DETAILED ACTION
In application filed on 11/13/2023, Claims 1-19 are pending. The claim set submitted on 11/13/2023 is considered because this is the most recent claim set with some preliminary amendments. Claims 1-6 are considered in the current office 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/31/2024, 01/16/2026 and 07/03/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 07/08/2026 is acknowledged. The traversal is on the ground(s) that:
"Although lack of unity of invention should certainly be raised in clear cases, it should neither be raised nor maintained on the basis of a narrow, literal or academic approach." MPEP § 1850 (II). Applicant respectfully notes that the International Searching Authority (ISA) did not reject these claims for lack of unity of invention, even though the ISA was considering the same prior art. Accordingly, Applicant respectfully submits that that the present case falls into the situation where the MPEP urges the Examiner to take the broad practical approach and Examine the claims, instead of making a narrow academic distinction. Rejoinder and examination of the non-elected claims are therefore respectfully requested. In any case, since claims 7-19 of Groups II and III depend from claim 1 of Group I, rejoinder of claims 7-19 upon the allowance of claim 1 is respectfully requested.
This is not found persuasive because:
Groups I-III lack unity on invention under 37 CFR 1.475 and PCT Rule 13.1 because even though the inventions of these groups require the technical feature of a “A marker for marking a predetermined structure within a biological sample, the marker comprising: a marker base having an affinity reagent configured to attach to the predetermined structure of the sample, and an attachment structure connected to the affinity reagent having at least two attachment sites, wherein the attachment structure comprises at least one cleavage site arranged between the two attachment sites, and wherein the attachment structure is capable of being cut at the at least one cleavage site by a cleaving agent in order to remove at least one attachment site from the marker base; and at least two reporters, each reporter comprising a linker structure having a complementary attachment site) configured to attach to one of the two attachment sites of the attachment structure, and a combination of at least two different fluorescent dyes arranged on the linker structure, wherein the combination of the at least two different fluorescent dyes is unique for each reporter, and wherein the complementary attachment site is unique for each reporter and configured such that each reporter attaches to a different attachment site of the marker base”, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Dunaway et al. (US20180142286A1).
Applicant should note that the findings of the International Searching Authority (ISA) and International Preliminary Examining Authority (IPEA) are not binding on U.S. examiners during national stage examination.
Under MPEP § 1893.03(e), the U.S. examiner is free to consider any portion of the international reports but will apply U.S. laws, regulations, and patentability standards independently.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 07/08/2026.
Examiner notes a typographical error in Group III, drawn to a device which recited Claims 8-9, should have been recited as 17-20 in the restriction requirement mailed 05/12/2026. Examiner submits that this acknowledgment does not change the Finality of the Restriction Requirement.
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 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.
Claims 1-3 and 5-6 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Dunaway et al. (US20180142286A1).
Regarding Claim 1, Dunaway teaches a marker (referred to as composition [Para 0005]) for marking (‘binding’) a predetermined structure (See Para 0009, 0005… the target binding domain comprises at least ten nucleotides and is capable of binding a target nucleic acid) within a biological sample (See Para 0120… The target nucleic acid can be obtained from a biological sample from a subject), the marker comprising:
a marker base (referred to as sequencing probes [Para 0004]) having an affinity reagent (referred to as target binding domain [Para 0004]) configured to attach to the predetermined structure (referred to as target nucleic acid sequence [Para 0215]) of the sample (See Para 0120… The target nucleic acid can be obtained from a biological sample from a subject), and
an attachment structure (referred to as barcode domain [Para 0004]) connected to the affinity reagent (referred to as target binding domain [Para 0004]) having at least two attachment sites (See Para 0005…the barcode domain comprising at least three attachment positions),
wherein the attachment structure (referred to as barcode domain [Para 0004]) comprises at least one cleavage site (referred to as cleavable linker [Para 0025]) arranged (See Para 0028-0031…a cleavable linker can be located in between any of primary secondary or tertiary nucleic acids) between the two attachment sites (See Para 0005…the barcode domain comprising at least three attachment positions), and
wherein the attachment structure (referred to as barcode domain [Para 0004]) is capable of being cut (See Para 0025…the cleavable linker can be a photo-cleavable linker (e.g., UV-light cleavable linker), a reducing agent cleavable linker, or an enzymatically cleavable linker. Preferably, the linker is a photo-cleavable linker) at the at least one cleavage site (referred to as cleavable linker [Para 0025]) by a cleaving agent (See Para 0025…‘reducing agent’) in order to remove at least one attachment site (See Para 0158…the cleavable linker modification can be located anywhere along the length of the sequencing probe, including, but not limited to, a region between the target binding domain and the barcode domain) from the marker base (referred to as sequencing probes [Para 0004]); and
at least two reporters (referred to as reporter probes [Para 0068]; See Para 0314…fluorescent reporters), each reporter (referred to as reporter probes [Para 0068]; See Para 0314…fluorescent reporters) comprising
a linker structure (referred to as a complementary nucleic acid sequence…[ Para 0160]); See Para 0273…a reporter probe is hybridized to the first attachment position (R1) of the sequencing probe; See Para 0144… the linker is a single stranded stem oligonucleotide that hybridizes to the single stranded oligonucleotide that contains the target binding domain and the single stranded) having a complementary attachment site (referred to as a complementary nucleic acid sequence within at least one attachment region within at least one attachment position of a barcode domain of a sequencing probe (Para 0160]) configured to attach to (See Para 0271…a reporter probe is still hybridized to position R3 of the barcode domain; See Para 0160…comprises (directly or indirectly) a detectable label is referred to herein as a “reporter probe” or “reporter probe complex,” these terms are used interchangeably herein. The reporter probe can be DNA, RNA or PNA. Preferably, the reporter probe is DNA) one of the two attachment sites (See Para 0005…the barcode domain comprising at least three attachment positions) of the attachment structure (referred to as barcode domain [Para 0004]), and
a combination of at least two different fluorescent dyes (See Para 0171…This dual combination of fluorescent dyes can include a duplicity of a single color, e.g. blue-blue) arranged on (See Para 0277…Each complementary nucleic acids is bound to one of four different fluorescent dyes) the linker structure (referred to as a complementary nucleic acid sequence…[ Para 0160]); See Para 0273…a reporter probe is hybridized to the first attachment position (R1) of the sequencing probe; See Para 0144… the linker is a single stranded stem oligonucleotide that hybridizes to the single stranded oligonucleotide that contains the target binding domain and the single stranded),
wherein the combination of the at least two different fluorescent dyes (See Para 0171…This dual combination of fluorescent dyes can include a duplicity of a single color, e.g. blue-blue) is unique for each reporter (See Para 0363… this example, each reporter complex is a 37 DNA oligomer branched structure designed to hold a total of 30 fluorescent dyes, with 15 dyes for each color of the color combination), and
wherein the complementary attachment site (referred to as a complementary nucleic acid sequence within at least one attachment region within at least one attachment position of a barcode domain of a sequencing probe (Para 0160]) is unique for each reporter (See Para 0277… each complementary nucleic acids is bound to one of four different fluorescent dyes) and configured such that each reporter (referred to as reporter probes [Para 0068]; See Para 0314…fluorescent reporters) attaches to a different attachment site (See Para 0383…After hybridization of the sequencing probes, reporter probes were sequentially hybridized to each of the three positions of the barcode domain (R1, R2 and R3) and the corresponding fluorescence data recorded; See Para 0380…Sequencing probes were hybridized to reporter probes in solution and properly formed sequencing probe-reporter probes were purified) of the marker base (referred to as sequencing probes [Para 0004]).
Regarding Claim 2, Dunaway teaches wherein the linker structures (referred to as a complementary nucleic acid sequence…[ Para 0160]); See Para 0273…a reporter probe is hybridized to the first attachment position (R1) of the sequencing probe; See Para 0144… the linker is a single stranded stem oligonucleotide that hybridizes to the single stranded oligonucleotide that contains the target binding domain and the single stranded) are formed by oligonucleotides or peptides (See Para 0144… the linker is a single stranded stem oligonucleotide that hybridizes to the single stranded oligonucleotide that contains the target binding domain and the single stranded oligonucleotide that contains the barcode domain).
Regarding Claim 3, Dunaway teaches wherein the cleavage site (referred to as cleavable linker [Para 0025]) is an enzymatic cleavage site (See Para 0025…or an enzymatically cleavable linker) and the attachment structure (referred to as barcode domain [Para 0004]) can capable of being cut (‘cleavable’) at the cleavage site (referred to as cleavable linker [Para 0025]) by an enzymatic cleaving agent (referred to as USER™ enzyme [Para 0158]).
Regarding Claim 5, Dunaway teaches wherein the cleavage site (referred to as cleavable linker [Para 0025]) is a photocleavage site (See Para 0025…the cleavable linker can be a photo-cleavable linker (e.g., UV-light cleavable linker)) and the attachment structure (referred to as barcode domain [Para 0004]) is capable of being cut (‘cleavable’) at the cleavage site (referred to as cleavable linker [Para 0025]) by photolysis (See Para 0028…photo-cleavable, thereby teaching “photolysis”).
Regarding Claim 6, Dunaway teaches, wherein the attachment sites (See Para 0005…the barcode domain comprising at least three attachment positions) of the attachment structure (referred to as barcode domain [Para 0004]) and/or the complementary attachment sites (this limitation is viewed as optional) are oligonucleotides (See Para 0143… barcode domains are present within the same single stranded oligonucleotide; See Para 0018…Each nucleic acid sequence comprising each attachment region in the barcode domain is from about 8 nucleotides to about 20 nucleotides in length).
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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over by Dunaway et al. (US20180142286A1) in view of O'Shea et al. (US20200308239A1).
Regarding Claim 4, Dunaway teaches wherein the enzymatic cleavage site (See Para 0025…or an enzymatically cleavable linker) is a target site (See Para 0025…or an enzymatically cleavable linker; Under BRI, the enzymatically cleavable linker has a target site) of an enzyme (See Para 0371… cleaved by the USER™ enzyme)).
Dunaway does not teach “target site of a restriction enzyme, a CRISPR/Cas target, or a recombinase target site”.
In the analogous art of probes that are expressed in a cell to label an intracellular target (such as protein or DNA) for both light and electron microscopy, O’Shea teaches “target site (See Para 0114…DNA binding proteins, such as transcription factors, can used as a targeting domain) of a restriction enzyme, a CRISPR/Cas target, or a recombinase target site (See Para 0114…Transcription activator-like effector nucleases (TALEN) are restriction enzymes that can be engineered to cut specific sequences of DNA.)”.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the marker of Dunaway to include “target site of a restriction enzyme, a CRISPR/Cas target, or a recombinase target site”, as taught by O’Shea for the benefit of having restriction enzymes that can be engineered to cut specific sequences of DNA (O’Shea, Para 0114), allowing for the provision of methods of detecting the location of a target antigen in a cell, comprising expressing a nucleic acid molecule encoding a FIREnano probe as described herein, and detecting the location of the detection tag and the ferritin nanoparticle on the probe in the host cell using fluorescence microscopy and EM, respectively, to detect the location of the target antigen in the cell (O’Shea, Para 0010).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OYELEYE ALEXANDER ALABI whose telephone number is (571)272-1678. The examiner can normally be reached on M-F 7:30am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797
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