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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/22/2025 has been entered.
Claim Status
Currently, claims 1-2, 4, 6-11, 13-17, 19-24 are pending in the instant application. Claims 25 to 36 have been canceled, claim 15 has been amended and claim 24 is withdrawn. This action is written in response to applicant’s correspondence submitted 12/17/2024. 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 Any rejections not reiterated in this action have been withdrawn as necessitated by applicant’s amendments to the claims.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 Non-Final.
Claims 1-2, 4, 6-11, 13-17, 19-23 are under examination.
Claim Objections
Claim 1 objected to because of the following informalities: claim 1 recites “the target binds quickly the plurality of targeting oligonucleotides when the sample is in contact with the system preventing said targeting oligonucleotides to bind to the signaling oligonucleotides”. This phrase is grammatically incorrect. It appears that it should recite the target binds quickly to the plurality of targeting oligonucleotides. Appropriate correction is required.
New Grounds of Rejection
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 1-2, 4, 6-11, 13-17, 19-23 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.
Claim 1 recites “wherein the system is (i) kinetically controlled by a first association constant (k1) between the targeting oligonucleotide and the target, a second association constant (k2) between the targeting oligonucleotide and the signaling oligonucleotide and a third association constant (k3) between the signaling oligonucleotide and an anchoring nucleotide and (ii) configured such that k1> k2 >k3, and wherein the target binds quickly the plurality of targeting oligonucleotides when the sample is in contact with the system preventing said targeting oligonucleotides to bind to the signaling oligonucleotides” the wherein clause renders the claim indefinite. The claim is directed to a product however the wherein clause describes a mechanism and comprises process steps. The recitation of kinetically controlled, target binds to targeting oligonucleotide, sample in contact with the system preventing targeting oligonucleotide to bind to signaling oligonucleotide comprise process steps. The recitation of a product and process in the same claim is indefinite (see MPEP 2173.05(p)). It is not clear what the features of the target oligonucleotide, target, signaling oligonucleotide and anchoring nucleotide and what the structural limitations of the oligonucleotide and target comprise such that the product is kinetically controlled, comprises the mechanism of k1> k2 >k3 occurs, and the target binds quickly the plurality of targeting oligonucleotide when sample is in contact with the system. Combining two separate statutory classes of invention in a single product claim raises questions of what the structural requirements of the claimed marker encompasses and one of ordinary skill in the art would not know known the metes and bounds of the target oligonucleotide, signaling oligonucleotide, anchor oligonucleotide and target and an evaluation of the possibility of infringement would not be able to be ascertained with a reasonable degree of certainty. It is unclear whether infringement occurs when one has a system comprising anchoring oligonucleotides, target oligonucleotides, and signal oligonucleotides or when one has a method for target binding quickly to targeting oligonucleotides preventing targeting oligonucleotides to bind to signaling oligonucleotides. The specification does not provide a standard for ascertaining the request degree of the claimed system and one of ordinary skill in the would not be reasonably apprised of the scope of the invention.
With regard to claim 1, the recitation of “quickly” is indefinite. It is unclear what is encompassed by the term “quickly”, it is a relative term, the metes and bounds of quickly are not defined and it is unclear when a target binds quickly and when a target does not bind quickly. Because the term is not defined in the specification and because there is no art recognized definition for this term as it relates to the claimed product, one of skill in the art cannot determine the metes and bounds of the claimed subject matter.
With regard to claim 2, the limitation of a system is configured such that k1 is at least 10 times higher than k2 and/or such that k2 is at least 10 times higher than k3. This recitation renders the claim indefinite. The recitation of requiring a product configured based on rate constant for a first, second and third reaction step renders the claim indefinite. This limitation encompasses processes steps. The recitation of a product and process in the same claim is indefinite (see MPEP 2173.05(p)). It is not clear what the features of the target oligonucleotide, target, signaling oligonucleotide and anchoring nucleotide and what the structural limitations of the oligonucleotide and target comprise such that the product is configured using rate constants. There are not structural requirements or limitations of the system and the recitation of a system configured using rate constants renders the claim indefinite. One of ordinary skill in the art would not know the metes and bounds of the claimed system and an evaluation of the possibility of infringement would not be able to be ascertained with a reasonable degree of certainty.
Claims 2, 4, 6-11, 13-17, 19-23 depend from claim 1 and are indefinite for the reasons applied to claim 1.
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.
Claims 1-2, 4, 6-11, 13-17, 19-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Han (Electrochemistry Comm, 2009, vol 11, pp 157-160). This rejection was previously presented and has been rewritten to address the amendment to the claims.
With regard to claim 1-2, and 6, Han teaches an E-AB biosensor that comprises oligonucleotides, Seq 1, Seq2, and Seq 3. Han teaches immobilization of a dsDNA comprising Seq 1 and Seq 2. The aptamer sequence, Seq 1 is hybridized with Seq 2, a 3’ end thiolated sequence that is complementary with Seq 1. The dsDNA form a monolayer on a gold disk electrode via thiol-gold covalence. The dsDNA modified electrode is incubated with a solution of the target, ATP. This incubation result in the formation of aptamer-target complex as well as dissociation from electrode surface. Seq 3 hybridizes to Seq 2 which has a reporter moiety at the 5’ end, ferrocene-moiety modified sequence. Seq 1 is the target oligonucleotide (targeting oligonucleotides is an aptamer). Seq 2 is the anchor oligonucleotide and Seq 3 is the signaling oligonucleotide. Seq 1 comprises a sequence that is identical to both Seq 2 and Seq3 ( first and second sequence that is identical to anchor and signaling oligonucleotide). Seq 2 is completely complementary to Seq 1 (target oligonucleotide) and Seq 3 is identical to Seq 1 and Seq 2 (signaling oligonucleotide comprises a first and second nucleic acid sequence, which is the same, that is complementary to a region of target oligonucleotide and anchoring oligonucleotide). See Scheme 1. Han teaches either Seq 1 or Seq 3 binds to Seq 2 depending on the presence of target, ATP (configured so to avoid hybridization between targeting oligonucleotide and signaling oligonucleotide in presence of target) (claim 6). Han does not teach single molecule or single nucleotide probes and teaches a concentration of probes (.6µM Seq 1, .5 µM Seq2 and 1 µM Seq 3) (see 1st column, pg. 158) as such the probes of Han comprise a plurality of probes. It is noted that the claims do not require a plurality of different probe sequences and any concentration amount of probes will be a plurality of each of the claimed probes. Han teaches binding the dsDNA of Seq 1 and Seq 2 followed by adding of ATP and Seq 3 (see 1st column, pg. 158). The dsDNA dissociates and Seq 1 binds ATP and Seq 3 binds Seq 2, therefore the biosensor is kinetically configured such that a first association constant between the target and target oligonucleotide is greater than signaling, which is greater than target oligonucleotide and signaling oligonucleotide which is greater than signaling oligonucleotide and anchoring nucleotide. The recitation of target binds quickly to targeting oligonucleotide does not provide any structural limitations to the system. However Han teaches the target binding to the targeting oligonucleotide over the signaling oligonucleotide and thus the target binds quickly to the targeting oligonucleotide. Because there is not structural limitations to a system configured such that k1 is 10 times higher than k2 or k2 is 10 times higher than k3, the biosensor of Han is capable of a system that is configured such that k1 is 10 times higher than k2, as the target oligonucleotide dissociates and binds ATP and not Seq 2 or Seq 3.
With regard to claim 4, Han teaches a concentration of .5 µM Seq2 and 1 µM Seq 3, which is a molar concentration of signaling probe, Seq 3 that is higher than the amount of anchoring oligonucleotide, Seq 2.
With regard to claim 7-11, Han teaches Seq 2 is a thiolated complementary sequence of Seq 1 (target oligonucleotide). Han teaches the anchoring oligonucleotide (Seq 2) is 25 nucleotides in length and substantially identical to targeting oligonucleotide. Han teaches Seq2 is complementary over the entire length of the signaling oligonucleotide, Seq 3 (first and second region of Seq 3). Han teaches Seq 2 is covalently associated with surface of substrate, wherein the substrate is gold disk electrode. See Experimental, 1st paragraph and 2nd column, pg. 158.
With regard to claim 13-16 and 17, Han teaches Seq 3. Seq 3 is the signaling probe and comprises a reporter moiety that is a redox-report. Seq 3 comprises ferrocene modified sequence (see 1st paragraph of experimental and 2nd column, pg. 158). Seq 3 is identical to Seq 1 (complementary over the entire length of second region of target oligo) (first and second sequence is the same).
With regard to claim 19-22, Han teaches Seq 1 is an aptamer sequence (targeting oligonucleotide, aptamer). Han teaches Seq 1 is 27 nucleotides. Han teaches Seq 1 which has a second region that is substantially identical to Seq 2, which is 25 nucleotides. Seq 1 is complementary over the entire length of the Seq 3 (signaling oligonucleotide) (see 1st paragraph of experimental and 2nd column, pg. 158).
Claims 1-2, 4, 6-7, 9-11, 13-15, 17, 20-21, and 23, are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hartwich (WO2011069501 A1, cited on IDS, translation printed 9/19/2024, citations are from translated doc)
With regard to claim 1-2 and 6, Hartwich teaches a system comprising target nucleic acid oligomers, signal nucleic acid oligomers that are modified with a detection label the signal oligomers are complementary to the probe oligomer and target oligomers (see claim 1). Han teaches a modified surface that comprises attached probe nucleic acid oligomer, target nucleic acid oligomers, and signal nucleic acid oligomers. The signal oligomers are modified with a detection label and complementary to the probe oligomers and target oligomers (see pg. 3, 1st paragraph). Hartwich teaches a competition assay between target oligomers and probe oligomers for signal oligomers and therefore the target and signal oligomers do not bind the probe oligomer at the same time (see pg. 4) (claim 6). Hartwich teaches hybridization of target with signal oligomers is faster than hybridization of signal oligomer to surface bound probe oligomers (controlled/configured by k1>k2>k3) (see pg. 4). Because there is not structural limitations to a system configured such that k1 is 10 times higher than k2 or k2 is 10 times higher than k3 or limitations for quickly binding, the support of Hartwich comprising the target oligomer, signal nucleic acid oligomer and probe oligomer is capable of a system that is configured such that k1 is 10 times higher than k2, as the target oligonucleotide binds the signal oligomer faster than hybridization of signal oligomer to probe oligomer.
With regard to claim 7, 9-10, Hartwich teaches probe nucleic acid oligomers are immobilized on a surface (anchoring oligomer). Hartwich teaches target nucleic acid oligomers interact with probe oligomers or with signal oligomer to form a double stranded hybrid. Target oligomers have at least one sequence region that is complementary to a portion of the probe oligomers (first sequence of anchoring oligomer) and a portion of signaling oligomers (second sequence complementary to target oligomer) (see pg. 7).
With regard to claim 11 and 17, Hartwich teaches the signal oligomer can have a redox-active detection label or fluorescent label (see pg. 6) Hartwich teaches an electrochemical detection and includes electrodes (see pg. 8) Hartwich teaches covalently bonded ferrocenes on signal oligomers and oligomers bound to electrodes (metallic electrode) (claim 11).
With regard to claim 13-15, Hartwich teaches the signal oligomers are modified with a detection label and complementary to the probe oligomers and target oligomers (first nucleic acid sequence is second nucleic acid sequence) (second nucleic acid seque4nce is complementary over length of second region of target oligomer and anchoring oligomer) (see pg. 3)
With regard to claims 20-21, Hartwich teaches the target probes bind to probe oligomer (anchoring probe) or signal oligomer (signaling probe) (see pg. 7). Hartwich teaches target oligomers have a sequence region that is complementary to a portion of the probe oligomer or signal oligomers (target oligomer that is second region is identical to first region of anchoring probe, second region is complementary over length of second sequence of signaling oligonucleotide)
With regard to claim 7 and 23, Hartwich teaches attachment of several types of probe nucleic acid oligomers to the surface. Hartwich teaches different probes oligomers are bound (See pg. 6) (plurality of different anchoring oligomers) (claim 23) Hartwich teaches the nucleic acid oligomers are covalently bound to the surface (see pg. 7) (claim 7). Hartwich teaches target oligomers of different subtypes with 24 test sites to detect the different subtypes (see ex 5) (plurality of different types of anchoring oligomers and target oligomers).
Response to Arguments
The response traverses the rejection on pages 7-11 of the remarks mailed 07/22/2025. The response asserts that claim 1 has been amended to recite that the target binds quickly the plurality of targeting oligonucleotides when the sample is in contact with the system preventing said targeting oligonucleotides to bind to the signaling oligonucleotides. It is noted that the examiner was not suggesting in the advisory action mailed 07/22/2025 to amend the claims to recite a target binding quickly to targeting oligonucleotide, the examiner was addressing that the claims are directed to a product and the traversal is with respect to method or functional limitations which do not structurally change the claimed components of the system as such Han and Hartwich anticipate the claimed system. The newly amended claim, as addressed above renders the claims indefinite because is it not clear what structural limitations are required such that a target binds quickly to a targeting oligonucleotides.
The response reiterates the remarks mailed on 06/30/2025 on pages 7-11. This response was addressed in the advisory action mailed 07/17/2025 and is maintained. It is noted as addressed in the previous office action that applicant continues to provide a traversal with respect to method steps and limitations of a method step, however the claims are directed to a product. The claimed system does not comprise any structural limitations that are distinguished from the prior cited art. While applicant points to a one pot system with the ability to detect in under 10 minutes, this is a method limitation and the method claims are not under examination. For these reasons and reasons made of record the rejection is maintained.
Conclusion
No claims are allowable.
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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/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699