DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed April 30, 2026. Currently, claims 1-4, 7-12, 15-23, 30 are pending. Claims 22-23, 30 have been withdrawn as drawn to non-elected subject matter.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow. This action is made FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
Election/Restrictions
Applicant's election without traverse of Group I, Claims 1-4, 7-12, 15-21 in the paper filed October 15, 2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application is a 371 of PCT/CN2021/128667, filed November 4, 2021 and claims priority to PCT/CN2020/126728, filed November 5, 2020.
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.
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.
Claims 1, 4, 7, 10, 12, 15-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kukla et al. (New Mircrobiol, Vol. 43, No. 2, pages 70-77, April 19, 2020) in view of Albuquerque et al. (Brazilian J. of Microbiology, Vol. 50, pages 435-443, 2019) in view of Vuong (PLOS one. Development of Real-Time PCR methods for the detection of bacterial meningitis pathogens without DNA extraction, February 1, 2016) and Genbank MK163634; Genbank AF030369; Genbank AJ001313 and Genbank AY281033 in view Buck et al. (BioTechniques (1999) 27(3): 528-536).
The prior art is replete in teachings of cpsA, lytA, sodC and crtA PCR multiplex reactions for detecting S. pneumoniae and N. meningitidis. The prior art also teaches the full length sequences for each of the regions.
Particularly, Kukla teaches improved laboratory diagnostics for detecting Streptococcus pneumoniae using qPCR (limitations of Claim 12). Kukla teaches analysis in respiratory tract samples (limitations of Claims 4, 7). The method relies upon the detection of cpsA and lytA genes thru qPCR. Table 2 provides the primers and probes used in the method. The primers and probes were previously used by Lang 2015 and Morais 2007. Kukla further teaches the qPCR assays included an internal positive control (page 72, col. 1). The probes of Kukla have a fluorescence emitter moiety and a quencher moiety (see Table 2).
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Albuquerque teaches multiple-PCR for amplifying crtA and lytA for detecting Streptococcus pneumoniae and Neisseria meningitidis in the same sample. Albuquerque teaches these bacterial pathogens are among the four most prevalent bacterial pathogens. Albuquerque uses the 16S rRNA as a universal control.
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Vuong teaches analysis of sodC and ctrA in real-time PCR methods. The probes of Vuong also have emitter and quencher moieties.
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The full length sequences for each of these genes is found in Genbank as provided below. The primers and probes of the instant claims are embedded within the full length sequences.
LOCUS MK163634 348 bp DNA linear BCT 26-FEB-2019
DEFINITION Streptococcus pneumoniae strain REO8567_CLIN autolysin gene,
partial cds.
1 cgcctttata tcgaactctt acgcaatcta gcagatgaag caggtttgcc gaaaacgctt
61 gatacaggga gtttagctgg aattaaaacg cacgagtatt gcacgaataa ccaaccaaac
121 aaccactcag accacgttga cccttatcca tatcttgcta aatggggcat tagccgtgag
181 cagtttaagc atgatattga gaacggcttg acgattgaaa caggctggca gaagaatgac
241 actggctact ggtacgtaca ttcagacggc tcttatccaa aagacaagtt tgagaaaatc
301 aatggcactt ggtactactt tgacagttca ggctatatgc ttgcagac
SEQ ID NO: 1 is located at positions 175-199 and SEQ ID NO: 2 is located at positions 320-297. SEQ ID NO: 3 is located 294-265.
LOCUS AF030369 4133 bp DNA linear BCT 16-JUL-1998
DEFINITION Streptococcus pneumoniae strain SP-VA92 alpha, 1-6-glucosidase
(dexB) gene, partial cds; putative regulatory protein (cpsA) and
CpsB (cpsB) genes, complete cds; and putative chain length
terminator (cpsC) gene, partial cds.
SEQ ID NO: 16 is located at positions 1741-1762 and Seq ID NO: 17 is located at positions 1822-1801. SEQ ID NO: 26 is located at nucleotides 1764-1790.
LOCUS AJ001313 3572 bp DNA linear BCT 15-APR-2005
DEFINITION Neisseria meningitidis sodC, mutY genes and IS1106 region.
SEQ ID NO: 31 is located at position 1726-1748 and SEQ ID NO: 32 is located at positions 1821-1798. SEQ ID NO: 40 is located at positions 1750-1778.
LOCUS AY281033 491 bp DNA linear BCT 25-JUL-2016
DEFINITION Neisseria meningitidis strain M9592 capsular transport protein
(ctrA) gene, partial cds.
SEQ ID NO: 45 is located at positions 325-343 and SEQ ID NO: 46 is located at positions 407-390. SEQ ID NO: 55 is located at 384-361.
Buck analyzed the effect of primer design strategy on the performance of DNA sequencing primers. Specifically, Buck invited primer submissions from a number of labs (39) (page 532, column 3), with 69 different primers being submitted (see page 530, column 1). Buck also tested 95 primers spaced at 3 nucleotide intervals along the entire sequence at issue, thereby testing more than 1/3 of all possible 18 mer primers on the 300 base pair sequence (see page 530, Page 11 column 1). When Buck tested each of the primers selected by the methods of the different labs, Buck found that every single primer worked (see page 533, column 1). Only one primer ever failed, No. 8, and that primer functioned when repeated. Further, every single control primer functioned as well (see page 533, column 1). Buck expressly states “The results of the empirical sequencing analysis were surprising in that nearly all of the primers yielded data of extremely high quality (page 535, column 2).” Therefore, Buck provides direct evidence that all primers would be expected to function, and in particular, all primers selected according to the ordinary criteria, however different, used by 39 different laboratories. It is particularly striking that all 95 control primers functioned, which represent 1/3 of all possible primers in the target region. This clearly shows that the selection and use of primers in primer extension methods yields predictable results.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date to design primers for multiplex analysis of cpsA, lytA, sodC and ctrA by designing any set of primer pairs and oligonucleotide probes designed from the known sequences to detect the presence of Neisseria meningitidis and S. pneumoniae in a biological sample using the multiplex real-time PCR methods resulting from the combined teachings of Kukla, Albuquerque and Vuong. An ordinary artisan would have been motivated to do so with a reasonable expectation of success, since: (i) Kukla, Albuquerque and Vuong each taught designing useful oligonucleotide primers and probes from the known GenBank sequences for cpsA, lytA, sodC and ctrA , (ii) the complete cpsA, lytA, sodC and ctrA sequences were known in the art at the time of the invention, and (iii) Buck establishes that essentially all primers designed from a known sequence are reasonably capable of functioning in nucleic acid amplification methods. Thus, absent any unexpected results with respect to the particular primers and probes recited in the claims, they are prima facie obvious in view of the combined teachings of the cited references.
Attention is also directed to KSR Int’l Co. v. Teleflex Inc. (550 U.S.____ , 127 S. Ct. 1727 (2007)) where the Supreme Court determined that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103 (KSR, 550 U.S. at____ , 82 USPQ2d at 1397).”
In the instant case, as discussed above, an ordinary artisan would have been motivated to design oligonucleotide primers and probes from the known cpsA, lytA, sodC and ctrA sequence for the detection of Neisseria meningitidis and S. pneumoniae in a biological sample based on the teachings of Kukla, Albuquerque and Vuong. The complete nucleotide sequence of the cpsA, lytA, sodC and ctrA genes, which is disclosed in Genbank MK163634; Genbank AF030369; Genbank AJ001313 and Genbank AY281033, presented the ordinary artisan with a finite number of possible primers and probes for amplification and hybridization, respectively. Then, since Buck taught that a large number of primers designed to detect the same target functioned reasonably well, an ordinary artisan would have expected predictable results, and thus would have had a reasonable expectation of success, when testing the finite number of possible amplification primers and probes suggested by GenBank Accession Number Genbank MK163634; Genbank AF030369; Genbank AJ001313 and Genbank AY281033, Kukla, Albuquerque and Vuong. Thus, the methods are prima facie obvious in view of the combined teachings of the cited references.
Response to Arguments
The response traverses the rejection. The response asserts that Buck is directed to sequencing primers and is not relevant for challenges designed with design of multiplex primers for DNA amplification and genotyping. This argument has been considered but is not convincing because response provides no evidence that design of primers for sequencing and design of primers for multiplex sequencing would not share the same design. The prior art teaches numerous multiplex reactions for analysis of the claimed targets. Specifically, Albuquerque is directed at multiplex for amplifying crtA and lytA. Vuong is for teaching analysis of sodC and ctrA in real-time PCR methods. There is no evidence on the record to suggest any unpredictability or undue experimentation required to design primers for known genes. Thus, for the reasons above and those already of record, the rejection is maintained.
Claims 2-3, 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kukla et al. (New Mircrobiol, Vol. 43, No. 2, pages 70-77, April 19, 2020) in view of Albuquerque et al. (Brazilian J. of Microbiology, Vol. 50, pages 435-443, 2019) in view of Vuong (PLOS one. Development of Real-Time PCR methods for the detection of bacterial meningitis pathogens without DNA extraction, February 1, 2016) and Genbank MK163634; Genbank AF030369; Genbank AJ001313 and Genbank AY281033 in view of Buck et al. as applied to Claims 1, 4, 7, 10, 12, 15-21 above and further in view of Vickery et al. (WO2004/104229, December 2, 2004).
Kukla, Albuquerque, Vuong and Genbank do not teach internal control nucleic acids of SEQ ID NO: 60-61 or a probe of SEQ ID NO: 133.
However, Vickery teaches internal control nucleic acids for nucleic acid amplification systems. Vickery teaches exogenous internal control nucleic acids were used. SEQ ID NO: 60 of the instant application is 94.4% identical to SE ID NO: 1 of Vickery. SEQ ID NO:61 is 100% identical to SEQ ID NO: 5 of Vickery. SEQ ID NO: 133 is 100% identical to SEQ ID NO: 10 of Vickery.
Therefore, it would have been prima facie obvious at the time the invention was made to have included internal control primers and probes of Vickery in the multiplex analysis of Kukla, Albuquerque, Vuong and Genbank. The ordinary artisan would have been motivated to have include the known IAC of Vickery to prevent the reporting of false negatives and to potentially allow accurate adjustments to quantitative data.
Response to Arguments
The response traverses the rejection. The response asserts Vickery does not cure the deficiency asserted by the above. This argument has been considered but is not convincing for the reasons provided above.
Thus for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable over the art.
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 JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
July 22, 2026
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