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 .
Response to Amendment
Applicant’s remark and amendment filed on 05/11/26 have been entered. Claims 1, 12, 15, 16, 18, 19, 22, 23, 25, 26, 30-32, and 34-38 remain pending and examined herein. Applicant’s amendment and remark have overcome each and every rejection under 112(b) set forth in Office Action mailed on 02/11/26.
Status of Application
The rejection of claims 31, and 32 under 35 U.S.C. 102(a)(1) under Samejima (WO 2020/059484; cited in previous OA) is withdrawn in view of Applicant’s remark.
The 103 rejection set forth in previous Office Action is maintained.
Claim Rejections - 35 USC § 103
Claims 1, 12, 15, 16, 18, 19, 22, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Bartholomew (US 2020/0048469).
Regarding claim 1, Bartholomew teaches a dipyrromethene-boron dyes of formula (I) paragraph 0032, wherein
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Bartholomew does not explicitly disclose the WSG is a water-soluble polymer comprising 6-24 monomeric units. Instead, Bartholomew discloses the WSG is a hydrophilic polymer and can comprise between 1 to 50 polymer units (WSG is a hydrophilic polymer, e.g., a polyethylene glycol, a modified PEG…In some cases, a WSG is (CH2)x(OCH2CH2)yOCH3 where each x is independently an integer from 0-20, each y is independently an integer from 0 to 50. Para. [0129]), which overlaps with the claimed range of 6 to 24.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have selected the overlapping portion of the ranges disclosed by the reference because selection of overlapping portion of ranges has been held to be a prima facie case of obviousness. See MPEP § 2144.05.I.
Regarding claim 12, Bartholomew discloses the claimed invention as discussed above in claim 1. Bartholomew discloses the claimed structure in paragraph 92
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Furthermore, Bartholomew discloses if Y1 is a WSG then R5 (claimed R2) is H (each R, R2, R4, R5 and R7 is independently H, C1-C6alkyl or substituted 01-C6alkyl; para. [0092]).
However, q is 6-20, which overlaps with the claimed range of 6-24. It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have selected the overlapping portion of the ranges disclosed by the reference because selection of overlapping portion of ranges has been held to be a prima facie case of obviousness. See MPEP § 2144.05.I.
Regarding claim 15 and 16, Bartholomew discloses the claimed invention as discussed above in claim 1. Bartholomew discloses an embodiment in paragraph 92 (R8 position is H for claim 16).
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Bartholomew discloses the R1 position of Bartholomew was a substituted alkyl (alkyl chain substituted with carboxylic acid).
Bartholomew does not teach all the claimed embodiments in a single compound but selection from the claimed substituents allows one of ordinary skill in the art to arrive at the claimed compounds. The specific embodiment discloses Y1 has 16 PEG repeat units, instead of 11 repeat units as claimed. Bartholomew discloses the WSG is a hydrophilic polymer and can comprise between 1 to 50 polymer units (WSG is a hydrophilic polymer, e.g., a polyethylene glycol, a modified PEG…In some cases, a WSG is (CH2)x(OCH2CH2)yOCH3 where each x is independently an integer from 0-20, each y is independently an integer from 0 to 50. Para. [0129])
It would have been obvious to one of ordinary skill in the art at the time the invention was made to select the instantly claimed dyes and appropriate WSG length as Bartholomew teaches these dyes with the same base structure and selection of the claimed substituents allows for the production of water soluble dyes with the absorbance maximums in the 550 to 600 nm range for the benefit of use in a variety of biological applications particularly diagnostic kits with parameters of interest of the dyes such as excitation and emission wavelengths , stokes shifts and fluorescence quantum yield being selected by selection of the claimed substituents. These tandem dyes have the benefit of narrow emission fluorophores. Substitution of the functionally equivalent substituents listed to arrive at the claimed structures and desired water solubility and absorbance maximum can be done through routine experimentation.
Regarding claim 18, Bartholomew discloses the claimed invention as discussed above in claim 15. Bartholomew discloses an embodiment in paragraph 92.
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Closest structure form Bartholomew, paragraph 92
The difference being the PEG in the claimed embodiment has 11 repeating unit whereas Bartholomew has 16 and an additional methyl substituent in the phenyl group attached to the alkenyl group. Within the same paragraph, Bartholomew the q can be anywhere between 6 and 20, which would have overlapped with the claimed range of 11. It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have selected the overlapping portion of the ranges disclosed by the reference because selection of overlapping portion of ranges has been held to be a prima facie case of obviousness. See MPEP § 2144.05.I. Furthermore, it is examiner’s position that it would have been obvious to one of ordinary skill in the art to have incorporated a methyl group in the phenyl group in the Bartholomew structure of para. 92 to derive one of the embodiments of claim 18 as Bartholomew has extensively discloses the ring may be substituted or unsubstituted (para. [0254])
Regarding claim 19, Bartholomew discloses the claimed invention as discussed above in claim 1. Bartholomew discloses the claimed structure in paragraph 92
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Bartholomew does not explicitly disclose the claimed structure in which R2 and R7 are substituted aryl. Bartholomew discloses the R2 and R7 can be substituted with aryl rings (para. [0035])
Bartholomew does not teach all the claimed embodiments in a single compound but selection from the claimed substituents allows one of ordinary skill in the art to arrive at the claimed compounds.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to select the instantly claimed dyes as Bartholomew teaches these dyes with the same base structure and selection of the claimed substituents allows for the production of water soluble dyes with the absorbance maximums in the 550 to 600 nm range for the benefit of use in a variety of biological applications particularly diagnostic kits with parameters of interest of the dyes such as excitation and emission wavelengths , stokes shifts and fluorescence quantum yield being selected by selection of the claimed substituents. These tandem dyes have the benefit of narrow emission fluorophores. Substitution of the functionally equivalent substituents listed to arrive at the claimed structures and desired water solubility and absorbance maximum can be done through routine experimentation.
Regarding claim 22, Bartholomew discloses the claimed invention as discussed above in claim 19. Bartholomew discloses the closest structure in paragraph 92 (Also see para. [0075]; [0130]; [0087]; [0272]; para. [0058])
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and paragraph 49
Bartholomew does not explicitly disclose the R2 and R7 of the structure shown in paragraph 92 are benzyl substituted with at least one WSG group (e.g. PEG). In paragraph 130, Bartholomew disclose in certain embodiment, the substituent in R1-R7 can be a benzyl substituted with at least one WSG group. (In some embodiments, one or more of the substituents is a benzyl substituted with at least one WSG groups (e.g., one or two WSG groups) selected from (CH2)x(OCH2CH2)yOCH3 where each x is independently an integer from 0-20 and each y is independently an integer from 0 to 50. Para. [0130]).
Bartholomew also discloses Z1 can be carboxylic acid (In certain instances of R1, Z1 is a carboxylic acid or an active ester thereof; para. [0058]).
Bartholomew does not teach all the claimed embodiments in a single compound but selection from the claimed substituents allows one of ordinary skill in the art to arrive at the claimed compounds such as the one shown below
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It would have been obvious to one of ordinary skill in the art at the time the invention was made to select the instantly claimed dyes as Bartholomew teaches these dyes with the same base structure and selection of the claimed substituents and length of WSG allows for the production of water soluble dyes with the absorbance maximums in the 550 to 600 nm range for the benefit of use in a variety of biological applications particularly diagnostic kits with parameters of interest of the dyes such as excitation and emission wavelengths, stokes shifts and fluorescence quantum yield being selected by selection of the claimed substituents. These tandem dyes have the benefit of narrow emission fluorophores. Substitution of the functionally equivalent substituents listed to arrive at the claimed structures and desired water solubility and absorbance maximum can be done through routine experimentation.
Regarding claim 37, Bartholomew discloses the claimed invention as discussed above in claim 1. Bartholomew discloses R1-R7 can be independently selected from L1-Z1. It would have been obvious to one of ordinary skill in the art at the time the invention was made to select the instantly claimed dyes as Bartholomew teaches these dyes with the same base structure and selection of the claimed substituents allows for the production of water soluble dyes with the absorbance maximums in the 550 to 600 nm range for the benefit of use in a variety of biological applications particularly diagnostic kits with parameters of interest of the dyes such as excitation and emission wavelengths, stokes shifts and fluorescence quantum yield being selected by selection of the claimed substituents. These tandem dyes have the benefit of narrow emission fluorophores. Substitution of the functionally equivalent substituents listed to arrive at the claimed structures and desired water solubility and absorbance maximum can be done through routine experimentation.
Claim(s) 23 and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bartholomew in view of Lakshmi (Halogenated boron-dypyrromethenes: synthesis, properties and applications, 2015) as cited in previous Office Action.
Regarding claims 23 and 25, Bartholomew discloses the claimed invention as discussed above in claim 1. With respect to formation of ring A, Bartholomew explicitly discloses the position R6 and R7 can be cyclically linked together (optionally any one or more pairs of substituents selected from R6 and R7, R2 and R3, R5 and R6, R3 and R4, R4 and R1 and R5 and R1, are cyclically linked and together form a divalent radical and together with the carbon atoms to which they are bound provide a 5- or 6-membered fused heterocycle, carbocycle, aryl or heteroaryl ring, para. [0035]). It would have been obvious to one of ordinary skill in the art at the time the invention was made to select the instantly claimed dyes as Bartholomew teaches these dyes with the same base structure and selection of the claimed substituents allows for the production of water soluble dyes with the absorbance maximums in the 550 to 600 nm range for the benefit of use in a variety of biological applications particularly diagnostic kits with parameters of interest of the dyes such as excitation and emission wavelengths, stokes shifts and fluorescence quantum yield being selected by selection of the claimed substituents. These tandem dyes have the benefit of narrow emission fluorophores. Substitution of the functionally equivalent substituents listed to arrive at the claimed structures and desired water solubility and absorbance maximum can be done through routine experimentation.
Even with the modification, Bartholomew, by itself, does not disclose the substituent of R1 to R7 (in claim 25 case, R5 specifically) can be a halogen (chlorine preferably).
In an analogous art, Lakshimi discloses halogenating BODIPYS and its potential benefits. In particular, Lakshimi discloses a mono halogenation scheme in which a chlorine is attached to the R5 position (Scheme 2b). It would have been obvious to one of ordinary skill in the art before the effective filing date to have incorporated halogen substituent (specifically chlorine as taught) from Lakshimi’s reaction scheme proposal to the method of Bartholomew to derive the claimed invention of claim 23 and 25. Doing so allows for the dyes to be employed as probes for photodynamic therapy (In addition, halogenated BODIPYs can find applications as probes for photodynamic therapy18 (PDT), a noninvasive methodology for the treatment of malignant tumours. The presence of heavy halogens increases the rate of intersystem crossing resulting in the population of the triplet state which is required for the generation of reactive oxygen species. Halogenated BODIPYs).
Allowable Subject Matter
Claims 26 and 30 are allowed.
Claims 31, 32, 34-36, and 38 are 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.
See the reasons for indicating of allowable subject matter in the 10/23/25 final office action.
Response to Arguments
Applicant's arguments filed 05/11/26 regarding Bartholomew have been fully considered but they are not persuasive.
Regarding claim 1, applicant argues the amendment as claimed limit to a specific embodiment as argued on page 22 of the remarks. Examiner respectfully disagrees. In the claim’s currently drafted form, the claim encompasses a large number of possible species beyond the one specifically argued. The examiner highlights the structures from Bartholomew paragraph 0092 and in the rejection shows how only one or two substitutions are needed to arrive at applicant’s dyes. Since the claimed dyes shard significant overlap with the exemplified compounds of Bartholomew and require only a few substitutions, the size of possibilities is not considered so large as to be unobvious.
Though the claim introduces limitation “provided that if R4 or R5 is substituted alkenyl…Y1 is -CCH2O(CH2CH2O)11CH3”, due to the conditional nature of the limitation, the claim, viewed as a whole, still includes a larger number of broader species beyond the one introduced by the conditional limitation.
For the reason above, the 103 rejection of Bartholomew is maintained.
Applicant’s arguments, see pages 19-21, filed 05/11/26, with respect to rejection of claims 1, 31, and 32 in view of Samejima (WO 2020/059484) have been fully considered and are persuasive. The rejection of claims 31 and 32 has been withdrawn.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICKEY HUANG whose telephone number is (571)272-7690. The examiner can normally be reached M-F 9:30-5:30 PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at 5712707698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/M.H./Examiner, Art Unit 1758 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
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