Detailed Action
► The applicant's Preliminary Amendment filed 27 DEC 2022 has been entered. Following the entry of the Preliminary Amendment, Claim(s) 18-29 and 34-41 is/are pending.
► The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Sequence Rules
► This application complies with the sequence rules and the sequence(s) have been entered by the Scientific and Technical Information Center.
► The listing of references in 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, they have not been considered.
Priority
► The priority dated afforded the instant claims is the filing date of earliest filed provisional application 62444734 filed 10 JAN 2017.
35 U.S.C. 102
► The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that may 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
35 U.S.C. 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.
► 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 Rejection(s) under 35 U.S.C. 103
► Claim(s) 18-29 and 34-41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schweitzer et al. PNAS 97(18) :10113-10119(2000) – hereinafter “Schweitzer”] in view of Kishi et al. [US 2019/016733 – hereinafter Kishi].
Claim 18 is drawn to a method for the multiplexed detection of targets (i.e, peptides or proteins) which comprises .
(a) combining a sample containing a plurality of protein or peptide targets with a plurality of primary binding partners, each of which binds specifically to a protein or peptide target and is linked to a probe strand, and producing a first reaction mixture comprising protein or peptide bound to primary binding partners;
(b) combining the first reaction mixture produced in step (a) with dNTPs, strand- displacing polymerase, and a plurality of catalytic molecules, each catalytic molecule comprising, 5' to 3', a first domain, a second domain, and a third domain, wherein the first domain is bound to the second domain, and the third domain is an unpaired 3' tochold domain complementary to the probe strand of one of the primary binding partners, and producing a second reaction mixture comprising nucleic acid concatemers bound to primary binding partners; and
(c) combining the second reaction mixture produced in step (b) with a plurality of signal strands, each signal strand linked to a different detectable molecule and comprising a domain complementary to the probe strand of one of the primary binding partners, and producing concatemers labeled by a plurality of signal strands.
Schweitzer teach, see the entire document , noting especially Fig.1 on pg.10114, a multiplex method for the detection of target molecule(s) (i.e. protein or peptides) which comprises most of the limitations recited by claim 1 For example Schweitzer teach immuno-RCA with detection of the concatemers produced by an RCA reaction by hybridization to labeled probes (i.e. signal strands). See also Kingsmore et al. [US2006/0166227- hereinafter “Kingmore”]. Kingsmore teach the equivalent method as disclosed in Schweitzer. Further note that the RCA reaction taught by Schweitzer uses a strand displacing DNA polymerase (i.e. phi 29 DNA polymerase) and dNTPs . That said, Schweitzer fails to teach the use of catalytic nucleic acid molecules to produce the concatemers as required by the claims. Rather, as noted above the concatemers of Schweitzer are rolling circle amplification products produced by RCA using phi 29 DNA polymerase) and dNTPs. However, other methods of forming concatemers were known. For example, Kishi teach a method termed Primer Exchange Reaction (i.e.PER) which uses catalytic nucleic acid molecules in combination with a strand displacing polymerase(s) and dNTPs to produce long stands of nucleic strands (i.e. concatamers), see Fig. 7-8, paras 32-33 and 71. Also note that the long nucleic acids stands produced by PER comprise repeat sequence regions (i.e. concatemers). Accordingly, absent an unexpected result it would have been prima facie obvious to the PHOSITA at the time of the invention to substitute the means, e.g. PER, of producing concatemers of Kishi for that of Schweitzer (i.e. RCA). Please note that substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
Claims 19-20 recite essentially the same method as Claim 1 except with slightly different wording. Most notably, Schweitzer teach a primary binding partner bound to a “bridge strand”, see Fig.1 top left panel. Also see the section on pg. 10114 entitled AB-DNA Conjugates. It appear the applicant in Claim(s) 19-20 is attempting to encompass an embodiment in which the concatemer / signal probe complex is formed separately (i.e.. away from the binding partner/target molecule complex and then subsequently hybridizing said complex via a bridge probe/capture probe to said binding partner. This in contrast to the embodiment of Claim 1 wherein the applicant is attempting to encompass a method wherein concatemer molecule /signal probe complex is formed while the binding partner (e.g. antibody) is in contact with the target molecule in sequential hybridization/wash steps However, it is noted that it would have been prima facie obvious to an ordinary practitioner to switch the order of ingredient addition, see MPEP 2144.04 which refers to In re Gibson, 39 F.2d 975,5 USPQ 230 (CCPA 1930) Selection of any order of mixing ingredients is prima facie obvious''.
As regards Claim(s) 21, Schweitzer teach a “primary binding partner” (i.e. an antibody bound to a target analyte bound to a “bridge strand”, see Fig.1 top left panel. Also see Collier et al. [US 8,445,199 (2013) – hereinafter “Collier”] who teach a primary binding partners (i.e.an antibody) comprising a bound concatemer with associated (i.e. hybridized) signal strands.
Claim 22 is drawn to an embodiment of the method of Claim 18 wherein the catalytic molecules and/or the probe strands are comprised of DNA and/or RNA.
Schweitzer teach this limitation. The oligo attached to the antibody is comprised of DNA., see Fig.1 top left panel and the section on pg. 10114 entitled “Ab-DNA conjugates”. In addition, see Kishi who teach catalytic molecules composed of DNA and/or RNA, see at least para 111.. Further note that antibody-RNA conjugates were well known as were RNA probes. See for example, para 39 in Vigneault et al [US 2020/0088725 – hereinafter “Vigneault”] wherein antibody-RNA conjugates are taught and para 6 in Si-Ammour et al.[US2006/0057590 - hereinafter “Si-Ammou”] wherein these inventors teach “RNA probes”.
Kishi teach the limitation(s) of Claim 23, see at least Fig. 1.
Kishi teach “stopper molecule/modifications” which terminate polymerization as recited by Claim(s) 24-25, see paras 37, 40, 72 and 171-172.
Kishi teach” loops” as recited by Claim 26, see at least para 78-79.
Regarding Claim 27, Kishi teach fluorophore labeled probes(signal strands and primers, see at least para 94 and 372 . In addition, Schweitzer teach the use of fluorophore labeled probes, see at least the legend in Fig. 1.
Regarding Claim(s) 28, both Schweitzer and Kishi teach the use of phi29 DNA polymerase. See the section entitled “ELISA” on pg.10114 of Schweitzer and para(s) 99 in Kishi.
Regarding Claim(s) 29, Kishi teach performing PER in cells, see at least paras 149 and Claims 27-29.
Regarding Claim(s) 34-35, both Schweitzer and Kishi teach imaging , see Figs. 3-5 in
Schweitzer and at least para(s) 144 in Kishi
As regards Claim (s) 36, Schweitzer teach a primary binding partner (i.e. antibodies) bound to a “bridge strand”, see Fig.1 top left panel. Also see Collier et al. [US 8,445,199 (2013) – hereinafter “Collier”] who teach a primary binding partners (i.e. antibodies) comprising a bound concatemer with associated hybridized signal strands.
Kishi teach “stopper molecule/modifications” which terminate polymerization as recited by Claim(s) 37, see paras 37, 40, 72 and 171-172.
Regarding Claim(s) 38, both Schweitzer and Kishi teach imaging , see Figs. 3-5 in
Schweitzer and at least para(s) 144 in Kishi
As regards Claim (s) 39, Schweitzer teach a primary binding partner (i.e. antibodies) bound to a “bridge strand”, see Fig.1 top left panel. Also see Collier et al. [US 8,445,199 (2013) – hereinafter “Collier”] who teach a primary binding partners (i.e. antibodies) comprising a bound concatemer with associated signal strands.
Regarding Claim(s) 40, Kishi teach fluorophore labeled probes(signal strands and primers, see at least para 94 and 372 . In addition, Schweitzer teach the use of fluorophore labeled probes, see at least the legend in Fig. 1.
Conclusion
C. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ethan Whisenant whose telephone number is (571) 272-0754. The examiner can normally be reached Monday-Friday from 8:30 am -5:30 pm EST or any time via voice mail. If repeated attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anne Gussow, can be reached at (571) 272-6047.
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/ETHAN C WHISENANT/Primary Examiner, Art Unit 1683 ethan.whisenant@uspto.gov
EXAMINER SEARCH NOTES
18 DEC 2025 - ECW
Databases searched: All available via PE2E SEARCH
CAplus, Medline and BIOSIS via STNext; and Google Scholar (note the search terms used below)
Reviewed the parent(s), if any, and any search(es) performed therein : see the BIB data sheet
Reviewed, the search(es), if any, performed by prior examiners including any international examiners.
Planned Search
Search terms:
All Inventor(s) e.g. Kishi J?/au
Immunoassay
Antibody-oligonucleotide conjugate$
Antibody-DNA conjugate$
Antibody-RNA conjugate$
Concatemer$
Strand displacement
Rolling Circle Amplification or RCA
Primer exchange reaction or PER
Label$ or Signal stand$ or probe$
Stop$ (molecule$ or modification$)
(DNA or RNA) polymerase
Terminate$ or ends or stop$
► See the Examiner’s PE2E SEARCH notes/strategy in IFW