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 .
Detailed Action
This office action is a response to applicant’s communication submitted July 22, 2026, wherein claims 1, 5, 17, 19, and 21 are amended and claim 11 is canceled. This application is a continuation of US application 16/183583, now US patent 11780863, filed November 7, 2018, which is a continuation of US application 15/246430, now US patent 10168446, filed April 24, 2016, which is a continuation of PCT/EP2015/053556, filed February 20, 2015, which claims priority to provisional application 61/943940, filed February 24, 2014.
Claims 1-5, 9, 10, 12, 13, 15-17, and 19-25 are pending in this application.
Claims 1-5, 9, 10, 12, 13, 15-17, and 19-25 as amended are examined on the merits herein.
Withdrawn Rejections
Applicant’s amendment, submitted July 22, 2026, with respect to the rejection of claim 5 under 35 USC 102(a)(1) for being anticipated by Chu et al., has been fully considered and found to be persuasive to remove the rejection as claim 5 has been amended to require that R3 be a specific linker that cannot be found in the structure disclosed by Chu et al. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted July 22, 2026, with respect to the rejection of claims 17, 19, and 20 under 35 USC 102(a)(1) for being anticipated by Zhu et al. as evidenced by Jia et al., has been fully considered and found to be persuasive to remove the rejection as claim 17 has been amended to require that embodiments wherein the cleavable group is phosphate the detectable label be one of a specific labels. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted July 22, 2026, with respect to the rejection of claim 11 under 35 USC 112(d) for failing to include all the limitations of base claim 5, has been fully considered and found to be persuasive to remove the rejection as claim 11 has been canceled. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted July 22, 2026, with respect to the rejection of claims 17 and 20 under 35 USC 102(a)(1) for being anticipated by Lo et al., has been fully considered and found to be persuasive to remove the rejection as claim 17 has been amended to require that embodiments wherein the cleavable group is phosphate the detectable label be one of a specific labels. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted July 22, 2026, with respect to the rejection of claim 1 under 35 USC 102(a)(1) for being anticipated by Shen Yumei et al., has been fully considered and found to be persuasive to remove the rejection as claim 1 has been amended to more specifically define the leaving group. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted July 22, 2026, with respect to the rejection of claims 21, 23, and 24 under 35 USC 103 for being obvious over Graham, has been fully considered and found to be persuasive to remove the rejection as base claim 21 has been amended to more specifically define the leaving group. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted July 22, 2026, with respect to the rejection of claims 21, 23, and 24 under 35 USC 103 for being obvious over Graham in view of Shen Yumei et al., has been fully considered and found to be persuasive to remove the rejection as base claim 21 has been amended to more specifically define the leaving group. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted July 22, 2026, with respect to the rejection of claims 21, 23, and 24 under 35 USC 103 for being obvious over Graham in view of Cavalli et al., has been fully considered and found to be persuasive to remove the rejection as base claim 21 has been amended to more specifically define the leaving group. Therefore the rejection is withdrawn.
Applicant’s amendment necessitates the following new grounds of rejection:
Claim Rejections - 35 USC § 102
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.
Claims 17 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bobrow. (Reference included with PTO-1449)
Independent claim 17 is directed to compound (VI) which comprises a phenyl ring attached to an enzymatically cleavable group, a methine bearing a leaving group, and a detectable label. Dependent claim 20 further define the identity of the variable LG in this structure.
Bobrow discloses a compound for use as a reporter in an analyte dependent activation system having the formula:
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. (column 2 lines 19-40) In particular, Z is described as a halogen, Y is a moiety capable of being cleaved by an enzyme, and -X-L is a linker connected to a detectable label. Furthermore Bobrow discloses fluorine as a preferred embodiment of the halogen. (column 3 lines 53-55) Galactose, which would be understood aby one of ordinary skill in the art as either alpha- or beta- galactosyl, is a preferred embodiment of Y. (column 3 lines 58-60) A wide variety of dyes can be used as the label L. (column 5 lines 15-24) Furthermore since the linker R3 is defined in present claim 17 as including a bond, any embodiment -X-L according to Bobrow could reasonably be considered to be the “detectable label” R4 in present claim 17. Therefore Bobrow anticipates the present claims.
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.
Claims 17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al. (NPL reference 2 cited in 8/11/2023 PTO-1449) in view of Beija et al. (Reference included with PTO-892)
Independent claim 17 is directed to compound (VI) which comprises a phenyl ring attached to an enzymatically cleavable group, a methine bearing a leaving group, and a detectable label. Dependent claim 20 further define the identity of the variable LG in this structure.
Zhu et al. discloses a fluorescent activity-based probe targeting phosphatases. (p. 2669 figure 1, p. 2670 scheme 1) This compound has the same substituted phenyl structure recited in present claim 17. Furthermore the phosphate group falls within the scope of enzyme cleavable groups recited in the present claims, the fluoromethylene group falls within the scope of leaving groups, and the Cy3 and attached linking structure falls within the scope of detectable labels or chromophores recited in the present claims. Regarding the group R3 recited in claim 17, the structure described by Zhu et al. falls within an embodiment wherein R3 is C(O)N(H)(CH2CH2O)n, for example, and the fluorophore is -CH2CH2N(H)C(O)-Cy3.
Zhu et al. does not further disclose an embodiment wherein the detectable label is a rhodamine chromogen. However, Beija et al. discloses that rhodamine compounds are fluorophores that are used for a variety of different applications in the field of molecular biology. (p. 2410 left column) In particular, they can be used for the fluorescent labeling of biomolecules. (p. 2410 right column)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use a rhodamine fluorophore in place of the Cy3 fluorophore appearing in Zhu’s probes. One of ordinary skill in the art would have fond this to be obvious based on the observation that these two fluorophores are both usable for the purpose of labelling biomolecules and that substituting one for another would be expected to be feasible with a reasonable expectation of success.
Therefore the invention taken as a whole is prima facie obvious.
Claims 17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al. (NPL reference 2 cited in 8/11/2023 PTO-1449) in view of Yasui et al. (Reference included with PTO-892)
Independent claim 17 is directed to compound (VI) which comprises a phenyl ring attached to an enzymatically cleavable group, a methine bearing a leaving group, and a detectable label. Dependent claim 20 further define the identity of the variable LG in this structure.
Zhu et al. discloses a fluorescent activity-based probe targeting phosphatases. (p. 2669 figure 1, p. 2670 scheme 1) This compound has the same substituted phenyl structure recited in present claim 17. Furthermore the phosphate group falls within the scope of enzyme cleavable groups recited in the present claims, the fluoromethylene group falls within the scope of leaving groups, and the Cy3 and attached linking structure falls within the scope of detectable labels or chromophores recited in the present claims. Regarding the group R3 recited in claim 17, the structure described by Zhu et al. falls within an embodiment wherein R3 is C(O)N(H)(CH2CH2O)n, for example, and the fluorophore is -CH2CH2N(H)C(O)-Cy3.
Zhu et al. does not further disclose an embodiment wherein the detectable label is a dabsyl or diazo chromogen. However, Yasui et al. discloses that dabsyl is a diazo-containing dye moiety that can be used to label proteins. (p. 401 left column last paragraph, right column first paragraph, p. 402 figure 1B)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use a dabsyl dye in place of the Cy3 fluorophore appearing in Zhu’s probes. One of ordinary skill in the art would have fond this to be obvious based on the observation that these two moieties are both usable for the purpose of labelling biomolecules and that substituting one for another would be expected to be feasible with a reasonable expectation of success.
Therefore the invention taken as a whole is prima facie obvious.
Claims 17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Lo et al. (NPL reference of record in previous action) in view of Beija et al. (Reference included with PTO-892)
Independent claim 17 is directed to compound (VI) which comprises a phenyl ring attached to an enzymatically cleavable group, a methine bearing a leaving group, and a detectable label. Dependent claim 20 further define the identity of the variable LG in this structure.
Lo discloses the compound
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R = dansyl
R = biotinyl (p. 38 scheme 2)
This compound has the same structure as that recited in claim 17, for reasons similar to those recited previously with respect to the reference Zhu et al. Lo et al. does not further disclose an embodiment wherein the detectable label is a rhodamine chromogen. However, Beija et al. discloses that rhodamine compounds are fluorophores that are used for a variety of different applications in the field of molecular biology. (p. 2410 left column) In particular, they can be used for the fluorescent labeling of biomolecules. (p. 2410 right column)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use a rhodamine fluorophore in place of the Cy3 fluorophore appearing in Lo’s probes. One of ordinary skill in the art would have fond this to be obvious based on the observation that these two fluorophores are both usable for the purpose of labelling biomolecules and that substituting one for another would be expected to be feasible with a reasonable expectation of success.
Therefore the invention taken as a whole is prima facie obvious.
Claims 17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Lo et al. (NPL reference of record in previous action) in view of Yasui et al. (Reference included with PTO-892)
Independent claim 17 is directed to compound (VI) which comprises a phenyl ring attached to an enzymatically cleavable group, a methine bearing a leaving group, and a detectable label. Dependent claim 20 further define the identity of the variable LG in this structure.
Lo discloses the compound
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R = dansyl
R = biotinyl (p. 38 scheme 2)
This compound has the same structure as that recited in claim 17, for reasons similar to those recited previously with respect to the reference Zhu et al. Lo et al. does not further disclose an embodiment wherein the detectable label is a rhodamine chromogen. However, Beija et al. discloses that rhodamine compounds are fluorophores that are used for a variety of different applications in the field of molecular biology. (p. 2410 left column) In particular, they can be used for the fluorescent labeling of biomolecules. (p. 2410 right column)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use a dabsyl dye in place of the Cy3 fluorophore appearing in Lo’s probes. One of ordinary skill in the art would have fond this to be obvious based on the observation that these two moieties are both usable for the purpose of labelling biomolecules and that substituting one for another would be expected to be feasible with a reasonable expectation of success.
Therefore the invention taken as a whole is prima facie obvious.
Conclusion
Claims 17 and 20 are rejected. Claims 1-5, 9, 10, 12, 13, 15-16, and 21-25 are seen to be allowable. Claim 19 is objected to for depending from a rejected base claim but would be allowable if rewritten in independent form incorporating all the limitations of the rejected base claim and any intervening claims. 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 ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 9/23/2026
