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 .
The Response of 29 May 2026 has been entered.
Claims 1-10 are currently pending.
Election/Restrictions
Applicant’s election without traverse of the invention of Group I, claims 1, 3 and 4, and a reaction enhancer as the species of kit component in the reply filed on 29 May 2026 is acknowledged. The restriction requirement of 9 April 2026 indicates that Group I includes claims 1 and 3, but as noted in Applicant's response, Group I should also include claim 4 (which was inadvertently omitted).
Claims 2 and 5-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 29 May 2026.
Claims 1, 3 and 4 are considered here.
Claim Objections
Claim 1 is objected to because of the following informalities:
The second recitation of "formula I:" in claim 1 should be deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 recites a kit "at least the nucleoside triphosphate photoaffinity probe according to claim 1". Where the kit comprises only the probe of claim 1, claim 3 does not further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 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 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Jelcic et al., Cell chemical biology 27.8 (2020): 1073-1083 in view of Joachimiak et al., Journal of Medicinal Chemistry 61.19 (2018): 8536-8562.
Jelcic teaches an ATP photoaffinity probe comprising a photo-crosslinker attached to the adenosine N6 position, wherein the crosslinker comprises a diazirine moiety for photo-induced crosslinking to targeted ATP-binding proteins and a "clickable" terminal alkyne moiety for click chemistry-mediated coupling to groups of interest, such as affinity tags (e.g., biotin) and/or labels (p. 1073, last ¶ to p. 1075, 1st ¶; Fig. 1; p. 1075, under Design and Verification of mipATP Probe). The crosslinker has the same structure as the crosslinker attached to the terminal phosphate group of the probe of formula (I) of the instant claims (cf. claim 1 vs. Jelcic, Fig. 1A). Jelcic teaches that large affinity tags such as biotin can alter ATP binding via steric exclusion or non-physiological interactions, and that the clickable alkyne moiety overcomes such problems by allowing for conjugation after probe-target complexes have formed (p. 1073, last ¶ to p. 1075, 1st ¶). Jelcic further teaches that ATP probes are commonly functionalized at the terminal γ-phosphate, which favors the identification of enzymatic (e.g., kinase) targets, and that modification of the N6 position of adenosine as in the probe of Jelcic allows for identification of allosteric ATP binders (e.g., receptors) (p. 1073, last ¶; p. 1080, 1st ¶ under DISCUSSION).
Claims 1 and 3 differ from Jelcic in that the crosslinker is bound to the terminal γ-phosphate via a phosphoramidate bond.
Joachimiak is a review article on ATP/GTP probes (Abstract). Joachimiak teaches that ATP probes are commonly labeled on the nucleoside base (as in Jelcic) or on the terminal γ-phosphate, and that the terminal phosphate probes enable labeling of numerous enzymes including kinases (p. 8538, 1st-2nd ¶). Joachimiak teaches a probe (Table 1, entry 9, molecule 15) comprising a crosslinker linked to the terminal γ-phosphate via a phosphoramidate bond comprising both a photocrosslinking moiety (benzophenone) and a terminal clickable alkyne moiety, and teaches that the probe was useful in labeling numerous GTP- and ATP-binding proteins (p. 8541, 1st full ¶). Joachimiak further teaches additional ATP/GTP probes labeled at the terminal γ-phosphate via a phosphoramidate bond with crosslinkers bearing various photocrosslinking moieties (including diazirine) and clickable alkyne tags (Tables 1, entries 4-8).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to make an ATP probe comprising a crosslinker with a diazirine photocrosslinking moiety and a "clickable" terminal alkyne moiety as taught by Jelcic wherein the crosslinker is attached at the terminal γ-phosphate via a phosphoramidate bond at taught by Joachimiak because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to attach the crosslinker of Jelcic to the terminal γ-phosphate because Joachimiak (and Jelcic) teaches that attachment to the terminal phosphate allows for effective labeling of kinases and other ATP-binding enzymes. Moreover, one of ordinary skill would have been motivated to make a terminal phosphate probe as taught by Joachimiak with the crosslinker of Jelcic because Jelcic teaches that the probe allows both photocrosslinking and conjugation with groups of interest such as affinity tags without interfering with ATP-target binding. Attaching the crosslinker of Jelcic to the terminal γ-phosphate would have led to predictable results with a reasonable expectation of success because both Joachimiak and Jelcic teach that ATP probes are commonly derivatized at either the terminal phosphate (as in Joachimiak) or the adenosine base as in Jelcic, and Joachimiak further teaches a variety of known probes that are derivatized at the terminal phosphate and comprise photocrosslinking and/or clickable moieties similar to those of Jelcic.
Regarding claim 3, the claim is drawn to a kit comprising "at least the nucleoside triphosphate photoaffinity probe according to claim 1". Since the kit need only comprise the probe, claim 3 is obvious under the same basis as claim 1.
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Jelcic in view of Joachimiak, as applied to claims 1 and 3 above, further in view of US5800991 to Haley et al.
The teachings of Jelcic and Joachimiak are set forth above. Regarding claims 3-4, Jelcic further teaches a step of labeling proteins with the probe in the presence of a binding buffer, which comprises a pH buffer and various salts, including MgCl2 (p. e7, under mipATP Labeling of Proteins in Isolated Membrane Fractions). The instant specification states that MgCl2 is a reaction (probe labeling) enhancer (Published Spec. US20240400604, [0016]-[0017]) .
Claims 3 and 4 differ from the combination of Jelcic in view of Joachimiak, as applied to claims 1 and 3 above, in that: the probe is comprised in a kit with an additional component which is a reaction enhancer (elected species of kit component).
Haley teaches kits comprising an ATP photoaffinity probe any substrates/materials necessary for the detection of the probe (col. 7, lines 5-21).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to prepare a test kit comprising the photoaffinity probe of Jelcic in view of Joachimiak together with materials needed for use of the probe such as the binding buffer of Jelcic because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to prepare a test kit comprising the photoaffinity probe of Jelcic in view of Joachimiak and the binding buffer of Jelcic in order to provide a convenient commercial product with all of the materials needed to apply the probe for its intended use of labeling target proteins. Preparing a test kit comprising the photoaffinity probe of Jelcic in view of Joachimiak and the binding buffer of Jelcic would have led to predictable results with a reasonable expectation of success because doing so would have required only assembling known components together in a kit in a known manner.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J YAMASAKI whose telephone number is (571)270-5467. The examiner can normally be reached M-F 930-6 PST.
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657
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