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 .
This action is in response to papers filed 10/21/2025.
Applicant’s election of carboplatin and pemetrexed in the reply filed on 2/20/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-4, 6-18 are pending.
The following rejections are modified necessitated by amendment. Response to arguments follows.
This action is FINAL.
Withdrawn Rejections
The 35 USC 112(b) rejection made in the previous office action is withdrawn based upon amendments to the claims.
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.
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.
Claim(s) 1-4, 6-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cabel et al (Annals of Oncology 2017 Vol 28 p. 1996-2001 cited on IDS) in view of Gadgeel et al. (Lung cancer 2018 Vol 125 p. 273).
With regard to claim 1, Cabal et al. teaches taking blood samples from patients before and during pembrolizumab treatment (p. 1997). Cabal et al. teaches these patients had NSCL cancer (p. 1999 results). Therefore Cabal et al. teaches monitoring the amount of ctDNA in the patient.
Cabal et al. teaches that increasing ctDNA is correlated with tumor burden and that increasing ctDNA suggests that treatment with pembrolizumab alone is not effective (p 2000). However Cabal et al. does not teach administering an effective amount of pembrolizumab and platinum-based doublet chemotherapy to patients with increasing ctDNA.
With regard to claims 3-4 , Cabel et al. teaches a method wherein variant allele fraction in a sample was measured before and after the administration of pembrolizumab (p 1997 ctDNA detection). Cabel et al teaches MAF (mutant allele frequency) and as such teaches independent measuring.
With regard to claim 6, Cabel et al. teaches analyzing replicate samples (figure 2 and figure 3 and p. 1999).
With regard to claim 7, Cabel et al. teaches that the cancer in some patient is shrinked during anti-PD1 therapy and therefore would be PD-L1 positive (p. 1999 1st column).
With regard to claim 8, Figure 3 discloses an increase of at least 50% ctDNA in a patient.
With regard to claim 9, Cabel et al taches sequencing cell free DNA (p. 1997 1st column).
With regard to claim 10, Cabel et al. teaches sequencing ctDNA and monitoring variations (p. 1997, 1999).
With regard to claim 11, Cabal et al. teaches taking blood samples from patients before and during pembrolizumab treatment (p. 1997).
With regard to claim 12, Cabel et al. taches measuring the fractions within a week and comparing to an 8 week measured (p 1997 ctDNA detection and table 1).
With regard to claim 13, Cabel et al. taches measuring the fractions within a week and comparing to an 8 week measured (p 1997 ctDNA detection and table 1). Although Cabel et al. does not teach within 4 weeks of treatment, Cabel suggests this time frame and indicates one would benefit from 4 week ctDNA monitoring to allow for early selection of patients to benefit to therapy (p. 2000 2nd column 1st paragraph).
With regard to claim 14-15, Cabel et al. teaches sequencing ctDNA and monitoring variations (p. 1997, 1999). Cabal et al. teaches taking blood samples from patients before and during pembrolizumab treatment (p. 1997).
With regard to claim 16, Cabal et al. teaches detection of mutations of KRAS, BRAF, and EGFR (p. 1997 1st column last paragraph).
With regard to claim 1, Gadgeel et al. teaches that combinations of pembrolizumab with carboplatin-paclitaxel or pemetrexed-carboplatin (platinum based doublet chemotherapy) (p. 277). Gadgeel et al. teaches manageable toxicity in patients with advanced NSCLC (p. 278).
With regard to claim 2, 17-18, Gadgeel et al. teaches carboplatin and pemetrexed (cohort C table 1).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Cabal et al. to further treatment patients that have increasing tumor burden after pembrolizumab treating with a further treatment of combinations of pembrolizumab with carboplatin-paclitaxel or pemetrexed-carboplatin (platinum based doublet chemotherapy). The ordinary artisan would be motivated to further treatment as Gadgeel et al. teaches these treatments have manageable toxicity in patients with advanced NSCLC (p. 278).
Response to Arguments
The reply traverse the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that although monitoring ctDNA and chemotherapy strategies were known, the prior art cited does not point to treating NSCLC patients with pembrolizumab and platinum based doublet chemotherapy in response to an increase ctDNA (p 6). The reply asserts that the treatment described in Gadgeel involves treating subjects that have untreated NSCLC(p. 6). The reply asserts that further Cabel does not teach combining pembrolixumab with other therapies (p. 6). The reply asserts that the instant claims are specific to identify patients who would benefit from additional treatment rather than exposing all NSCLC patients to unnecessary chemotherapy treatments (p. 6).
These arguments have been reviewed but have not been found fully persuasive.
As noted by the reply monitoring ctDNA and treatments strategies was known in the prior art. The reply appears to be asserting that it was not known to treat with pembrolizumab and platinum based doublet chemotherapy based upon increased ctDNA. However, Cabal et al. teaches that increasing ctDNA is correlated with tumor burden and that increasing ctDNA suggests that treatment with pembrolizumab alone is not effective (p 2000). As such it would be obvious to the ordinary artisan to alter treatment based upon increased ctDNA. Gadgeel et al. teaches that combinations of pembrolizumab with carboplatin-paclitaxel or pemetrexed-carboplatin (platinum based doublet chemotherapy) (p. 277). Gadgeel et al. teaches manageable toxicity in patients with advanced NSCLC (p. 278). As such Gadgeel et al. teaches one particular treatment method for advanced NSCL patients. It would be obvious to one of ordinary skill in the art at the time of the effective filing date that based upon the suggestion of Cabal et al. to treat patients with increased ctDNA with a different treatment regimen. As Gadgeel et al teaches one for advanced NSCL patients it would be obvious to further treat the patients with a different treatment after determining increased ctDNA.
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 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