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 claims filed 2/16/2023 are under consideration.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-7, 9-11, 13-15, 19-22, 24, 46, 50-51, 54, 57 and 91 in the reply filed on 11/13/2025 is acknowledged. The traversal is on the ground(s) that the application is based the discovery of methods that utilize a detectable marker situated at an internal location within an oligonucleotide or aptamer, such that binding of the oligonucleotide or the aptamer to a target results in restriction of internal rotation of the marker producing a detectable change. The traversal is further that the Office never explained its basis for concluding the groups lack unity in view of this shared technical feature. This is not found persuasive because the binding of the oligonucleotide or the aptamer to a target results in restriction of internal rotation of the marker producing a detectable change is a property of the methods that flows from the structures as claimed used in the active method steps. Upon further consideration, the groups require the technical feature of contacting the target analyte with a spherical nucleic acid (SNA) comprising a nanoparticle core and an attached oligonucleotide comprising an internally located detectable marker, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Mirkin (US 2016/0053260 A1; previously cited) and Wei (WO 2018/081193 A1). Mirkin teaches a spherical nucleic acid having a nanoparticle core and an oligonucleotide (para. 29) and contacting a target molecule with it (para. 9, 39 and 52). The oligonucleotide includes an internally located Cy5, as a detectable marker (para. 29). Wei teaches the common technical feature as described below in the rejections under 35 USC 102.
The requirement is still deemed proper and is therefore made FINAL.
Claims 29-31, 32-33, 35, 66 and 69 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/13/2025.
The election of species requirement of 6/13/2025 is withdrawn.
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 on a submitted IDS, they have not been considered.
It is noted that several references on the 11 different IDSs have been lined through, primarily because they were duplicate citations.
Specification
The amendments to the specification dated 2/16/2023 are acknowledged.
The use of terms, which are trade names or marks used in commerce (e.g., Alexa Fluor™, Organomation® or pHrodo™), has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 1-4, 6-7, 9-11, 13-15, 19-22, 24, 46, 50-51, 54, 57 and 91 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 1, the claim recites “the contacting results in binding of the target analyte to the oligonucleotide” and “the binding results in restriction of internal rotation of the marker, resulting in a detectable change and thereby detecting the target analyte”. The language describes a property of the method that is based on the structural elements of the “spherical nucleic acid”, which as explicitly claimed are: 1) a “nanoparticle core”; and 2) an “oligonucleotide” attached to the nanoparticle core having a “detectable marker situated at an internal location within the oligonucleotide”. It is unclear what additional elements, e.g., structures, orientations, positioning, etc., are required, if any, in order to confer the recited properties.
Claims 2-4, 6-7, 9-11, 13-15, 19-22, 24, 46, 50-51, 54, 57 and 91 depend directly or indirectly from claim 1 and are rejected for the same reason.
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.
(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.
Claim(s) 1-4, 6-7, 9-11, 13-15 and 46 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Wei (WO 2018/081193 A1).
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Regarding claim 1, Wei teaches a series of steps involving analyte binding in Fig. 2, which is reproduced below:
The figure depicts contacting a “target analyte” with a nanoparticle “core” having an attached “oligonucleotide” comprised of two hybridized polynucleotides. The “oligonucleotide” includes a “marker” dye that is either in a dark state or brightened state based on analyte binding during the “contacting” of the two elements. The “marker” is not located on either end of the “oligonucleotide” and thus is “at an internal location”. The structure of Wei has all the structural elements of the claimed “spherical nucleic acid”.
The binding of the analyte results in the “marker” being restricted from internally rotating and being held near the nanoparticle. The binding of the analyte results in a “detectable change”, i.e., dark state versus brightened state.
See p. 7, lines 25-29; and p. 11, line 24 to p. 12, line 23.
Regarding claim 2, one would recognize that based on how the structure of Wei is formed (p. 10, lines 13-23) that multiple oligonucleotides are attached to the surface of the nanoparticle.
Regarding claim 3, Wei teaches the detectable change is an “increase in fluorescence” due to the brightened state as depicted above.
Regarding claim 4, Wei teaches the “oligonucleotide” is an aptamer for cortisol (p. 10, lines 13-14).
Regarding claim 6, Wei teaches the fluorescence in the brightened state is dependent on whether internal rotation is possible or not as depicted above.
Regarding claim 7, the above detectable marker is viscosity sensitive based on its size change with the binding of the analyte making the structure less compact.
Regarding claim 9, Wei teaches the detectable change is proportional to the concentration of the target analyte as Wei generated a standard curve correlating signal intensities with analyte concentrations (p. 10, lines 24-32).
Regarding claim 10, Wei teaches the analyte is cortisol (as noted above), which is a lipid.
Regarding claim 11, the claim limits the scope of the ion option. The claim does not require the analyte to be an ion. The claim broadly encompasses a lipid analyte and is rejected for the same reason as claim 10.
Regarding claims 13 and 14, the claims limit the scope of the ion option. The claim does not require the analyte to be an ion. The claim broadly encompasses a lipid analyte and is rejected for the same reason as claim 10.
Regarding claim 15, Wei teaches the aptamer is ssDNA or ssRNA (p. 3, lines 13-14).
Regarding claim 46, Wei teaches the nanoparticle “core” is metallic as depicted in Figure 2 reproduced above.
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) 19-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei (WO 2018/081193 A1).
Regarding claim 19-21, Wei teaches a series of steps involving analyte binding in Fig. 2, which is reproduced above.
The figure depicts contacting a “target analyte” with a nanoparticle “core” having an attached “oligonucleotide” comprised of two hybridized polynucleotides. The “oligonucleotide” includes a “marker” dye that is either in a dark state or brightened state based on analyte binding during the “contacting” of the two elements. The “marker” is not located on either end of the “oligonucleotide” and thus is “at an internal location”. The structure of Wei has all the structural elements of the claimed “spherical nucleic acid”.
The binding of the analyte results in the “marker” being restricted from internally rotating and being held near the nanoparticle. The binding of the analyte results in a “detectable change”, i.e., dark state versus brightened state.
See p. 7, lines 25-29; and p. 11, line 24 to p. 12, line 23.
Wei further teaches the “marker” dye is located between the termini of the nucleic acid within the “oligonucleotide”. The nucleic acid having the “marker” dye is made of two ODNs of different length (p. 6, lines 10-22; and Figure 1b).
The ordinary artisan would be able to modify the teachings of Wei in order to arrive at the claimed structures of claims 19-21. Through routine optimization one would be able to design positioning of the “marker” dye such that it efficiently does not emit when the analyte is not present but does when present.
Claim(s) 22, 24 and 91 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei (WO 2018/081193 A1) in view of Mirkin 1 (US 2016/0053260 A1).
Regarding claim 22, 24 and 91, Wei teaches the elements of claims 1 above as required by claims 22, 24 and 91.
Wei does not teach the additional elements specific to claims 22, 24 and 91.
However, Mirkin 1 teaches other uses of structures of Wei includes nucleic acids to inhibit gene products (para. 8 and 20) and immune modulation (para. 20). Further, it is known that single stranded nucleic acids are immune system stimulatory. Both nucleic acids inhibiting gene products and nucleic acids for immune modulation are broadly encompassed by a “therapeutic agent”.
It would have been prima facie obvious to have modified the method of Wei by including additional nucleic acids on the nanoparticle that inhibit gene products and/or that are immune system stimulatory in the context of or related to cortisol levels.
Claim(s) 50, 51, 54 and 57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei (WO 2018/081193 A1) in view of Mirkin 2 (US 2017/0232109 A1).
Regarding claims 50, 51, 54 and 57, Wei teaches the elements of claims 1 and 46 above as required by claims 50, 51, 54 and 57.
Wei does not teach the additional elements specific to claims 50, 51, 54 and 57.
However, Mirkin 2 teaches that nanoparticle “cores” for attaching nucleic acids were known, including those made of proteins and gold-protein complexes (para. 70). Mirkin 2 further teaches the proteins are catalytically active (para. 70 and 216), the formation of a product of the reaction is an additional detectable change. Mirkin further teaches contacting an additional target with an agent, such as 5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside (X-gal) (para. 235).
It would have been prima facie obvious at the time of invention to have modified the method of Wei by substituting for the use of the “cores” taught by Mirkin 2. One would have been motivated to make such modifications as it allows one to further investigate additional analytes in the context of or related to cortisol levels.
Conclusion
No claims allowed.
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.
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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.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682