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.
Information Disclosure Statement
The Information Disclosure Statements filed on 05/24/2023 have been acknowledged and considered.
Drawings
The drawings are objected to because multiple Figures within the Drawings are not in black and white. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Election/Restriction
Applicant’s election without traverse of Group III, claims 13-19, in the reply filed on 10/27/2025 is acknowledged.
Regarding the election of species, Applicant elected:
One as the specific number of kinases and AGC as the specific mutated kinase;
ATP as the specific analog-nanoparticle conjugate;
In vivo as where the kinase is;
A cell line as the specific type of cell;
An LCP nanoparticle as what the nanoparticle comprises;
N6-TNP-benzyl-ATP as the specific ATP or ADP analog;
Serine/threonine kinase as the specific type of kinase;
Fluorescence as the specific detectable label;
ATP or ADP analog is not thio-substituted as what the method entails; and
An assay testing a compound suspected of kinase modulation as what the cell is contacted with.
Applicant's election with traverse of the multiple species elections in the reply filed on 10/27/2025 is acknowledged. The traversal is on the grounds that upon the allowance of a generic claim, there is no additional burden for examination once a generic claim has been found allowable. This is not found persuasive because there are currently no allowable claims, therefore, as stated in the Restriction Requirement mailed on 08/25/2025, the species are independent or distinct because the claims to different species recite the mutually exclusive characteristics of such species including different numbers of mutated kinases, different analog-nanoparticle conjugates, different locations for the kinase, different types of cells, different type of nanoparticles, different ATP and ADP analogs, different types of kinases, different detectable labels, different components used and different compounds. In addition, these species are not obvious variants of each other based on the current record. The species will be rejoined if a generic claim is found allowable.
The requirement is still deemed proper and is therefore made FINAL.
Amendments and Claim Status
As discussed above, in the reply filed on 10/27/2025, Applicant elected Group III, encompassing claims 13-19. Therefore, claims 1-12 and 20 are 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.
Claim Objections
Claim 13 is objected to because of the following informalities: Claim 13 uses present and past tense language. For example, ‘the one or more mutated kinases are contacted’ is in the present tense while ‘the detectable label was transferred’ is in the past tense. Appropriate correction is required.
Claim 18 is objected to because of the following informalities: Claim 18 recites “The system of claim 14, further comprising further comprising contacting the …” in line 1 of the claim. Further comprising is recited twice. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 recites “… wherein the one or more mutated kinases are contacted with an ATP or ADP analog-nanoparticle conjugate …” in lines 4-5, “… detecting a detectable label on a substrate from the ATP or ADP analog …” in lines 8-9 and “… the detectable label was transferred from the ATP or ADP analog-nanoparticle conjugate to the substrate …” in lines 10-11, which are all method steps. It is unclear how the aforementioned method steps are intended to limit the system. A system, which is a product, is a tangible, physical thing, not a method. Thus, it is unclear how the method steps are intended to limit the system. Method steps are given patentable weight to the extent that the steps structurally limit the product. These method steps are interpreted as intended uses because the Examiner cannot determine from the claims as-written, in light of the Specification, how the steps are structurally limiting the product, the system, by reciting method steps. The method steps are not being examined as limitations of the system as they do not impart a structural limitation to the system. Claim 13, and all claims dependent upon claim 13, are rendered indefinite.
Claim 13 recites “wherein the ATP or ADP analog comprises a detectable label, and after a predetermined period of time, detecting a detectable label on a substrate from the ATP or ADP analog-nanoparticle conjugate contacts the one or more mutated kinases” in lines 7-9 of the claim. It is unclear exactly what the scope of the claim is in the last portion of the recited lines. It appears, when the claim is taken as a whole, the scope of the claim is intended to mean the ATP or ADP analog-nanoparticle conjugate comes into contact with the mutated kinase. However, the Examiner cannot ascertain the full scope or metes and bounds of the claim as it is unclear what “wherein the ATP or ADP analog comprises a detectable label, and after a predetermined period of time, detecting a detectable label on a substrate from the ATP or ADP analog-nanoparticle conjugate contacts the one or more mutated kinases” means. Thus, claim 13, and all claims dependent upon claim 13, are indefinite. It is suggested to amend the claim to recite “… detecting a detectable label on a substrate from the ATP or ADP analog-nanoparticle conjugate when it contacts the one or more mutated kinases …” or “… detecting a detectable label on a substrate from the ATP or ADP analog-nanoparticle conjugate once it contacts the one or more mutated kinases …,” or something similar.
The limitations within claim 13 that are clear include: “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” from lines 2-3 and “wherein the ATP or ADP analog comprises a detectable label” from line 7 of the claim. However, the “ATP or ADP analog” lacks antecedent basis because the limitation regarding the ATP or ADP analog is part of the method step that is being interpreted as an intended use. Even so, for the purposes of compact prosecution and applying prior art, Claim 13 is being interpreted as: A system for detecting kinase activity, comprising: 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, wherein the system comprises an ATP or ADP analog and wherein the ATP or ADP analog comprises a detectable label.
Claim 15 recites “wherein the system determines the presence of the substrate in a sample, wherein the substrate is a known substrate for the one or more kinases, or detecting the presence of a previously unknown substrate for the one or more kinases” in lines 1-3 of the claim. ‘Detecting the presence of a previously unknown substrate’ is unclear because the substrate is either known or unknown. Also, it is unclear what previously is intended to add to the limitation. Furthering the indefiniteness, “previously” is a relative term which renders the claim indefinite. The term “previously” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, claim 15 is rendered indefinite. For the purposes of examination and applying prior art, this claim is interpreted as an intended use of the system because the method steps within the claim do not impart a structural limitation to the system.
Claim 15 recites “… or, detecting the presence of a previously unknown substrate for the one or more kinases” in lines 2-3 of the claim. As-written, “detecting the presence of a previously unknown substrate for the one or more kinases” is the last member of the Markush group present in claim 15. However, the preamble states the system determines the presence of the substrate, yet the last option in the Markush group states detecting the presence of a previously unknown substrate. Thus, it is unclear whether the system is determining or detecting. It is suggest to amend the claim to recite: “The system of claim 13, wherein the system: determines the presence of the substrate in a sample, wherein the substrate is a known substrate for the one or more kinases, or detects the presence of a previously unknown substrate for the one or more kinases.”
Claim 16 recites “AGC kinases (PKA, PKG, PKC, PKN, PDK1, AKT, SGK, RSK, RSKR, RSKL, GRK, NDR, MAST, DMPK, YANK, AND PTF subfamilies) …, CMGC kinases (CDK, MAPK, GSK3 and CLK subfamilies) …” in lines 2-5 of the claim. The use of parentheses in this manner renders the claim indefinite as it is exemplary language because it is unclear, and one of ordinary skill in the art would not be able to determine, if the species within the parentheses are simply suggestions or if the species within the parentheses are actual limitations of the claim. It is noted Applicant has elected a specific species, an AGC kinase, and the entire scope of the claim is not being examined at this time. However, the use of parentheses still renders the claim indefinite.
Claims 17-18 further recite method steps. 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 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).
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, wherein the one or more mutated kinases comprise a mutation that enlarges an ATP binding pocket of the kinase, wherein the system comprises an ATP or ADP analog and wherein the ATP or ADP analog comprises a detectable label.
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 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 or the use of a well.
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).
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.
Regarding claim 14, as disclosed above regarding claim 13, Shokat discloses the ATP analog N6(benzyl)ATP, the ATP analog elected.
Regarding claim 15, see 112b above. 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, see 112b above. 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.
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 1 of ‘518 recites:
A system for detecting kinase activity in vivo, comprising:
a well that comprises cells that comprise one or more mutated kinases, wherein the one or more mutated kinases comprise a mutation that enlarges an ATP binding pocket of the kinase,
wherein the cell is contacted with 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, detecting a detectable label on a substrate from the ATP analog-nanoparticle conjugate contacts the one or more mutated kinases in cellulo, and
wherein the detectable label was transferred from the ATP analog-nanoparticle conjugate to the substrate of the one or more mutated kinases.
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.
Conclusion
Claims 13-19 are rejected.
No claims are allowed.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653