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 .
Claim Status
Currently, claims 1-27 are pending in the instant application. Claim 1 has been amended while claim 27 is withdrawn. This action is written in response to applicant' s correspondence submitted 09/15/2025. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant' s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is FINAL.
The amendment to the specification mailed 09/15/2025 has been entered. The amendment to the specification places the application in sequence compliance.
The nonstatutory double patenting rejection of Claims 1-25 as being unpatentable over claim 1,44-48, 50-55, 57-65 of copending Application No. 17285456 (reference application) is withdrawn due the abandonment of application 17285456.
The nonstatutory double patenting rejection of Claims 1-25 as being unpatentable over claim 1-2, 4-9, 11-12, 15-16, 18, 147-155, of copending Application No. 17161267 is withdrawn due to the abandonment of application 17161267.
Maintained Rejections
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.
Claims 1-5, 8-26 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kennedy-Darling (US 2021/0147905). This rejection was previously presented and has been rewritten to address the amendment to the claims.
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Kennedy-Darling teaches a method comprising contacting a biological sample with an antibody conjugated to a first oligonucleotide, contacting a first binding region of a second oligonucleotide contacting a second binding region of a second oligonucleotide with a third oligonucleotide wherein the third oligonucleotide comprises a detection component thereby connectively coupling said biological sample to a detection component (see para 3). The first and second oligonucleotide bound can encompass a partially double stranded first oligonucleotide conjugated to an antibody. Kennedy Darling teaches removing the hybridized third oligonucleotide by denaturing, leaving the capture agents and associated oligonucleotides still bound. Kennedy Darling teaches this step removes hybridized probes, leaving the capture agents and associated oligonucleotides intact and in place (see para 132). Kennedy Darling teaches the nucleotides is at least 10 nucleotides in length and is complimentary to at least a portion of the oligonucleotide. Kennedy Darling teaches the oligonucleotide can be RNA or DNA (see para 3). Kennedy Darling teaches the enzyme can be HRP (see para 83) and is a detection component (claims 2-4, 14-16). Kennedy Darling teaches fluorescent dye (see para 82) (claim 5 and 26). Kennedy Darling teaches the oligonucleotide can be a RNA, DNA, synthetic nucleotides, is at least 10 nucleotides in length, and a longer oligonucleotide can be selected over the first oligonucleotide, single or double stranded (para 58 and 70) (claims 9-13 and 21-25)
Response to Arguments
The response traverses the rejection on pages 7-9 of the remarks mailed 09/15/2025. The response asserts the specification defines a reactive species on page 16, lines 2-11 and reiterates the passage. The passage that applicant references is not an explicit definition for a reactive species but merely examples of what a reactive species can correspond or encompass. For example the specification states reactive species can correspond to any one or more of a variety of different chemical or biochemical species and moieties. This is an example of what is encompassed by a reactive species but it is not a definition.
The response points to figure 1 of Kennedy-Darling as an antibody conjugated to a first oligonucleotides binds to biological feature of interest in a sample. A second oligonucleotides binds to the first oligonucleotides and a third oligonucleotides conjugated to a detection component binds to the second oligonucleotides to localize the detection component at the location of the biological feature of interest. The response asserts that the office’s interpretation appears to rest on a designation of one of the foregoing oligonucleotides as a reactive species and the office provides no indication that any other moiety in Kennedy-Darling constitutes a reactive species. The response asserts that Kennedy-Darling fails to describe methods that include the steps of contacting the biological sample with a second agent wherein the second agent comprises a first reactive species and a second oligonucleotide to at least a portion of the first oligonucleotides and contacting the biological sample with a first labeling species wherein the first labeling species reacts with a first reactive species to deposit the first labeling species in the biological sample. This response has been reviewed but not found persuasive.
The rejection addresses that the first and second oligonucleotide of Kennedy-Darling encompass a partially double stranded first oligonucleotides conjugated to an antibody. The oligonucleotides are not considered to be the reactive species. The rejection addresses an enzyme comprising horseradish peroxidase and cites instant claims 3-4, which further limit the first reactive species, therefore the rejection does not consider the oligonucleotides as the reactive species but the enzymes taught by Kennedy-Darling as the reactive species, which is an example of a reactive species indicated in the instant specification. Additionally Kennedy-Darling teaches contacting the biological sample with a second agent wherein the second agent comprises a first reactive species and a second oligonucleotide to at least a portion of the first oligonucleotides. Specifically the third oligonucleotide comprises a detection component and Kennedy-Darling teaches the detection component encompasses the enzyme including horseradish peroxidase (see para 82-82). The third oligonucleotide binds to the second oligonucleotide of Kennedy-Darling. As stated above the first and second oligonucleotide of Kennedy is considered to be the first oligonucleotide of the instant claims and the third oligonucleotide of Kennedy-Darling is considered to be the second oligonucleotide and a first reactive species. Additionally the third oligonucleotide may deliver an enzyme that delivers a fluorophore or enzymatic amplification of signal (contacting the biological with a first labeling species that reacts with the first reactive species to deposit first labeling species). Additionally the use of HRP as taught by Kennedy Darling is described which is a first labeling species that reacts with a first reactive species to deposit a first labeling species (see para 84-85). For these reasons and reasons of record, the rejection of Kennedy-Darling is maintained.
Claims 1-26 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bobrow (US20190376956A1). This rejection was previously presented and has been rewritten to address the amendment to the claims.
With regard to claim 1, Bobrow teaches a multiplex assay that comprises a sample is bound to a target specific binding partner (antibody) which is linked to a nucleic acid strand comprising a barcode and contacting an enzyme linked to a nucleic acid strand complementary to the nucleic acid strand comprising a barcode (see para 174). The sample is contacted with a substrate conjugate (labeled substrate containing a detectable label). The detectable label reacts with the enzyme to form an activated substrate conjugate that results in deposition of detectable labels on the sample (see para 175). Bobrow teaches two target molecules are detecting, each target bound to respective antibodies, each antibody linked to a distinct nucleic acid strand (see para 177). The target specific binding part linked to a nucleic acid strand comprises a first oligonucleotide conjugated to a binding species. The enzyme linked to a nucleic acid strand complementary to the nucleic acid strand comprising a barcode is a first reactive species and a second oligonucleotide conjugated to the first reactive species and hybridizes to the first oligonucleotide. Bobrow teaches removing the second agent following deposition of the first labeling species. Bobrow teaches the bound label is released by dehybridization of the nucleic acid strands (see para 52) Bobrow teaches repeating the steps for a 2nd target which comprises a third agent that comprises a third oligonucleotide conjugated toa second binding species and a fourth oligonucleotide conjugated to a portion of the third oligonucleotide and second reactive species followed by depositing the second labeling species in the sample (see para 177).
With regard to claim 2-4, Bobrow teaches the reactive species is an enzyme. Borrow teaches horseradish peroxidase (see para 232).
With regard to claim 5-7 and 26, Bobrow teaches a phenolic substrate is enzymatically converted into an activate state resulting in deposition of labels. Bobrow teaches the phenolic substrate is tryamide (see para 219). Bobrow teaches fluorescent tyramide reagents (see ex 1)
With regard to claim 8, Bobrow teaches the binding species are antibodies (see para 174 and 177).
With regard to claim 9-13, Bobrow teaches the nucleic acid strand are 10, 11, 12, 13, 14, 15, 18 or 20 nucleotides long (see para 245). Bobrow teaches a nucleic acid strand comprising a barcode (102, fig 1) and a complementary nucleic acid strand which is complementary to the barcode (104, fig 1). Figure 1 depicts the second strand is longer than the first strand. Borrow teaches an intermediate strand that comprises a first region complementary to a corresponding region linked to the target specific binding partner and a second region comprising repeated sequences, each of the sequences specifically binds directly or indirectly to corresponding sequence linked to enzyme (multiple sequences complementary to different portions) (see para 289)
With regard to claims 14-16, Bobrow teaches both enzymes in the multiplex assay are horseradish peroxidase (see ex 1).
With regard to claims 17-20, Bobrow teaches the first and third oligonucleotide is different from the second and fourth oligonucleotide. Bobrow teaches the first labeling species is different than the second labeling species. Bobrow teaches the first antibody is different than the second antibody (see example 1 and para 177).
With regard to claim 21-25, Bobrow teaches the nucleic acids comprise RNA or DNA single strands (see para 244). Bobrow teaches the single strand comprises a synthetic nucleotide (see para 244). Bobrow further teaches an intermediate strand with a first region complementary to nucleic acid strand linked to target specific binding partner, which would comprise a first oligonucleotide that is partially double stranded and then a region that is complementary to the nucleic acid strand linked to the enzyme.
Response to Arguments
The response traverses the rejection on page 9-12 of the remarks mailed 09/15/2025. The response addresses Fig 1B of Bobrow. The response asserts that Bobrow states the following conditions must be met with respect to the nucleic acid strand and points to para 160-162. It is noted that this is not a requirement as Bobrow teaches in some embodiments, a method for testing a sample for the presence of one or more target comprises (see para 157 preceding the cited sections). The response asserts that cleavage of the first and/or second releasable linker to remove enzyme from the sample is a common feature. The response asserts that in each of the examples the enzyme introduced into the sample is deactivated via the addition of a TCEP solution. The response asserts that Bobrow does not describe methods in which enzyme is removed from the sample by dehybridizing probe and asserts that Bobrow method for enzyme removal is subsequent labeling operations. The response asserts that Bobrow does not describe or suggest method that include the step of removing the second agent from the biological sample following deposition of the first labeling species by dehybridizing the second oligonucleotide from the first oligonucleotide. This response has been thoroughly reviewed but not found persuasive. Bobrow teaches in some embodiments the bound label is released without the use of a releasable linker. Bobrow teaches the bound label is released by dehybridization of the nucleic acid strands (see para 52, 107, 208, claim 25). Because Bobrow teaches releasing the second agent by dehybridizing the second oligonucleotides from the first oligonucleotide, Bobrow anticipates the claims. For these reasons and reasons of record this rejection is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-2, 14-15, 30-33, 35, 42-43 and 47, 54-55, of copending Application No. 17039888 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 1 is generic to all that is recited in claims 1-2, 14-15, 30-33, 35, 42-43, 47, and 54-55 in ‘888. Specifically the method comprising contacting a biological sample with a first target analyte, a second agent, a third agent and a fourth agent, wherein the analyte comprises a binding species conjugated to an oligonucleotide and the third agent comprising an third oligonucleotide conjugated to a second binding species and the second and fourth agents comprise and second and fourth oligonucleotide with a labeling species is encompassed by claim 1 of ‘888.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
The response does not address the supposed errors of the rejection. The response request the double patenting rejection be held in abeyance until the claims of the present application are otherwise held to be allowable. For these reasons the rejection in maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached on 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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