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 .
Election/Restrictions
Applicant’s election of Group I, claims 1, 2, 4, 5, 9, 13, 14, 16, 30, 50, 54, 55, 57, 61, 71, 74, 76, 81, 88, and 199 in the reply filed on 06/26/2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 95, 170, 184 and 193 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/26/2026.
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.
Claim 61 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 61 is internally inconsistent. Claim 61 recites: “wherein…the anchoring reagent is covalently immobilized on the surface”. But claim 61 then goes on say “the first and second binding partners comprise…complementary oligonucleotides, a receptor ligand pair, an antigen-antibody pair, a hapten-antibody pair, an epitope-antibody pair, a mimitope-antibody pair, an aptamer-target molecular pair, hybridization partners, or an intercalator-target molecule pair…biotin…streptavidin, avidin, an anti-biotin antibody…”. These are not covalent interactions. Generally speaking, “binding partners” are non-covalent interactions.
As all limitations of the claim cannot be simultaneously satisfied, no examination over the prior art is possible for claim 61.
Claim Rejections - 35 USC § 102
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, 5, 9, 13, 14, 30, 50, 55, 57, 71, 76, 81, 88 and 199 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Aghvanyan (US 2017/0089892, IDS ref). Note: Applicant has chosen to draft the claims with numerous alternatives within a claim. The rejection of a claim based on one recited alternative should not be construed as indicating the reference does not disclose the other alternatives. Therefore, should Applicant amend a claim by simply deleting the rejected alternative, the Examiner will review the reference to see if any of the remaining alternatives is disclosed, and may issue a rejection based on such disclosed alternative. This will not preclude finality of such rejection. Therefore, Applicant is advised to review the reference in its entirety prior to making any amendments.
Regarding claim 1, Aghvanyan disclosed:
A method for detecting an analyte, comprising:(a) contacting a template oligonucleotide with a first complex that comprises: (1) the analyte; and (2) a detection reagent that binds the analyte, wherein the detection reagent comprises a nucleic acid primer;
See Fig. 2a and description at paragraph [0170]. The “template oligonucleotide” corresponds to connector sequence 209a and the “first complex” is comprised of capture reagent 202, the analyte (A), first detection reagent 204 comprising a first proximity probe 205, and second detection reagent 206 comprising a second proximity probe 207. The “detection reagent” is comprised of detection reagent 204 and proximity probe 205, and the “nucleic acid primer” corresponds to proximity probe 205.
(b) hybridizing the nucleic acid primer to the template oligonucleotide to form a second complex and extending the nucleic acid primer with a polymerase, thereby forming an extended oligonucleotide;
See Fig. 2a and description at paragraph [0170]. Following ligation of the connector sequences, proximity probe 205 is extended by a polymerase (see paragraph [0180]: “polymerase”) in a rolling circle amplification to generate an extension product. See also Example 1, paragraph [0277]: “Phi29 DNA polymerase”.
(c) binding the extended oligonucleotide to one or more labeled probes, wherein each labeled probe comprises (1) a detection oligonucleotide that is capable of binding to the extended oligonucleotide; and (2) a detectable label;
See Fig. 2a and description at paragraph [0170]: “…the amplicon also includes two or more detection sequences which are complementary to labeled detection probes that are hybridized to the amplicon…”. See also Example 1, paragraph [0277]: “The detection probe was the sequence CAG TGA ATG CGA GTC CGT CT (SEQ ID No. 6). To incorporate the electrochemiluminescence label SULFO-TAG (Meso Scale Diagnostics), the detection probe was synthesized with a terminal biotin label and was pre-bound to SULFO-TAG labeled streptavidin.”
and (d) detecting the detectable label, thereby detecting the analyte,
Paragraph [0170]: “…the amplicon also includes two or more detection sequences which are complementary to labeled detection probes that are hybridized to the amplicon and used to measure the amount of amplicon bound to the surface.” Paragraph [0013]: “…binding the extended sequence to a detection probe having a detectable label, measuring the detectable label and correlating the measurement to the amount of analyte in the sample.”
wherein the second complex is bound to a surface,
See Fig. 2a: both the first and second complexes are bound to a surface.
and wherein: (i) the detection oligonucleotide comprises RNA, a modified nucleic acid, or a combination thereof
See Example 1, paragraph [0277]: “The detection probe was the sequence CAG TGA ATG CGA GTC CGT CT (SEQ ID No. 6). To incorporate the electrochemiluminescence label SULFO-TAG (Meso Scale Diagnostics), the detection probe was synthesized with a terminal biotin label and was pre-bound to SULFO-TAG labeled streptavidin.” The detection probe corresponds to the claimed “detection oligonucleotide”. It was modified with biotin.
Regarding claim 2, see Example 1, paragraph [0277]: “The detection probe was the sequence CAG TGA ATG CGA GTC CGT CT (SEQ ID No. 6). To incorporate the electrochemiluminescence label SULFO-TAG (Meso Scale Diagnostics), the detection probe was synthesized with a terminal biotin label and was pre-bound to SULFO-TAG labeled streptavidin.” The detection probe corresponds to the claimed “detection oligonucleotide”. It was modified with biotin.
Regarding claim 5, the “detection oligonucleotide” in paragraph [0277] was 20 nucleotides in length.
Regarding claim 9, see Example 1, paragraph [0277]: “Phi29 DNA polymerase”. This is a strand-displacing polymerase.
Regarding claim 13, as shown in Fig. 2a and explained in paragraph [0170], the “template” (which corresponds to connector sequence 209a is a linear oligonucleotide, and its 5’ and 3’ ends are ligated (to the 3’ and 5’ ends, respectively, of connector sequence 209b) thereby forming a circular template.
Regarding claim 14, the discussion of Fig. 2a and Example 1 above meets the second (RCA) option of the claim.
Regarding claim 30, the claim can be construed as having the following 4 alternatives:
1-the extending comprises rolling circle amplification (RCA);
2-the method comprises the terminating [referring to d(ii) of claim 1];
3-the method produces an assay signal range, and the assay signal range is characterized by any one of (I) to (III); and/or
4-the extended oligonucleotide is characterized by any one of (IV) to (V).
In this case, Aghvanyan’s extending comprises rolling circle amplification (RCA) as discussed above.
Regarding claim 50, as shown in Fig. 2a and discussed at paragraph [0170], Aghvanyan’s method comprised an anchoring reagent comprising an anchoring oligonucleotide. See Example 1, paragraph [0276]; the anchoring oligonucleotide was modified at the 3’ end with ThioMC3-D.
Regarding claim 55, see Fig. 2a and Example 1, paragraph [0276]: “…an anchoring moiety (immobilized as a BSA-oligonucleotide conjugate, the oligonucleotide selected to be specific for a rolling circle amplicon).”
Regarding claim 57, see Example 1, paragraph [0276]; the anchoring oligonucleotide was 35 nucleotides (AAGAGAGTAGTACAGCAGCCGTCAAAAAAAAAAAA), which is “about” 30. The instant specification states: “As used herein, "about" can mean plus or minus 10% of the provided value.” However, at paragraph [0176], Aghvanyan teaches (emphasis provided): “In one embodiment, a hybridization sequence is selected to regions of the amplicon that are not associated with binding to the proximity or detection probes (the “inert” regions). In a more specific embodiment, the hybridization sequence is complementary to the full length of the inert region of the amplicon is included (preferably, about 25 nucleotides in length), alone or in combination with a poly(A) arm of e.g., up to 30 nucleotides in length.” Thus, Aghvanyan teaches the anchoring oligonucleotide can be comprised of only a sequence complementary to the inert region of the amplicon that is “about 25 nucleotides in length”.
Regarding claim 71, as shown in Fig. 2a and discussed in paragraph [0170], there is a capture reagent 202. The analyte is first contacted with the capture reagent, and then with the detection reagent (first detection reagent 204 comprising first proximity probe 205). At paragraph [0007], Aghvanyan disclosed the capture reagent and the detection reagent could each be an antibody, antigen, ligand, receptor, oligonucleotide, hapten, epitope, mimitope, or an aptamer. At paragraph [0009], Aghvanyan disclosed the order of binding the analyte to the capture reagent and the detection reagent could be any of the orders recited in claim 71.
Regarding claim 76, Aghvanyan satisfies at least option II: see Fig. 2a and paragraph [0170]: anchoring reagent 203. See Example 1, paragraph [0277]: “The detection probe was the sequence CAG TGA ATG CGA GTC CGT CT (SEQ ID No. 6). To incorporate the electrochemiluminescence label SULFO-TAG (Meso Scale Diagnostics), the detection probe was synthesized with a terminal biotin label and was pre-bound to SULFO-TAG labeled streptavidin.” The detection probe corresponds to the claimed “detection oligonucleotide”. It was modified with biotin.
Regarding claim 81, Aghvanyan’s Fig. 2a (paragraph [0170]) proximity probe 205 corresponds to the claimed “primer”. In Example 1, paragraph [0274], this is indicated as SEQ ID NO 2 and has the sequence SH-AAA AAA AAA ATA TGA CAG AAC TAG ACA CTC TT. This comprises the sequence of instant SEQ ID NO: 1 (underlined). Therefore, Aghvanyan’s primer comprises SEQ ID NO: 1.
Regarding claim 88, Aghvanyan meets at least the option of the label capable of being measured by electrochemiluminescence; see Example 1, paragraph [0277].
Regarding claim 199, Aghvanyan meets at least option IV for the same reasons discussed for claim 1. As to the limitation:
wherein the anchoring reagent is immobilized on a surface, or wherein the first complex further comprises a capture reagent that binds the analyte, wherein the capture reagent is immobilized or capable of being immobilized to the surface, and wherein the anchoring reagent is linked to the capture reagent
The emphasized “or” is considered to separate two alternatives. Aghvanyan satisfies at least the first alternative, in that the anchoring reagent is immobilized on a surface as shown in Fig. 2a.
As to the limitation:
wherein the binding sequence is capable of forming an aptamer or a tertiary oligonucleotide structure, and the anchoring reagent comprises a protein, an antibody, a hapten, or an affinity tag capable of binding to the aptamer or tertiary oligonucleotide structure
Aghvanyan disclosed (paragraph [0007]): “The anchoring reagent can include an oligonucleotide sequence, aptamer, aptamer ligand, antibody, antigen, ligand, receptor, hapten, epitope, or a mimetope; and optionally, the anchoring region can include an aptamer and the anchoring reagent can include an aptamer ligand.” An aptamer ligand is “an affinity tag capable of binding to the aptamer”.
Aghvanyan also appears to meet option V, which is similar to option IV except that instead of an aptamer/affinity tag capable of binding to the aptamer, requires:
wherein the binding sequence comprises a binding moiety, and the anchoring reagent comprises a protein or antibody capable of binding the binding moiety
In this regard, Aghvanyan disclosed (paragraph [0007]): “The anchoring region can comprise a nucleic acid sequence and the anchoring reagent can include a DNA-binding protein.” That is, the nucleic acid sequence is the “binding moiety”, and the DNA-binding protein is a protein capable of binding the binding moiety.
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.
Claim(s) 2, 4 and 54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Aghvanyan (US 2017/0089892, IDS ref) in view of Raj (US 2012/0129165).
The teachings of Aghvanyan have been discussed.
Regarding claims 2, 4 and 54, Aghvanyan did not disclose a 2’-O-methyl modification of the “detection oligonucleotide”, which corresponds to the “probe” of Fig. 2a (“one or more labeled probes” of paragraph [0170]) or in the anchor oligonucleotide.
Raj disclosed (paragraph [0009]): “Non-natural nucleotides that increase the binding affinity of probes include 2'-O-methyl ribonucleotides.”
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to modify the method of Aghvanyan by incorporating 2’-O-methyl modified nucleotides into the detection oligonucleotide and anchor oligonucleotide in order to increase the binding affinity of these oligonucleotides for their respective targets.
Claim(s) 74 is/are rejected under 35 U.S.C. 103 as being unpatentable over Aghvanyan (US 2017/0089892, IDS ref) in view of Feaver (US 2004/0248103, IDS ref).
The teachings of Aghvanyan have been discussed. Aghvanyan did not disclose contacting the first or second complex with the polymerase and the labeled probes simultaneously.
Feaver taught a related method in which two half-circle probes (HCPs) were hybridized to two proximity probes bound to an analyte and ligated to form an amplification target circle (ATC), which served as a template for rolling circle amplification (RCA). See abstract, Fig. 1, paragraph [0021]. Feaver disclosed (paragraph [0290]): “During or after rolling circle amplification, a cocktail of detection probes can be added, where the cocktail contains color combinations that are specific for each ATC or HCP.” As the polymerase would necessarily be present “during” rolling circle amplification, this implies that the complex of the proximity probes and analyte are in contact with the polymerase and the detection probes simultaneously. Feaver taught “fluorescent change” probes for this (paragraph [0017]), including molecular beacon probes.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to modify the method of Aghvanyan by contacting the “second complex” (containing the ligated, circularized probe) with the polymerase for carrying out RCA and the labeled detection probes simultaneously, since Feaver taught the detection probes could be added during or after RCA.
Conclusion
Claim 16 is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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, GARY BENZION can be reached at 571-272-0782. 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.
/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681
