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 .
The amended claims filed 4/29/2026 are under consideration.
The amendments and arguments presented in the papers filed 4/29/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 2/6/2026 listed below have been reconsidered as indicated.
a) Any objections or rejections of claim 2, 5, 6, 49, 51 and 52 are rendered moot in view of the cancellation of the claims.
b) The rejections of claims 17, 18, 28 and 32 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of the amendments to the claims.
c) The rejections of claims 1, 7, 8, 15, 18, 19, 23, 29, 30, 32, 34, 40, 44 and 46 under 35 U.S.C. 102(a)(1) as being anticipated by Oikonomopoulou (Biol chem. 2008. 389:747-756) are withdrawn in view of the amendments to claim 1 incorporating the elements of claims 51 and 52.
d) The rejections of claim(s) 13 under 35 U.S.C. 103 as being unpatentable over Oikonomopoulou (Biol chem. 2008. 389:747-756) in view of Vieregg (J Am Chem Soc. 2013. 135:9691-9699) are withdrawn in view of the amendments incorporating the elements of claims 51 and 52.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Priority
The present application is a 371 national stage entry of PCT/US20/55657 (filed 10/15/2020), which claims benefit of US provisional application 62/915,310 (filed 10/15/2019).
Priority is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on a submitted IDS, they have not been considered.
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 53, 55 and 57 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.
Regarding claim 53, the claim recites “the tagged creatine transporter” in line 2. The recitation lacks proper antecedent basis as no “tagged creatine transporter” is previously set forth or described in the claim.
Claims 55 and 57 depend from claim 53 and are rejected for the same reason.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 7, 8, 15, 18, 19, 23, 29, 30, 32, 34, 40, 44 and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oikonomopoulou (Biol chem. 2008. 389:747-756; previously cited) in view of Wright (J Am Chem Soc. 2009. 131:10692-10700; previously cited).
PNG
media_image1.png
405
980
media_image1.png
Greyscale
Regarding claim 1, Oikonomopoulou teaches an ABRA-ELISA assay (p. 754, KLK6 ABRA-ELISA) as depicted in Fig. 3A, which is reproduced below and includes Examiner annotations mapping claim limitations:
Oikonomopoulou teaches contacting KLK6 as a “biological molecule” with a “probe molecule” in the form of a biotinylated proline-lysine-containing ABP (Fig. 3A). The “probe molecule” includes the “binding element” proline-lysine, the “reporter group” biotin and a “reactive moiety” (Fig. 3A). The “binding element” proline-lysine is a small molecule. The “reactive moiety” forms a covalent bond to irreversibly modify the enzyme active-site nucleophile (p. 748, left column). The proline-lysine binds the “probe molecule” to KLK6 as they are targets of the KLK6 enzyme (p. 754, KLK6 ABRA-ELISA). These elements of Oikonomopoulou are relevant to step (a) of claim 1.
Oikonomopoulou teaches contacting the above conjugate with a “detectable molecule” comprising the “functional moiety” streptavidin that reacts with the biotin “reporter group” (Fig. 3A). These elements of Oikonomopoulou are relevant to step (b) of claim 1.
Oikonomopoulou teaches the complex of the “detectable molecule”, the “biological molecule” and the “probe molecule” is contacted with a “solid support” in the form of an antibody capture plate and the “solid support” includes a capture antibody as a “recognition moiety” (Fig. 3A; p. 754, KLK6 sandwich-type ELISA). These elements of Oikonomopoulou are relevant to step (c) of claim 1.
Oikonomopoulou teaches detecting the above complex on the “solid support” using fluorescence (Fig. 3A). Oikonomopoulou teaches quantifying the amount of KLK6 (Fig. 4). These elements of Oikonomopoulou are relevant to step (d) of claim 1.
Oikonomopoulou does not teach including a “substrate” as encompassed by claim 1.
However, Wright demonstrates that using inhibitors as “substrates” that increase or decrease the amount of probe labeling using ABPP probes (p. 10700, left column) was known.
It would have been prima facie obvious to the ordinary artisan at the time of filing to have modified the method of Oikonomopoulou by including “substrates” that can interchange KLK6 between its active and proform state (Fig. 3). Using “substrates” that increase the amount of active KLK6 leads to more ABP labeling while using “substrates” that increase the amount of proform KLK6 leads to less ABP labeling. Alternatively, one could screen form “substrates” that block the ABP from interacting with and labeling KLK6.
Claim 1 also recites:
the probe molecule is a substrate-competitive probe if the amount of the bound detectable conjugate formed in the presence of the substrate for the biological molecule is less than the amount of the bound detectable conjugate formed in the absence of the substrate, or
the probe molecule is a substrate-cooperative probe if the amount of the bound detectable conjugate formed in the presence of the substrate for the biological molecule is greater than the amount of the bound detectable conjugate formed in the absence of the substrate.
The language does not set forth any additional active method steps that further limit the scope claim 1. The language sets forth information that is relevant to an intended use of the claimed active method steps based on the information that is gathered. Because the language does not limit the scope of the claim, the prior art does not need to address those elements.
Regarding claim 7, as noted above, Oikonomopoulou teaches the “binding element” is proline-lysine, a small molecule having a molecular weight of less than 300 Da.
Regarding claim 8, as noted above, Oikonomopoulou teaches KLK6, a protein, as the “biological molecule”.
Regarding claim 15, Oikonomopoulou teaches using capture antibodies against KLK6 as noted above. The binding sites of the capture antibodies are “epitope tags”.
Regarding claim 18, Oikonomopoulou teaches the “reactive moiety” forms a covalent bond to irreversibly modify the enzyme active-site nucleophile and thus, is “a moiety that forms a covalent bond with a nucleophilic moiety in the side chain of a naturally occurring alpha amino acid”.
Regarding claim 19, Oikonomopoulou teaches alkaline phosphatase as a “chromophore” or “luminophore” that produces fluorescence (Fig. 3A).
Regarding claim 23, as noted above, Oikonomopoulou teaches alkaline phosphatase, a non-fluorochrome chromophore.
Regarding claim 29, as noted above, Oikonomopoulou teaches a “solid support” in the form of an antibody capture plate, or a microtiter plate (p. 754, KLK6 sandwich-type ELISA).
Regarding claims 30 and 32, as noted above, Oikonomopoulou teaches the “recognition moiety” is an antibody against “epitope tags” of KLK6.
Regarding claim 34, as noted above, Oikonomopoulou teaches the detection is via an ELISA assay.
Regarding claim 40, Oikonomopoulou teaches the method is performed on purified KLK6 calibrators (p. 754, KLK6 sandwich-type ELISA).
Regarding claim 44, Oikonomopoulou teaches performing the method on a cell supernatant (Fig. 4), as a “cell-based assay”.
Regarding claim 46, Oikonomopoulou teaches performing the method on a cell supernatant (Fig. 4), as a “cell-based assay” where the biological molecule is expressed within the cell and released to the supernatant.
Response to the traversal of the rejections over Oikonomopoulou and Wright
The Remarks summarize the rejections over Oikonomopoulou and Wright (p. 8-9).
The Examiner’s position is detailed in the above rejections.
The Remarks argue the Examiner acknowledges that Oikonomopoulou does not disclose or suggest quantifying the amount of the bound detectable conjugate; and that the probe molecule is a substrate-competitive probe if the amount of the bound detectable conjugate formed in the presence of the substrate for the biological molecule is less than the amount of the bound detectable conjugate formed in the absence of the substrate, or the probe molecule is a substrate-cooperative probe if the amount of the bound detectable conjugate formed in the presence of the substrate for the biological molecule is greater than the amount of the bound detectable conjugate formed in the absence of the substrate (p. 9).
The arguments have been fully considered but are not persuasive. Oikonomopoulou is deficient regarding the substrate of claim 1. Oikonomopoulou teaches quantifying the amount of KLK6 (Fig. 4).
Claim 1 also recites:
the probe molecule is a substrate-competitive probe if the amount of the bound detectable conjugate formed in the presence of the substrate for the biological molecule is less than the amount of the bound detectable conjugate formed in the absence of the substrate, or
the probe molecule is a substrate-cooperative probe if the amount of the bound detectable conjugate formed in the presence of the substrate for the biological molecule is greater than the amount of the bound detectable conjugate formed in the absence of the substrate.
The language does not set forth any additional active method steps that further limit the scope claim 1. The language sets forth information that is relevant to an intended use of the claimed active method steps based on the information that is gathered. Because the language does not limit the scope of the claim, the prior art does not need to address those elements.
The Remarks summarize the Wright reference and Wright does not disclose or suggest that the identification of whether the probe itself is substrate-competitive or substrate-cooperative or that such analysis is a technical problem that needs to be addressed. Importantly, Wright is concerned with analyzing the P450 enzyme itself, and does Wright discloses a suite of Cytochrome P450-directed, activity-based probes (ABPs) (p. 9-10).
The arguments have been fully considered but are not persuasive. The identification of the probe as substrate-competitive or substrate-cooperative is not a limiting element of the claim as noted above. The alleged deficiency of Wright is supplied by the teachings of Oikonomopoulou.
The Remarks argue the rejections rely on hindsight reasoning (p. 10).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
The Remarks argue the references do not acknowledge the benefits of the claimed method and simply states that there is no reasonable expectation of success (p. 10).
The arguments have been fully considered but are not persuasive. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
The arguments provide no evidence or rationale of why a reasonable expectation of success does not exist. MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, counsel’s mere arguments that no reasonable expectation of success exists cannot take the place of evidence in the record.
It is noted that the Response above should not be construed as an invitation to file an after final declaration. See MPEP 715.09 [R-3].
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oikonomopoulou (Biol chem. 2008. 389:747-756; previously cited) in view of Wright (J Am Chem Soc. 2009. 131:10692-10700; previously cited) as applied to claim 8 above, and in further view of Vieregg (J Am Chem Soc. 2013. 135:9691-9699; previously cited).
Regarding claim 13, the combination of Oikonomopoulou and Wright renders obvious the elements of claim 1 as described above.
Oikonomopoulou does not teach the “biological molecule” of claim 13.
However, Vieregg teaches a “probe molecule” that is DNA or RNA based and interacts with a DNA or RNA molecule via hybridization. The “probe molecule” covalently attaches to the “biological molecule” (Figure 2).
It would have been prima facie to modify the format of the method of Oikonomopoulou for the detection of nucleic acids using the “probe molecule” of Vieregg. One would have been motivated to make the modification because it allows one to study and detect a range of nucleic acid targets. The modification includes adding the biotin tag of Oikonomopoulou to the nucleic acid of Vieregg, a process that is well-known in the field and using capture antibodies that bind nucleic acids or an epitope tag attached to the nucleic acids.
Claim(s) 17, 26 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oikonomopoulou (Biol chem. 2008. 389:747-756; previously cited) in view of Wright (J Am Chem Soc. 2009. 131:10692-10700; previously cited) as applied to claims 1 and 19 above, and in further view Sanman (Annu Rev Biochem. 2014. 83-249-273; previously cited).
Regarding claims 17 and 28, the combination of Oikonomopoulou and Wright renders obvious the elements of claims 1 and 19 as described above.
Oikonomopoulou does not teach the “reporter group” of claim 17 or the “functional moiety” of claim 28.
However, Sanman demonstrates the state of the art regarding ABPs, such as those described by Oikonomopoulou.
Regarding claims 17 and 28, Sanman teaches that as substitute for biotin as an affinity handle or “reporter group”, azides and alkynes may be used (p. 261).
Regarding claim 26, Sanman teaches an azido-biotin molecule is known.
One would recognize that when using azides and alkynes as “clickable handles”, one would be the “reporter group” and the other would be the “functional moiety”.
One would be motivated to use these alternative “reporter groups” and “functional moieties” because Sanman teaches they may be used as a latent reporter tag that may be converted into affinity probe and that they are more cell permeable that biotin for example (p. 261).
Conclusion
Claims 53, 55 and 57 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Claims 54, 56 and 58 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.
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 JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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, Wu-Cheng Winston Shen can be reached at 5712723157. 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.
/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
Prosecution Insights