Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Status of Claims
Claims 24-43 are pending and the subject of this Final Office Action.
Claim Interpretations
During prosecution, claims receive their broadest reasonable interpretation in light of the specification. MPEP § 2111; see In re Zletz, 893 F.2d 319, 322 (Fed. Cir. 1989) (“An essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.”).
Here, the “reagent mixture” defined in claim 24, and kit of primers in claim 43, and used in claim 34 requires “the 3’ terminal nucleotide of each forward primer” to “base pairs with a different point mutation in the KRAS gene relative to other forward primers in said set, wherein said point mutation is selected from the following point mutations: 34A, 34C, 34T, 35A, 35C, 35T and 38A.” In other words, the claims require seven different primers, each primer directed to point mutations 34A, 34C, 34T, 35A, 35C, 35T and 38A.
Claim Rejections - 35 USC § 112- Indefiniteness
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 32 is 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 32 has the following unrecognized symbol:
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Double Patenting- Obvious Type
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Instant claims 24-43 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-12 U.S. Patent No. 8,361,720, in view of Krypuy and Di Fore.
The conflicting claims are directed to the same real-time Invader assay as the instant, except the instant claims are directed to detecting Kras mutations. However, such mutations were of interest at the time of the invention to diagnose various cancers. Thus, merely applying the same real-time Invader assay to Kras mutations was prima facie obvious at the time of the invention.
Instant claims 24-43 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-18 of U.S. Patent No. 8,715,937, in view of Krypuy and Di Fore.
The conflicting claims are directed to the same real-time Invader assay as the instant, except the instant claims are directed to detecting Kras mutations and specific cycling temperatures. However, first, U.S. Patent No. 8,715,937 specifically states that “amplifying” and “detecting” encompasses the same cycling parameters as the instant claims (cols. 11-12; Examples 1-5). Second, such Kras mutations were of interest at the time of the invention to diagnose various cancers. Thus, merely applying the same real-time Invader assay to Kras mutations was prima facie obvious at the time of the invention.
Instant claim 24-43 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-12 of US 11352674, in view of Tadokoro et al. (Quantitation of viral load by real-time PCR-monitoring Invader reaction, Journal of Virological Methods 155 (2009) 182–186, 12/4/2008) or ALLAWI (US 2009/0253142, published 10/8/2009) or KRAEDER (US 2011/0136118, published 7/9/2011), in view of MA (US 2008/0160524, published 7/3/2008) and ALLAWI (hereinafter “ALLAWI2”; US 2006/0147955, published 7/6/2006), in further view of Krypuy et al. (High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer, BMC Cancer 2006, 6:295) and Di Fore et al. (Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy, British Journal of Cancer (2007) 96, 1166 – 1169).
The conflicting kit and composition claims teach flap assay oligos and forward and reverse primers, along with polymerase and dNTPs, rendering the instant claims obvious. Specifically, the conflicting claims teach the same sequences of flap assay oligos and primers which have the same designs as the instant claims. The conflicting claims also teach thermostable polymerase and deoxynucleotide triphosphates. The conflicting claims also teach forward and reverse primers that each hybridize to the human KRAS gene. A skilled artisan would have been motivated to combine the conflicting claimed subject matter into a single kit or composition to allow convenient flap assay kit or composition.
As to claims 34-42 here, the prior art renders the cycling conditions claimed obvious, as explained below in the obviousness rejections.
Instant claim 24-43 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-12 of US 10626465, in view of Tadokoro et al. (Quantitation of viral load by real-time PCR-monitoring Invader reaction, Journal of Virological Methods 155 (2009) 182–186, 12/4/2008) or ALLAWI (US 2009/0253142, published 10/8/2009) or KRAEDER (US 2011/0136118, published 7/9/2011), in view of MA (US 2008/0160524, published 7/3/2008) and ALLAWI (hereinafter “ALLAWI2”; US 2006/0147955, published 7/6/2006), in further view of Krypuy et al. (High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer, BMC Cancer 2006, 6:295) and Di Fore et al. (Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy, British Journal of Cancer (2007) 96, 1166 – 1169).
The conflicting kit and composition claims teach flap assay oligos and forward and reverse primers, along with polymerase and dNTPs, rendering the instant claims obvious. Specifically, the conflicting claims teach the same sequences of flap assay oligos and primers which have the same designs as the instant claims. The conflicting claims also teach thermostable polymerase and deoxynucleotide triphosphates. The conflicting claims also teach forward and reverse primers that each hybridize to the human KRAS gene. A skilled artisan would have been motivated to combine the conflicting claimed subject matter into a single kit or composition to allow convenient flap assay kit or composition.
As to claims 34-42 here, the prior art renders the cycling conditions claimed obvious, as explained below in the obviousness rejections.
Instant claim 24-43 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-12 of US 10093987, in view of Tadokoro et al. (Quantitation of viral load by real-time PCR-monitoring Invader reaction, Journal of Virological Methods 155 (2009) 182–186, 12/4/2008) or ALLAWI (US 2009/0253142, published 10/8/2009) or KRAEDER (US 2011/0136118, published 7/9/2011), in view of MA (US 2008/0160524, published 7/3/2008) and ALLAWI (hereinafter “ALLAWI2”; US 2006/0147955, published 7/6/2006), in further view of Krypuy et al. (High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer, BMC Cancer 2006, 6:295) and Di Fore et al. (Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy, British Journal of Cancer (2007) 96, 1166 – 1169).
The conflicting kit and composition claims teach flap assay oligos and forward and reverse primers, along with polymerase and dNTPs, rendering the instant claims obvious. Specifically, the conflicting claims teach the same sequences of flap assay oligos and primers which have the same designs as the instant claims. The conflicting claims also teach thermostable polymerase and deoxynucleotide triphosphates. The conflicting claims also teach forward and reverse primers that each hybridize to the human KRAS gene. A skilled artisan would have been motivated to combine the conflicting claimed subject matter into a single kit or composition to allow convenient flap assay kit or composition.
As to claims 34-42 here, the prior art renders the cycling conditions claimed obvious, as explained below in the obviousness rejections.
Instant claim 24-43 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-16 of US 9783856, in view of Tadokoro et al. (Quantitation of viral load by real-time PCR-monitoring Invader reaction, Journal of Virological Methods 155 (2009) 182–186, 12/4/2008) or ALLAWI (US 2009/0253142, published 10/8/2009) or KRAEDER (US 2011/0136118, published 7/9/2011), in view of MA (US 2008/0160524, published 7/3/2008) and ALLAWI (hereinafter “ALLAWI2”; US 2006/0147955, published 7/6/2006), in further view of Krypuy et al. (High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer, BMC Cancer 2006, 6:295) and Di Fore et al. (Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy, British Journal of Cancer (2007) 96, 1166 – 1169).
The conflicting kit and composition claims teach flap assay oligos and forward and reverse primers, along with polymerase and dNTPs, rendering the instant claims obvious. Specifically, the conflicting claims teach the same sequences of flap assay oligos and primers which have the same designs as the instant claims. The conflicting claims also teach thermostable polymerase and deoxynucleotide triphosphates. The conflicting claims also teach forward and reverse primers that each hybridize to the human KRAS gene. A skilled artisan would have been motivated to combine the conflicting claimed subject matter into a single kit or composition to allow convenient flap assay kit or composition.
As to claims 34-42 here, the prior art renders the cycling conditions claimed obvious, as explained below in the obviousness rejections.
Instant claim 24-43 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-22 of US 9127318.
The conflicting kit and composition claims teach flap assay oligos and forward and reverse primers, along with polymerase and dNTPs, rendering the instant claims obvious. Specifically, the conflicting claims teach the same sequences of flap assay oligos and primers which have the same designs as the instant claims. The conflicting claims also teach thermostable polymerase and deoxynucleotide triphosphates. The conflicting claims also teach forward and reverse primers that each hybridize to the human KRAS gene. A skilled artisan would have been motivated to combine the conflicting claimed subject matter into a single kit or composition to allow convenient flap assay kit or composition.
As to claims 34-42 here, conflicting claim 11 sets forth these same conditions.
Instant claim 24-43 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-22 of US 12060620, in view of Tadokoro et al. (Quantitation of viral load by real-time PCR-monitoring Invader reaction, Journal of Virological Methods 155 (2009) 182–186, 12/4/2008) or ALLAWI (US 2009/0253142, published 10/8/2009) or KRAEDER (US 2011/0136118, published 7/9/2011), in view of MA (US 2008/0160524, published 7/3/2008) and ALLAWI (hereinafter “ALLAWI2”; US 2006/0147955, published 7/6/2006), in further view of Krypuy et al. (High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer, BMC Cancer 2006, 6:295) and Di Fore et al. (Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy, British Journal of Cancer (2007) 96, 1166 – 1169).
The conflicting kit and composition claims teach flap assay oligos and forward and reverse primers, along with polymerase and dNTPs, rendering the instant claims obvious. Specifically, the conflicting claims teach the same sequences of flap assay oligos and primers which have the same designs as the instant claims. The conflicting claims also teach thermostable polymerase and deoxynucleotide triphosphates. The conflicting claims also teach forward and reverse primers that each hybridize to the human KRAS gene. A skilled artisan would have been motivated to combine the conflicting claimed subject matter into a single kit or composition to allow convenient flap assay kit or composition.
As to claims 34-42 here, the prior art renders the cycling conditions claimed obvious, as explained below in the obviousness rejections.
Claim Rejections - 35 USC § 103 - Maintained
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 24-43 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Tadokoro et al. (Quantitation of viral load by real-time PCR-monitoring Invader reaction, Journal of Virological Methods 155 (2009) 182–186, 12/4/2008) or ALLAWI (US 2009/0253142, published 10/8/2009) or KRAEDER (US 2011/0136118, published 7/9/2011), in view of MA (US 2008/0160524, published 7/3/2008) and ALLAWI (hereinafter “ALLAWI2”; US 2006/0147955, published 7/6/2006), in further view of Krypuy et al. (High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer, BMC Cancer 2006, 6:295) and Di Fore et al. (Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy, British Journal of Cancer (2007) 96, 1166 – 1169).
The instant claims were prima facie obvious at the time of the invention because the instant claimed method constitutes merely applying known real-time Invader assay with an added preamplification step to known Kras mutations of interest at the time of the invention to yield an expected high-sensitivity and specificity Kras detection assay. See KSR Int'l v. Teleflex Inc., 550 U.S. 398, 416 (2007) (“The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.”).
Applicants are encouraged to either (a) amend the claims to recite specific, novel, non-obvious primers and/or probes (i.e . SEQ ID NOS: 1-5 or 9-10), or (b) demonstrate objective and unexpected results commensurate in scope with the instant claims and compared to the closest prior art.
I. Well-Known Real-Time Invader-Plus/Cycling Detection Assay For SNPs (Including Kras) Yields High Sensitivity
All of Tadokoro, ALLAWI and KRAEDER teach real-time Invader assay which yielded assays with increased dynamic range, increased specificity, faster detection, and lower costs (ALLAWI at Abstract & paras. 0177-0198; KRAEDER at para. 0014). Specifically, Tadokoro teaches the following cycling parameters:
a four-step PCR reaction was carried out for 35 cycles (95°C for 10 s, 61–69°C for 10–60 s, 50°C for 30 s, and °C for 30 s) in a LightCycler 480. Fluorescence values of FAM (carboxyfluorescein; wave length/bandwidth: excitation, 485/20 nm; emission, 530/25 nm) were measured at 65°C in each cycle
(pg. 183, col. 1). Similarly, ALLAWI teaches the following cycling parameters: “real time PCR thermocycler programmed for: 95°C-2 min; and 40 cycles of (95 C-20 seconds->50°C-45 seconds->60°C-30 seconds). Data is collected at the end of each 50°C-45 seconds step” (paras. 0204 & 0208) (emphasis added). Similarly, KRAEDER teaches “[t]he samples were incubated at: 42°C, 30 min; 95°C, 2 min; and then 40 cycles (95°C, 20 sec; 50°C, 30 sec; 60°C, 1 min)” (paras. 0071, 0075, 0083, 0084 & 0091; see also claims 1-20).
Furthermore, adjusting temperatures and cycles constitute routine optimization of known result-effective variables. See In re Aller, 220 F.2d 454, 456 (CCPA 1955); In re Antonie, 559 F.2d 618 (CCPA 1977). Specifically, all of Tadokoro, ALLAWI and KRAEDER explain that cycling temperatures were dependent on targets, multiplexes, primers, oligos, polymerases, etc. (Tadokoro at pgs. 182-86; ALLAWI at paras. 0014, 0056, 0058, 0062, 0064, 0133, 0164-0168, 0173, 0178, 0180 & 0182-0190; Fig. 2; KRAEDER at paras. 0021, 0039-0042, 0049 & 0064).
II. Well-Known Pre-Amplification to Increase Detection Sensitivity
In addition, MA specifically teaches to add a preamplification step to further increase sensitivity (MA at para. 0466-0469 (“[0466] f) Signal Enhancement Through Pre-Amplification [0467] The present invention further provides methods of increasing reaction signal by amplifying target nucleic acid prior to detection.”). In other words, preamplification in Invader assays was well-known to increase sensitivity.
Such a conclusion is further confirmed by ALLAWI2:
Direct genotyping by the INVADER assay typically uses from 5 to 100 ng of human genomic DNA per SNP, depending on detection platform. For a small number of assays, the reactions can be performed directly with genomic DNA without target pre-amplification, however, with more than 100,000 INVADER assays being developed and even larger number expected for genome-wide association studies, the amount of sample DNA may become a limiting factor.
[ . . . ]
The present invention provides for the design and characteristics of highly multiplex PCR including hundreds to thousands of products in a single reaction. For example, the target pre-amplification provided by hundred-plex PCR reduces the amount of human genomic DNA required for INVADER-based SNP genotyping to less than 0.1 ng per assay. The specifics of highly multiplex PCR optimization and a computer program for the primer design are described below
(paras. 0152 & 0155) (emphases added). Furthermore, ALLAWI2 teaches to optimize cycles and temperatures based on numerous parameters (paras. 0026, 0032, 0035, 0146, 0149 & 0165; Examples 1-14).
Thus, both MA and ALLAWI2 demonstrate that preamplification was a well-known technique expected to increase sensitivity in PCR reactions, including Invader assays.
III. Well-Known Kras SNPs of Interest at the Time of the Invention
Last, both Krypuy and Di Fore demonstrate that there was a strong interest in detecting Kras codon 12 and 13 mutations to diagnose various cancers such as colon cancer and adenomas (Krypuy at Abstract and throughout; Di Fore at Abstract and throughout).
IV. Conclusion: Obvious to Apply Well-Known Invader Assay Steps Known to Increase Assay Sensitivity to Kras Mutation/SNP Detection with Reasonable Expectation of Success
In sum, in the absence of novel and non-obvious primers or probes, or unexpected results, the claimed real-time Invader assay to detect Kras mutations was prima facie obvious at the time of the invention because it constitutes “[t]he combination of familiar [Invader and PCR assay] elements according to known methods [which] is likely to be obvious when it does no more than yield predictable results.”). See KSR, 550 U.S. at 416.
Response to Arguments
Applicants’ arguments and amendments in the Reply filed 3/20/2015 were unpersuasive because: (a) as to the prima facie case, (i) both MA and ALLAWI teach pre-amplification steps similar to the instant first set of cycles to increase sensitivity in INVADER assays, (ii) all of Tadokoro, ALLAWI and KRAEDER teach the same real-time INVADER assay of the instant second set of cycles which yielded assays with increased dynamic range, increased specificity, faster detection, and lower costs, and (iii) at the least ALLAWI teaches specific primer and oligonucleotide design parameters for multiple SNP detection using known SNPs from freely-available databases for INVADER assays; and (b) as to the unexpected results argument, Applicants fail to compare the closest prior art (INVADER Plus or real-time INVADER assays), much less provide unexpected results reasonably commensurate in scope with the broad claims.
First, the prima facie case is maintained because each element if explicitly or implicitly taught in the prior art of record. For example, as to SNP detection using the second set of cycles, all of Tadokoro, ALLAWI and KRAEDER teach the same real-time INVADER assay of the instant second set of cycles which yielded assays with increased dynamic range, increased specificity, faster detection, and lower costs. As to the first set of pre-amplification cycles, both MA and ALLAWI teach pre-amplification steps similar to the instant first set of cycles to increase sensitivity in INVADER assays; and further optimization using known parameters (e.g. temperature, time, etc.) was a matter of routine optimization. Finally, as to the seven primers for kras mutations, at the least ALLAWI teaches extensive primer/oligo design parameters in order to detect SNPs (such as known kras SNPs from freely-available databases, or as demonstrated by Krypuy and Di Fore) using INVADER assays, including 3’-end mismatches for SNP discrimination (“In some embodiments, the single step reaction comprises a multipurpose oligonucleotide configured to serve as a reverse transcription primer, a polymerase chain reaction primer, and as a cleavage structure forming oligonucleotide (e.g., a probe or INVADER oligo in an invasive cleavage reaction).”; paras. 0031-0032, 0034, 0037, 0039, 0120, 0146, 0158-0196 & 0200-0240 and Figs. 1 & 8; it is also noted that allele-specific PCR was a known technique to increase sensitivity and specificity (c.f. Parsons et al. (Genotypic selection methods for the direct analysis of point mutations, Mutat Res. 1997 Oct;387(2):97-121))).
Second, as to the preferred unexpected results, Applicants do not compare the closest prior art (INVADER Plus or real-time INVADER assays), much less provide unexpected results reasonably commensurate in scope with the broad claims. For example, Applicants assert that
While there have been several reports of assays that can detect single nucleotide polymorphisms (SNPs) in a sample, single tube reactions that can accurately detect one out of 100 copies of a single point mutation in a clinical sample have not been described
(Reply at pg. 12). However, Applicants provide no evidence; instead simply concluding that their claimed invention overcomes this supposed limitation. Even if Applicants provided evidence, yet numerous prior-art single-tube methods yielded such limits of detection. c.f. ALLWAI (“Thus, the single step reaction of the present invention comprising reverse transcription, PCR, and detection by the INVADER assay performed in a single tube without intervening purification or addition steps provides an efficient and sensitive (e.g., as little as one copy of viral RNA provided >3 FOZ signal, Table 2) method of detecting target RNA in a sample.”; para. 0432; see also para. 0092); see also Parsons et al. (Genotypic selection methods for the direct analysis of point mutations, Mutat Res. 1997 Oct;387(2):97-121), at Fig. 1). Even more, allele-specific PCR (similar to instant seven-forward-primer method using allele-specific 3’-ends) was known to yield LOD of 1 copy per 100 on its own (Parsons at Fig. 1).
Even more important, the basis for Applicants’ conclusion is that “[d]etecting cancer-specific point mutations in a clinical sample, e.g., in a biopsy or a stool sample, can be extremely challenging because clinical samples contain wild-type versions of the mutated sequence in non-cancerous cells” (Reply at pg. 12) (emphasis added). Yet, the claims fail to include this limitation.
However, even with this limitation, Applicants would still not overcome the prima facie case of obviousness unless they provide unexpected results evidence that is reasonably commensurate in scope with the claimed invention. Applicants only provide “an embodiment” (Reply at pg. 12); yet a single example is not enough to reasonably cover the broad scope of the claimed invention directed to any kras SNP(s) using any of the broad cycling parameters, much less any additional reagents that increase sensitivity and specificity in amplification reactions. C.f. Hedman et al. (Overcoming Inhibition in Real-Time Diagnostic PCR, in Methods in Molecular Biology: PCR Detection of Microbial Pathogens, Ch. 2, pgs. 17-48, 8/1/2009).
Applicants are encouraged to provide more data points to reasonably cover the entire claimed range of any kras SNP(s) using any primers and any other INVADER components or amplification components. For example, holding all other variables constant and demonstrating unexpected results evidence for the detection of at least three different seven-forward-primer combinations using the claimed cycling parameters.
Suggested Claim Amendments and Evidence
Applicants are encouraged to either (a) amend the claims to recite specific, novel, non-obvious primers and/or probes (i.e . SEQ ID NOS: 1-5 or 9-10), or (b) demonstrate objective and unexpected results commensurate in scope with the instant claims and compared to the closest prior art. See Bristol-Myers Squibb Co., v. Teva Pharma. USA, Inc., 2013-1306, Slp op. at 14-17 (Fed. Cir. 2014) (explaining requirements for unexpected results to overcome prima facie obviousness); In re Geisler, 116 F.3d 1465, 1469–70 (Fed. Cir. 1997) (“When an applicant seeks to overcome a prima facie case of obviousness by showing improved performance in a range that is within or overlaps with a range disclosed in the prior art, the applicant must ‘show that the [claimed] range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range.”) (quoting In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990)); In re Peterson, 15 F.3d 1325, 1329 (Fed. Cir. 2003) (“the applicant’s showing must be commensurate in scope with the claimed range”); In re Clemens, 622 F.2d 1029, 1035 (CCPA 1980) (“In order to establish unexpected results for a claimed invention, objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support.”).
Allowable Subject Matter
Inclusion of SEQ ID NOS: 1-7 or 11-17 would be allowable because the prior art of record fails to teach or suggest the combination of the specific primers or flap oligos of SEQ ID NOS: 1-7 or 11-17, respectively, used in an INVADER assay as claimed; much less the evidenced results in the Specification at Example 2).
Prior Art
The following prior art is considered pertinent: LYAMICHEV (US 2005/0186588); HALL (US 2009/0142752); Tadokoro et al. (Rapid quantification of periodontitis-related
bacteria using a novel modification of Invader PLUS technologies, Microbiological Research 165 (2010) 43—49, 8/20/2008); Oler et al. (A rapid, microplate SNP genotype assay for the leptinob allele, Journal of Lipid Research Volume 49, 2008, 2/13/2008); Sasaki et al. (Nras and Kras mutation in Japanese lung cancer patients: Genotyping analysis using LightCycler, ONCOLOGY REPORTS 18: 623-628, 2007); Ayogi et al. (PCR, in Molecular Biology Problem Solver: A Laboratory Guide, Ch. 11, pgs. 291-329, Ed. Alan S. Gerstein, 2001); Noutsias et al. (Preamplification techniques for real-time RT-PCR analyses of endomyocardial biopsies, BMC Molecular Biology 2008, 9:3); (JP2011019512 A); Tsuchihashi et al. (Progress in high throughput SNP genotyping
methods, The Pharmacogenomics Journal (2002) 2, 103–110).
Conclusion
No claims are allowed.
This is a CON of applicant's earlier Application No. 17/739892, which includes U.S. 13/594674 as a parent. All claims are identical to, patentably indistinct from, or have unity of invention with the invention claimed in the earlier application (that is, restriction (including lack of unity) would not be proper) and could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the earlier application. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action in this case. See MPEP § 706.07(b). 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 Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 8am-6pm.
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/AARON A PRIEST/Primary Examiner, Art Unit 1681
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