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 .
Response to Amendment
The Amendment filed 12/03/2025 in which claims 1-3, 5, 6, 11, and 12 were amended, and claims 4 was canceled, has been entered. Claims 7-9, 17-18 were previously withdrawn.
Claims 1-3, 5, 6 and 10-16 are under examination on the merits.
Drawings
(Previous objection, withdrawn) Applicant’s amendments to the Drawings submitted on 12/03/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 09/04/2025.
Specification
(Previous objection, withdrawn) Applicant’s amendments to the Specification submitted on 12/03/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 09/04/2025.
Claim Objections
(Previous objections, withdrawn as to claims 1-6, 11 and 12). The previous objection of claim 4 is moot in view of Applicant’s cancelation of this claim. Applicant’s amendments to claims 1-3, 5, 6, 11 and 12 have overcome previous objections to those claims.
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.
(previous rejection, withdrawn as to claims 1-6, 10-16) Claims 1-6, 10-16 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing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.
See claims 1-3, 5, 6, 10-16 as submitted on 12/03/2025.
The previous rejection of claim 4 is moot in view of Applicant’s cancelation of this claim.
Applicant’s amendments to claims 1 and 11, have overcome previous rejection to claims 1-3, 5, 6, 10-16.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
(new rejection, necessitated by amendment as to claim 13) Claim 13 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 13 recites “wherein in the composition, the first probe, the second probe and the third probe carry fluorescent reporter groups that do not interfere with each other”. It is not clear how this statement further limits the subject matter recited in claim 1 because claim 1 already recites “wherein the first probe, the second probe and the third probe carry fluorescent reporter groups that do not interfere with each other.”
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
(previous rejection, withdrawn as to claim 1-6, 10-16) Claims 1-6, 10-16 were rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below. See MPEP § 2106 for analysis framework.
See claims 1-3, 5, 6, 10-16 as submitted on 12/03/2025.
The previous rejection of claim 4 is moot in view of Applicant’s cancelation of this claim.
Applicant’s amendments to claims 1 and 11, have overcome previous rejection to claims 1-3, 5, 6, 10-16.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(previous rejection, withdrawn as to claim 4, maintained and modified as necessitated by amendment as to claims 1-3, 5, 6, 10, 13-16) Claims 1-3, 5, 6, 10, 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Jung et al., in view of Wu et al. and Li et al. (prior art of record).
See claims 1-3, 5, 6, 10-16 as submitted on 12/03/2025.
The previous rejection of claim 4 is moot in view of Applicant’s cancelation of this claim.
Regarding claim 1 the amended claim recites “amplifying an area as shown in SEQ ID NO: 3 in an N gene of SARS-CoV-2” on line 2 and “wherein the first probe, the second probe, and the third probe carry fluorescent reporter groups that do not interfere with each other.” However, the cited prior art already teaches these limitations as follows.
As previously explained, Jung et al. teach a comparative analysis of compositions for assaying for the presence of SARS-CoV-2 in a sample comprising primer and probe sets for SARS-CoV-2 (Abstract). Jung et al. further disclose compositions comprising multiple primer probe sets, wherein a first primer pair and probe set is directed to an N gene of SARS-CoV-2; and a second and third primer pair and probe sets are directed to an ORF1ab gene of SARS-CoV-2 (Abstract, page 1). Jung et al. further teach that a composition comprising primer-probe sets targeting ORF1ab and the nucleocapsid gene of SARS-CoV-2 should be selected for sensitive and reliable laboratory confirmation of SARS-CoV-2 (page 6).
Jung et al. do not explicitly teach a primer-probe set for amplification of an area in SEQ ID NO:1 nor SEQ ID NO:2 nor SEQ ID NO:3.
However, Wu et al. teach nucleotide the full length nucleotide sequences of ORF1ab and the N gene of SARS-CoV-2 available as GenBank Accession No. NC_045512 since 02/03/2020 which provide a template for primer and probe set design. The sequences in GenBank Accession No. NC_045512 correspond to sequences for the ORF1ab and N gene and comprise instant SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3. The sequences of Wu et al. share 100% sequence identity with instant SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, alignments of record and provided below.
• Alignment 1: Qy is instant SEQ ID NO: 1, and Db is Wu et al.’s ORF1ab
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Alignment 2: Qy is instant SEQ ID NO: 2, and Db is Wu et al.’s ORF1ab
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Alignment 3: Qy is instant SEQ ID NO: 3, and Db is Wu et al.’s N gene
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Li et al. teach a method for designing primers and probes specifically for detection of SARS-CoV-2 by RT-qPCR based on known sequences of SARS-CoV-2 such that the sensitivity and specificity of the detection process can be improved for accurate diagnosis and timely treatment of SARS-CoV-2 infection (Abstract, page 1).
With respect to the new limitation in claim 1 of “wherein the first probe, the second probe, and the third probe carry fluorescent reporter groups that do not interfere with each other”, Jung et al. teach the use of probes comprising a fluorescent dye which serve as reporters of amplification (page 4). Further, Li et al. teach the use of probes comprising fluorescent labels such as FAM®, HEX®, VIC®, etc., wherein the signals do not interfere with one another (Fig. 4, Table 6).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have combined the teachings of Jung et al. about a composition for PCR amplification comprising primer-probe sets directed to SARS-CoV-2 ORF1ab and the N gene, with the teachings of Wu et al. and Li et al. about the template sequence and primer-probe set design method to arrive at the claimed invention for the benefit of formulating a composition with improved sensitivity and specificity for reliable laboratory confirmation of SARS-CoV-2. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had reasonable expectation of success in combining the teachings of Jung et al. with the sequence template of Wu et al. and the primer-probe set design method of Li et al. to arrive at the claimed invention given that the methods of primer-probe design for PCR amplification and formulation of compositions for PCR amplification are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claims 2, 3, 5 and 6, it is noted that the amendment to claims 2, 3, 5, and 6, was made to overcome the previous objections or rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 09/04/2025. No new limitations were introduced to these claims in the amendment filed on 12/03//2025. As previously explained, the teachings of Jung et al., Wu et al., and Li et al. are explained above. Similarly, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have combined the teachings of Jung et al., Wu et al., and Li et al. with reasonable expectation of success to arrive at the claimed primer-probe sets as recited in claims 2, 3, 5 and 6.
Regarding claim 10, it is noted that no amendment were introduced to claim 10. As previously explained, Jung et al. teach the use of a primer-probe set for an internal control (page 4, 6). Further, Li et al. teach the use of primer-probe sets targeting internal controls, one such primer-probe set targets the human ribonuclease P (RNase P) gene (page 10, Table 6).
Regarding claim 13, it is noted that no amendments were introduced to claim 13. As previously explained, Jung et al. teach the use of probes comprising a fluorescent dye which serve as reporters of amplification (page 4). Further, Li et al. teach the use of probes comprising fluorescent labels such as FAM®, HEX®, VIC®, etc., wherein the signals do not interfere with one another (Fig. 4, Table 6).
Regarding claims 14 and 15, it is noted that no amendments were introduced to claims 14 and 15. As previously explained, Jung et al. teach the use of 300 nM of primers and probes for the target detection (page 5). Further, Li et al. teach primer concentrations for probe-based assays in the range of 300-900 nM (page 6, Table 2). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Therefore, the claimed ranges recited in claims 14 and 15 merely represent obvious variants and/or routine optimization of the values of the cited prior art.
Regarding claim 16, it is noted that no amendment was introduced to claim 16. As previously explained, Jung et al. teach a kit comprising compositions for assaying for the presence of SARS-CoV-2 in a sample comprising primer and probe sets for SARS-CoV-2 ORF1ab and N gene for sensitive and reliable laboratory confirmation of SARS-CoV-2 (Abstract, page 6).
Accordingly, claims 1-3, 5, 6, 10, 13-16 were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
(previous rejection, maintained as to claims 11 and 12) Claims 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Jung et al., Wu et al. and Li et al., as applied to claims 1-3, 5, 6, 10, 13-16 above, further in view of Eder et al. (prior art of record).
See claims 11 and 12 as submitted on 12/03/2025.
Regarding claims 11 and 12, it is noted that no amendments were introduced to claims 14 and 15. As previously explained, the teachings of Jung et al., Wu et al., and Li et al. are explained above. Li et al. further teach the use of primer-probe sets targeting internal controls, one such primer-probe set targets the human ribonuclease P (RNase P) gene which is used as an effective internal control due to its ubiquitous presence in all cells and cellular compartments. (page 10, Table 6).
Neither Jung et al., nor Wu et al., nor and Li et al. teach a sequence for the RNase P gene.
However, Eder et al. teach a sequence for the human RNase P gene highly conserved across multiple taxonomic phyla (Abstract). The sequence of Eder et al. in GenBank Accession No. U77665 corresponds to sequences for the RNase P gene and comprises instant SEQ ID NO: 4. Said sequences of Eder et al. shares 100% sequence identity with instant SEQ ID NO: 4, see alignment provided below.
• Alignment 4: Qy is instant SEQ ID NO: 4, and Db is Eder et al.’s RNase P gene
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It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have combined the teachings of Jung et al., Wu et al., and Li et al. with the teachings of Eder et al. about an internal control template sequence to arrive at the claimed invention for the benefit of including an internal control comprising the human RNase P gene which is ubiquitous in all cells and cellular compartments. It also would have been prima facie obvious to one of ordinary skill in the art to use the sequence template of Eder et al. and the primer design method taught by Li et al. to design primer-probe sets for amplification of the RNAse P gene. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had reasonable expectation of success in combining the teachings of Jung et al., and Wu et al. with the sequence template of Eder et al. and the primer-probe set design method of Li et al. to arrive at the claimed invention given that the methods of primer-probe design for PCR amplification and formulation of compositions for PCR amplification are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, claims 11 and 12 were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 12/03/2025 have been fully considered but they are not persuasive.
Applicant contends on page 3 of the Remarks submitted on 12/03/2025:
1. The prior art does not teach the selection of specific regions, and the regional screening in the present application requires creative experimental support
Wu et al. only disclosed the full-length sequences of the ORF1ab and N genes of SARS-CoV-2, without performing functional partitioning of the sequences or suggesting which regions are suitable as qPCR amplification targets (e.g., avoiding secondary structures, ensuring amplification efficiency, etc.). The full-length ORF1ab gene alone contains more than 20 kb of nucleotide fragments, resulting in a vast number of potential amplification regions. It is impossible to identify effective targets solely based on the disclosed sequences…
2. The technical solution of the present application achieves unexpected technical effects beyond conventional expectations
(1) Significantly higher sensitivity than the prior art
In Example 5, Applicant compared the N gene primer-probe of the present application (targeting the region of SEQ ID NO: 3) with similar products from US CDC and The University of Hong Kong, using low-concentration SARS-CoV-2 samples (5-10 copies/mL) including viral culture fluid, bronchoalveolar lavage fluid, and plasma samples. The detection rate of the present application is significantly higher than that of similar products from US CDC and The University of Hong Kong, demonstrating superior sensitivity…
In response:
Applicant's arguments against the references individually are not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, the combination of the teachings of Jung et al. with the sequence template of Wu et al. and the primer-probe set design method of Li et al. teach the composition of claim 1. Given that all of the elements of the instant claims were clearly taught by the cited prior art along with clear motivations to combine such teachings it is herein maintained that one of ordinary skill in the art would have been able to arrive at the claimed invention with reasonable expectation of success as explained above in detail given.
With respect to Applicant’s alleged unexpected results, the cited prior art already teaches clear motivations for targeting the N gene as well as the ORF1ab region of SARS-CoV-2. For instance, Jung et al. teach compositions comprising multiple primer probe sets, wherein a first primer pair and probe set is directed to an N gene of SARS-CoV-2; and a second and third primer pair and probe sets are directed to an ORF1ab gene of SARS-CoV-2 (Abstract, page 1). Jung et al. further teach that a composition comprising primer-probe sets targeting ORF1ab and the nucleocapsid gene of SARS-CoV-2 should be selected for sensitive and reliable laboratory confirmation of SARS-CoV-2 (page 6). Therefore the results presented in Examples 5-7 are considered entirely expected and consistent with the prior art. It is not clear why Applicant refers to such a result as unexpected. Further, it is noted that signal from PCR amplification is subject to routine optimization such as adjusting GC content of the primer-probe sets, temperature, selection of other reagents in the reaction mix, etc. Accordingly, the levels of signal sensitivity and other outputs of the PCR reaction are considered to be those determined by routine optimization.
Conclusion
No claims are allowed.
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 MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672