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 .
Status of the Applications, Amendments and/or Claims
This action is written in response to applicant's correspondence(s) submitted on 04/30/2026 and 05/08/2026. In the papers of 04/30/2026 and 05/08/2026, Applicant amended claim 8 and added new claims 11-12. In the paper of 04/30/2026, Applicant submitted a new Declaration under 37 C.F.R. 1.132, filed by Kentaro Tsuji and filed new Affidavit drawings on 05/08/2026. While the black and white Affidavit drawings of 05/08/2026 are now more legible, the results are not analyzable as colored drawings are not submitted. This Office action relies solely on Applicant’s interpretation of the Affidavit’s drawings as summarized in Tsuji declaration of 04/30/2026 and the Remarks of 05/08/2026. Claims 1-12 are pending.
Response to Arguments
Withdrawn Objections or Rejection(s)
The objection to claim 8 for omitting the limitation “wherein” is withdrawn in view of the amendments made to claim 8.
Maintained Rejection(s)
The rejection of claims 1-10 under 35 U.S.C. 103 as being unpatentable over Kwon et al. (2012, Tuberculosis and Respiratory Diseases, 72(3), pp.293-301) as evidenced by the iQTM SuperMix bulletin by Biorad (2012) in view of GenBank Accession No. EU790488 (submitted June 03, 2008, retrieved on July 10, 2024 from http://www.ncbi.nlm.nih.gov/nuccore/EU790488) and/or GenBank Accession No. AY786579 (submitted Oct 2004, retrieved on July 10, 2024 from http://www.ncbi.nlm.nih.gov/nuccore/AY786579), and An et al. (US2003/0050470), and Santa Lucia et al. (2007, PCR Primer Design. Humana Press: pp 3-33) is maintained in view of the arguments below which were considered and found to be non-persuasive because the instant claims are still not commensurate in scope with the unexpected results reported. Applicant seemingly argues that unexpected results observed for the instant primer pairs as recited by claim 1 appear to be primarily revealed at the annealing temperature condition of 65 °C for 20 sec.
Specifically, Applicant discloses that higher temperature annealing conditions near 65°C…are technically important in terms of specificity and detection performance of the present experiments (see Remarks of 05/08/2026, pg 7, 2nd paragraph and Tsuji 2026 Declaration, paragraphs 5-8).
Applicant also state (see Remarks of 05/08/2026, pg 7, last paragraph) that the instant primer pairs which are designed only in the highly conserved part of mecA, have been selected through screening by PCR at the annealing temperature of 65°C (Examples section). The primer pairs of the present application are thus also designed to be able to react at a higher annealing temperature for the purpose of enhancing the specificity in accordance with its intended use for clinical samples containing large amounts of host DNA (Tsuji 2026 Declaration, para 8).
Applicant report in the Tsuji 2026 Declaration (paragraphs 5 and 7) that amplification are observed only for the instant primer pair combinations recited for claim 1 at template of 6,000 copies/reaction and 20 copies/reaction under the annealing temperature conditions of 65 °C for 20 sec, while the primer pair of Kwon et al. showed no amplification.
Based on this report, a detection limit for Kwon primer pair at 65 °C for 20 sec cannot be determined for comparison to the instant primer pairs which provided detection limits of 2.6, 5.2 or 10.4 copies at annealing condition of 65 °C, 20 sec. However, in contrast to Applicant’s reports, Kwon already teach that their MecA primer pair does amplify and t achieves a detection limit at 30 copies under an experimental condition that is distinct from that tested by the Applicant.
Applicant believes the lower GC content of Kwon’s MecA primer pair, thus a need for lower annealing temperature may explain the lack of amplification they observe (see Remarks of 05/08/2026, pg 8, 1st para).
Concerning Applicant’s remarks, Applicant state that when annealing temperature was lowered to 57°C for 30 sec, Kwon’s primer pair (6,000, 600, or 60 copies) showed amplification but with the tendency to a slower rise of the amplification curve and a lower peak of the melting curve than the primer pairs of the present application (see Remarks of 05/08/2026, pg 6, last para and pg 7, 1st and 2nd paragraphs and Tsuji 2026 Declaration (para 7); see also Remarks of 05/08/2026, pg 8, 1st para). It is unclear to the Office whether this evidence of lower amplification amplitude for Kwon’s primer pair at 57°C for 30 sec, supports non-specific amplification by Kwon’s primer pair, use of non-optimal template DNA amounts or inferiority in sensitivity and specificity of Kwon’s primer pair. Applicant’s arguments implicate nonspecific amplification of target fragments as being typically promoted by lower annealing temperature (and suggests that a lower peak observed for one of the instant primer pairs SEQ ID NOS 6 and 12 at the lower annealing temperature might be indicative of nonspecific amplification).
The Office’s conclusion based on the statement above, again, is that a detection limit for Kwon primer pair (implicated for non-specific amplification under Applicant’s tested condition of 57 °C for 30 sec) cannot be determined, for comparison with the instant primer pairs which provided detection limits of 2.6, 5.2 or 10.4 copies at the annealing temperature condition of 65 °C for 20 sec.
The Office certainly acknowledges Applicant’s observation of a slower rise of the amplification curve and a lower peak of the melting curve for Kwon’s primer pair using template DNA at 6,000, 600, or 60 copies and Applicant’s conclusion that this observation supports a conclusion of inferior sensitivity and specificity of Kwon’s primer pair relative to the primer pairs of the present application as an overall trend, as there was also no prospect of amplification curve improvement by raising the annealing temperature to 65 °C for 20 sec (see Remarks of 05/08/2026, pg 8, 1st para and Tsuji 2026 Declaration, Figs. 3A to 3C).
Applicant argues that because of the amplification behaviors observed for Kwon’s primer pair, at both the annealing temperature of 65 °C and 57 °C, they conclude that the instant primer pairs exhibit detection performance superior to the Kwon primer pair (see Remarks of 05/08/2026, pg 8, 1st para). The Office is not fully persuaded since the lag/slower rise of amplification curve observed for Kwon’s primer pair is similarly observed at 60 copies of the instant SEQ ID NOS 6 and 12 primer at 57 °C for 30 sec and this lag disappears from the instant SEQ ID NOS 6 and 12 at higher template DNA (600, 6000) copies at 57 °C for 30 sec and certainly at 60 copies at 65 °C for 20 sec.
Applicant finally argues that Kwon employs probe-based PCR, whereas the present application employs an intercalator-based PCR (see Remarks of 05/08/2026, pg 7, 4th para).
In view of this statement in the Remarks, the Examiner concludes that the instant claims are not commensurate in scope with the unexpected results since there is an indicated difference in scope between the instant intercalator based PCR method versus Kwon’s probe-PCR method and this difference is not readily gleaned from any of limitations recited by the instant claims.
The Office review fails to appreciate Applicant’s claim to unexpectedly high sensitivity of the instant primer pairs as compared to the primer pairs taught by Kwon et al. where it is not clear what role Applicant’s unclaimed intercalator play in the detection limits of 2.6, 5.2 or 10.4 copies, and/or what role the annealing condition at 65 °C, 20 sec play in the detection limits of 2.6, 5.2 or 10.4 copies of the instant primer pairs as recited by claim 1.
Further concerning Applicant’s observation that SEQ ID NOS: 1a and 8a generated by Applicant by appending two bases to the 5’ end of the primer SEQ ID NO: 8 (5’-GT added to SEQ ID NO: 8) in the combination designated as SEQ ID NOS: 1a and 8a (see Table 4 of page 2 of the new Affidavit drawings of 05/08/2026), Applicant report that no difference in amplification efficiency was detected when 6000 copies and 50 copies profiles of SEQ ID NOS: 1a and 8a are compared with SEQ ID NOS: 1 and 8, but lower specificity from nonspecific amplification was observed in the negative control (Tsuji 2026 Declaration, § 6, Experiment 2, Fig. 3C and Remarks of 05/08/2026, pg 8, last para).
The observation above offers no helpful insight to the Office on the criticality of the primer sequence/region amplified by SEQ ID NOS: 1 and 8, and/or SEQ ID NOS: 1a and 8a.
The Examiner in a prior Office action found the report of different amplification behaviors at the annealing temperature of 65 °C for Kwon’s primer pair (which amplifies nucleotides 279-393 of GenBank AY786579) and the instant SEQ ID NOS: 13-14 (which amplifies nucleotides 308-429 of GenBank AY786579) perplexing, and raised the question of why the Kwon primer pair shows no amplification at the annealing temperature of 65 °C and at 6,000 copies, whereas SEQ ID NOS: 13 and 14 (the comparative primer pair of the present application) positioned nearer the Kwon primer pair showed stable amplification at 6,000 copies and unstable amplification at 20 copies (although these results are consistent with its detection limit of 100.4 copies/reaction) (see Remarks of 05/0/2026, pg 9, 2nd para; and Tsuji 2026 Declaration, § 5, Experiment 1, Figs. 1A and 1C).
Applicant counter by stating that there is no predictable expectation that primers designed at closer positions on a target gene sequence act similarly as reflected by other primer pairs of the present application, some of whose amplification products are neighboring or overlapped.
Applicant disclosed that detection limits observed for three neighboring instant primer pairs for amplifying nucleotide region of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488 are as follows:
(SEQ ID NOS: 1 and 8 for amplifying nucleotides 1043-1329: detection limit 2.6);
(SEQ ID NOS: 2 and 9 for amplifying nucleotides 1042-1332: detection limit 5.2);
(SEQ ID NOS: 1 and 9 for amplifying nucleotides 1043-1332: detection limit 10.4);
were 2.6 copies, 5.2 copies and 10.4 copies, respectively at the annealing temperature of 65 °C.
Applicant concludes in view of the detection limits of the instant primer pairs reported above, that the varying limits show the criticality of each primer sequence/region and that the instant primer combinations have an unexpectedly high sensitivity and their detection limits are highly unpredictable.
Response to Amendment
The declaration under 37 CFR 1.132 filed by Kentaro Tsuji on 04/30/2026 (hereafter named Tsuji’s Declaration) is insufficient to overcome the rejection of claims 1-12 under 35 U.S.C. 103 set forth below in this Office action because of the following.
Tsuji’s Declaration and the new Affidavit drawings submitted on 05/0/2026 restates the same observations previously reported in the declaration under 37 CFR 1.132 filed by Dr. Koh Amano on 07/01/2025 with some minor modifications which involves the inclusion of SEQ ID NOS: 13 and 14 in some experimental analysis and the inclusion of amplification results for appended primer pair SEQ ID NOS 1 and 8.
The Office acknowledges here all of declarant’s reported findings for certain instant primer pairs relative to Kwon’s primer pair, particularly reported for the results observed for Experiment 1, 2 and 3 (see pg 2-4, para 5 of Tsuji’s Declaration for Experiment 1, pg 4-5, para 6 of Tsuji’s Declaration for Experiment 2 and pg 5-6, para 7 of Tsuji’s Declaration for Experiment 3).
Experiment 1 provides a comparative analysis of the amplification curve profiles for (SEQ ID NOS: 13 and 14), in addition to primer pair combinations (SEQ ID NOS: 6 and 10), (SEQ ID NOS: 6 and 12), (SEQ ID NOS: 1 and 8) and (SEQ ID NOS: 1 and 9) and (Kwon’s primer pair).
Declarant reports stable amplification at template of 6,000 copies/reaction and 20 copies/reaction under the annealing temperature conditions of 65°C for 20 sec, for the instant primers whereas the Kwon primer pair showed no amplification under the same conditions.
Experiment 2 provides a comparison of SEQ ID NOS 1 and 8 with SEQ ID NOS: 1a and 8a (using 6000 copies and 50 copies template DNA at 65 ºC, 20 sec), where SEQ ID NOS: 1a has an addition of two nucleotides, i.e. 5’-CT appended to the end of SEQ ID NO: 1, and SEQ ID NOS: 8a has an addition of two nucleotides, i.e. 5’-GT appended to the end of SEQ ID NO: 8.
Declarant reports no difference in amplification but for the negative control, nonspecific amplification was observed for the SEQ ID NOS: 1a and 8a combination. This nonspecific amplification result was construed to mean less sensitivity of the appended primers.
Experiment 3 provides a comparison of detection sensitivity among primer pairs combinations (SEQ ID NOS: 6 and 10), (SEQ ID NOS: 6 and 12), (SEQ ID NOS: 1 and 8) and (SEQ ID NOS: 1 and 9) and (Kwon’s primer pair) at 57 ºC, 30 sec in the presence of template DNA at 6000, 600, and 60 copies. It is unclear why declarant omits (SEQ ID NOS: 13 and 14) at 57 ºC, 30 sec as suggested in the prior Office action.
Declarant reports amplification of Kwon’s primer pair differs from the instant primers (SEQ ID NOS: 6 and 10), (SEQ ID NOS: 6 and 12), (SEQ ID NOS: 1 and 8) and (SEQ ID NOS: 1 and 9) as there is a slow rise in the amplification curve with a lower peak for Kwon’s primer pair, suggesting low sensitivity at 6000 and 600 copies of template DNA. Declarant concludes this profile indicates inferior sensitivity and specificity.
Declarant further reports the amplification of (SEQ ID NOS 6 and 12) at 60 copies of template DNA, shows a slow rise in the amplification curve with a lower peak revealing nonspecific amplification.
The declaration results provided above is taken by declarant to reveal as a whole better detection performance for the instant primer pairs as compared to Kwon’s primer pair.
However, the Office is not persuaded as the slow lag in amplification of Kwon’s primer pair at annealing temperature of 57 ºC, 30 sec at every template DNA copies tested may simply indicate non-optimal amounts of template DNA similar to that observed for SEQ ID NOS 6 and 12 at 60 copies of template DNA and the lack of any amplification of Kwon’s primer pair at 65 ºC, 20 sec also indicates non-optimal conditions for amplification. It is difficult to establish and conclude that the instant primers do exhibit better performance when the conditions under which Kwon’s primer pair are tested are not ideal.
At best, the only conclusion that the Office can assert from the results of the declaration’s experiments 1 and 3 is that the annealing temperature at 65 ºC, 20 sec plays a role in the detection of better amplification amplitude seen in the instant primer pair combinations recited by claim 1.
Furthermore, it is useful to note that the comparison of neighboring three primer pairs of the present application is for amplification measured under annealing temperature of 65 ºC, 20 sec.
The instant SEQ ID NOS: 1 and 8 for amplifying nucleotides 1043-1329 of mecA sequence having the Genbank Accession No. EU790488 shows an observed detection limit at 2.6 copies under an annealing temperature condition at 65 ºC, 20 sec).
The instant SEQ ID NOS: 2 and 9 for amplifying nucleotides 1042-1332 of mecA sequence having the Genbank Accession No. EU790488 shows an observed detection limit at 5.2 copies under an annealing temperature condition at 65 ºC, 20 sec.
The instant SEQ ID NOS: 1 and 9 for amplifying nucleotides 1043-1332 of mecA sequence having the Genbank Accession No. EU790488 shows an observed detection limit at 10.4 copies under an annealing temperature condition at 65 ºC, 20 sec.
The declaration omits disclosure of the detection limits of SEQ ID NOS: 1 and 8, SEQ ID NOS: 2 and 9 and SEQ ID NOS: 1 and 9 under an annealing temperature condition at 57 ºC, 30 sec.
Claim Rejections - 35 USC § 103
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 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 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 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Kwon et al. (2012, Tuberculosis and Respiratory Diseases, 72(3), pp.293-301) as evidenced by the iQTM SuperMix bulletin by Biorad (2012) in view of GenBank Accession No. EU790488 (submitted June 03, 2008, retrieved on July 10, 2024 from http://www.ncbi.nlm.nih.gov/nuccore/EU790488) and/or GenBank Accession No. AY786579 (submitted Oct 2004, retrieved on July 10, 2024 from http://www.ncbi.nlm.nih.gov/nuccore/AY786579), and An et al. (US2003/0050470), and Santa Lucia et al. (2007, PCR Primer Design. Humana Press: pp 3-33).
Claim 1 is construed as being directed to a method of detecting a mecA gene sequence in a sample comprising performing PCR to generate an amplification product using DNA prepared from the sample and a primer pair and detecting the mecA gene sequence in the amplification product, or by analyzing the amplification product,
wherein the primer pair is selected from the group consisting of
a primer pair consisting of SEQ ID NO:3 and SEQ ID NO:7,
a primer pair consisting of SEQ ID NO:2 and SEQ ID NO:9,
a primer pair consisting of SEQ ID NO: 1 and SEQ ID NO:8,
a primer pair consisting of SEQ ID NO: 1 and SEQ ID NO:9,
a primer pair consisting of SEQ ID NO:4 and SEQ ID NO: 11,
a primer pair consisting of SEQ ID NO:5 and SEQ ID NO: 12,
a primer pair consisting of SEQ ID NO:6 and SEQ ID NO: 10, and
a primer pair consisting of SEQ ID NO:6 and SEQ ID NO: 12.
Kwon et al. (claims 1 and 3-8 and 11)
Regarding claim 1, Kwon et al. teach a detection method for a mecA gene sequence in a sample, comprising:
a step of performing PCR using DNA prepared from the sample and a primer pair for amplifying the DNA (see Kwon et al., pg 295, right col., text of section 6, “Quantitative PCR” and pg 296, Table 2, wherein Kwon et al. teach a qPCR assay that uses mecA forward primer (F mecA) 5’- ACGAGTAGATGCTCAATA-‘3 and mecA reverse primer (R mecA) 5’-GACGCTATGATCCCAATC-‘3); and a step of detecting the mecA gene sequence in an amplification product obtained by the PCR step using the mecA probe (P mecA) 5’-CalRed610-AACTACGGTAACATTGATCGCAACG-BHQ2) (pg 296, Table 2).
The F mecA forward primer of Kwon et al. hybridizes nucleotides 234-251 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488 while the R MecA reverse primer of Kwon et al. hybridizes nucleotides 348-331 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488.
The mecA (P mecA) probe of Kwon et al. hybridizes nucleotides 265-289 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488.
The primer pair of Kwon et al. amplify nucleotides 234-348 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488.
Regarding claims 3-5, Kwon et al. teach an iQTM SuperMix which contains antibody-mediated hotstart iTaq DNA polymerase which is a thermostable DNA polymerase enzyme derived from a thermostable organism (claim 3), or a thermophile, or hyperthermophile (claim 4). The antibody-mediated hotstart iTaq DNA polymerase of the iQ SuperMix of Kwon et al. is derived from Thermus aquaticus (see section of the iQ SuperMix Bulletin from BioRad entitled Kit Contents).
Regarding claim 6, Kwon et al. teach an iQTM SuperMix which comprise dNTP, Mg source, an antibody-mediated hotstart iTaq DNA polymerase i.e. an enzyme for PCR, and pH buffer solution, or sterile water (see Kwon et al., pg 295, right col. section 6; and see section of the iQ SuperMix Bulletin from BioRad entitled Kit Contents).
Regarding claim 7, Kwon et al. teach P mecA probe comprising Cal610Red and BHQ2 labeling substances. The CalRed610 is a fluorescent dye (see Kwon et al., pg 296, Table 2).
Regarding claim 8, Kwon et al. teach use of a container, pipette, pipette tip, microtube, clean bench for the PCR step (pg 296, right col., section 3, pg 295, right col., section 6).
Regarding claims 9-10 and 12, Kwon et al. teach the mecA primer pair having a detection limit of 100 fg, or 30 copies (pg 296, right col., section 2 and see pg 298, Figure 1).
Regarding claim 11, Kwon et al. teach sample is a clinical sample (Kwon et al. disclose samples consisting of a BAL and bronchial washing samples were collected directly from patients admitted to the ICU) (pg 294, left col, section 1 and pg 294, right col., section 2).
Omitted from Kwon et al. (claims 1-2, 9-10)
Regarding claim 1, Kwon et al. do not teach the primer pair consisting:
(SEQ ID NOS: 1, 8) for amplifying nucleotides 1043-1329 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488,
(SEQ ID NOS: 1, 9) for amplifying nucleotides 1043-1332 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488,
(SEQ ID NOS: 2, 9) for amplifying nucleotides 1042-1332 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488,
(SEQ ID NOS: 3, 7) for amplifying nucleotides 880-1191 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488,
(SEQ ID NOS: 4, 11) for amplifying nucleotides 1308-1849 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488,
(SEQ ID NOS: 5, 12) for amplifying nucleotides 1409-1799 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488,
or
(SEQ ID NOS: 6, 12) for amplifying nucleotides 1542-1799 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488.
Regarding claims 1-2, Kwon et al. do not teach primer pair consisting (SEQ ID NOS: 6, 10) for amplifying nucleotides 1542-1944 of Staphylococcus aureus subsp. aureus strain HM1 MecA gene having the GenBank Accession No. EU790488.
Regarding claims 9-10 and 12, Kwon et al. do not teach the primer pair has a detection limit of 10.4 copies, or 5.2 copies, or 2.6 copies.
GenBank
Genbank teach a 1944 bp Staphylococcus aureus subsp. aureus strain HM1 MecA oligonucleotide having the GenBank Accession No. EU790488 which is identical to and indistinguishable from the instant SEQ ID NOS: 1-12 (see % homology to GenBank Accession No. EU790488 as stated in the claim interpretations provided above).
Genbank teach a 2007 bp St Staphylococcus aureus mutant PBP2a (mecA) gene having the GenBank Accession No. AY786579 which is identical to and indistinguishable from the instant SEQ ID NOS: 1-12 (see % homology to GenBank Accession No. AY786579 as stated in the claim interpretations provided above).
An et al. (2003)
Regarding primer and/or probe design, An et al. teach at paragraphs [0065]-[0067]:
"Various probes and primers can be designed around the disclosed nucleotide sequences. Primers may be of any length but, typically, are 10-20 bases in length. By assigning numeric values to a sequence, for example, the first residue is 1, the second residue is 2, etc., an algorithm defining all primers can be proposed:
n to n+y
where n is an integer from 1 to the last number of the sequence and y is the length of the primer minus one (9 to 19), where n+y does not exceed the last number of the sequence. Thus, for a 10-mer, the probes correspond to bases 1 to 10, 2 to 11, 3 to 12 . . . and so on. For a 15-mer, the probes correspond to bases 1 to 15, 2 to 16, 3 to 17 . . . and so on. For a 20-mer, the probes correspond to bases 1 to 20, 2 to 21, 3 to 22 . . . and so on."
Therefore, An et al. not only taught designing primers of any length based on a known sequence, but also taught an algorithm for defining all possible primers of a given length based on a known sequence. In this respect, An et al. taught that all possible subsequences of a known sequence could be considered as a primer for that sequence. While An et al. was discussing in particular sequences having to do with prostate, bladder and breast cancer (see Abstract), one of ordinary skill in the art would have recognized that the principles of designing primers and probes based on a disclosed nucleotide sequence would have applied to any nucleotide sequence under study.
SantaLucia et al. (2007)
SantaLucia et al. teach on page 14, “over the last 10 years (1996–2006), I have informally polled scientists who are experts in PCR and asked: “What percentage of the time does a casually designed PCR reaction ‘work’ without any experimental optimization?” In this context, “work” means that the desired amplification product is made in good yield with a minimum of artifact products such as primer dimers, wrong amplicons, or inefficient amplification. By “casually designed,” I mean that typical software tools are used by an experienced molecular biologist. The consensus answer is 70–75%.
If one allows for optimization of the annealing temperature in the thermocycling protocol (e.g., by using temperature gradient optimization), magnesium concentration optimization, and primer concentration optimization, then the consensus percentage increases to 90–95%."
Thus, SantaLucia et al. teach primers casually designed to a target sequence have a reasonable expectation of success at hybridizing, amplifying and detecting a target sequence.
It would have been prima facie obvious to an ordinary skilled artisan, wanting to detect the presence of resistant Staphylococcus aureus subsp. aureus HM1 MecA strain in a sample, before the effective filing date of the instant invention, to provide alternative primers that are functionally equivalent MecA specific primers to the MecA forward and reverse primers taught by Kwon et al.
Based on the teachings of Kwon et al., Genbank Accession No. EU790488 or Genbank Accession No. AY786579 and SantaLucia et al. (2007) and An et al., and particularly concerning primer/probe design, the ordinary skilled artisan would have readily being apprised of how to make and use the instant SEQ ID NOS: 1-12 which are derived from Genbank Accession No. EU790488/ GenBank Accession No. AY786579.
The ordinary skilled artisan would have had a reasonable expectation at making and using the instant SEQ ID NOS: 1-12 as primer(s) and/or probe(s) as SantaLucia et al. elaborates that sequences casually designed for use as primers are generally successfully at hybridizing, amplifying and/or detecting, particularly when further optimized as taught by SantaLucia et al.
The ordinary skilled artisan would have been readily apprised on modifying and testing and optimizing select primer sequences to derive a detection limit of at a specific copy number.
In view of the combined teachings of all of the cited reference(s), the instant claims 1-12 are prima facie obvious.
Conclusion
No claims are currently allowed.
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 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.
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
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