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 9/16/2025.
Applicant’s election without traverse of Group II and the species of ALK/RET/ROSI with Seq ID No. 1,52,182,83,161,189,195,213,227 in the reply filed on 9/13/2023 is acknowledged.
Claims 9-15 and 17-26 are pending. Claims 1-8 and 16 have been cancelled.
Claim 11 is withdrawn as being drawn to a nonelected species.
The rejections for claims 9-10,12-15,17-25 are maintained with response to arguments following. . Claim 26 appears free of the art.
This action is FINAL.
Claim Objections
Claim 17 is objected to as being drawn to a claim that is dependent on a rejected claim. It is suggested that the claim be amended to recite independent claim language to place the claim in condition for allowance.
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) 9-10, 12-15, 23-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lira et al. (The journal of molecular Diagnostics Vol 16 2014 p. 229) in view of Barnhart et al. (US Patent Application Publication 2013/0237442 September 12, 2013 previously cited).
With regard to claims 9-10, 12, 23-25 Lira et al. teaches a method of detecting fusion genes in a sample with cancer (p. 229). Lira et al. teaches a method of using a composition comprising primers and probes to ALK fusion genes, RET fusion genes, and ROS1 fusion genes however, does not teach the use of internal control (p. 230-231). Lira et al. teaches amplifying and determining a fusion gene which includes E13:A20, K15:R12; C6: R34 (table 2). Lira et al. teaches the probes have labels (p. 234 last full paragraph).
With regard to claim 13, Lira et al. teaches a sample that includes DNA (table 2).
With regard to 15, Lira et al. teaches qRT-PCR (para 234 2nd column 3rd paragraph).
However, Lira et al. teaches a method of using primers to the recited fusion genes, however, does not teach the use internal control (p. 378).
With regard to claims 9-10, 12, 23-25 Barnhart et al teaches that qRTPCR can be used to detect multiplex of targets (para 88). These complexes include both primers and probes for each target region (para 88). Therefore Barnhart teaches a method of determining the presence of multiple targets based upon carrying out amplification and detection under conditions that allow formation and detection of amplification products that are present in the sample. Barnhart et al. teaches that these probes are labeled with fluorescent labels (para 88). Further, Barnhart et al. teaches a primer and labelled probe that are used for detection of an internal control (para 101).
With regard to claim 14, Barnhart et al. taches methods of detecting target biomarker levels (abstract). Barnhart et al. teaches that samples can be obtained from plasma for RNA analysis of the individual (para 87).
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 to method of Lira et al. to use the qualitative method of Barnhart et al. in order to determine the levels of known fusion genes in a sample. The ordinary artisan would be motivated to modify the method of Lira et al. as Barnhart et al. teaches that one can measure levels of a biomarker in plasma to determine levels of a known target using an internal control. The ordinary artisan would be motivated to determine changes in expression based upon use of an internal control so that expression levels can have a comparison to a standard.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following.
The reply asserts that Lira et al. and Barnhart does not use common primer and probe to amplify and detect each of the fusion genes (p. 2). The reply asserts the primer assay of Lira is a capture and reporter probes and therefore does not teach any amplification (p. 3). The reply asserts that the second assay is RT-PCR followed by sanger sequencing but does not teach a primer and probe for each of the fusion genes (p. 3). The reply asserts that with the third method that the PCR amplification requires a tag which is distinct from the common primer and probe of the method (p. 4). The reply asserts that Barnhart does not provide the determine of more than one fusion gene with a primer set including a common primer and common probes (p. 4). The reply asserts that the unique primers and probes of the target genes are distinct from the use of common primers and probes (p. 4-5).
These arguments have been reviewed but have not found persuasive.
The claims require specific primers and probes for each of the fusion gene and a “common” probe and primer for ALK. However, the term “common” is not defined in the specification and as such it would encompass any primer or probe capable of hybridizing/amplifying ALK. The reply appears to assert that there is a difference between specific (unique) and common probes and primers, however, the claims do not require any structural distinction. Further, the reply appears to arguing the references separately, however, it is the combination of references that suggests the method. Lira et al. teaches that these fusion sites are known and can be detected. Further, Lira et al. suggests primers and probes can be developed. It is noted that reply asserts that Lira et al. methods are distinct from the claimed method, however, the claims requires primers and probes to each fusion region, carrying out amplification and determining presence. The claims therefore would encompass any method of amplification and determination including those taught by Barnhart.
14. Claim(s) 18-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lira et al. (The journal of molecular Diagnostics Vol 16 2014 p. 229) and Barnhart et al. (US Patent Application Publication 2013/0237442 September 12, 2013) as applied to claims 9-10,12-15, 23-25 in view of Bagovich et al. (US Patent Application Publication 2016/0304937 October 20, 2016 previously cited).
Lira et al. teaches a method of detecting fusion genes in a sample with cancer (p. 229). Lira et al. teaches a method of using a composition comprising primers and probes to ALK fusion genes, RET fusion genes, and ROS1 fusion genes however, does not teach the use of internal control (p. 230-231). Lira et al. teaches amplifying and determining a fusion gene which includes E13:A20, K15:R12; C6: R34 (table 2). Lira et al. teaches the probes have labels (p. 234 last full paragraph). Barnhart et al. taches methods of detecting target biomarker levels (abstract). Barnhart et al. teaches that samples can be obtained from plasma for RNA analysis of the individual (para 87). Barnhart et al. teaches that quantitative RT PCR was performed on samples using internal controls (para 101).
However, Lira et al. and Barnhart et al. do not teach using cfRNA from the recited plasma for detection.
With regard to claim 18, Bagovich et al. teaches detection of ALK fusions in cfRNA (para 87-90).
With regard to claims 19-20, Bagovich et al. teaches detection of 20 copies (para 90).
With regard to claim 21, Bagovich et al. does not teach “down to less than 10 copies”, however, the claims do not require that less than 10 copies are detected, but rather that the assay is capable of such a detection. As the combination of art teaches qRT-PCR (the same assay as is claimed), the assay would be capable of such detection.
With regard to claim 22, Bagovich et al. teaches single detection reactions of ALK, RET and ROS1 (Takeuchi p. 378 and Barnhardt para 87-101).
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 Lira et al. and Barnhart, to use one of the finite number of types of cells in plasma samples from a pregnant subject including the cfRNA as taught by Bagovich et al. The ordinary artisan would be motivated to detect the sample in order to use a known assay (qRT-PCR) to detect the level of regions associated with cancer.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that Begovich does not cure the deficiencies of Lira et al in view of Barnhart (p. 6). This argument has been reviewed and is not persuasive for the reasons set forth above.
Conclusion
Claim 26 is in condition for allowance.
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.
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