DETAILED ACTION
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 examiner 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114.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 03/10/2026 has been entered.
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 .
Claims Status
Claims 51 and 62 are canceled.
Claims 1, 2, 4, 10, 12, 19-28, 35, 40, 43-50, 55, and 63-65 are pending.
Claims 1, 2, 4, 10, 12, 19-28, 35, 40, 43-50, 55, and 63-65 are examined.
Withdrawn Objections/Rejections
The objection to the Specification is withdrawn in view of the amendments submitted.
The rejection of claims 1, 2, 4, 20, 25-28, 40, 44, 49, and 50 under 35 U.S.C. 102(a)(1) as being anticipated by Vu et al. is withdrawn in view of the claim amendments submitted.
The rejection of claims 12, 19, 21-23, 36, 43, and 45-47 under 35 U.S.C. 103 as being unpatentable over Vu et al. in view of Rhodes et al. is withdrawn.
The rejection of claims 51, 55, and 62 under 35 U.S.C. 103 as being unpatentable over Vu et al. in view of Rhodes et al., and further in view of Karkera et al. is withdrawn.
The rejection of claims 24 and 48 under 35 U.S.C. 103 as being unpatentable over Vu et al., in view of Howarth et al. is withdrawn.
The rejection of claims 10 and 35 under 35 U.S.C. 103 as being unpatentable over Vu et al., in view of Chin et al. is withdrawn.
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Information Disclosure Statement
The Information Disclosure Statements filed 03/10/2026 is in compliance with the provisions of 37 CFR 1.97 and has therefore been considered. A signed copy of the IDS document is included with this Office Action.
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.
Claims 1, 2, 4, 10, 12, 19-28, 35, 40, 43-50, 55, and 63-65 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. This is a new grounds of rejection.
With respect to claim 1 , the claim recites the limitation of “identifying any sequence reads associated with the one or more breakpoints […]; determining candidate fusion sequence reads associated with common breakpoints of one or more breakpoints”. The claim is indefinite because it is unclear if the “one or more breakpoints” of the common breakpoints are the same “one or more breakpoints” of the step wherein it is identified if the sequence reads are associated with the one or more breakpoints.
With respect to claims 1 and 27, the claim recites the limitation of “causing administration of a therapeutic to a subject”. The claims are indefinite because it is unclear if the administration of the therapeutic to the subject is occurring within the confines of the claim as the claim does not recite an active step of administration, and if it is administered within the confines, what is performing the administration.
With respect to claims 1 and 55, the claim recites the limitation of ”the sequence reads were generated from cell-free DNA”. The claims are indefinite because it is unclear if generating sequence reads from cfDNA is occurring within the confines of the claim and if this is an active step.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 55 is eligible under 35 U.S.C. 101 because the administration of erdafitinib to a patient with a fusion event comprising a FGF2/3 rearrangement integrates any judicial exceptions into a practical application.
Claims 1-2, 4, 10, 12, 19-28, 35, 36, 40, 43-51, and 62 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to an abstract idea of mental steps, mathematic concepts, or a natural law without significantly more. Any newly recited portion is necessitated by claim amendment.
The MPEP at MPEP 2106.03 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of
matter?
(2A)(1) Are the claims directed to a judicially recognized exception, i.e. a law of nature,
a natural phenomenon, or an abstract idea?
(2A)(2) If the claims are directed to a judicial exception under Prong One, then is the
judicial exception integrated into a practical application?
(2B) If the claims are directed to a judicial exception and do not integrate the judicial
exception, do the claims provide an inventive concept?
With respect to step (1): Yes, the claims recite methods.
With respect to step (2A)(1): The claims recite an abstract idea of mental processes.
“Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection” (MPEP 2106.04). Abstract ideas include mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (procedures for observing, evaluating, analyzing/judging and organizing information (MPEP 2106.04(a)(2)). Laws of nature or natural phenomena include naturally occurring principles/relations that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature (MPEP 2106(b)).
Mental processes recited in claims 1:
aligning a plurality of sequence reads to a reference sequence
determining one or more breakpoints in an alignment of a plurality of sequence reads of the plurality of sequence reads to the reference sequence
identifying any sequence reads associated with the one or more breakpoints in the alignment as candidate fusion sequence reads
determining candidate fusion sequence reads associated with common breakpoints of one or more breakpoints
grouping the candidate fusion sequence reads based on one or more common breakpoints
assembling the candidate fusion sequence reads in the groups into one or more contigs
aligning the contigs from the groups of the plurality of groups to the reference sequence
determining, based on the alignments of the contigs from the groups, one or more candidate fusion events comprising aligning candidate fusion sequence reads for the group to the contig, and applying a spread test to the alignments
applying one or more criteria to the one or more candidate fusion events
determining, based on applying the one or more criteria to the one or more candidate fusion events, one or more fusion events
Mental processes recited in claim 27:
aligning a plurality of sequence reads to a reference sequence
determining, based on one or more breakpoints in the alignments of a sequence read to the reference sequence, one or more candidate fusion sequence reads of the plurality of sequence reads
grouping, based on one or more common breakpoints, the one or more candidate fusion sequence reads into one or more container data structures
for the container data structures, assembling the one or more candidate fusion sequence reads into one or more contigs
for the container data structures, aligning the one or more contigs to the reference sequence
determining, based on one or more criteria, one or more aligned contigs indicative of a fusion event, comprising aligning candidate fusion sequence reads for the group to the contig, and applying a spread test to the alignments
wherein the subject is associated with the plurality of sequence reads and has been determined to have a fusion event, wherein the fusion event comprises a FGF2/3 rearrangement
Dependent claims 2, 4, 10, 12, 19-26, 28, 35, 36, 40, and 43-50 recite additional steps that either are directed to abstract ideas or further limit the judicial exceptions in independent claim 1, and as such, are further directed to abstract ideas. Hence, the claims explicitly recite numerous elements that individually and in combination constitute abstract ideas. The relevant recitations are:
Claim 2: “identifying any sequence reads associated with the one or more breakpoints in the alignment as candidate fusion sequence reads comprises at least one of: discarding alignment having a mappability score below a threshold or discarding alignments that are logical, or both”
Claim 4: “determining that at least two candidate fusion sequence reads comprise a breakpoint in a same chromosome and at a same orientation; determining that at least two candidate fusion sequence reads comprise a breakpoint at a same position; determining that at least two candidate fusion sequence reads comprise a breakpoint within a threshold number of bases from a position; determining that at least two candidate fusion sequence reads comprise a plurality of breakpoints in a same chromosome and at a same orientation; determining that at least two candidate fusion sequence reads comprise a plurality of breakpoints at same positions; or determining that at least two candidate fusion sequence reads each comprise a plurality of breakpoints within a threshold number of bases from a plurality of positions”
Claim 10: “generating a de Bruijn graph for the groups and wherein assembling the candidate fusion sequence reads in the groups into one or more contigs comprises linearizing the de Bruijn graphs to generate a contig for the groups”
Claim 12: “performing one or more error correction procedures, wherein the one or more error correction procedures comprise at least one of: resolving mismatches between candidate fusion sequence reads and the reference sequence; inserting padding between at least two candidate fusion sequence reads; or discarding one or more candidate fusion sequence reads having an unaligned portion that exceeds a threshold”
Claim 19: “determining, for the candidate fusion events, a distance between a breakpoint of the one or more aligned contigs and a location of at least one probe of a panel; and discarding any candidate fusion event associated with an aligned contig of the one or more contigs containing no breakpoint with a distance from the location of at least one probe of a panel less than a threshold”
Claim 20: “determining one or more genes of interest; and discarding any candidate fusion event associated with an aligned contig of the one or more contigs containing no breakpoint that is associated with the one or more genes of interest”
Claim 21: “determining, for the candidate fusion events, that a breakpoint of the one or more aligned contigs is a deletion; and discarding any candidate fusion event is associated with an aligned contig of the one or more contigs comprising a deletion located within a number of bases away from another deletion”
Claim 22: “determining, for the candidate fusion events, that a breakpoint of the one or more aligned contigs is a deletion; and discarding any candidate fusion event associated with an aligned contig of the one or more contigs comprising a deletion comprising a number of bases less than a threshold”
Claim 23: “discarding any candidate fusion even associated with an aligned contig of the one or more contigs comprising an insertion or a deletion that is completely embedded in an intronic region”
Claim 24: “determining, for the candidate fusion event, for the one or more aligned contigs, a ration of molecules to reads; and discarding any candidate fusion event associated with an aligned contig of the one or more contig that is associated with a ration of molecules to reads greater than a threshold and that is not associated with a double stranded supporting molecule”
Claim 25: “determining, for the candidate fusion event, for pairs of breakpoints of the one or more aligned contigs, a sequence abutting the breakpoints of the pair of breakpoints; aligning the sequences abutting the breakpoints of the pair of breakpoints; determining an alignment score for the alignment of the sequences abutting the breakpoints of the pair of breakpoints; and discarding any candidate fusion event associated with an aligned contig of the one or more contigs based on the alignment score exceeding a threshold”
Claim 26: “determining, for the candidate fusion events, for pairs of breakpoints of the one or more aligned contigs, a sequence centered on the breakpoints of the pair of breakpoints; aligning the sequences centered around the breakpoints against each other; determining an alignment score for the alignment of the sequences centered around the breakpoints; and discarding any candidate fusion event associated with an aligned contig of the one or more contigs based on the alignment score exceeding a threshold”
Claim 28: “determining that at least two candidate fusion sequence reads comprise a breakpoint in a same chromosome and at a same orientation; determining that at least two candidate fusion sequence reads comprise a breakpoint at a same position; determining that at least two candidate fusion sequence reads comprise a breakpoint within a threshold number of bases from a position; determining that at least two candidate fusion sequence reads comprise a plurality of breakpoints in a same chromosome and at a same orientation; determining that at least two candidate fusion sequence reads comprise a plurality of breakpoints at same positions; or determining that at least two candidate fusion sequence reads comprise a plurality of breakpoints within a threshold number of bases from a plurality of positions”
Claim 35: “for the groups, assembling the one or more candidate fusion sequence reads into a graph data structure; and linearizing the graph data structure to generate one or more contigs”
Claim 36: “performing one or more error correction procedures, wherein the one or more error correction procedures comprise at least one of: resolving mismatches between candidate fusion sequence reads and the reference sequence; inserting padding between at least two candidate fusion sequence reads; or discarding one or more candidate fusion sequence reads having an unaligned portion that exceeds a threshold”
Claim 40: “applying one or more of a footprint test or a spread test, wherein applying the footprint test comprises determining that a threshold number of families of candidate fusion sequence reads that support the contig span the breakpoint(s), and wherein applying the spread test comprises determining that a threshold amount of spread exists between at least two families of candidate fusion sequence reads that support the contig and span the breakpoint(s)”
Claim 43: “determining a distance between a breakpoint of the one or more aligned contigs and a location of at least one probe of a panel; discarding any aligned contig of the one or more contigs containing no breakpoint with a distance from the location of at least one probe of a panel less than a threshold”
Claim 44: “determining one or more genes of interest; and discarding any aligned contig of the one or more contigs containing no breakpoint that is associated with the one or more genes of interest”
Claim 45: “determining that a breakpoint of the one or more aligned contigs is a deletion; and discarding any aligned contig of the one or more contigs comprising a deletion located within a number of bases away from another deletion”
Claim 46: “determining that a breakpoint of the one or more aligned contigs is a deletion; and discarding any aligned contig of the one or more contigs comprising a deletion comprising a number of bases less than a threshold”
Claim 47: “discarding any aligned contig of the one or more contigs comprising an insertion or a deletion that is completely embedded in an intronic region”
Claim 48: “determining, for the one or more aligned contigs, a ratio of molecules to reads; and discarding any aligned contig of the one or more contig that is associated with a ratio of molecules to reads greater than a threshold and that is not associated with a double stranded supporting molecule”
Claim 49: “determining, for pairs of breakpoints of the one or more aligned contigs, a sequence abutting the breakpoints of the pair of breakpoints; aligning the sequences abutting the breakpoints of the pair of breakpoints; determining an alignment score for the alignment of the sequences abutting the breakpoints of the pair of breakpoints; and discarding any aligned contig of the one or more contigs based on the alignment score exceeding a threshold”
Claim 50: “determining for pairs of breakpoints of the one or more aligned contigs, a sequence centered on the breakpoints of the pair of breakpoints; aligning the sequences centered around the breakpoints against each other; determining an alignment score for the alignment of the sequences centered around the breakpoints; and discarding any aligned contig of the one or more contigs based on the alignment score exceeding a threshold”
With respect to step (2A)(2): The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone or in combination to determine if the judicial exception is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exception, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
Claims 1 and 27 recite the following additional elements:
generating a plurality of sequence reads from cell-free (cfDNA) derived from a sample
causing administration of a therapeutic to a subject, wherein the therapeutic is erdafitinib
None of the dependent claims recite additional elements, alone or in combination, which would integrate a judicial exception into a practical application.
Lastly, the claims have been evaluated with respect to step (2B): Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims lack a specific inventive concept. Under said analysis, Applicant is reminded that the judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements above do not rise to the level of significantly more than the judicial exception. As directed in the MPEP at 2106.07(a).III, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to claims 1 and 27: The additional elements of the sequence reads being generated from cell-free DNA (cfDNA) derived from a sample, and administration a therapeutic of erdafitinib does not rise to the level of significantly more than the judicial exception. The Specification at paragraph [0106] discloses that erdafitinib is an FDA-approved drug. Furthermore, it is unclear if the administration of the therapeutic is occurring within the confines of the claims, as explained in the 112(b) rejection above. As recited in the MPEP at 2106.05(d).II with respect to Mayo, 566 U.S. at 79, 101 USPQ2d at 1968, determining the level of a biomarker in blood by any means is a routine and convention technique, and Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157), detecting DNA in a sample is a routine and conventional activity. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. Individually, the limitations of the claims and the claims as a whole have been found lacking.
Response to Arguments
Applicant states that “claims 1 and 27 are amended so as to positively recite administration of a therapeutic agent, a feature previously recited in former claims 51 and 62. Whereas Examiner did not acknowledge fully subject matter eligibility of former claims 51 and 62 based on an alternative recitation of generating a report or administering a therapeutic agent, presently amended claims 1 and 27 result in administration of treatment without alternative. As such, subject matter eligibility should be acknowledged for the presently amended claims for at least this reason alone”.
It is respectfully submitted that the rejection under 35 USC 101 is maintained. As described in the 112(b) rejection, it is unclear if independent claims 1 and 27 actively recite a step of administering the treatment, and thus the judicial exceptions are not integrated into a practical application. Furthermore, in the previous Office Action mailed 09/10/2025, the Examiner states on page 11 “Dependent claims 51 and 62 recite the additional element of administering erdafitinib, which does not integrate judicial exceptions into a practical application because the claims do not require the administration of the erdafitinib therapeutic, as the administration is recited in the alternative and instead a notification could be generated.” It is acknowledged that claims 1 and claims 27 do not provide an alternative for the erdafitinib treatment, but due to the indefiniteness issues the rejection is maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Emilie A Smith whose telephone number is (571)272-7543. The examiner can normally be reached 9am - 5pm.
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/E.A.S./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686
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