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 supplement amended claims filed 6/15/2023 are under consideration.
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.
Specification
The amendments to the specification filed 4/14/2022 are acknowledged.
Claim Interpretation
Claim 6 states “wherein the binding element is a component of a library comprising a plurality of binding elements”. The claim does not require an active method step of providing the “library”. The claim does not set forth any limitation regarding the structure of the binding element as incorporated into the “probe molecule”.
Claim 7 further limits the “binding elements” of the “library”, which is not required by the method as presently claimed. The “binding element” of the “probe molecule” is limited to the extent that it has one of the characteristics described in the claim.
Claims 51 and 52 are interpreted as further limiting the embodiments of claim 49 in which both step (a) and step (d) are limited.
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 17, 18, 28, 32, 51 and 52 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 17, the phrase “e.g.,”, which essentially means "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 18, the phrase “e.g.,”, which essentially means "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 28, the phrase “e.g.,”, which essentially means "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 32, the phrase “the epitope tag” in the last line lacks proper antecedent basis.
Regarding claim 51, the claim states “i.e., the probe molecule is a substrate-competitive probe”. It is unclear if this statement further limits the scope of the claim or is merely identifying the probe molecule with an alternative name.
Regarding claim 52, the claim states “i.e., the probe molecule is a substrate-cooperative probe”. It is unclear if this statement further limits the scope of the claim or is merely identifying the probe molecule with an alternative name.
Regarding claims 51 and 52, the claims require limiting step (d) as described in claim 49, but does not require limiting step (a). The claims refer to “the substrate” which is not a required element of the claim. Thus, the claim is incomplete because it refers to an element that is not specifically required by the claims. Amending the claim to recite “wherein step (a) further comprises a substrate for the biological molecule and step (d) further comprises quantifying the amount of the bound detectable conjugate” may overcome this rejection.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1, 2, 6, 7, 8, 15, 18, 19, 23, 29, 30, 32, 34, 40, 44, 46 and 49 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oikonomopoulou (Biol chem. 2008. 389:747-756).
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Regarding claim 1, Oikonomopoulou teaches an ABRA-ELISA assay (p. 754, KLK6 ABRA-ELISA) as depicted in Fig. 3A, which is reproduced below and including 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 “reactive moiety” forms a covalent bond to irreversibly modify the enzyme active-site nucleophile (p. 748, left column). The proline-lysine bind 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). These elements of Oikonomopoulou are relevant to step (d) of claim 1.
Regarding claim 2, as noted above, Oikonomopoulou teaches the “binding element” is proline-lysine, a small molecule.
Regarding claim 6, the claim does not limit the structure of the “binding element” based on describing where it is “from” or what it is “part of”.
Oikonomopoulou anticipates claim 6 for the same reason as claim 1 described above.
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.
Regarding claim 49, Oikonomopoulou teaches quantifying the amount of KLK6 (Fig. 4).
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) 5 and 13 is/are rejected 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).
Regarding claims 5 and 13, Oikonomopoulou teaches an ABRA-ELISA assay (p. 754, KLK6 ABRA-ELISA) as depicted in Fig. 3A, which is reproduced above and including Examiner annotations. 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 “reactive moiety” forms a covalent bond to irreversibly modify the enzyme active-site nucleophile (p. 748, left column). The proline-lysine bind 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). These elements of Oikonomopoulou are relevant to step (d) of claim 1.
Oikonomopoulou does not teach the “binding element” of claim 5 or 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) in view of Sanman (Annu Rev Biochem. 2014. 83-249-273).
Regarding claims 17 and 28, Oikonomopoulou teaches an ABRA-ELISA assay (p. 754, KLK6 ABRA-ELISA) as depicted in Fig. 3A, which is reproduced above and including Examiner annotations. 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 “reactive moiety” forms a covalent bond to irreversibly modify the enzyme active-site nucleophile (p. 748, left column). The proline-lysine bind 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). These elements of Oikonomopoulou are relevant to step (d) of claim 1..
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).
Claim(s) 51 and 52 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oikonomopoulou (Biol chem. 2008. 389:747-756) in view of Wright (J Am Chem Soc. 2009. 131:10692-10700).
Regarding claims 51 and 52, Oikonomopoulou teaches an ABRA-ELISA assay (p. 754, KLK6 ABRA-ELISA) as depicted in Fig. 3A, which is reproduced above and including Examiner annotations. 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 “reactive moiety” forms a covalent bond to irreversibly modify the enzyme active-site nucleophile (p. 748, left column). The proline-lysine bind 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). These elements of Oikonomopoulou are relevant to step (d) of claim 1.
Oikonomopoulou does not teach the additional elements specific to claims 51 and 52.
However, Wright teaches 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.
Conclusion
No claims allowed.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682