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 .
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.
Status of Claims
Claims 1, 3, 5-6, 11-13, 40, 41, 50, 51, 68, 71, 99, and 101-107 are pending. Claims 41, 50, 51, 68, and 71 are drawn to the nonelected invention. Claims 1, 3, 5-6, 11-13, 40, 99 and 101-107 are under examination.
Maintained Rejections
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.
Claims 1, 3, 5-6, 11-13, 40, 99 and 101-106 are rejected under 35 U.S.C. 103 as being unpatentable over Liang et al. (US2016/0266131A1, published 09/15/2016, of record) in view of Suzuki et al. (US Patent No. 8193350B2, 06/05/2012, of record).
With respect to claims 1, 99, and 101, Liang teaches a water-soluble light harvesting multichromophores that have an ultraviolet absorption maximum and the multichromophores include a conjugated segment including a fused 6-5-6 tricyclic co-monomer (see abstract). Liang further teaches in the abstract that the multichromophores may include an acceptor chromophore covalently linked to the multichromophore in energy-receiving proximity. Liang teaches acceptor chromophore refers to a light-absorbing molecule that is capable of receiving or absorbing energy transferred from the multichromophore and the acceptor chromophore can either emit as light the energy received from the multichromophore or dissipate the energy as heat (see middle of para. [0121]). Liang further teaches any convenient fluorescent dye is utilized in the polymeric tandem dyes as an acceptor chromophore and fluorescent dye and fluorophore are used interchangeable and they may be a BODIPY and derivatives such as BODIPY FL, BODIPY 530/550, BODIPY 558/568, BODIPY 564/570, BODIPY 581/591, BODIPY 630/650, BODIPY 650/665, BODIPY R6G, BODIPY TMR, BODIPY TR (see para. [00126]) which would read on an acceptor fluorophore configured in energy-receiving proximity to the light harvesting multichromophore and having a structure of formula (I). Liang teaches the multichromophore having formula (V) and linked to an acceptor chromophore—C1 which would read on L1 is a linker and Z is the light harvesting multichromophore (see paras. [0128]-[0135] and [0153]). Liang teaches PEG water soluble moieties are linked to C1 wherein the dye is linked to L1 that is PEG moiety (see para. [0153]). Liang teaches the fluorene co-monomer has sidechain group with PEG moieties (O(CH2CH2O)n wherein n is 8-16 (see para. [0183]). Liang teaches the subject polymeric dyes are for labeling, separation, detection and/or analysis (see para. [0214]).
Formula (V) as follows:
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Liang teaches the polymeric tandem dye of formula (V) having the claimed G1, G2, F, M1, M2, L, and wherein a, c, d, and f are each independently 0 or 1 (see paras. [0128]-[0133]), which would read on w, x, y, and z represent % molarity of the units in the multichromophore of formula (XIIa). For example, Liang teaches the multichromophores include, as part of the polymeric backbone (see para. [0095]).
With respect to having an emission spectrum with a FWHM of 35 nm or less in width when measured in phosphate buffered saline (PBS), the recitation is directed to the intended use of when the compound is measured in PBS. The recitations of intended use of the claimed BODIPY compounds must result in a structural difference between the claimed BODIPY compounds (i.e., formula I) and the prior art’s BODIPY compounds in order to patentably distinguish the claimed compounds from the prior art’s compounds. Because BODIPY compounds of the prior art read on the claimed BODIPY compounds, the prior art’s BODIPY compounds are capable of producing the emission spectrum in PBS.
Even though Liang teaches the acceptor chromophore may be BODIPY and derivatives (i.e., as claimed N1), Liang does not explicitly exemplify the claimed BODIPY fluorophore derivatives of formula (I) with an emission spectrum that has a FWHM of 35 nm or less in width.
Suzuki teaches a novel fluorescent compound having a high light fastness, high fluorescence quantum yield and sharp absorption spectrum, which emits fluorescence having a wavelength in long wavelength region, as well as its use as a labeling agent and having the boron dipyrromethene skeleton (see abstract). Suzuki teaches, for example, that fluorescent compounds 6-8 have a very small full width at half maximum height and so have a sharp fluorescence spectrum and it was proved that the higher the electron donating property of the introduced groups, the larger the amount of the shift to longer wavelength (see col. 53, lines 64-67). Suzuki further teaches the FWHM (nm) is below 35 nm in width (see Table 4). Suzuki teaches that fluorescent compound according to the present invention has a long fluorescence wavelength, measurement can be attained even in the presence of biological substances such as body tissues, blood, lipids, and water without being optically disturbed by these substances (see col. 3, lines 55-67). Suzuki teaches in Fig. 1 that fluorescent compound 8 retained the absorbance of 95% or more even after 1 week and the results show that fluorescent compound 8 has a very high light fastness. Thus, it is thought that the compound can be applied to analysis reagent used for a long time or used as a novel dye material or optical material having a high durability, which could not be attained by the conventional dyes (see 54, lines 48-57).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have used any of the disclosed BODIPY fluorophore derivatives (see para. [0126]) with the polymeric tandem dye of formula (V) as taught by Liang because Liang teaches said BODIPY derivatives are utilized in the polymeric tandem dyes as acceptor chromophores (C1) and these disclosed BODIPY structures have the ability to receive or absorb energy transferred from the multichromophore and emit light energy received from the multichromophore. Because the disclosed BODIPY fluorophore derivatives are conjugated to formula (V) for a specific purpose, as taught by Liang, it would be obvious to have attached the disclosed BODIPY for its functional ability in polymeric tandem dye. Thus, it would have been obvious that the BODIPY fluorophore derivatives that read on the structures of the instant claimed formula (I) would produce the claimed function.
Furthermore, it would have been obvious to have used formula (V) of Liang with the BODIPY fluorophore derivatives of Suzuki because Suzuki teaches that (1) their BODIPY fluorophore derivatives have a high light fastness that contain high fluorescence quantum yield to produce a sharp absorption spectrum and (2) the compound can be applied to analysis reagent used for a long time, which could not be attained by the conventional dyes. Because Liang recognizes the functional aspects of BODIPY structures with respect to formula (V), it would have been obvious to have used Suzuki's BODIPY fluorophore derivatives for its sharp absorption spectrum.
With respect to the L1 linker, it would have been obvious to have used PEG moieties ((CH2CH2O)n wherein n is 8-16) to conjugate BODIPY fluorophore derivatives in formula (V) because Liang teaches the acceptor chromophore (C1) covalently attached in formula (V) and the PEG moieties are recognized linkers in polymeric tandem dye structures. Additionally, it would have been obvious to have used the PEG moieties of the light harvesting multichromophore to conjugate Suzuki’s BODIPY fluorophore derivatives because Liang teaches attaching the BODIPY or derivatives to the water soluble light harvesting multichromophore for detection.
The person would have a reasonable expectation of success in conjugating BODIPY fluorophore derivatives in formula (V) because it has been well recognized by Liang to attach BODIPY fluorophore derivatives as acceptor chromophores.
With regard to claim 3, Liang teaches the acceptor chromophore of formula V may be BODIPY FL, BODIPY 530/550, BODIPY 558/568, BODIPY 564/570, BODIPY 581/591, BODIPY 630/650, BODIPY 650/665, BODIPY R6G, BODIPY TMR, BODIPY TR (see para. [00126]) which would read on the polymeric tandem dye with instant formula (I). Therefore, it would have been obvious that Liang’s acceptor fluorophore produces the claimed function when used in formula V.
With regard to claim 5, Liang teaches PEG water soluble moieties are linked to the acceptor chromophore (see para. [0153]). Liang does not explicitly teach that the structure of formula (I) is substituted with a water soluble group (i.e., PEG). However, it would have been obvious to have used PEG as a substituent because Liang recognizes PEG moieties as linkers for the polymeric tandem dye.
With regard to claim 6, Liang teaches L1 is a non-conjugated linker (see para. [0118]).
With regard to claims 11-13, Liang does not teach the structure of formula (lla) or (llb). As stated above, Suzuki teaches fluorescent compounds 6-8 (see col. 53, lines 64-67) which would read on the limitations Z11 and Z12 and the R21-R23. Thus, it would have been obvious to have used the polymeric tandem dyes of Liang with the BODIPY fluorophore derivatives of Suzuki because Suzuki teaches that their BODIPY fluorophore derivatives have a high light fastness that contain high fluorescence quantum yield and sharp absorption spectrum.
With regard to claim 40, Liang teaches in Example 1 a plurality of F1,M1,M2, and L1 are substituted with water solubilizing groups (WSGs) as claimed (see para. [0262], structure 1).
With respect to claims 102-105, as stated above, Liang teaches PEG moieties (CH2CH2O)n wherein n is 8-16 (see para. [0183]), which would read on the linker has a backbone of between 2-100 atoms, 4-100 atoms, 4-20 atoms and linear linker.
With respect to claim 106, Liang teaches BODIPY FL, BODIPY R6G, BODIPY TMR, BODIPY 581/591, BODIPY TR, BODIPY 630/650 and BODIPY 650/665 (see para. [0126]).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3, 5-6, 11-13, 40, 99 and 101-106 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-44 of U.S. Patent No. 9719998B2 (‘998) (of record 05/25/2023) in view of in view of Liang et al. (US2016/0266131A1, published 09/15/2016, of record) and Suzuki et al. (US Patent No. 8193350B2, 06/05/2012, of record).
With respect to instant claims 1 and 99, Patent No. ‘998 recites:
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And an acceptor chromophore -C1 covalently linked to the multichromophore in energy-receiving proximity therewith and a, c, d, and f are each independently 0 or 1 and b and e are 1 or 2.
Patent ‘998 does not recite BODIPY fluorophore derivatives of formula (I) and having an emission spectrum with a FWHM of 35 nm or less in width when measured in PBS.
It would have been obvious to the person at the time of filing to have used the recited structures of Patent ‘998 with any of the disclosed BODIPY fluorophore derivatives as taught by Liang because Liang teaches said BODIPY derivatives are utilized in the polymeric tandem dyes as acceptor chromophores (C1) and conjugated to the polymeric tandem dye for being capable of receiving or absorbing energy transferred from the multichromophore and emitting light energy received from the multichromophore. Because any of the disclosed BODIPY fluorophore derivatives can be conjugated to the polymeric tandem dye as taught by Liang, the disclosed BODIPY fluorophore derivatives that have the structures of the claimed formula (I) would be obvious to be attached to said structures recited in Patent ‘988 for its ability to receive or absorb energy transferred and emit light energy received from the multichromophore to produce emissions. Thus, the conjugation of these BODIPY fluorophore derivatives to said structures would produce the claimed emission, as Liang discloses BODIPY fluorophore derivatives having the claimed formula (I).
Furthermore, it would have been obvious to have used the structures as recited in Patent ‘998 with the BODIPY fluorophore derivatives of Suzuki because Suzuki teaches that (1) their BODIPY fluorophore derivatives have a high light fastness that contain high fluorescence quantum yield to produce a sharp absorption spectrum and (2) the compound can be applied to analysis reagent used for a long time or optical material having a high durability, which could not be attained by the conventional dyes. Therefore, the person would have used the BODIPY fluorophore derivatives of Suzuki because Liang recognizes the function of incorporating BODIPY fluorophore derivatives to said structures and Suzuki teaches that the fluorescent compound 8 has a long fluorescence wavelength, measurement can be attained even in the presence of biological substances, and the compound can be applied to analysis reagents.
With respect to having an emission spectrum with a FWHM of 35 nm or less in width when measured in PBS, the recitation is directed to the intended use of when the compound is measured in PBS. The recitation of intended use of the claimed BODIPY compounds must result in a structural difference between the claimed BODIPY compounds (i.e., formula I) and the prior art’s BODIPY compounds in order to patentably distinguish the claimed compounds from the prior art’s compounds. Because BODIPY compounds of the prior art read on the claimed BODIPY compounds, the prior art’s BODIPY compounds are capable of producing the emission spectrum in PBS.
With respect to the L1 linker, it would have been obvious to have used PEG moieties ((CH2CH2O)n wherein n is 8-16) to conjugate BODIPY fluorophore derivatives with the recited structures of Patent ‘998 because Liang teaches the acceptor chromophore (C1) covalently attached in formula (V) and the PEG moieties are recognized linkers in polymeric tandem dye structures. Additionally, it would have been obvious to have used the PEG moieties of the light harvesting multichromophore to conjugate Suzuki’s BODIPY fluorophore derivatives because Liang teaches attaching the BODIPY or derivatives to the water soluble light harvesting multichromophore for detection.
The person would have a reasonable expectation of success in conjugating BODIPY fluorophore derivatives to the Patent’s structures because it has been well recognized by Liang to attach BODIPY fluorophore derivatives as acceptor chromophores.
With respect to instant claim 3, Patent ‘998 does not recite explicitly recite the claimed function. However, it would have been obvious that the BODIPY fluorophore of Liang or Suzuki would produce the claimed function, as it reads on the claimed formula (I).
With respect to instant claim 5, Patent ‘998 claim 9 recites the water solubilizing structure.
With respect to instant claim 6, Patent ‘998 claim 35 recites a PEG moiety.
With respect to instant claims 11-13, Patent ‘998 does not recite the structure of formula (IIa) or formula (IIb). As stated above, Suzuki teaches fluorescent compounds 6-8 (see col. 53, lines 64-67) which would read on the limitations Z11 and Z12 and the R21-R23. Thus, it would have been obvious to have used the recited structures of Patent ‘998 with the BODIPY fluorophore derivatives of Suzuki because Suzuki teaches that their BODIPY fluorophore derivatives have a high light fastness that contain high fluorescence quantum yield and sharp absorption spectrum.
With respect to instant claim 40, Patent ‘998 claim 9 recites:
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wherein n is 1-20 (PEG), which reads on the claimed water solubilizing group.
With respect to instant claims 101 and 105, Patent ‘988 claim 35 recites PEG moiety.
With respect to instant claims 102-104, Patent ‘998 recites in claim 9 that PEG structure (CH2CH2O) wherein n is 1-20. Because the recited PEG linker overlaps in lengths with the instant claimed length of 2-100 atoms, 4-100 atoms, and 4-20 atoms, it would have been prima facie obvious to have produced the instant claimed lengths.
With respect to instant claim 106, Patent ‘998 does not recite the claimed BODIPY dyes. Liang teaches BODIPY FL, BODIPY R6G, BODIPY TMR, BODIPY 581/591, BODIPY TR, BODIPY 630/650 and BODIPY 650/665 (see para. [0126]). It would have been obvious to have used these dyes because Liang has disclosed that these dyes are convenient fluorescent dyes (see para. [0126]).
Allowable Subject Matter
Claim 107 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The closest prior art of record is Liang. The reference teaches polymeric tandem dyes with BODIPY derivatives as fluorophores. However, Liang does not teach or reasonably suggest the claimed N1 having the chemical structures as recited in claim 107.
Response to Arguments
Applicant's arguments filed 05/12/2026 have been fully considered but they are not persuasive.
Applicant argues on page 15 that in fact, Applicant’s explanation of unexpected results does not begin with the П conjugated backbone. Instead, the unexpected results are understood by beginning with fluorophore N1. Applicant further argues on page 16 that the inventors recognized an advantage of BODIPY dyes (narrow emission spectra) but also a disadvantage (small Stokes shift). To overcome this technical disadvantage, the inventors modified the arrangement to be a tandem dye. Applicant argues on page 17 that merely creating a backbone with Liang does not generate the claimed Stokes shift. The large Stokes shift comes from beginning with a BODIPY dye and adding a donor chromophore (i.e., the backbone) absorbing at a much lower wavelength (e.g., 400 nm).
The arguments are not found persuasive with respect to the unexpected result arguments. Liang does teach BODIPY FL, BODIPY R6G, BODIPY TMR, BODIPY 581/591, BODIPY TR, BODIPY 630/650 and BODIPY 650/665 as acceptor chromophores (see para. [0126]), which would read on formula I (N1) of claims 1 and 106. Additionally, Liang also teaches the claimed G1-F1-M1-M2-L1-G2 polymeric backbone (see above, Liang’s Formula V). Therefore, there is an expectation of property when combining Liang’s said BODIPY dyes and said polymeric backbone. Note that the claims are directed to a product.
The question is whether the polymeric backbones in Table 2 (D1-D8) are different from Liang’s polymeric backbone (i.e., donor backbone). If these polymeric backbone structures are different from Liang’s polymeric backbone, then these backbone chemical structures are required in the claims to be commensurate in scope with the superior results as invoked by Applicant. The evidence provided in Table 2 as argued by Applicant appears to have a more defined chemical structure than the claimed polymeric tandem dyes of formula (XIIa). However, nowhere in the specification discloses the structures of D1-D8.
Similarly, Applicant argues unexpected results with respect to the nonstatutory double patenting rejections. The arguments are not found persuasive for the reasons stated above. For the reasons, the rejections are maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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