DETAILED CORRESPONDENCE
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 the papers filed May 29, 2026. Currently, claims 1-4, 16-17 are pending. Claims 16-17 have been withdrawn as drawn to non-elected subject matter.
Election/Restrictions
Applicant's election without traverse of Group I, Claims 1-14 in the paper filed May 29, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application is 371 of PCT/JP2022/036170, September 28, 2022 and claims priority to foreign Japan PCT/JP2021/036697, filed October 4, 2021.
It is noted that a translation of the foreign document has not been received.
Claim Rejections - 35 USC § 112- Second Paragraph
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.
Claims 1-14 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 pre-AIA the applicant regards as the invention.
Claim 1 is directed to a sample DNA including a genomic DNA, a free DNA…. “Including” has been read as “for example” or “such as”. The phrase "including" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The claim similarly recites a list of structural variations but it is unclear whether these are required limitations of merely examples. Each of the claims depending on Claim 1 are similarly indefinite.
Claim 1 requires the primer pair set is select in “accordance” with the specification structural variation however it is unclear what “in accordance” requires. The specification nor the art teaches what “in accordance” encompasses or requires. Clarification is required.
Claim 11 is indefinite because it is unclear what obtaining subjects from one individual over time encompass. Subjects are individuals. It is not clear how subjects are obtained from one individual over time. Applicant is further requested to review the claim in its entirety for grammatical clarity (see present/absence, for example). Clarification is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
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.
Claim(s) 1-3, 9-14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Harvey et al. (US 6,849,400, February 1, 2005).
Harvey teaches methods for detecting and measuring spliced nucleic acids such as bcr-abl spliced mRNA. Harvey teaches the methods are suitable for detecting any of a variety of known translocations that occur requiring only the design of primers and probes for known sequences involved in the translocations (col 17, lines 26-30). Harvey teaches target nucleic acids are amplified using primers directed to sites on normally non-proximal portion of the nucleic acid (col. 15, lines 40-50). As shown in Figures 1A-C, primers are designed to different regions of the translocation. The primers are capable of detecting splicing events using the same primers because different sized products result (col. 15, lines 60-65). Additionally internal controls may be used that bind to the normal target (col. 16).
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With respect to Claim 2, the primers in Figure 1C only bind to the abl sequence, on the same chromosome.
With respect to Claim 3, the reverse primers, namely T7-abl primer are the same for both the translocations and the internal control (see Figure 1)
With respect to Claim 10, Harvey teaches extracting nucleic acid prior to analysis (col 6, lines 20-30).
With respect to Claim 11, Harvey teaches clinical monitoring of a patient’s response to therapy where a disease or medical condition is associated with a particular type and/or level of mRNA present in a biological sample (col. 10, lines 45-50).
With respect to Claim 12, Harvey teaches analysis of blood and bone marrow (Example 1).
With respect to Claim 13, Harvey teaches analysis of translocation associated with diseases (col 2, lines 45-55).
With respect to Claim 14, the method of Harvey does not sequence the product but relies up on probes for detection.
Claim(s) 1-4, 10, 12-14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by JP2021/122180, August 30, 2021.
JP2021/122180 teaches a method for analyzing the presence or absence of a chromosomal translocation. JP2021/122180 teaches analysis of translocations using primers to different regions to amplify the different sequences.
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A regions to amplify the different sequences. As seen in Figure 1B, primers are designed that flank the expected translocation, both wild-type and mutant.
With respect to Claim 2, the primers in Figure 1B (normal) only bind to one chromosome.
With respect to Claim 3, the forward primers, namely Fw1(s) are the same for both the translocations and the normal sequence (see Figure 1).
With respect to Claim 4, JP2021/122180 teaches BCR-ABL1 fusion genomic DNA transcripts were evaluated by real-time PCR (RT-PCR). JP2021/122180 teaches the method allows quantifying disease DNA. JP2021/122180 teaches quantification by digital PCR.
With respect to Claim 10, JP2021/122180 teaches extracting nucleic acid prior to analysis.
With respect to Claim 12, JP2021/122180 teaches analysis of blood and bone marrow (Example 1).
With respect to Claim 13, JP2021/122180 teaches analysis of translocation associated with diseases, namely BCR-ABL1.
With respect to Claim 14, the method of JP2021/122180 does not sequence the product but relies up on probes for detection.
Claim Rejections - 35 USC § 103
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.
Claim(s) 5-9, 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over JP2021/122180, August 30, 2021 in view of Seligmann al. (US 10,294,515, May 21, 2019).
JP2021/122180 teaches a method for analyzing the presence or absence of a chromosomal translocation. JP2021/122180 teaches analysis of translocations using primers to different regions to amplify the different sequences.
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A regions to amplify the different sequences. As seen in Figure 1B, primers are designed that flank the expected translocation, both wild-type and mutant. These primers
JP2021/122180 does not teach differentially labeling probes for fluorescence detection.
However, Seligmann teaches methods of detecting gene fusions with probes.
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Seligmann teaches the methods can be used to quantify gene fusions. Seligmann teaches determining a ratio of the fusion probe and the second probe to determine the presence and percentage of nucleic acid. The probes are different labels (col. 12, lines 55-65). Seligmann teaches the labels may be fluorophores (col. 21, lines 20-30). Seligmann teaches detecting probes with probe 1 and 2 that are differentially labeled for the different gene 1 and 2 (col 16, lines 45-50).
With respect to Claim 11, Seligmann teaches the method may be used for analyzing response to drugs (col. 2, lines 5-12).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention to have modified the chromosomal translocation method of JP2021/122180 to further detect the nucleic acids amplified with differentially labeled probes to provide a ratio of the different target nucleic acids. Seligmann teaches the different probes detect the different species of nucleic acids and provide a comparison of two different species. The ordinary artisan would be motivated to determine the frequency and quantity of the two nucleic acid species.
Conclusion
No claims allowable over the art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lin teaches methods for detecting internal tandem duplication mutations (WO 2014/071272, May 8, 2014)
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached on (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
July 30, 2026
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