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 .
Priority
This application claims benefit of priority to Provisional Application 63/187,965 filed on 05/13/2021. This application is also a Continuation in Part of 17/741,518 filed on 05/11/2022. Support for the instant claims can be found in the Provisional Application, therefore, for the purposes of applying prior art, the effective filing date of the claimed invention is 05/13/2021.
Drawings
The Drawings filed 05/29/2026 are accepted by the Examiner.
Amendments and Claim Status
In the reply filed 05/29/2026, Applicant amended claims 13 and 15-18. Claims 1-12 and 20 remain withdrawn by the Examiner as they are not encompassed by the elected group.
Claims 1-20 are currently pending.
Claims 1-12 and 20 are withdrawn by the Examiner.
Claims 13-19 are under examination.
Non-Compliant Amendment
Claim 13 does not have the required markings for an amended claim. Claim 13 recites: “a well that comprises one or more mutated kinases, wherein the one or more mutated kinases comprise a mutation that enlarges an ATP binding pocket of the kinase and wherein the system comprises an ATP or ADP analog-nanoparticle conjugate that comprises a detectable label conjugated to a ribose of the ATP or ADP
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 13-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 13 has been amended to recite “wherein the system comprises an ATP or ADP analog-nanoparticle conjugate that comprises a detectable label conjugated to a ribose of the ATP or ADP” in lines 3-5. Applicant indicates support for “a detectable label conjugated to a ribose of the ATP or ADP” can be found in Figure 5A. Figure 5A of the instant disclosure shows a kinase substrate being reacted with A*TPyS to form a thiphosphorylated kinase substrate. Figure 5A further shows a mutant kinase with constituents in the binding pocket. However, Figure 5A does not show anything specifically conjugated to a ribose of the ATP or ADP. Additionally, the instant Specification when describing Figure 5A simply states “wild type kinase utilizes normal ATP to phosphorylate its substrates. In contrast, the mutated kinase, with enlarged ATP binding pocket, accepts bulky A*TPyS and was able to transfer the thiophosphate group onto the substrates” (Specification, Paragraph [0020]). Further, ‘ribose’ is not recited anywhere in the instant disclosure. Thus, there is no information within the instant disclosure supporting the newly added limitation of “a detectable label conjugated to a ribose of the ATP or ADP.” This is new matter.
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 13-19 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 13 is directed to a system for detecting kinase activity. A single claim which claims both a product and the method steps of using that product is indefinite. See MPEP 2173.05(p)(II). Claim 13 as amended recites “an ATP or ADP analog-nanoparticle conjugate that comprises a detectable label conjugated to a ribose of the ATP or ADP” in lines 4-5 and goes on to recite “the detectable label on a substrate from the ATP or ADP analog-nanoparticle conjugate once it contacts the one or more mutated kinases” in lines 10-11 and further recites “the detectable label transfers from the ATP or ADP analog nanoparticle conjugate to the substrate of the one or more mutated kinases” in lines 13-14. It is unclear how many detectable labels are present because the claim contradicts itself in where ‘the detectable label’ is present. It is unclear if the detectable label is present on the ATP or ADP analog nanoparticle conjugate, a substrate or is just simply present in the system and becomes attached to something during one of the recited method steps. Thus, it is generally unclear how many detectable labels are present, where the detectable labels are present or if they are attached to something. Therefore, claim 13 and all claims dependent upon claim 13 are rendered indefinite.
Claims 17-18 as-amended remained rejected because Applicant has no clarified the structural components required by the system. Method steps are given patentable weight to the extent that the steps structurally limit the product. Claims 17-18 do not impart a structural limitation to the system itself. For the reasons listed above, the claims are rendered indefinite and are being interpreted as intended uses.
Claim 17 as-amended recites the limitation "detecting with the detector" in line 6. There is insufficient antecedent basis for this limitation in the claim. Claim 14, the claim from which claim 17 depends, does not recite ‘a detector’ nor does claim 13, the claim from which claim 14 depends. Thus, claim 17 lacks proper antecedent basis.
Claim 18 as-amended recites the limitation “detecting with the detector” in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 14, the claim from which claim 17 depends, does not recite ‘a detector’ nor does claim 13, the claim from which claim 14 depends. Thus, claim 18 lacks proper antecedent basis
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 13-19 are rejected under 35 U.S.C. 103 as being unpatentable over Shokat (US 6390821 B1, 05/21/2002) in view of Wang et al. (WO 2019014419 A1, 01/17/2019) and Huang et al. (US 20120201872 A1, 08/09/2012).
Regarding claims 13 and 16, see 112b above. As stated above, the system is interpreted to be directed to a product. Thus, the method steps are given weight to the extent that the steps structurally limit the product. Therefore, claim 13 is being interpreted as: A system for detecting kinase activity, comprising: a well that comprises one or more mutated kinases, an ATP or ADP analog-nanoparticle conjugate and a detectable label. The ‘capable of’ limitations are interpreted as intended uses
Shokat discloses engineered protein kinases which can utilize modified nucleotide triphosphate substrates that are not as readily used by the wild-type forms of those enzymes, and methods of making and using them (See entire document, Abstract). More specifically, Shokat discloses Figure 9 which shows one kinase (Src) containing a notch cut out which represents the I338G mutation which creates an extra space in the adenine binding pocket of the kinase (Column 12, Lines 18-21), reading on a mutated kinase comprising a mutation that enlarges an ATP binding pocket of the kinase. Further, Example 1 describes twelve ATP analogs which were used in the studies on mutant v-Src (Column 14, Lines 54-55). One of the twelve ATP analogs synthesized by Shokat used in the study on mutant v-Src was N6(benzyl)ATP (Column 26, Example 1, Analog #5), reading on the elected ATP analog. Shokat further discloses labeling the phosphate on the orthogonal substrate, e.g., by using radioactive phosphorous (32P) (Column 7, Lines 55-56), reading on the ATP analog comprising a detectable label. Shokat further discloses mutant v-Src cells (Column 44, Lines 30-34), meaning the mutated kinases were in cells.
Shokat further discloses there is high degree of functional homology between the serine/threonine and the tyrosine kinase catalytic domains as shown by affinity labeling of the identical catalytically active lysine residue in both kinase families (Column 28, Lines 26-30). Additionally, based on the functional similarity between the PKA and v-Src kinases, the decision was made to mutate positions V323 and I338 in the v-Src catalytic domain, which corresponds to V104/M12 in PKA (Column 28, Lines 65-66 – Column 29, Lines 1-2). Shokat states:
it is worth noting that Applicant is not aware of any wild-type protein kinases which contain an alanine at the position corresponding to I338 in v-Src (position 120 in PKA). If a sterically demanding amino acid side chain at this position also plays a critical role in determining the specificity of other kinases, it should well be possible to engineer them to accept orthogonal substrates using an approach very similar to the one described here, and such engineered kinases would be well within the scope of the present invention (Column 31, Lines 19-29).
Shokat also states that while the discussion focuses mainly on tyrosine kinases, the discussion is generally applicable to serine/threonine kinases as well (Column 2, Lines 58-61). It is noted Applicant elected AGC as the specific type of mutated kinase. AGC is a species of serine/threonine kinase and PKA is a species of AGC kinase. Thus, PKA is a species of the elected mutated kinase.
Overall, Shokat discloses a mutated kinase comprising a mutation that enlarges the ATP binding pocket of the kinase and an ATP analog comprising a detectable label.
Shokat does not disclose mutating the PKA kinase, the use of a well or an ATP analog-nanoparticle conjugate.
However, as discussed above, Shokat discloses the high degree of functional homology between serine/threonine and tyrosine kinase catalytic domains and the specific amino acids in PKA, a serine/threonine kinase, corresponding to the amino acids in v-Src that were mutated in the study. Also, it would be possible, and within the scope of the Shokat’s invention, to engineer other kinases to accept orthogonal substrates if they have a sterically demanding amino acid side chain in a specific position using Shokat’s approach.
Additionally, Wang et al. disclose in vitro kinase assays (Page 31, Line 5). Further, the kinase assay was performed in a 96-well plate to measure activity of a detectable label (Page 31, Lines 6-12).
Further, Huang et al. disclose methods and compositions for delivering bioactive compounds to a cell, tissue or physiological site (See entire document, Abstract). More specifically, Huang et al. disclose the need for delivery vehicles for delivering macromolecules to appropriate cellular targets and lipid-comprising vehicles that meet that need (Paragraph [0004]). Targets for the lipid-comprising vehicles include multiple types of kinases, including cytoplasmic tyrosine kinases such as Src (Paragraph [0254]). Compositions include delivery system complexes comprises a biodegradable ionic precipitate comprising a bioactive compound, wherein the precipitate is encapsulated by a liposome, wherein the bioactive compound can comprise any type of bioactive compound and wherein the delivery system complexes can be formulated into liposome/calcium phosphate (LCP) nanoparticles (Paragraph [0005]).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize PKA as the kinase to be mutated in the approach of Shokat because Shokat specifically stated the approach could be utilized to engineer other kinases to accept orthogonal substrates, and also gave the amino acid position of PKA that corresponds to the amino acid of v-Src that was mutated, motivated by the desire to determine if PKA could be mutated in the same fashion with a reasonable expectation of success as Shokat specifically stated the approach is generally applicable to serine/threonine kinases. It would have been further obvious to utilize a well plate in the kinase assay of Shokat because it was a known technique as disclosed by Wang et al. for in vitro kinase assay motivated by the desire to effectively measure the activity of a detectable label with a reasonable expectation of success.
It would have been further obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized an LCP nanoparticle to form an ATP analog-nanoparticle conjugate in the system of Shokat because the target of Shokat is a cytoplasmic tyrosine kinase, specifically, Src, and utilizing an LCP nanoparticle was a known and effective means of delivering a bioactive compound, of which ATP analogs are, to a specific target, including Src kinases, within a cell as taught by Huang et al.
Regarding claim 14, as disclosed above regarding claim 13, Shokat discloses the ATP analog N6(benzyl)ATP, the ATP analog elected.
Regarding claim 15, the method steps are given weight to the extent that the steps structurally limit the product. The method steps of this claim do not structurally limit the product, therefore, this claim is interpreted as an intended use of the system.
Regarding claims 17-18, the method steps of these claims are given weight to the extent that the steps structurally limit the product. The methods steps of these claims do not structurally limit the product, therefore, these claims are interpreted as intended uses of the system.
Regarding claim 19, Shokat discloses Example 5, testing the mutant v-Src for the ability to bind orthogonal ATP analogs (Column 30, Lines 32-33). More specifically, assays were carried out wherein the kinase was added to the twelve different ATP analogs to determine activity (Column 30, Lines 35-45), reading on an array wherein multiple different substrates are used to detect activity of the substrate on the mutated kinase.
Shokat does not disclose the use of a well.
However, Wang et al. disclose in vitro kinase assays (Page 31, Line 5). Further, the kinase assay was performed in a 96-well plate to measure activity of a detectable label (Page 31, Lines 6-12).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize a well plate in the kinase assay of Shokat because it was a known technique as disclosed by Wang et al. for in vitro kinase assay motivated by the desire to effectively measure the activity of a detectable label.
USC § 103 – Response to Arguments
Applicant's arguments filed 05/29/2026 have been fully considered but they are not persuasive.
Applicant argued the combination of Shokat and Wang fails to teach each and every element of the invention as claimed because Shokat detects activity based on the y-phosphate group whereas in the instant invention the detectable label is attached to the ribose of ATP or ADP (Page 11). Applicant further argues fluorescence in the instant invention is dependent upon ATP pocket engagement not phosphate transfer and is therefore structurally and functionally distinguishable from Shokat (Page 12). Applicant lastly argues that the chemistry of Shokat cannot be used with live cells without nanoparticles and that Wang does not provide a solution for delivering the analogs into live cells (Page 12).
The Examiner respectfully disagrees. The detectable label being attached to the ribose of ATP or ADP has been addressed in the modified rejection set forth above (See 112b above). Regarding the fluorescence being dependent upon ATP pocket engagement, the fluorescence in Shokat occurs based upon engagement with the ATP binding pocket. Lastly, the use of live cells is not claimed.
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 13-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-20 of copending Application No. 17/741,518 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application and ‘518 are directed to a system for detecting kinase activity. More specifically, claim 13 of ‘518 recites:
A system for detecting kinase activity in vivo, comprising:
a well and a detector positioned to detect an analyte in the well, wherein the well comprises live cells that comprise one or more mutated kinases, and wherein the one or more mutated kinases comprise a mutation that enlarges an ATP binding pocket of the kinase,
an ATP analog-nanoparticle conjugate capable of intracellular delivery of the ATP analog-nanoparticle conjugate,
wherein the ATP analog comprises a detectable label, and after a predetermined period of time, a detectable label on a substrate from the ATP analog-nanoparticle conjugate when it contacts the one or more mutated kinases in cellulo is capable of being detected, and
the detectable label is capable of being transferred from the ATP analog-nanoparticle conjugate to the substrate of the one or more mutated kinases;
wherein the detector is capable of measuring the detectable label being transferred from the ATP analog-nanoparticle conjugate to the substrate of the one or more mutated kinases in the live cells.
Thus, the teachings read on and anticipate the claimed invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Double Patenting – Response to Arguments
Applicant's arguments filed 05/29/2026 have been fully considered but they are not persuasive.
Applicant requests abeyance until these claims or the claims of the co-pending application are allowable.
The Examiner maintains the double patenting rejection as the claims of ‘518 remain pending and are not patentably distinct from the instant claims.
Conclusion
Claims 13-19 are rejected.
No claims are allowed.
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 ASHLEY T WHITE whose telephone number is (571)272-0683. The examiner can normally be reached Monday - Friday 8:30 - 5:00 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
Prosecution Insights