DETAILED ACTION
Response to Amendment
This is a final office action in response to a communication filed on December 11, 2025. Claims 1-9 and 11-20 are pending in the application.
Status of Objections and Rejections
All objections from the previous office action are withdrawn in view of Applicant’s amendment.
The rejection of claims 10 and 20 is obviated by Applicant’s cancellation.
All rejections under 35 U.S.C. 103 from the previous office action are maintained.
New grounds of rejection are necessitated by the amendments.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim(s) 1-9 and 11-19 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 11 recite the limitation “that is proportional to a quantity of the target sequence in a target cell” in last two lines, which is not disclosed in the specification and is deemed to be new matter. The specification only discloses identifying a target sequence of nucleotides, but not disclose to the determined quantity of the target sequence is proportional to a quantity of the target sequence in a target cell. Applicant fails to provide support for this limitation in its Response, and thus is requested to identify the relevant disclosure in the specification as filed.
All subsequent dependent claims 2-9 are rejected due to their dependencies on rejected base claim 1.
All subsequent dependent claims 12-19 are rejected due to their dependencies on rejected base claim 1.
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(s) 1-9 and 11-19 is/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 pre-AIA the applicant regards as the invention.
Claim 1 recites “the electrophoretic mobility shift” in line 7. There is insufficient antecedent basis for this limitation in the claim. It is suggested to be “an electrophoretic mobility shift.”
All subsequent dependent claims 2-9 are rejected due to their dependencies on rejected base claim 1.
Claim 11 recites “the electrophoretic mobility shift” in line 11. There is insufficient antecedent basis for this limitation in the claim. It is suggested to be “an electrophoretic mobility shift.”
All subsequent dependent claims 12-19 are rejected due to their dependencies on rejected base claim 1.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 3-4, 7-8, 11, 13-14, and 17-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li (WO 2018/227426), supported by Moller (2020/0354768) as an evidence.
Regarding claim 1, Li teaches a computer-implemented method (¶4: a controller comprising one or more computer processors programmed to separate biological sample or portion) for detecting one or more nucleic acids comprising a target sequence of nucleotides (¶209: a method for sample analysis; ¶110: a target nucleic acid), the method comprising:
incubating molecular beacons (MBs) with the one or more nucleic acids (¶106: a nucleic acid modified by conjugation or binding with a reporter agent; ¶307: a reporter agent may be a molecular beacon), each nucleic acid comprising a sequence of nucleotides (¶110),
wherein the molecular beacons are configured to generate a fluorescence signal when bound with the target sequence (¶109; ¶303: the reporter agent can yield a detectable signal, and the intensity of the detectable signal can be proportional to the amount of target nucleic acid; ¶304: optically-active dye (e.g., a fluorescent dye) can be used as a reporter agent);
performing electrophoresis by applying voltage (¶327: the power supply can provide a voltage to the electrodes, resulting in a field strength or voltage gradient needed for electrophoresis); and
determining, using the fluorescent signal (¶303: a detectable signal; ¶304: optically-active dye (e.g., a fluorescent dye) can be used as a reporter agent) and the electrophoretic mobility shift of the MBs and the one or more nucleic acids during electrophoresis (¶328: mobility shift electrophoresis), a quantity of the target sequence in the one or more nucleic acids that is proportional to a quantity of the target sequence in a target cell (¶303: the intensity of the detectable signal can be proportional to the amount of the amplified DNA product and/or the original target RNA amplified).
Regarding claim 3, Li teaches wherein the target sequence is a micro ribonucleic acid (miRNA) (¶106: micro-RNA, i.e., miRNA).
Regarding claim 4, Li teaches wherein the target sequence is a single strand ribonucleic acid (ssRNA) (as evidenced by Moller, ¶9, miRNA is a single stranded RNA).
Regarding claim 7, Li teaches the computer-implemented method further comprising:
obtaining blood of a patient (¶296);
isolating ribonucleic acid (RNA) from red blood cells (RBCs) of the blood of the patient (¶301; here Examiner notes that when the target RNA in the blood is to be detected, the target RNA must be isolated from other components of the blood, e.g., RBCs).
Regarding claim 8, Li teaches wherein a gel used in electrophoresis is not stained (¶304: reporter agent is used as an optically-active dye, e.g., a fluorescent dye and a nucleic acid binding dye; ¶384: image sensor; laser sensor; ¶372: gels can comprise or be used in conjunction with dyes, e.g., protein stains; here Examiner notes that when a fluorescent dye is used for optical detection, the gel does not need to be stained).
Regarding claim 11, Li teaches a system, comprising:
at least one computer hardware processor (Fig. 26; ¶278: computer processor 2605); and
at least one non-transitory computer-readable storage medium storing processor-executable instructions (Fig. 26; ¶278: memory 2610; ¶276: machine executable code) that, when executed by the at least one computer hardware processor, cause the at least one computer hardware processor to perform a computer implemented method (¶276) for detecting one or more nucleic acids comprising a target sequence of nucleotides (¶209: a method for sample analysis; ¶110: a target nucleic acid), the method comprising:
incubating molecular beacons (MBs) with the one or more nucleic acids (¶106: a nucleic acid modified by conjugation or binding with a reporter agent; ¶307: a reporter agent may be a molecular beacon), each nucleic acid comprising a sequence of nucleotides (¶110), wherein the molecular beacons are configured to generate a fluorescence signal when bound with the target sequence (¶109; ¶303: the reporter agent can yield a detectable signal, and the intensity of the detectable signal can be proportional to the amount of target nucleic acid; ¶304: optically-active dye (e.g., a fluorescent dye) can be used as a reporter agent);
performing electrophoresis by applying voltage (¶327: the power supply can provide a voltage to the electrodes, resulting in a field strength or voltage gradient needed for electrophoresis); and
determining, using the fluorescent signal (¶303: a detectable signal; ¶304: optically-active dye (e.g., a fluorescent dye) can be used as a reporter agent) and the electrophoretic mobility shift of the MBs and the one or more nucleic acids during electrophoresis (¶328: mobility shift electrophoresis), a quantity of the target sequence in the one or more nucleic acids that is proportional to a quantity of the target sequence in a target cell (¶303: the intensity of the detectable signal can be proportional to the amount of the amplified DNA product and/or the original target RNA amplified).
Regarding claim 13, Li teaches wherein the target sequence is a micro ribonucleic acid (miRNA) (¶106: micro-RNA, i.e., miRNA).
Regarding claim 14, Li teaches wherein the target sequence is a single strand ribonucleic acid (ssRNA) (as evidenced by Moller, ¶9, miRNA is a single stranded RNA).
Regarding claim 17, Li teaches the further comprising:
obtaining blood of a patient (¶296);
isolating ribonucleic acid (RNA) from red blood cells (RBCs) of the blood of the patient (¶301; here Examiner notes that when the target RNA in the blood is to be detected, the target RNA must be isolated from other components of the blood, e.g., RBCs).
Regarding claim 18, Li teaches wherein a gel used in electrophoresis is not stained (¶304: reporter agent is used as an optically-active dye, e.g., a fluorescent dye and a nucleic acid binding dye; ¶384: image sensor; laser sensor; ¶372: gels can comprise or be used in conjunction with dyes, e.g., protein stains; here Examiner notes that when a fluorescent dye is used for optical detection, the gel does not need to be stained).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 2 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Kolesar (US 6,261,781).
Regarding claims 2 and 12, Li discloses all limitations of claims 1 and 11, respectively. Li does not discloses wherein the target sequence is a mutated sequence.
However, Kolesar teaches a method of detection of DNA and RNA target se1quences, including mutated sequences with deletion or point mutation using electrophoresis and laser-induced fluorescence (Col. 4, ll. 51-55).
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 Li for detecting mutated target sequence as taught by Kolesar because electrophoresis is a suitable technique for detection of mutated sequence. Applying a known technique to a known method ready for improvement to yield predictable results is prima facie obvious. MPEP 2141(III)(D).
Claim(s) 5-6 and 15-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Vu (US 2012/0046191).
Regarding claims 5 and 15, Li discloses all limitations of claims 1 and 11, respectively. Li does not discloses wherein the target sequence is a single strand deoxyribonucleic acid (ssDNA).
However, Vu teaches a method for detecting target biomolecules (¶7), using nanoparticle probe complex by gel electrophoresis and transfer to membrane for Western blot analysis (¶14). The target nucleic acid molecules (¶68) include DNA or RNA, double stranded (ds) or single stranded (ss) (¶59).
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 Li for detecting single strand DNA as taught by Vu because electrophoresis is a suitable technique for detection of ssDNA. Applying a known technique to a known method ready for improvement to yield predictable results is prima facie obvious. MPEP 2141(III)(D).
Regarding claims 6 and 16, Li discloses all limitations of claims 1 and 11, respectively. Li does not discloses the method or the system further comprising conjugating the one or more nucleic acids with streptavidin beads.
However, Vu teaches a kit for the separation and detection of a target biomolecule of interest using nanoparticle probes (¶144). The nanoparticle probe includes a specific binding agent that specifically binds the target biomolecule of interest, using a linker, e.g., streptavidin, to link the detectable nanoparticle and the specific binding agent (¶145). Thus, Vu teaches the conjugation between the target biomolecule and the specific binding agent linked to streptavidin nanoparticles.
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 Li by incorporating streptavidin nanoparticles for separation and detection of a target biomolecule as taught by Vu because use of nanoparticle probes is standard procedure (¶133) so that streptavidin nanoparticles would provide the support to the binding agent for binding the target biomolecule for detection of target sequence of nucleic acids. Applying a known technique to a known method ready for improvement to yield predictable results is prima facie obvious. MPEP 2141(III)(D).
Claim(s) 9 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Hochstrasser (US 2002/0150569).
Regarding claims 9 and 19, Li discloses all limitations of claims 1 and 11, respectively. Li does not discloses where electrophoresis comprises applying a first voltage for a first period of time and a second voltage for a second period of time.
However, Hochstrasser teaches running electrophoresis at a voltage which is increased linearly from 300 to 3500 V during 3 hours, then for 3 additional hours at 3500 V, and finally for 17 hours at 5000 V (¶18). Thus, Hochstrasser teaches the electrophoresis is performed by applying a first voltage for a first period of time and a second voltage for a second period of time.
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 Li for running electrophoresis by applying a first voltage for a first period of time and a second voltage for a second period of time as taught by Hochstrasser because it is a suitable technique for voltage application of electrophoresis. Applying a known technique to a known method ready for improvement to yield predictable results is prima facie obvious. MPEP 2141(III)(D).
Response to Arguments
Applicant’s arguments have been considered but are unpersuasive.
Applicant argues Li discloses detecting amplified nucleic acids does not mean detecting a quantity of the target sequence that is proportional to a quantity of the target sequence (Response, p. 8, para. 2). This argument is unpersuasive because this limitations is deemed to be new matter and Li explicitly discloses the intensity of the detectable signal can be proportional to the amount of the amplified DNA product and/or the original target RNA amplified (Li, ¶303).
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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 CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached M-F: 8:30am - 5:30pm.
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/C. SUN/Primary Examiner, Art Unit 1795