DETAILED ACTION
The present Office Action is responsive to the Amendment received on November 26, 2025.
Election/Restrictions
Applicants’ election without traverse of the species SEQ ID Number 1 and 64 from Table 1 and 2 (respectively), remains in effect, and because Applicants did not distinctly point out the supposed error of this requirement.
Claims 11-13 also remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions without traverse.
Claim Objections
Claims 9 and 10 are objected to because of the following informalities:
Claims 9 and 10 make reference to a list of genes found on a Table 1 and 2 (respectively).
MPEP 2173.05(s) states:
“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The rejection of claims 1-10, 14, and 15 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point out and distinctly claim the subject matter, made in the Office Action mailed on September 18, 2025 is withdrawn in view of the Amendment received on November 26, 2025.
Claim Rejections - 35 USC § 103
The rejection of claims 1-7 under 35 U.S.C. 103 as being unpatentable over Raymond et al. (US 2022/0259659 A1, published August 18, 2022, priority August 19, 2019) in view of Jensen et al. (Biochemistry, 1997, vol. 36, pages 5072-5077) is withdrawn in view of a reconsideration of the claims and the arguments presented in the Amendment received on November 26, 2025.
Specifically because the first oligonucleotide anneals to the “V” region of a target nucleic acid comprising the rearranged immune 5’-VDJ-3’ regions, it is implicit that the first oligonucleotide must anneal to the V region of the nucleic acid and extend away from the regions DJ. Therefore, Applicants’ arguments presented on page 8 of the Amendment received November 26, 2025 apply and the rejection is withdrawn.
The rejection of claims 8-10 under 35 U.S.C. 103 as being unpatentable over Raymond et al. (US 2022/0259659 A1, published August 18, 2022, priority August 19, 2019) in view of Jensen et al. (Biochemistry, 1997, vol. 36, pages 5072-5077), as applied to claims 1-7 above, and further in view of Livingston et al. (US 2017/0335386 A1, published November 23, 2017) and Pugh et al. (WO 2017/177308 A1, published October 2017), made in the Office Action mailed on September 18, 2025 is maintained for the reasons of record.
Rejection - Maintained
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.
The rejection of claims 14 and 15 under 35 U.S.C. 103 as being unpatentable over Raymond et al. (US 2022/0259659 A1, published August 18, 2022, priority August 19, 2019) in view of Jensen et al. (Biochemistry, 1997, vol. 36, pages 5072-5077), as applied to claims 1-7 above, and further in view of Yang et al. (Acta Biochim Biophys Sin., 2018, vol. 50, no. 11, pages 1166-1172), made in the Office Action mailed on September 18, 2025 is maintained for the reasons of record.
Applicants’ arguments presented in the Amendment received on November 26, 2025 have been carefully considered but they do not apply for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
The teachings of Raymond et al. and Jensen et al. have already been discussed above.
While Raymond et al. teach that gene rearrangement can be detected via their disclosed method, the artisans do not explicitly teach that other types of rearrangements can also be detected and sequenced, such as gene fusion based on splice variants sites (claims 14 and 15).
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the teachings of Raymond et al. and Jensen et al. to detect other types of rearrangement sequences, such as splice variants and gene fusion products (as taught by Yang et al.). Doing so would have been an obvious application because the first oligonucleotide (of Raymond et al.) would have been applied to first target a first gene sequence of a known fused gene, followed by its isolation and a second oligonucleotide would have been applied to the second gene sequence, wherein the presence of the extended construct would have indicated the presence of a fusion gene.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Response to Arguments:
Applicants traverse the rejection (page 6, Response).
Applicants depict the method of Raymond (of record) as characterized by the Figure 3 of the disclosure (page 6, Response). From this characterization, Applicants state that while Raymond may teach, “(i) hybridizing a first oligonucleotide to a target and extending that bound first oligonucleotide; (ii) and hybridizing a second oligonucleotide to a target and extending that bound second oligonucleotide, the first and second oligonucleotides of Raymond are bound to and extended along different target nucleic acid molecules” (emphasis added). Specifically, Applicants state that the J-specific probe is extended along a strand of a denatured fragment (step 3 of FIG. 3); while the V-specific probe is extended along a denatured amplification product (see step 6 of FIG. 3) (page 7, Response).
Applicants contrast their invention in that the “claimed invention requires that the first and second oligonucleotides are bound and extended along the same target molecule” (page 7, Response) and that step (e) of the claimed invention “requires that the second oligonucleotide be hybridized to the first primer extension complex, where the first primer extension complex includes the target nucleic acid and an extended first oligonucleotide,” referring to FIG. 2 of the pending application (page 7, Response).
The above statements and contentions have been carefully considered but they have not been found persuasive for the following reasons.
The rejection primarily surrounds the interpretation claim terms. The first of which is the interpretation surrounding what is considered a “first primer extension product “that comprises the at least one target nucleic acid and the extended first oligonucleotide”.
According to Applicants’ interpretation, this can only be embodied by what is represented by Applicants’ Figure 2 (reproduced below):
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As seen, this interpretation does show a first primer extension complex that comprises the first extended oligonucleotide (the right side where the primer is extended toward the right terminus) and at least one target nucleic acid (the top strand).
However, the Office contends this is not the only interpretation that applies to the term, “first primer extension complex”. An alternative interpretation of the same complex can be represented by what was disclosed by Raymond (reproduced from Fig. 5B):
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As seen, this structure is also a first primer extended complex, wherein this complex comprises the at least one target nucleic acid (top strand) and an extended first oligonucleotide (the bottom strand).
Therefore, Applicants’ interpretation of what is considered a “first primer extension complex” does not distinguish the structure away from the structure produced by Raymond.
Next, regarding the “argument”1 that the first and the second primers are “bound to and extended along the same target molecule,” (page 7, Response), the Office has considered this argument in depth, but has concluded that the argument is not found persuasive because the claim does not recite what is shown by Applicants’ narrow claim interpretation.
Initially, the same target molecule does not mean that the first and the second primers are bound and extended along the same strand of the target nucleic acid molecule. In fact, this very embodiment (i.e., same strand being used by the first and second oligonucleotides in the extension reaction) was indicated by the Office Action (on page 22) as being an allowable limitation:
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Applicants, however, have not amended the claims to the suggestion, but simply applied their “narrow” interpretation to the claims as previously recited.
This, however, is not found persuasive as discussed below.
The issues surround: (1) the interpretation of the step (e) that recites, “hybridizing a second oligonucleotide comprising a sequence complementary to the J gene to the rearranged immune sequence in the captured first primer extension complex”; (2) interpretation of step (f) that recites the extension of “the hybridized second oligonucleotide with a second polymerase” that produces a second oligonucleotide extension complex comprises “the at least one target nucleic acid and the extended second oligonucleotide”; and (3) whether this would result in the “liberation” of the extended first oligonucleotide”
Issue (1):
Raymond teaches a second oligonucleotide comprising a sequence complementary to J gene in the capture first primer extension complex. This is clearly shown in Fig. 3 (step 6):
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Raymond clearly teaches that the first extension complex that comprises the above discussed extended first oligonucleotide (see step 4, FIG. 3) is purified and this complex is contacted with a V-specific probe (above). While the artisans teach that the complex is first denatured, the hybridization of the V probes progress in the presence of both the target nucleic acid and the extended first oligonucleotide and therefore, the limitation would be met.
Therefore, the teachings of Raymond meet the limitations of the claims as presently recited based on the above interpretation.
Next, Applicants contend that Raymond does not teach hybridizing a first oligonucleotide to a target nucleic acid molecule including at least one adapter as required by the claimed invention, but rather discloses introducing adapters after the hybridization of a first oligonucleotide (page 8, Response).
This argument lacks merit because the claims do not require that the target nucleic acid molecules comprise adapters prior to step (b), but simply requires that target nucleic acid molecule includes at least one adapter. In fact, the claim preamble recites that the “at least one target nucleic acid includes a rearranged immune sequence having a V gene, a D gene, and a J gene” and provides no additional structural detail relating to the adapter. Therefore, Office broadly construes that the adapter can be provided at any step of the process which is indeed provided by Raymond.
Next, Applicants contend that Raymond does not disclose capturing a first primer extension complex via a capture moiety of a first oligonucleotide as required by step (d) of the claimed invention, but describes “capturing a complex which has not been extended” (page 7, bottom to page 8, 1st paragraph, Response).
This argument has been carefully considered but has not been found persuasive because whether the capture occurs before or after, the resulting product would have been the same, that is, the purification of first-primer extension complex. And as discussed by KSR (citation omitted), modification steps that result in a predictable outcome (i.e., purification of the first primer extension complex) would have been obvious.
For these reasons, Applicants’ arguments are deemed unpersuasive and the rejection is maintained.
Double Patenting
The rejection of claims 1-8, 14, and 15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,264,315 (herein, “the ‘315 patent”) in view of Raymond et al. (US 2022/0259659 A1, published August 18, 2022, priority August 19, 2019), made in the Office Action mailed on September 18, 2025 is withdrawn in view of the arguments presented in the Office Action mailed on November 26, 2025.
The Office notes that for the rejection of claims 14 and 15, the rejection is withdrawn because claims of the ‘315 patent explicitly claims that the second oligonucleotide is hybridized to the same strand of the target nucleic acid (which first oligonucleotide is hybridized) and therefore, the claim interpretation made for the rejection of claim 14 and 15 (based on Raymond in view of Jensen) does not apply.
The rejection claims 9 and 10 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,264,315 (herein, “the ‘315 patent”) and Raymond et al. (US 2022/0259659 A1, published August 18, 2022, priority August 19, 2019), as applied to claims 1-8, 14, and 15 above, and further in view of Livingston et al. (US 2017/0335386 A1, published November 23, 2017) made in the Office Action mailed on September 18, 2025 is withdrawn in view of the arguments presented in the Office Action mailed on November 26, 2025.
Conclusion
Claims 1-8 are allowable. Claims 9 and 10 are objected to. Claims 14 and 15 are rejected.
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.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 February 14, 2026
/YJK/
1 While Applicants argue that the first and the second primer anneal to the “same” target molecule, which appears to mean the same “strand” of the target molecule, this limitation is nowhere to be found.