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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/03/2025 has been entered.
Applicant’s election without traverse of a mutation of EGFR in the reply filed on 2/16/2024 is acknowledged. It is noted that the species has been cancelled and therefore the next species will be searched.
Claims 1-9 are pending.
The following rejections are newly applied based upon amendments to the claims, however, the arguments with regard to 35 USC 103 are responded to as much as they would apply to the newly presented rejection.
This action is NONFINAL.
Withdrawn Rejections
The 35 USC 103(a) rejection made in the previous office action is withdrawn based upon the cancelation of the recited genes.
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.
Claim 1-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-9 are indefinite over the phrase “the biological sample on a solid support, wherein the blood sample” in claim 1. The claims recite “the blood sample”. There is insufficient antecedent basis for this limitation in the claim. The claims appear to suggest that the biological sample and the blood sample are the same, however, it is not clear from the claims if the biological sample is limited to blood. Therefore the metes and bounds are unclear.
Claim 4 is indefinite as claim 1 requires that the biological sample is blood whereas claim 4 requires either a blood or plasma sample.
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claims 1-5, 7-9 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Fernando et al. (Clinical Biochemistry Vol 45 2012 p. 1497 cited on a previous PTO892) in view of Janku et al. (US Patent Application 2015/01362256 effective filing date 8/21/2014).
With regard to claim 1, Fernando et al. teaches preparing cfRNA in a blood sample (p. 1498 1st column 2nd -5th para). Fernando et al. teaches isolating RNA from blood using a tube with a stabilizer (BCT and K3EDTA tubes) (p. 1498 1st column 2nd -5th para). Fernando et al. teaches BCT tubes allow for the stabilization of cfRNA at room temperature. This solid support is the same used in the instant specification (p 20 of the specification). This is placed into an on column DNase treatment to remove DNA and then cfRNA was eluted (p. 2 1st column last para and p. 2 2nd column 1st para) and as such digests DNA and then elutes. Fernando then teaches that this RNA can be reversed transcribed to cDNA as it teaches the use of assays that use cDNA (1498 1st column 2nd -5th para). Therefore Fernando et al. teaches steps a to d. As such Fernando et al. teaches all the steps of isolating cfRNA to reverse transcribe cDNA but does not teach step e.
With regard to claim 2, Fernando et al. teaches passing the water two times (1498 1st column 2nd -5th para) and as such the elute step is passed over the same column.
With regard to claim 3, Fernando et al does suggest that cfRNA from cancer patients can be used for screening or diagnosis of diseases and monitoring of therapy for cancer (p. 1497). Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of effective filing to modify the method of Claim 3 to use samples from cancer patients. The ordinary artisan would be motivated to use this sample from a finite number of potential samples as Fernando suggests that cfRNA can be isolated from the blood. The ordinary artisan would have a reasonable expectation of success as Fernando et al. teaches that this methodology can isolate cfRNA that is detectable and measurable in a PCR analysis procedure.
With regard to claim 4-5, Fernando et al. teaches a method wherein the plasma is processed within 3 days (1498 1st column 2nd -5th para) and therefore teaches a range that is within 7 days.
However, Fernando et al. does not teach detection of BRAF in cfRNA.
With regard to claim 1, Janku et al. teaches using PCR to detect BRAF mutations (para 93). Janku et al. teaches that BRAF mutational analysis was performed using cfDNA samples from plasma from blood samples (Para 91-96). Janku et al. teaches that cfDNA can be amplified but also cfRNA and cfmRNA can be detected (para 48).
With regard to claim 7, Janku et al. teaches sequencing cDNA (para 47 and 104).
With regard to claims 8-9, Janku et al. teaches a method of using PCR and next generation sequencing (para 82, 104).
Therefore it would be prima facie obvious to modify the method of Fernando to perform associations with known cancer biomarkers, including BRAF as taught by Janku. The ordinary artisan would have a reasonable expectation of success as Janku suggest that BRAF can be detected using isolated cfDNA, cfmRNA, or cfRNA. It would be obvious to take a method of cDNA prepared from cfRNA (Fernando) to detect any know sample including that of the cfRNA for BRAF detection (Janku). The ordinary artisan would reasonable determine that samples prepared by Fernando can be used to screen cDNA that is specific for any known target in the sample including KRAS of Janku.
Response to Arguments
The reply traverses the rejection. A summary of arguments is provided below with response to arguments following. The reply asserts that Fernando does not provide any teaching, data or suggestion that cfRNA is present in biological samples to detect (p. 4). The reply asserts that there are multiple challenges for clinical utility of cfRNA p. 4). The reply asserts that Fernando underscores the unpredictably and technical hurdles (p. 4). The reply asserts that there is no indication that cfRNA is presented in detectable amount (p. 5).
This arguments has been reviewed but have not been found persuasive.
The reply appears to be arguing because there are challenges that it would not be obvious to detect BRAF from a cfRNA from the blood. Although there are challenges, the prior art provides that BRAF can be detectable in Janku (e.g. plasma sample). Janku et al. teaches using PCR to detect BRAF mutations (para 93). Janku et al. teaches that BRAF mutational analysis was performed using cfDNA samples from plasma from blood samples (Para 91-96). Janku et al. teaches that cfDNA can be amplified but also cfRNA and cfmRNA can be detected (para 48). Fernando teaches a method of isolating and reverse transcribing to obtain cDNA from a blood sample. Janku et al. teaches that cDNA from a blood sample can be used to detect mutations of BRAF. It is noted that cfRNA does not need to be detected but rather the cDNA that is produced by reverse transcribing cfRNA. Therefore the prior art suggests the required steps of the claims.
12. Claims 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fernando et al. (Clinical Biochemistry Vol 45 2012 p. 1497 cited on previous PTO892) and Janku et al. (US Patent Application 2015/01362256 effective filing date 8/21/2014) as applied to claims 1-5, 7-9 in view of Malecki et al (US Patent Publication 2012/0093730 April 19, 2012 cited on previous PTO892).
Fernando et al. teaches preparing cfRNA in a blood sample (p. 1498 1st column 2nd -5th para). Fernando et al. teaches isolating RNA from blood using a tube with a stabilizer (BCT and K3EDTA tubes) (p. 1498 1st column 2nd -5th para). Fernando et al. teaches BCT tubes allow for the stabilization of cfRNA at room temperature. This solid support is the same used in the instant specification (p 20 of the specification). This is placed into an on column DNase treatment to remove DNA and then cfRNA was eluted (p. 2 1st column last para and p. 2 2nd column 1st para) and as such digests DNA and then elutes. Fernando then teaches that this RNA can be reversed transcribed to cDNA as it teaches the use of assays that use cDNA (1498 1st column 2nd -5th para). Janku et al. teaches using PCR to detect BRAF mutations (para 93). Janku et al. teaches that BRAG mutational analysis was performed using cfDNA samples from plasma from blood samples (Para 91-96). Janku et al. teaches that cfDNA can be amplified but also cfRNA and cfmRNA can be detected (para 48).
However, Fernando et al. and Janku do not teach using random hexamers to reverse transcribe the RNA to cDNA.
With regard to claim 6, Malecki et al teaches that cell free RNA can be transcribed into cDNA using random hexamers (para 91, 167).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of effective filing to modify the method of Fernando et al. and Janku to include a routine method of transcribing to cDNA by use of hexamers. The ordinary artisan would have a reasonable expectation of success as Fernando et al. teaches that this methodology can isolate cfRNA that is detectable and measurable in a PCR analysis procedure and Janku et al. teaches methods of cfRNA, cfmRNA, cfDNA for use in a type of PCR based sequencing of NGS (such as those taught by Janku).
Response to Arguments
The reply traverses the rejection. A summary of arguments is provided below with response to arguments following. The reply does not provide any further arguments other than what has been addressed above.
Conclusion
13.No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682