisional application 63/211362, filed June 16, 2021. Status of the Application Applicant’s preliminary amendment, received May 29, 2024, wherein claims 6, 7, 12, 13, 16 - 18, 20, 21, 23, 26, 28, 30, 32 to 40, 42, and 43 are canceled and c laims 19, 22, 25, 27, 29, 31, and 41 are amend ed, is acknowledged. Claims 1 - 5, 8 - 11, 14, 15, 19, 22, 24, 25, 27, 29, 31, 41, and 44 are pending and examined on the merits herein. Claim Rejections - 35 USC § 112 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. Claim 41 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for a method of determining the presence or absence of one or more disease or condition in a subject comprising steps (a) and (b), wherein the one or more disease or condition is associated with deposit of amyloid or amyloid-like protein , does not reasonably provide enablement for determining the presence o r absence of the full scope of diseases encompassed by claim 41. The Applicant’s attention is drawn to In re Wands , 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman , 230 USPQ 546 ( BdApls 1986) at 547 the court recited eight factors: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. Nature of the invention : The invention of claim 41 is drawn to a method of determining the presence or absence of one or more disease or condition in a subject comprising steps (a) and (b) as recited in the claim. The state of the prior art : The state of the art does not provide an expectation that the presence or absence of any disease or condition may be determined by practicing the method of claim 41. Yang (Publication no. US 20160326126 A1; cited in PTO-892) teaches molecular rotor fluorophores useful for detection of amyloid or amyloid - like proteins. Yang teaches t he fluorophores are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound (cover page, Abstract). Many of these fluorophores disclosed by Yang have chemical structure s that fall within the genus of compounds recited in present claim 1 (for example, pp. 176-178, claim 42). In addition, Yang teaches working examples showing detection of amyloid in transgenic mice that produce human beta-amyloid in tissues (p. 169, [0148]-[0150] ) , and in live animals (p. 169-170, [1051]-[1055]). However, Yang does not teach embodiments in which these compounds are used to detect proteins or other molecules or macromolecules that are not amyloid or amyloid-like protein. Therefore, on the effective filing date of the present application, one of ordinary skill in the art would have expected the method of claim 41 may be used to detect amyloid or amyloid-like protein, and thus be reasonably applied to detect diseases or conditions that show deposit of amyloid or amyloid-like protein. However, one of ordinary skill in the art would not have expected the method of claim 41 to determine the presence or absence diseases not associated with deposit of amyloid or amyloid-like protein. The relative skill of those in the art : The relative skill of those in the art is high. The predictability or unpredictability of the art : The lack of prior art disclosing a method to determine the presence or absence of any disease or condition in a subject means that one skilled in the art cannot predict the usefulness of such a method . In addition, in view of the working examples disclosed by Yang and discussed above, one of ordinary sk ill in the art would have expected that diseases associated by deposit of amyloid or amyloid-like protein may be detected by the method of claim 41. However, one of ordinary skill in the art would have found a claim that the method of claim 41 may effectively determine the presence of absence of diseases or conditions not associated with deposit of amyloid or amyloid-like protein to be unpredictable. Therefore , the invention of claim 41 is unpredictable. The breadth of the claims : The scope of claim 41 includes a method of determining the presence or absence of one or more disease or condition in a subject comprising steps (a) and (b) recited in the claim . In this instance, the scope of disease s or condition s encompassed by the claim is extremely broad and would reasonably include any disease or condition that may have an effect on a subject. The amount of direction or guidance presented : The specification provides that amyloid plaque accumulation is the hallmark of many neurodegenerative disorders, and a pproaches to clinically diagnose and monitor the progression of these diseases include targeting of amyloid deposits with small - molecule imaging agents. The specification provides that fluorescence-based small molecule imaging of amyloids is a low cost, accessible, and non-radioactive technique for to detection of the amyloid deposits . The specification states that f luorescent compounds that maintain their brightness, spectroscopic properties, and specificity for binding amyloids in neuronal tissue, and exhibit superior chemical/hydrolytic stability in physiologically relevant solutions are disclosed in the present invention (p. 1, [0003]). Therefore, the specification provides guidance for detecting amyloid and amyloid-like proteins, which are associated with many neurodegenerative disorders. However, the specification does not provide guidance that would provide enablement for detecting diseases not associated with deposit of amyloid or amyloid like protein. The presence or absence of working examples : The specification provides working examples that are all directed to evaluating these compounds’ affinity for amyloid proteins and their fluorescent properties when bound to amyloid proteins in compositions and in tissue samples (e.g., see the examples on pp. 150-155, [0540]-[ 0561]). The specification does not provide working examples for detecting other molecular markers, such as those associated with diseases that do not exhibit of deposit of amyloid or amyloid-like protein. Note that a lack of working examples is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art such as determining the presence or absence of any disease or condition in a subject using the method of claim 41. The quantity of experimentation required : In order to practice the invention of the method of claim 41 with full scope of diseases or conditions , one of ordinary skill in the art would be required to undertake a novel and extensive research program to show that said method may detect molecular markers associated with diseases that do not show deposit of amyloid or amyloid-like protein. Because this research would need to be exhaustive, and because different disease and conditions would be expected to require detection of unique molecular markers with different chemical and biochemical properties in different tissue types, it would constitute an undue and unpredictable search burden. Genentech, 108 F.3d at 1366, sates that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.” Therefore, in view of the Wands factors, as discussed above, particularly the breadth of the claims and the nature of the invention, Applicants fail to provide information sufficient to practice the method of claim 41 with the full scope of diseases and conditions. Claims 1-5, 8-11, 14, 15, 27, 29, 31, 41, and 44 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. Claim 1 claims a compound having the formula ( Ia ) or ( IIa ) as shown in the claim, wherein variable group WSG is defined as a water soluble group. Claims 2-5, 8-11, 14, 15, 27, 29, 31, 41, and 44 depend from claim 1 and claim the same scope of water-soluble group recited in claim 1. The scope of water-soluble group recited in present claim 1 encompasses an infinite number of chemical groups that exhibit solubility in water. In addition, water solubility is not correlated with any particular structural featur e, but is rather a characteristic of an arbitrarily large number of unrelated structural features which are not necessarily related to the disclosed function of these compounds. Therefore, these claims are drawn to a broad genus of compounds with significant structural variation . Th is full genus of compounds is not adequately described in the specification or claims as originally filed in such a way as to reasonably convey to one skilled in the art that the inventor, at the time the application was filed, had possession of all or even most of the claimed compounds. MPEP 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species . Additionally, MPEP 2163 states that the written description requirement for a claimed genus may be satisfied through reduction to drawings or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. The examiner directs Applicant’s attention to MPEP 2163 , which states: 1. A laundry list of groups does not provide written description for every species: “ Fujikawa v. Wattanasin , 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a “laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species);” 2. In an unpredictable art such as synthetic organic chemistry, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species. A representative number of species for each genus is: “ What constitutes a “representative number” is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a “representative number” depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly.” 3. A representative number of species within a genus with substantial variation must have a sufficient variety of species to reflect the genus: “ A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.” MPEP 2163.04 states that when rejecting a claim as failing to meet the written description requirement, the rejection must: (A) Identify the claim limitation(s) at issue; and (B) Establish a prima facie case by providing reasons why a person skilled in the art at the time the application was filed would not have recognized that the inventor was in possession of the invention as claimed in view of the disclosure of the application as filed. A general allegation of “unpredictability in the art” is not a sufficient reason to support a rejection for lack of adequate written description. A simple statement such as “Applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘____’ in the application as filed.” may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported. See Hyatt v. Dudas , 492 F.3d 1365, 1370, 83 USPQ2d 1373, 1376 (Fed. Cir. 2007) (holding that “ [MPEP] § 2163.04 [subsection] (I)(B) as written is a lawful formulation of the prima facie standard for a lack of written description rejection.”). The instant claims have been considered as follows: (A) The limitations lacking adequate description are: All groups described in claim 1 represented by WSG except for the WSG groups recited in embodiments 17-26 of the instant specification (pp. 123-124, [0421]-[0431]). (B) A person of ordinary skill in the art would not have recognized that the inventor had possession of all the compounds having the groups described in (A) in view of the instant specification. First, the variables of (A) cause WSG to encompass a n infinite number of widely variant species with the disclosure of WSG as a water-soluble group. The examiner notes that no reduction to drawings, disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or a combination of such identifying characteristics has been provided in the instant specification for the scope of water soluble groups as presently claimed. The specification only discloses synthetic guidance for compounds wherein the water soluble group is a polyalkylene group . The disclosure provides no convincing description that Applicant made and used any of the infinite number of claimed species which have no representative species in the instant disclosure , and the specific ation does not address inherent difficulties during synthesis and work-up of chemically complex water soluble groups , such as large polyalkylene polymers, polysaccharides, specific protein species, nucleic acids, or complex heterocycles. In conclusion, the genus of compounds encompassed by claim 1 include an infinite number of WSG groups. The limited scope of disclosure of WSG groups fail s to have adequate written description which would convince one of ordinary skill in the art that the inventor had possession of all the claimed compounds at the time of invention. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant [inventor] has invented the subject matter which is claimed." In re Barker , 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977) (see MPEP 2163 I). In addition, "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee [inventor] was in possession of the invention that is claimed." (see MPEP 2163(I)). This rejection may be overcome by amending or canceling claims such that the scope of the WSG is as encompassed by embodiments 17-26 of the instant specification (pp. 123-124, [0421]-[0431]). The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 8 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 8 depends from claim 2 and requires R 3 , R 4 , R 5 , and R 6 are hydrogen. However, claim 2 depends from claim 1 and requires the structure of formula ( Ia ), which does not include variable groups R 3 , R 5 , and R 6 . Therefore, claim 8 fails to include all the limitations of the claim upon which it depends . The examiner notes that requiring R 3 , R 5 , and R 6 as hydrogen effectively converts the structure of formula IIa into a structure of formula Ia , which is already required in claim 2. If the claim 8 is intended to limit R 4 , then requiring only R 4 as hydrogen would overcome this rejection. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 102 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims 1-5, 8-11, 14, 15, 19, 22, 25, 27, 29, 31, 41, and 44 are rejected under 35 U.S.C. 102 FILLIN "Insert either \“(a)(1)\” or \“(a)(2)\” or both. If paragraph (a)(2) of 35 U.S.C. 102 is applicable, use form paragraph 7.15.01.aia, 7.15.02.aia or 7.15.03.aia where applicable." \d "[ 2 ]" (a)(1) and 35 U.S.C. 102(a)(2) as being FILLIN "Insert either—clearly anticipated—or—anticipated—with an explanation at the end of the paragraph." \d "[ 3 ]" anticipated by Yang (Publication no. U S 20160326126 A1 ; cited in PTO-892). Yang teaches and claims the compound shown below (p. 174 , claim 40, fourth structure shown ). This compound has the structure of formula ( Ia ) with W 1 as C(R 4 ) 2 , with R 1 , R 2 , and R 4 each as hydrogen , and with WSG as the first structure shown in claim 19. In addition, this compound has the structure of formula ( IIa ), with W 1 as C(R 4 ) 2 , with R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 each as hydrogen , and with WSG as the first structure shown in claim 19. This compound satisfies all limitations of claims 1-5, 8-10, 14, 15, and 19. Yang also teaches and claims the compound shown below (p. 174, claim 40, sixth structure shown). This compound has the structure of formula ( Ia ), with W 1 as N(R 14 ), with R 1 and R 2 as hydrogen, with R 14 as C 1 alkyl, and with WSG as the first structure shown in claim 19. In addition , This compound has the structure of formula ( IIa ), with W 1 as N(R 14 ), with R 1 , R 2 , R 3 , R 5 , and R 6 as hydrogen, with R 14 as C 1 alkyl, and with WSG as the first structure shown in claim 19. This compound satisfies all limitations of claims 1, 2, 4, 5, 9, and 19. Yang teaches and claims the compound shown below (p. 176 , claim 42, fifth structure shown ). This compound has the structure of formula ( Ia ) with W 1 as C(R 4 ) 2 , with R 1 , R 2 , and R 4 as hydrogen, and with WSG as the first structure shown in claim 22. In addition, this compound has the structure of formula ( IIa ) with W 1 as C(R 4 ) 2 , with R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 as hydrogen, and with WSG as the first structure shown in claim 22. This compound satisfies all limitations of claims 1-5, 8-10, 14, 15, and 22. Yang teaches and claims the compound shown below (p. 177, third structure shown, part of claim 42). This compound has the structure of formula ( Ia ) with W 1 as C(R 4 ) 2 , with R 1 , R 2 , and R 4 as hydrogen, and with WSG as the first structure shown in claim 25. In addition, this compound has the structure of formula ( IIa ), with W 1 as C(R 4 ) 2 , with R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 as hydrogen, and with WSG as the first structure shown in claim 25. This compound satisfies all limitations of claims 1-5, 8-10, 14, 15, and 25 . As a final example , Yang teaches and claims the compound shown below (p. 17 8 , first structure shown, part of claim 42). This compound has the structure of formula ( Ia ) with W 1 as C(R 4 ) 2 , with R 1 as unsubstituted C 1 alkyl, with R 2 and R 4 as hydrogen, and with WSG as the first structure shown in claim 25. In addition, this compound has the structure of formula ( IIa ), with W 1 as C(R 4 ) 2 , with R 1 as unsubstituted C 1 alkyl, with R 2 , R 3 , R 4 , R 5 , and R 6 as hydrogen, and with WSG as the first structure shown in claim 25. This compound satisfies all limitations of claims 1- 3, 5, 8-1 1 , 14, 15, and 25 . In addition, Yang teaches and claims a pharmaceutical composition comprising a compound according to claim 1 (p. 178, claim 92) , which would include the compounds above, and further claims the composition comprising one or more pharmaceutically acceptable additive s , carrier s or excipient s selected from the group listed therein (p. 178, claim 93). Therefore, Yang anticipates claim 27. Yang teaches that the ir disclosure further provides a composition comprising a compound according the disclo s ure (Formula I or II) , which would include the compounds above, and an amyloid or amyloid like protein (pp. 23-24, [0155], lines 1-4 ). Therefore, Yang anticipates claim 29. Yang teaches a method a method of detecting an amyloid or amyloid like protein comprising: a) contacting a compound according to any one of embodiments Pl-P66 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 b) 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 (p. 131, [0695]). Embodiment P23 includes the compound below (p. 119, [0642], fourth structure), which as discussed above, satisfies all limitations of claim 1. Therefore, Yang anticipates claim 31. Finally, Yang teaches a method of determining the presence or absence of one or more disease or condition in a subject comprising: a) administering to the subject an effective amount of a compound according to any one of embodiments Pl-P66 or a pharmaceutical composition thereof, wherein in presence of the disease or condition the administered compound forms a detectable complex; and b) detecting the formation of the detectable complex such that presence or absence of detectable complex correlates with the presence or absence of the disease or condition (p. 132, Embodiment P83, [0705]). Yang further teaches this method may be applied to a disease or condition that is Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), Lewy body dementia (LBD), or Down's syndrome (p. 132, Embodiment P86, [0708]). As stated above, Embodiment P23, as one example, includes a compound that satisfies all limitations of claim 1. Therefore, Yang anticipates claims 41 and 44 . Thus Yang anticipates claims 1-5, 8-11, 14, 15, 19, 22, 25, 27, 29, 31, 41, and 44. C laim 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 . Claims 1 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Yang (Publication no. U S 20160326126 A1 ; cited in PTO-892). Claim 24 depends from claim 1 and requires WSG is -(unsubstituted - C 1 -C 10 alkyl)-R 33 -R 37 , wherein R 33 is u nsubstituted 5 to 10 membered heteroarylene ; and R 37 is -(unsubstituted C 1 -C 6 alkyl)- ( unsubstituted 5 to 10 membered heterocycloalkyl ). Yang teaches as described in the above rejection under 35 U.S.C. § 102. In addition, Yang teaches embodiment 21, which requires the WSG is -(C 1 -C 10 alkyl)-R 33 -R 37 , wherein R 33 is C 1 -C 10 heteroarylene ; an d R 37 is -(C 1 -C 6 alkyl)(C 1 -C 10 heretocycloalkyl ) (p. 136, [0770]), Yang further teaches the WSG as the structure of embodiment 25 (p. 136, [0774]; structure shown below), which satisfies all limitations of the WSG of embodiment 21. Finally, Yang teaches the structure shown below (p. 178, fourth structure, part of claim 42). This structure has the WSG as –(unsubstituted C 1 alkyl)-(5-membered heteroarylene )- (unsubstituted C 1 alkyl)-(6-membered heterocycloalkyl ) . This structure also satisfies the requirements of the WSG of embodiment 21 of Yang described above. Yang further defines the terms "cycloalkyl" and " heterocycloalkyl ," by themselves or in combination with other terms, represent, unless otherwise stated, cyclic versions of "alkyl" and " heteroalkyl ", respectively (p. 26, [205], lines 1-4). Yang additionally teaches that the substituent groups they define in their specification, e.g., "alkyl," " heteroalkyl ," "aryl" and "heteroaryl" , are meant to include both substituted and unsubstituted forms of the indicated radical (p. 27, [0212], lines 1-3) (emphasis added). Yang does not teach a specific compound with WSG as required by claim 24, specifically with R 37 as unsubstituted 5 to 10 membered heterocycloalkyl . It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to modify the above compound claimed by Yang, which satisfies the WSG of embodiment 21, by substituting the substituted heterocycloalkyl group of said compound for an unsubstituted heterocycloalkyl group. One of ordinary skill in the art would have been motivated to modify the above comp ound claimed by Yang by substituting the substituted heterocycloalkyl group of said compound for an unsubstituted heterocycloalkyl group, because Yang teaches the compound above, which satisfies all requirements of claim 24 except R 37 as unsubstituted to 10 membered heterocycloalkyl group, teaches an embodiment wherein WSG is -(C 1 -C 10 alkyl)-R 33 -R 37 , wherein R 33 is C 1 -C 10 heteroarylene ; and R 37 is -(C 1 -C 6 alkyl)(C 1 -C 10 heretocycloalkyl ) , and further teaches that the term heterocycloalkyl is intended to embrace substituted and unsubstituted forms of said functional group. Accordingly, in view of embodiment 21 of Yang, one of ordinary skill in the art would have considered the full scope of heterocycloalkyl groups at position R 37 , including both 6-membered substituted heterocycloalkyl group s and 6-membered unsubstituted heterocycloalkyl group s , because each of these groups is suggested by embodiment 21 and Yang’s definitions of substituent groups, and because the resulting derivative may be effective when practicing the methods of detecting amyloid or amyloid-like protein disclosed by Yang. Therefore the invention taken as a whole is prima facie obvious. 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 1-5, 8-11, 14, 15, 19, 22, 25 , and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 13, 14 , 18, 19, and 22 of U.S. Patent No. 10 , 005 , 745 (reference patent, hereinafter ‘ 745 ; cited in PTO-892 ). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘ 745 anticipate the claimed invention. The present application and ‘745 each include Jerry Yang as an inventor. Claim 13 of ‘745 claims the compound shown below. This compound is discussed in the above rejection under 35 U.S.C. § 102 and satisfies all limitations of claims 1-5, 8-10, 14, 15, and 19 . Claim 14 of ‘745 claims the compound shown below. This compound is discussed in the above rejection under 35 U.S.C. § 102 and satisfies all limitations of claims 1-5, 8-10, 14, 15, and 25. Claim 22 of ‘745 claims the compound shown below. This compound is discussed in the above rejection under 35 U.S.C. § 102 and satisfies all limitations of claims 1-5, 8-10, 14, 15, and 22. Claim 22 of ‘745 also claims the compound shown below. This compound is discussed in the above rejection under 35 U.S.C. § 102 and satisfies all limitations of claims 1- 3, 5, 8-1 1 , 14, 15, and 25. Claim 18 of ‘745 claims a pharmaceutical composition comprising a compound according to claim 1 , which encompasses the above compounds, and claim 19 claims the pharmaceutical composition further comprising one or more pharmaceutically acceptable additive, carrier, or excipient selected from the group recited in the claim. Claims 1, 24, 29, 31, 41, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, FILLIN "Pluralize \“Claim\” if necessary, and insert the claim number(s) of the U.S. Patent." 1 4, 18, 19, and 22 of U.S. Patent No. 10 , 005 , 745 (reference patent, hereinafter ‘745 ; cited in PTO-892 ) in view of Yang (Publication no. U S 20160326126 A1 ; cited in PTO-892). Claims 13, 14 , 18, 19, and 22 of ‘ 745 claim as described in the above nonstatutory double patenting rejection. Claims 13, 14 , 18, 19, and 22 of ‘745 do not claim the WSG of present claim 24, the composition of present claim 29 , or the methods of present claims 31, 41, and 44. Yang teaches as described in the above rejection under 35 U.S.C. § 102 and 35 U.S.C. § 103. It would therefore have been prima facie obvious to modify the compound s of claim s 13, 14, or 22 and substitute their water soluble groups for the water soluble group of present claim 24, because Yang teaches each of the water soluble groups shown in the compounds of claims 13, 14, and 22 above, Yang renders obvious alternative water soluble groups, including the water soluble group of present claim 24, and Yang teaches these compounds as used in methods for detecting amyloid and amyloid-associated diseases. Accordingly, one of ordinary skill in the art would have considered the compounds claimed by ‘745 with alternative water soluble groups disclosed in the prior art, including the group of present claim 24, because said compounds may be useful for the purposes of detecting amyloid associated diseases. Moreover, it would have been prima facie obvious to use the compounds claimed by ‘745 when practicing the methods of detecting amyloid in a solution and detecting amyloid-associated diseases taught by Yang , because the compounds claimed by ‘745 are the same compounds disclosed by Yang that may be used when practicing the methods taught by Yang and recited in in present claims 31, 41, and 44 . Such methods would also require the composition comprising amyloid and a compound of present claim 1, as recited in claim 29 . Claims 1-5, 8-11, 14, 15, 19, 22, 25, 29 , and 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 13, and 14 of U.S. Patent No. 10,370,345 (reference patent, hereinafter ‘345 ; cited in PTO-892 ). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘345 anticipate the claimed invention. The present application and ‘345 each include Jerry Yang as an inventor. Claim 1 of ‘345 claims 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, comprising: ( i ) forming a detectable complex in the body part or the body area following the treatment by contacting an effective amount of a compound of Formula Ic , or a salt or solvate thereof, or a pharmaceutical composition thereof, with the amyloid deposit; and (ii) detecting the detectable complex, wherein a decrease of detectable complex as compared to before the treatment indicates that the patient is responsive to the treatment; wherein the compound of Formula Ic has the structure as shown. Claim 13 of ‘345 claims the compound of Formula Ic is selected from a group that includes the structure shown below. Claim 14 of ‘345 claims the compound of Formula Ic is selected from a group that includes the structures shown below. These compounds are discussed in the above rejection under 35 U.S.C. § 102 and satisfy all limitations of claims 1-5, 8-11, 14, 15, 19, 22, and 25 . In addition, t he method of claim 1 of ‘345, when practiced with a compound of claim 13 or 14 of ‘345 , would anticipate the method of present claim 31. In this instance, the presence or absence of the detectable complex correlates with the step of determining the change in amount of detectable complex when practicing the method of claim 1 of ‘345. Finally, practicing the method of claim 1 of ‘345 with a compound of claim 13 or 14 would anticipate the composition of present claim 29 , because these compounds would form a composition with an amyloid deposit . Claims 1, 24, 2 7 , 31, 41, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 13, and 14 of U.S. Patent No. 10,370,345 (reference patent, hereinafter ‘345 ; cited in PTO-892 ) in view of Yang (Publication no. U S 20160326126 A1 ; cited in PTO-892). The examiner asserts that claim 31 is anticipated by the claims of ‘345. However, claim 31 would also be obvious over the claims of ‘345 in view of Yang. Claims 1, 13, and 14 of ‘345 claim as described in the above nonstatutory double patenting rejection. Claims 1, 13, and 14 do not claim the WSG of present claim 24, the composition of present claim 27, or the methods of present claims 31, 41, and 44. Yang teaches as described in the above rejection under 35 U.S.C. § 102 and 35 U.S.C. § 103. It would therefore have been prima facie obvious to modify the compounds of claims 13 or 14 and substitute their water soluble groups for the water soluble group of present claim 24, because Yang teaches the water soluble groups shown in the compounds of claims 13 and 14 above, Yang renders obvious alternative water soluble groups, including the water soluble group of present claim 24, and Yang teaches these compounds as used in methods for detecting amyloid and amyloid-associated diseases. Accordingly, one of ordinary skill in the art would have considered the compounds claimed for use in the methods of ‘345 with alternative water soluble groups disclosed in the prior art, such as those groups disclosed by Yang, because said compounds may also be useful for the purposes of detecting amyloid and amyloid-associated diseases. Moreover, it would have been prima facie obvious to use the compounds claimed by ‘ 345 when practicing the methods of detecting amyloid in a solution and detecting amyloid-associated diseases taught by Yang, because the compounds claimed by ‘ 345 are the same compounds disclosed by Yang that may be used when practicing the methods taught by Yang and recited in in present claims 31, 41, and 44. Finally, because Yang discloses pharmaceutical compositions comprising their compounds, which are the same compounds claimed by ‘345, and pharmaceutically acceptable excipient s, one of ordinary skill in the art would have contemplated the pharmaceutical composition of present claim 29. Claims 1-5, 8-1 0 , 14, 15 , 25 , and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim FILLIN "Pluralize \“Claim\” if necessary, and insert the claim number(s) of the U.S. Patent." 1 8 of U.S. Patent No. 10 , 934 , 264 (reference patent, hereinafter ‘264 ; cited in PTO-892 ). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘264 anticipate the claimed invention. The present application and ‘264 each include Jerry Yang as an inventor. Claim 18 of ‘264 claims a method for monitoring the response of a patient having a disease or condition characterized by amyloid deposit to a treatment, the method comprising ( i ) forming a detectable complex following the treatment by contacting an effective amount of a compound of the formula: (ii) detecting the formation of the detectable complex, wherein a decrease of detectable complex as compared to before the treatment indicates that the patient is responsive to the treatment; wherein the disease or condition is selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Lewy body dementia, Down's syndrome, and Creutzfeldt-Jakob disease. The compound of claim 18 is discussed in the above rejection under 35 U.S.C. § 102 and satisfies all limitations of claims 1-5, 8-10, 14, 15, and 25. Moreover, practicing the method of claim 18 of ‘264 would necessarily require formation of a composition of present claim 29. Claims 1-5, 8-1 1 , 14, 15, 19, 22, 27, 29, 31, 41, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 18 and 19 of U.S. Patent No. 10 , 934 , 264 (reference patent, hereinafter ‘264 ; cited in PTO-892 ) in view of Yang (Publication no. U S 20160326126 A1 ; cited in PTO-892). The present application and ‘264 each include Jerry Yang as an inventor. Claim 18 of ‘264 claims as described in the above nonstatutory double patenting rejection. Claim 19 of ‘264 claims a method of detecting an amyloid or amyloid like protein, the method comprising ( i ) contacting the compound of formula ( Ic ), a pharmaceutically acceptable salt thereof, or a solvate thereof 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; wherein the compound of Formula ( Ic ) is as defined in claim 19, with R 84 as hydrogen or C 1-10 alkyl and the WSG as shown in claim 19. Yang teaches as described in the above rejection under 35 U.S.C. § 102 and 35 U.S.C. § 103. It would therefore have been prima facie obvious to modify the compound for use in the method of claim 18 with the alternative WSG groups shown in claim 19 or the alternative R 84 groups of claim 19, because each of the compounds of claims 18 and 19 are useful for the purposes of detecting amyloid or amyloid-like protein, and thus one of ordinary skill in the art would have recognized the above modifications would produce a compound that may be used when practicing the method of claims 18 and 19. Such a compound would satisfy all limitations of present claims 1-5, 8-11, 14, 15, 19, and 22. Moreover, it would have been prima facie obvious to modify the compounds claimed by claim 18 of ‘264 by substituting their water soluble groups for the water soluble group of present claim 24, because Yang teaches the compound of claim 18 of ‘264, Yang renders obvious alternative water soluble groups for this compound , including the water soluble group of present claim 24, and each of claim 18 of ‘264 and Yang recognize these compounds as used in methods for detecting amyloid and amyloid-associated diseases. Accordingly, one of ordinary skill in the art would have considered the compounds claimed by ‘ 264 with alternative water soluble groups disclosed in the prior art, such as those disclosed by Yang, because said compounds may also be useful for the purposes of detecting amyloid associated diseases in the methods taught by Yang and claimed by ‘264. In addition, i t would have been prima facie obvious to prepare the composition of present claims 27 in view of ‘ 264 claiming the compounds for use in the method of clai ms 18 and 19, which involves detecting amyloid, and Yang teaching the same compounds for detecting amyloid and the formulations of these compounds with pharmaceutically acceptable excipients, as required by present claims 27 . Finally, it would have been prima facie obvious to practice the methods of claims 31, 41, and 44 in view of ‘264 claiming the compounds for use in the method of claim s 18 and 19, which involves detecting amyloid, and Yang teaching the same methods of claims 31, 41, and 44 using the compounds disclosed by ‘264. Claims 1-5, 8-11, 14, 15, 19, 25 , and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s FILLIN "Pluralize \“Claim\” if necessary, and insert the claim number(s) of the U.S. Patent." 1 , 12-17, and 20 of U.S. Patent No. 11,718,596 (reference patent, hereinafter ‘596 ; cited in PTO-892 ). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘596 anticipate the claimed invention. The present application and ‘596 each include Jerry Yang as an inventor. Claim 1 of ‘596 claims a compound of Formula ( Ie ) as shown in the claim. Claim 12 of ‘596 depends from claim 1 and claims Ar is and EDG is . Claims 13-15 further narrow the EDG and WSG, and claim 16 requires the WSG is . C laim 17 claims wherein R 84 is optionally substituted C 1 -C 4 alkyl. Finally, claim 20 of ‘596 claims a pharmaceutical composition comprising a compound of according to claim 1 and a pharmaceutically acceptable carrier . The compound and composition claimed by claims 1, 12-17, and 20 of ‘596 satisfies all limitations of present claims 1-5, 8-11, 14, 15, 19, 25, and 27. Claims 1, 22, 24, 29, 31, 41, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims FILLIN "Pluralize \“Claim\” if necessary, and insert the claim number(s) of the U.S. Patent." 1 , 12-17, and 20 of U.S. Patent No. 11,718,596 (reference patent, hereinafter ‘596 ; cited in PTO-892 ) in view of Yang (Publication no. US 20160326126 A1; cited in PTO-892). The present application and ‘596 each include Jerry Yang as an inventor. Claims FILLIN "Pluralize \“Claim\” if necessary, and insert the claim number(s) of the U.S. Patent." 1 , 12-17, and 20 of ‘596 claim as described in the above nonstatutory double patenting rejection. Claims FILLIN "Pluralize \“Claim\” if necessary, and insert the claim number(s) of the U.S. Patent." 1 , 12-17, and 20 of ‘596 do not claim the WSG of present claim s 22 and 24, the composition of present claim 29, or the methods of present claims 31, 41, and 44. Yang teaches as described in the above rejection under 35 U.S.C. § 102 and 35 U.S.C. § 103. It would therefore have been prima facie obvious to modify the compounds recited by claims 1 and 12-17 of ‘596 by substituting the water soluble groups for the water soluble group of present claim s 22 and 24, because Yang teaches compounds that satisfy the limitations of claims 1 and 12-17 of ‘596, Yang renders obvious alternative water soluble groups for said compounds, including the water soluble group of present claim s 22 and 24, and Yang teaches these compounds as used in methods for detecting