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 .
Election/Restrictions
Applicant’s election without traverse of Invention 1, claims 1-4, 8-10, 13-15, and 19-20, in the reply filed on September 24, 2026 is acknowledged.
Claims 5-7, 11-12, and 16-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 24, 2026.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Status of Claims
Claims 1-20 are pending.
Claims 5-7, 11-12, and 16-18 have been withdrawn from consideration.
Claims 1-4, 8-10, 13-15, and 19-20 are under examination.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on January 23, 2024 (Application No. 202410088933.4). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Acknowledgment is made of applicant's claim for foreign priority based on a PCT application filed on February 2, 2024. It is noted, however, that applicant has not filed a certified copy of the PCT/CN2024/075367 application as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement filed June 20, 2024 is acknowledged and has been considered by the examiner.
Specification
The use of the term "Pluronic® F-127,” which is 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.
Claim Objections
Claim 9 is objected to because of the following informalities:
Claim 9 lists a series of chemical structure names as options for the organic coating agent in the claimed nanoparticle. As many of the chemical structure names include commas in the names, such items should be separated by semicolons so a reader can better discern where the structure name starts and ends.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8-10 and 19-20 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.
Claim 8 recites “a fluorescent probe coated nanoparticle.” Claim 8 further requires an organic coating agent that coats the surface of the fluorescent probe. The examiner notes that the typical meaning of the phrase “a fluorescent probe coated nanoparticle” on its own is that there is a nanoparticle coated with fluorescent probes on the exterior surface of the nanoparticle. However, the latter clause in claim 8 requires an organic coating agent coating the fluorescent probe, which requires the fluorescent probe to not be on the outer surface of the nanoparticle and instead have a coating material surrounding it. The terminology of “coating agent” suggests this organic material is on the surface of the nanoparticle. Therefore, the scope of this claim is rendered indefinite because it is not clear whether the claimed nanoparticle is decorated with fluorescent probes on the exterior surface or if the nanoparticle has an exterior shell of the organic coating agent. For the purpose of examination, the examiner will interpret the organic coating agent to be the exterior surface of the nanoparticle, as this is required in the structural limitation of the latter half of the claim. Furthermore, as claims 9-10 and 19-20 depend upon claim 8 and fail to further define this feature, these claims are rejected due to this dependence.
Claim 9 contains the trademark/trade name "Pluronic.” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the and, accordingly, the identification/description is indefinite. For the purpose of examination, the examiner will interpret the scope of this option in the list to be equivalent to that of poloxamer 407.
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 1-4, 8-10, 13-15, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Huang (Li, M.; et al., Adv. Mater., 2023) in view of Peng (Xu, X.; et al., Adv. Funct. Mater., 2020), Yin (Li, Y.; et al., Polym. Chem., 2023), and Lee (Lee, K. W.; et al., Adv. Mater., 2023).
Huang teaches a NIR-II fluorophore, nanoparticles comprising the fluorophore, and its use in bioimaging (pg. 1, Abstract). More specifically, Huang teaches the fluorescent probe AS1 (pg. 3, Figure 1a). Huang teaches that AS1 is a NIR-II emitting probe (Figure 1e). Huang teaches forming nanoparticles with AS1 in the core and a shell of DSPE-PEG (Figure 1c). Huang teaches that the fluorescent nanoparticles emit in the NIR-II range (pg. 4, Figures 2b, 2f, and 2i). Huang teaches the use of the fluorescent probe loaded nanoparticles in fluorescence imaging in cells (pg. 8, Figure 5) and in vivo imaging in mice (pg. 10, Figure 6).
Huang does not teach a fluorescent probe having a structure represented by formula I of instant claim 1.
Peng teaches near infrared absorbing organic small molecules (pg. 1, Abstract). One near infrared absorbing molecule of Peng is Y6 (pg. 2, Figure 1a). Peng also teaches a modified version of Y6, termed Y6-T (pg. 2, Figure 1a) wherein the 2FIC ending groups of Y6 were substituted to CPTCN groups (pg. 2, left column, paragraph 3). Peng teaches that the CPTCN group is less electron withdrawing, which increased the levels of the HOMO/LUMO of the NIR absorbing molecule (pg. 2, left column, paragraph 3). Peng teaches that both Y6 and Y6-T are suitable for use in non-fullerene polymeric solar cells (pg. 7, Conclusion).
Yin teaches NIR-II fluorescent probes and their use in nanoparticles for bioimaging applications (pg. 3008, Abstract). More specifically, Yin teaches BTP-2TCID, BTP-4CN, and BTP-TCID-2CN (pg. 3009, Scheme 1). Yin teaches that such molecules have an A-D-A’-D-A structure of donors and acceptors with a ladder-type BTP core (pg. 3009, left column, paragraph 3). Yin teaches that the three structures differ in the terminal electron withdrawing acceptor groups (pg. 3009, right column, paragraph 1; and Scheme 1). Yin teaches that these fluorophores emit light in the NIR-II range (pg. 3010, Figure 1c). Yin also teaches forming nanoparticles with the fluorescent probes and coating them with the organic coating Pluronic® F-127 (poloxamer 407) (Scheme 1; and pg. 3010, right column, paragraph 2). Yin teaches administering the nanoparticles to mice and performing fluorescence imaging (pg. 3015, Figure 5).
Lee teaches that organic optoelectronic materials are being explored and used for biomedical applications including imaging and phototherapies (pg. 1, Abstract). Lee teaches that organic optoelectronic device research, such as organic solar cells, has been undergoing speedy development (pg. 1, left column, paragraph 1). Lee teaches that organic optoelectronic materials often have good light-harvesting ability, bright fluorescence, and low cytotoxicity (pg. 1, right column, paragraph 1). Lee teaches that since 2014, organic optoelectronic materials have shown rapid development for biomedical applications (pg. 1, right column, paragraph 3). Lee teaches that such organic optoelectronic materials can be assembled into nanoparticles by coating them with an amphiphilic polymer (pg. 5, Figure 4a). Lee teaches several examples of the use of organic optoelectronic materials being used in biomedical applications, including Y6 (pg. 3, Table 1; pg. 10, Figure 8a). Lee summarizes that Y6 has been prepared in nanoparticles using DSPE-PEG (pg. 10, section 4.2.2). Lee teaches that similar classes of molecules are used for fluorescence imaging applications, similarly involving DSPE-PEG nanoparticles (pg. 11, Section 4.2.3). Lee concludes that organic optoelectronic materials have great application potential in biomedicine (pg. 20, left column, last paragraph).
A person of ordinary skill in the art would recognize that each of Huang, Peng, and Yin teach organic molecules that absorb near infrared light having similar core donor or donor-acceptor-donor structures that only vary in the end electron withdrawing groups. While Peng describes the Y6 and Y6-T molecules in the context of organic solar cells, it would be recognized that Lee teaches that organic optoelectronic materials, such as those used in organic solar cells, have utility in biomedical applications. Indeed, the Y6 of Peng is identical in structure to the AS1 of Huang. It would also be recognized that Yin demonstrates that the terminal acceptor groups can be asymmetric on these fluorescent probes, with each end having a different structure.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the AS1 fluorescent probe of Huang by substituting one of the difluoro terminal electron withdrawing acceptor groups with the thiophene-containing CPTCN end group of Y6-T of Peng because this group serves the same purpose in this class of molecules and because Yin teaches that such probes can have asymmetric terminal groups and Lee teaches that molecules from organic optoelectronics should be applied to biomedical applications (MPEP § 2143(I)(B) and 2143(I)(G)). This combination would have predictably yielded the compound of formula I-b of the instant application.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this modification because Peng teaches that Y6-T is a derivative of Y6 (the examiner notes that Y6 of Peng and AS1 of Huang have the same structure) and demonstrates that the 2FIC and CPTCN end groups are interchangeable (pg. 2, left column, paragraph 3; and Figure 1a). Additionally, Yin demonstrates the feasibility of preparing such materials with asymmetric end groups by preparing BTP-TCID-2CN (Scheme 1).
The skilled artisan would have been motivated to make this modification because Peng demonstrates that the CPTCN group can impart higher energy HOMO/LUMO on a molecule and that the CPTCN group is suitable for replacing 2FIC on the same core donor group. The skilled artisan would have been motivated to make the asymmetric modification because Yin teaches this can be a way to more narrowly tailor the properties of such fluorophores. Additionally, the skilled artisan would have been motivated to utilize the teachings of Peng because Lee teaches that organic optoelectronic materials are useful for biological applications such as fluorescence imaging similar to that which is taught by Huang.
Regarding claim 1, Huang teaches a NIR-II fluorescent probe AS1 (Figure 1a). AS1 reads on most of the structure of formula I of claim 1 wherein R1 is C11 linear alkyl, R2 is C8 branched alkyl, R3 is 2FIC (as defined in Peng) (which reads on the second listed structure option of R3 wherein two X atoms are H and two are F, a halogen). Additionally, Peng teaches the introduction of 2-(6-oxo-5,6-dihydro-4H-cyclopenta[c]thiophen-4-ylidene)malonitrile (CPTCN) as an end electron withdrawing acceptor group in a derivative of AS1 (pg. 2, left column, paragraph 3; and Figure 1a). For the reasons described above, in view of Yin and Lee, it would have been prima facie obvious to substitute one of the 2FIC end groups of AS1 in Huang with the CPTCN group of Peng. The resulting molecule would have the same CPTCN group required in the structure of formula I. This molecule taught by the combined teachings fully reads on the structure of formula I. Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 1 obvious.
Regarding claim 2, Huang teaches that R1 is C11 linear alkyl, R2 is C8 branched alkyl (Figure 1a). Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 2 obvious.
Regarding claim 3, Huang teaches that two of the X in R3 are H and two of the X are F (Figure 1a). Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 3 obvious.
Regarding claim 4, as described above, the modification of AS1 of Huang with the substitution of one end group for the CPTCN of Peng would result in a fluorescent probe of formula I-b. Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 4 obvious.
Regarding claim 8, Huang teaches preparing a nanoparticle with the fluorescent probe wherein the fluorescent probe is coated by the organic molecule DSPE-PEG. The examiner interprets this to read on an organic coating agent coating on a surface of the NIR-II organic fluorescent probe. Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 8 obvious.
Regarding claim 9, Huang teaches preparing the nanoparticle using DSPE-PEG (figure 1a), which is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol). Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 9 obvious.
Regarding claim 10, Huang teaches that the nanoparticles prepared had diameters of 16.6 nm, 45.0 nm, 56.0 nm, and 75.5 nm (pg. 4, second paragraph). The 56.0 nm and 75.5 nm embodiments fall within the claimed range, rendering it obvious (MPEP § 2144.05(I)). Additionally, Huang teaches that this modulation of nanoparticle diameter is achieved by preparing the DSPE-PEG and fluorescent probe mixture in an organic solvent mixture of chloroform and THF at different volume ratios prior to addition to water under sonication (pg. 4, second paragraph). Furthermore, per MPEP § 2144.04(IV), changes in size generally do not establish patentability. Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 10 obvious.
Regarding claim 13, Huang teaches using the nanoparticles comprising the organic NIR-II fluorescent probe as a fluorescence contrast agent for imaging in mice (Figure 5). The examiner interprets this to read on the limitation “bioimaging contrast agent.” Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 13 obvious.
Regarding claim 14, as described above, the modification of AS1 of Huang with the substitution of one end group for the CPTCN of Peng would result in a fluorescent probe of formula I-b. Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 14 obvious.
Regarding claim 15, as described above, the modification of AS1 of Huang with the substitution of one end group for the CPTCN of Peng would result in a fluorescent probe of formula I-b. Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 15 obvious.
Regarding claim 19, the examiner interprets this claim to be a product-by-process claim. See MPEP § 2113. Accordingly, the patentability of a product does not depend on its method of production. If the product is the same as or obvious from a product of the prior art, the claim is unpatentable even if the prior product was made by a different process. Accordingly, the examiner interprets the scope of claim 19 to be a nanoparticle of claim 8 wherein the NIR-II organic fluorescent probe has the structure represented by formula I of claim 1. As described above, the combined teachings of Huang, Peng, Yin, and Lee render obvious the structure of formula I of claim 1. As Huang also teaches the preparation of similar fluorescent probes in nanoparticles (Figure 1) and the combined teachings render obvious claim 8, this nanoparticle also reads on claim 19. As the combined product is a nanoparticle of claim 8 comprising NIR-II organic fluorescent probe of formula I, it reads on claim 19 regardless of the methods taught in these references for making such a fluorophore (MPEP § 2113). Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 19 obvious.
Regarding claim 20, as described above, the combined teachings of Huang, Peng, Yin, and Lee render the nanoparticle of claim 8 obvious. Furthermore, Huang teaches the use of such a nanoparticle as a fluorescence contrast agent for imaging in mice (Figure 5). The examiner interprets this to read on the limitation “bioimaging contrast agent.” Therefore, the combined teachings of Huang, Peng, Yin, and Lee render claim 20 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 1-4, 8-10, 13-15, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-10 and 13-15 of copending Application No. 18/781,717 in view of Peng (Xu, X.; et al., Adv. Funct. Mater., 2020), Yin (Li, Y.; et al., Polym. Chem., 2023), and Lee (Lee, K. W.; et al., Adv. Mater., 2023).
The conflicting claims of copending Application No. 18/781,717 (the copending ‘717 application) are drawn to a nanoparticle comprising a NIR-II organic fluorescent compound of structure formula I of claim 6 of the copending ‘717 application. The nanoparticle has an organic encapsulation matrix covering a surface of the NIR-II organic fluorescent compound.
The conflicting claims of copending Application No. 18/781,717 do not teach a fluorescent probe according to formula I of instant claim 1 or a nanoparticle comprising said fluorescent probe.
As described above, Peng teaches near infrared absorbing organic small molecules (pg. 1, Abstract). One near infrared absorbing molecule of Peng is Y6 (pg. 2, Figure 1a). Peng also teaches a modified version of Y6, termed Y6-T (pg. 2, Figure 1a) wherein the 2FIC ending groups of Y6 were substituted to CPTCN groups (pg. 2, left column, paragraph 3). Peng teaches that the CPTCN group is less electron withdrawing, which increased the levels of the HOMO/LUMO of the NIR absorbing molecule (pg. 2, left column, paragraph 3). Peng teaches that both Y6 and Y6-T are suitable for use in non-fullerene polymeric solar cells (pg. 7, Conclusion).
As described above, Yin teaches NIR-II fluorescent probes and their use in nanoparticles for bioimaging applications (pg. 3008, Abstract). More specifically, Yin teaches BTP-2TCID, BTP-4CN, and BTP-TCID-2CN (pg. 3009, Scheme 1). Yin teaches that such molecules have an A-D-A’-D-A structure of donors and acceptors with a ladder-type BTP core (pg. 3009, left column, paragraph 3). Yin teaches that the three structures differ in the terminal electron withdrawing acceptor groups (pg. 3009, right column, paragraph 1; and Scheme 1). Yin teaches that these fluorophores emit light in the NIR-II range (pg. 3010, Figure 1c). Yin also teaches forming nanoparticles with the fluorescent probes and coating them with the organic coating Pluronic® F-127 (poloxamer 407) (Scheme 1; and pg. 3010, right column, paragraph 2). Yin teaches administering the nanoparticles to mice and performing fluorescence imaging (pg. 3015, Figure 5).
As described above, Lee teaches that organic optoelectronic materials are being explored and used for biomedical applications including imaging and phototherapies (pg. 1, Abstract). Lee teaches that organic optoelectronic device research, such as organic solar cells, has been undergoing speedy development (pg. 1, left column, paragraph 1). Lee teaches that organic optoelectronic materials often have good light-harvesting ability, bright fluorescence, and low cytotoxicity (pg. 1, right column, paragraph 1). Lee teaches that since 2014, organic optoelectronic materials have shown rapid development for biomedical applications (pg. 1, right column, paragraph 3). Lee teaches that such organic optoelectronic materials can be assembled into nanoparticles by coating them with an amphiphilic polymer (pg. 5, Figure 4a). Lee teaches several examples of the use of organic optoelectronic materials being used in biomedical applications, including Y6 (pg. 3, Table 1; pg. 10, Figure 8a). Lee summarizes that Y6 has been prepared in nanoparticles using DSPE-PEG (pg. 10, section 4.2.2). Lee teaches that similar classes of molecules are used for fluorescence imaging applications, similarly involving DSPE-PEG nanoparticles (pg. 11, Section 4.2.3). Lee concludes that organic optoelectronic materials have great application potential in biomedicine (pg. 20, left column, last paragraph).
A person of ordinary skill in the art would recognize that each of Peng, Yin, and the conflicting claims of the copending ‘717 application teach organic molecules having similar core donor or donor-acceptor-donor structures that only vary in the end electron withdrawing groups. While Peng describes the Y6 and Y6-T molecules in the context of organic solar cells, it would be recognized that Lee teaches that organic optoelectronic materials, such as those used in organic solar cells, have utility in biomedical applications. Indeed, the Y6 of Peng is identical in structure to the formula I-b of conflicting claim 4 of the copending ‘717 application, which is an embodiment of formula I of conflicting claim 6. It would also be recognized that Yin demonstrates that the terminal acceptor groups can be asymmetric on these fluorescent probes, with each end having a different structure. It would be recognized that both Y6 and Y6-T of Peng are embodiments of formula I of conflicting claim 6 (as indicated by formulas I-b and I-c of conflicting claim 4).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the nanoimaging agent of the copending ‘717 application by substituting one of the R3 groups in the symmetric molecules of formulas I-b and I-c such that the product has asymmetric acceptor groups wherein one is the difluoro form and the other is the thiophene form because Peng teaches these group serves the same purpose in this class of molecules and because Yin teaches that such probes can have asymmetric terminal groups and Lee teaches that molecules from organic optoelectronics should be applied to biomedical applications (MPEP § 2143(I)(B) and 2143(I)(G)). This combination would have predictably yielded the compound of formula I-b of claim 4 of the instant application.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this modification because Peng teaches that Y6-T is a derivative of Y6 (the examiner notes that Y6 and Y6-T of Peng and formulas I-b and I-c of conflicting claim 4 of the copending ‘717 application have the same structure) and demonstrates that the 2FIC and CPTCN end groups are interchangeable (pg. 2, left column, paragraph 3; and Figure 1a). Additionally, Yin demonstrates the feasibility of preparing such materials with asymmetric end groups by preparing BTP-TCID-2CN (Scheme 1). Yin also specifically demonstrates taking two symmetric fluorophores and exchanging one end group from each to create the asymmetric form.
The skilled artisan would have been motivated to make this modification because Peng demonstrates that the CPTCN group can impart higher energy HOMO/LUMO on a molecule and that the CPTCN group is suitable for replacing 2FIC on the same core donor group. The skilled artisan would have been motivated to make the asymmetric modification because Yin teaches this can be a way to more narrowly tailor the properties of such fluorophores. Additionally, the skilled artisan would have been motivated to utilize the teachings of Peng because Lee teaches that organic optoelectronic materials are useful for biological applications such as fluorescence imaging.
Regarding instant claim 1, conflicting claim 6 of the copending ‘717 application is drawn to a nanoimaging agent comprising a NIR-II organic fluorescent compound. The examiner interprets this to be a NIR-II organic fluorescent probe. The probe in the nanoparticle of conflicting claim 6 has a structure similar to that of formula I of instant claim 1, but the structure of conflicting claim 6 is symmetric. As described above, in view of the teachings of Peng, Yin, and Lee, it would have been prima facie obvious to modify the structure of formula I of conflicting claim 6 in the copending ‘717 application to make it an asymmetric probe with the difluoro group on one side and the thiophene group on the other. The resulting fluorophore would read on the structure of formula I of instant claim 1.
Regarding instant claim 2, conflicting claim 6 of the copending ‘717 allows for the corresponding R1 and R2 groups to be branched or linear alkyl groups. Additionally, Peng teaches a core wherein R1 is C11 linear alkyl and R2 is C8 branched alkyl.
Regarding instant claim 3, the above described combination of the conflicting claims of the copending ‘717 application and Peng, Yin, and Lee would result in an R3 group wherein two of the X in R3 are H and two of the X are F (Figure 1a).
Regarding instant claim 4, the above described combination of the conflicting claims of the copending ‘717 application and Peng, Yin, and Lee would result in a compound of formula I-b of instant claim 4.
Regarding instant claim 8, conflicting claim 6 of the copending ‘717 application is drawn to a nanoimaging agent comprising the fluorescent organic molecule wherein an organic material covers the surface of the NIR-II organic fluorescent compound. The examiner interprets this to read on a nanoparticle comprising an organic coating agent on a surface of a NIR-II organic fluorescent probe.
Regarding instant claim 9, conflicting claim 7 of the copending ‘717 application teaches organic materials covering the surface of the NIR-II fluorescent probe. This list overlaps with several of the instantly claimed structures, including 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol).
Regarding instant claim 10, Yin teaches that nanoparticles comprising 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) and a similar structure fluorophore can have sized of 171.8 nm, 178.3 nm, and 112.3 nm (pg. 3010, right column, paragraph 2; and Figure 2D), which are within the claimed range.
Regarding instant claim 13, conflicting claim 6 of the copending ‘717 application recites that the nanoparticle is a nanoimaging agent. Thus, the nanoparticle is for imaging applications. Furthermore, Lee and Yin teach that such nanoparticles are useful for biomedical imaging applications.
Regarding instant claim 14, the above described combination of the conflicting claims of the copending ‘717 application and Peng, Yin, and Lee would result in a compound of formula I-b of instant claim 14.
Regarding instant claim 15, the above described combination of the conflicting claims of the copending ‘717 application and Peng, Yin, and Lee would result in a compound of formula I-b of instant claim 15.
Regarding instant claim 19, the examiner interprets this claim to be a product-by-process claim. See MPEP § 2113. Accordingly, the patentability of a product does not depend on its method of production. If the product is the same as or obvious from a product of the prior art, the claim is unpatentable even if the prior product was made by a different process. Accordingly, the examiner interprets the scope of claim 19 to be a nanoparticle of claim 8 wherein the NIR-II organic fluorescent probe has the structure represented by formula I of claim 1. As described above, the combined teachings of the conflicting claims of the copending ‘717 application, Peng, Yin, and Lee render obvious the structure of formula I of claim 1 and the nanoparticle of claim 8 comprising the fluorophore of claim 1. As the combined product is a nanoparticle of claim 8 comprising NIR-II organic fluorescent probe of formula I, it reads on claim 19 regardless of the methods taught in these references for making such a fluorophore (MPEP § 2113).
Regarding instant claim 20, as described above, the combined teachings of the conflicting claims of the copending ‘717 application, Peng, Yin, and Lee render the nanoparticle of claim 8 obvious. Furthermore, conflicting claim 6 of the copending ‘717 application recites that the nanoparticle is a nanoimaging agent. Thus, the nanoparticle is for imaging applications. Furthermore, Lee and Yin teach that such nanoparticles are useful for biomedical imaging applications.
This is a provisional nonstatutory double patenting rejection.
Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
As pertinent prior art, the examiner cites Zou (CN 115974895 A). Figure 1 of this reference depicts two different examples of organic molecules with similar structures to that of the instant application (and the above cited Huang, Peng, and Yin references). In both of these reaction products, the electron withdrawing end groups are different on each side. The examiner notes that, like Yin, this is another example that such molecules can be prepared in an asymmetric manner. The examiner has provided the original language patent application publication for this reference, as the only discussed teaching of this reference is just the chemical structure of Figure 1, which does not require a translation to be understood.
As pertinent prior art, the examiner cites Pan (Pan, H. M.; et al., J. Am. Chem. Soc., 2023). Pan teaches asymmetric fluorophores (pg. 516, Abstract). More specifically, Pan teaches asymmetric NIR-II emitting polymethine dyes (pg. 518, Scheme 2). Pan teaches the preparation of these dyes in nanoparticles with mPEG-DSPE (pg. 521, Figure 3). Pan teaches performing fluorescence imaging in cells and mice using these nanoparticles (pg. 522, Figure 4). Pan teaches that the asymmetric fluorophores displayed higher quantum yields than their symmetric analogs (pg. 517, Scheme 1; and pg. 518, Scheme 2). The examiner notes that these are similar biomedical imaging NIR-II emitting dyes used in nanoparticles and that Pan also teaches preparation with asymmetric end groups.
As pertinent prior art, the examiner cites Kastantin (Kastantin, M.; et al., J. Phys. Chem. B, 2010). Kastantin teaches DSPE-PEG nanoparticles (pg. 1, Abstract; and pg. 2, right column, second paragraph). Kastantin also teaches conjugating fluorescein and rhodamine to the terminal amine of the DSPE-PEG via NHS coupling (pg. 2, left column, last paragraph through first paragraph in right column). The examiner notes that this reference provides an example of attaching a fluorophore to the exterior surface of a nanoparticle having an organic lipid core.
Conclusion
No claim is allowed.
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/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
