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 .
Priority
This application is a CIP of 17529666 filed 11/18/2021, now U.S. Patent No. 11,702,709 which is a CIP of 17332837 filed 05/27/2021, now U.S. Patent No. 11,920,188 which claims benefit of U.S. Serial Application No. 63/147,613 filed 02/09/2021.
Status of the Applications, Amendments and/or Claims
This action is written in response to applicant's correspondence(s) submitted on 09/24/2025. In the paper of 09/24/2025, Applicant amended claims 4-5, 9-11, 14 and 16-20. Accordingly, claims 1-22 are pending.
Election/Restrictions
Applicant’s elections of the following species without traverse, in the reply filed on 09/24/2025 are acknowledged.
Concerning species group A, Type of SARS-Cov-2 detection method, Applicant elects choice (b).
(b) Method to detect, genotype and identify a SARS-CoV-2 variant in a subject, comprising: performing in a single assay a combined reverse transcription and asymmetric PCR amplification
reaction on total RNA using a set of fluorescently labeled primer pairs comprising an unlabeled primer and a fluorescently labeled primer, primer pairs being selective for sequences within a Spike gene;
hybridizing the plurality of fluorescently labeled SARS-CoV-2 amplicons to a plurality of nucleic acid probes and at least one control probe to which the fluorescently labeled SARS-CoV-2 amplicons do not hybridize, each of said nucleic acid probes attached to specific positions on a solid microarray support;
washing the microarray at least once;
imaging the microarray to detect fluorescent signals above threshold for all the nucleic acid probes produced upon hybridization to the fluorescently labeled SARS-CoV-2 amplicons;
measuring at least N fluorescent signals above the threshold from hybridization of the fluorescently labeled SARS-CoV-2 amplicons to the universal probes thereby detecting the SARS-CoV-2 in the sample;
genotyping the Spike gene at each target sequence,
the step comprising:
comparing the fluorescent signals from hybridization of the fluorescently labeled SARS-CoV-2 amplicons to the wild type probes and from the hybridization of the fluorescently labeled SARS-CoV-2 amplicons to the mutant probes at each position on the microarray; and
analyzing directly a relative size of the fluorescent signal from hybridization to the mutant probes vs. the fluorescent signal from hybridization to the wild type probes to produce a hybridization pattern of wild type vs. mutant genotyping at each target sequence in SARS-CoV- 2; and
identifying a variant of SARS-CoV-2 as a known variant of concern or a known variant of interest or a combination thereof or as an unknown variant by comparing the hybridization pattern to a known pattern of wild type vs. mutant genotype variation among known SARS-CoV-2 variants.
Concerning species group B, selection of primer pair, Applicant elects choice (j), a specific combination consisting SEQ ID NO: 266 and SEQ ID NO: 138 (generates amplicon 2) and SEQ ID NO: 11 and SEQ ID NO: 139 (generates amplicon 3).
Concerning species group C, selection of universal probe, Applicant elects the Universal probe combination consisting of SEQ ID NOS: 235-236 (to hybridize to Amplicon 2) and SEQ ID NOS: 282-286 (to hybridize to Amplicon 3).
Concerning species group D, selection of wildtype probe, Applicant elects the wildtype probe set consisting of SEQ ID NOS: 235 (to hybridize to amplicon 2) and SEQ ID NOS: 287 (to hybridize to amplicon 3).
Concerning species group E, selection of mutant probe, Applicant elects the mutant probe set consisting of SEQ ID NOS: 236 (to hybridize to amplicon 2) and SEQ ID NOS: 288 and 289 (to hybridize to amplicon 3).
No claims are withdrawn from further consideration pursuant to 37 CFR 1.142(b). The elections above were made without traverse in the reply filed on 09/24/2025.
Status of the claims
Claims 1-22 are pending and currently under review.
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 2, 4, 9, 14, 18 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.
Claims 2-3 and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite because each recite the limitation “measuring at least N fluorescent signals above the threshold from hybridizing of the fluorescently labeled SARS-CoV-2 amplicons to the universal probes”. The phrase “at least N” renders the limitation above and the noted claims indefinite since N has not been limited to any numerical value nor is “N” defined within these claims.
Also, where a numerical value is provided for N signals (e.g. for the recited claim 3, N is equal to or greater than 6 fluorescent signals), the meaning of the limitation “SARS-COV-2 is detected by measuring at least 6 fluorescent signals above the threshold from hybridizing of the fluorescently labeled SARS-CoV-2 amplicons to the universal probes”, is also unclear. It is unclear if this limitation is directed to detecting the fluorescent signals that are above a threshold at least 6 universal probe site of the microarray, or if something else is intended.
Claim 4 recites the limitation “wherein the Spike gene is genotyped at each target sequence, the method further comprising” which is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph for being indefinite and confusing. As a first matter, it is unclear whether the limitation “wherein the Spike gene is genotyped” is intended to constitute an active process step, i.e. it is unclear whether or not this limitation is requiring a step of genotyping each target sequence of the Spike gene. Amendment and/or clarification is required.
Furthermore, claim 4 is again rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph for being indefinite and confusing because it is unclear whether the processes recited following the phrase “method further comprising” are directed to processes for accomplishing the process of genotyping of each selected target sequence of the Spike gene, or whether the processes recited following the phrase “method further comprising” are unrelated to genotyping the spike target sequences, and are simply processes that are required to be actively practiced following the imaging process recited by clam 1.
Claim 4 recites the limitation “analyzing directly a relative size of the fluorescent signal from hybridization to the mutant probes vs. the fluorescent signal from hybridization to the wild type probes to produce a hybridization pattern of wild type vs. mutant genotyping among all the target sites in SARS-COV- 2”.
The phrase “analyzing directly a relative size” renders claim 4 indefinite and confusing. It is not understood what is intended by “relative size of the fluorescent signal…”.
It is unknown if the analyzing limitation of claim 4 noted above, is directed to generating a hybridization pattern of fluorescent signals across all the probe sites on the solid microarray support, the generated hybridization pattern of each probe site has a value corresponding to fluorescent signal of mutant probes divided by fluorescent signal of wildtype probes.
It is unknown if the analyzing limitation of claim 4 noted above, is directed to generating a hybridization pattern of fluorescent signals across all the probe sites on the solid microarray support, the generated hybridization pattern comprise a fluorescent value at each probe site that is a normalized value to the fluorescent signal of wildtype probes.
Claims 9 and 18 each recite the limitation “wherein the universal probes comprise the nucleotide sequences of SEQ ID NOS: 235 and 236 in a mix, 33 and 153 to hybridize to amplicon 2”.
The limitation recites the phrase “in a mix”, which renders these claims as a whole confusing and indefinite.
It is not known if the limitation is simply directed to the microarray support comprising at least the universal probes consisting of the nucleotide sequences of SEQ ID NOS: 153, 253, 235 and 236 attached thereto; or whether the limitation is directed to a the microarray support having at least the universal probes comprising the nucleotide sequences of SEQ ID NOS: 233, 153 attached thereto and to which a solution of universal probes comprising the nucleotide sequences of SEQ ID NOS: 235 and 236 are applied. The meaning of “in a mix” is not so easily discerned and it is unclear if the probes that are in a mix are attached to the solid support or are in a solution applied to a solid support.
Claims 9 and 18 each recite the limitation “SEQ ID NOS: 36 and 282, 283, 284, 285 and 286 in a mix, 290, and 292 and 293 in a mix to hybridize to amplicon 3”.
This limitation recites the phrase “in a mix” which renders these claims as a whole confusing and indefinite. It is not known if the limitation is simply directed to the microarray support having at least the universal probes comprising the nucleotide sequences of SEQ ID NOS: 36, 282-286, 290, 292 and 293 attached thereto so as to hybridize to amplicon 3; or whether the limitation is directed to applying to the microarray support comprising the plurality of universal probes attached thereto, a solution comprising of universal probes comprising the nucleotide sequences of SEQ ID NOS: 36, 282-286, 290, 292 and 293 so as to hybridize amplicon 3.
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 1-4, 6, 12-15 and 21-22 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Hogan et al. (US2022/0364157A1, filed 11/17/2020).
Regarding claims 1-4, 6-8, 12-15 and 21-22, Hogan et al. teach a combined reverse transcription and asymmetric PCR amplification reaction performed on isolated total RNA to obtain fluorescent labeled COVID-19 virus specific amplicons (para [0008]-[0010], para [0057], [0061], [0293]).
Hogan et al. teach using at least one fluorescent labeled primer pair selective for a target nucleotide sequence in the COVID-19 virus, the fluorescent labeled primer pair comprising an unlabeled primer and a fluorescently labeled primer (para [0008]-[0010], para [0057]).
Hogan et al. teach employing at least two fluorescent labeled primer pairs selective for the target nucleotide sequence in the COVID-19 virus and in the at least one other non-COVID-19 virus, and nucleic acid probes having a sequence corresponding to sequence determinants in the COVID-19 virus and the at least one of the other non-COVID-19 virus (para [0161], [0008], [0079], [0083]-[0084], [0086], [0091], [0096]; Table 1 teach RNase P primers SEQ ID NOS: 43-44 and Table 2: SEQ ID NOS: 71-72).
Hogan et al. teach fluorescent labeled COVID-19 virus amplicons generated are hybridized to a plurality of nucleic acid probes, each attached to a solid microarray support. Each of the nucleic acid probes have sequence corresponding to a sequence determinant in the COVID-19 virus (para [0008], [0075], para [0083]-[0084]). Hogan et al. also teach a RNase P probe (para [0079], [0174]), mutant and wildtype and universal or pan SARS-COV-2 probes (para [0167], Table 19, para [0161]).
Hogan et al. teach washing microarray at least once and imaging to detect at least one fluorescent signal from the hybridized fluorescent labeled COVID-19 virus amplicons (para [0008], [0075]).
Regarding claims 12 and 21, Hogan et al. teach primer ratio of 4:1 (para [0028], [0061], [0215]). Hogan et al. teach one fluorescent primer pair comprising one unlabeled primer and a fluorescently labeled primer that is provided in excess of about 4-fold to about 8-fold (para [0061]).
Regarding claims 13 and 22, Hogan et al. teach a nasopharyngeal swab, a nasal swab, a mouth swab, a mouth swab or saliva (para [0177]-[0180]).
Accordingly, Hogan et al. (US2022/0364157A1) teach the instant claims 1-4, 6, 12-15 and 21-22.
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 1-4, 9-11, 14 and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11 of U.S. Patent No. 11,702,709B2 in view of Hogan et al. (US2022/0364157A1 filed Nov 17, 2020).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of both applications are each directed to methods for detecting severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) comprising:
obtaining the sample;
isolating total RNA;
performing in a single assay a combined reverse transcription and asymmetric PCR amplification on the total RNA using at least one fluorescent labeled first primer pair comprising an unlabeled primer and a fluorescently labeled primer selective for target sequences in the spike gene of SARS- CoV-2 or COVID-19 virus so as to generate at least one fluorescently labeled COVID-19 virus cDNA amplicon;
hybridizing the fluorescently labeled SARS- CoV-2 amplicons, or COVID-19 virus amplicons to a plurality of nucleic acid probes attached to a solid microarray support, said nucleic acid probes comprising SEQ ID NOS: 28, 33, 35-38, 40-45, 47, 52-54, 59, 62, 153-155, 176, 179-180, 182-183, 186, 235-236.
washing the microarray at least once;
imaging the microarray to detect at least one fluorescent signal from the hybridized fluorescent labeled COVID-19 virus amplicons.
The instant claims 1-4, 9-11, 14 and 18-20 differ from the claim 11 of U.S. Patent No. 11,702,709B2 as claim 11 of the U.S. Patent No. 11,702,709B2 do not recite/provide at least one control probe attached to a solid microarray support, the control probe does not hybridize the fluorescently labeled SARS- CoV-2 amplicons, or COVID-19 virus amplicons.
Hogan et al. (US2022/0364157A1 filed Nov 17, 2020) teach providing at least one control probe attached to a solid microarray support. The control probe of Hogan et al. does not hybridize to fluorescently labeled SARS- CoV-2 amplicons, or COVID-19 virus spike gene sequences i.e. Hogan et al. particularly provides a RNase P control sequence in a well, and/or RNase P control sequence attached to a solid microarray support (see para [0061] and SEQ ID NOS: 21-22 of Table 1; SEQ ID NOS: 43-44 of Table 37, and SEQ ID NOS: 71-72 of Table 38; see also, Fig. 14 and para [0024], and Figs. 16C-16D and para [0026]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify claim 11 of U.S. Patent No. 11,702,709B2 by applying the teachings of Hogan et al. of providing RNAse P sequence that do(es) not hybridize to fluorescently labeled SARS-COV-2 amplicons, or to spike gene sequences of SARS-COV-2 as a routine matter of practice, and use the RNAse P reference/control sequence as an internal probe to identify false negative results, or utilized to normalize the probe hybridization imaging results collected from a microarray comprising spike gene probes for detecting severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in a test sample of a subject.
Conclusion
No claims are currently allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLAYINKA A OYEYEMI whose telephone number is (571)270-5956. The examiner can normally be reached Monday -Thursday: 9:00 am - 5:00 pm, EST.
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OLAYINKA A. OYEYEMI
Examiner
Art Unit 1681
/OLAYINKA A OYEYEMI/Examiner, Art Unit 1681
/GARY BENZION/Supervisory Patent Examiner, Art Unit 1681