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 .
DETAILED ACTION
1.The Applicant’s response to the office action filed on July 22, 2026 is acknowledged.
Status of the Application
2. Claims 74-93 are pending under examination. Claims 1-73 are canceled. The Applicant’s arguments and the amendment have been fully considered and found persuasive in-part for the following reasons.
Objection to Specification-Withdrawn
3. The objection to the specification has been withdrawn in view of the persuasive arguments.
Double Patenting-Withdrawn
4. The rejection of claims under obviousness type of double patenting has been withdrawn in view of terminal disclaimer.
Claim Rejections - 35 USC § 103-Maintained
5. 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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1.Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 74-93 are rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. (US 2016/0138091) in view of Desai et al. (WO 2018/175779).
Chee et al. teach a system of claims 74-75, comprising: (a) a first substrate having a biological sample attached thereto; (b) a first nucleic acid probe capable of hybridizing to a first nucleic acid at a spatial location in the biological sample, wherein the first nucleic acid probe comprises a barcode sequence (identity tag) which corresponds to a sequence of the first nucleic acid (para 0057-0060, 0162-0167, 0120-0126, 0135-0136, 0186-0201); and
(d) a plurality of oligonucleotide capture agents capable of directly or indirectly capturing a second nucleic acid from the biological sample, wherein the plurality of oligonucleotide capture agents are attached to the first substrate or to a second substrate, and wherein an oligonucleotide capture agent of the plurality of capture agents comprises: (i) a capture domain capable of directly or indirectly capturing the second nucleic acid, and (ii) a spatial barcode corresponding to the oligonucleotide capture agent's position on the first substrate or on the second substrate (para 0127, 0135-0136, 0168-0170).
With reference to claim 76, Chee et al. teach that the system further comprises an electrophoretic transfer system configured to direct the second nucleic acid from the biological sample on the first substrate toward the plurality of oligonucleotide capture agents on the second substrate (para 0192, 0233).
With reference to claim 77-81, 87, Chee et al. teach that the first nucleic acid probe is a circularizable probe and the first nucleic acid is an RNA, a cDNA, or a rolling circle amplification (RCA) product wherein the second nucleic acid is an RNA in the biological sample and a reverse transcriptase and a template switching oligonucleotide (para 0131-0135, 0202-0206).
With reference to claims 82-84, Chee et al. teach that the second nucleic acid is a ligation product, and the system further comprises a pair of probes capable of hybridizing to a target RNA in the biological sample to generate the ligation product using ligation templated on the target RNA, wherein the pair of probes are linear probes and the capture domain comprises a free 3' end (para 0131-0135, 0142-0144).
With reference to claims 85-86, Chee et al. teach that the capture domain comprises a poly(dT) sequence, a random sequence, or a gene-specific sequence and the oligonucleotide capture agent further comprises a universal domain which is 5' to the spatial barcode, wherein the universal domain comprises: (i) an amplification domain (priming sequence); and/or (ii) a cleavage domain (para 0132-135, 0143, 0127).
With reference to claims 88-89, Chee et al. teach a reagent for generating a spatially labeled polynucleotide comprising (i) a sequence of the second nucleic acid or complement thereof and (ii) a sequence of the spatial barcode or complement thereof and a reagent for releasing the spatially labeled polynucleotide or a portion thereof from the second substrate for analysis (para 0132-0135).
With reference to claim 90, Chee et al. teach a reagent for sequencing the spatially labeled polynucleotide or portion thereof (para 0144-0159).
With reference to claim 91, Chee et al. teach a fluorescence microscope for imaging the biological sample on the first substrate and detecting the detectably labeled probe at the spatial location in the biological sample (para 0196).
With reference to claim 92-93, Chee et al. teach that the biological sample is a cell or tissue sample and the system further comprises a polymerase and dNTPs for generating the RCA product (para 0162-167, 0187, 0135).
However, Chee et al. did not specifically teach a detectably labeled probe that hybridizes to the barcode sequence.
Desai et al. teach reagents and methods for detecting nucleic acids using proximity ligation-in situ hybridization (PLISH), wherein PLISH utilizes probes that bind to target nucleic acid, and reagents for rolling circle amplification, wherein the reagents comprise imager oligonucleotides (detectably labeled probes) that hybridizes to the barcode sequence for efficient detection and automated imaging of target nucleic acids in situ by fluorescence microscopy (page 3, line 14 to line 5 on page 5, page 8, line 13 to line 31
on page 9). Desai et al. also teaches a bridge oligonucleotide that is capable of hybridizing to RCA product of the circularized probe and detectably labeled probe (page 5, line 17-21, page 8, line 13 to line 31 on page 9).
It would have been obvious to one skilled in the art before the effective filing date of the invention to modify the method of analyzing a biological sample as taught by Chee et al. with detectably labeled probes as taught by Desai et al. to develop an improved sensitive nucleic acid detection system. The ordinary person skilled in the art would have motivated to modify the method as taught by Chee et al. with detectably labeled probes as taught by Desai et al. and have a reasonable expectation of success
that the combination would result in an improved sensitive and efficient method because Desai et al. explicitly taught use of imager oligonucleotides (detectably labeled probes) for increased efficiency of detecting target nucleic acids in-situ (page 8, line13-21, page 3, line 14 to line 20 on page 4) and such a modification is considered obvious over the cited prior art.
Response to Arguments:
With reference to the rejection of claims under 35 USC 103 as being obvious over Chee et al. in view of Desai et al., the Applicant’s arguments and the amendment have been fully considered and found unpersuasive. With reference to the Applicant’s arguments drawn to no teaching of oligonucleotide capture agents as amended and citing different portions of the specification to support the limitation, the Applicant’s arguments and the amendment have been fully considered and found unpersuasive. Chee et al. (para 0168-0170, 0237) teach oligonucleotide comprising capture agent (an antibody or affinity agent), which is within the scope of the oligonucleotide capture agent because the Applicant cited portion para 0282 of the specification discloses capture agent or capture probe is an oligonucleotide-antibody conjugate. With reference to the Applicant’s arguments drawn to address tag of Chee et al. is not a barcode, the arguments have been found unpersuasive. Chee et al. para 0168, 0124-0125, 0237 teach that the address tag/identity tag uniquely identifies target sites in a biological sample, which is within the scope of a barcode. With reference to no motivation to combine Chee et al. identity tag with imager oligonucleotides of Desai, the Applicant’s arguments were found unpersuasive. As discussed in the rejection Chee et al. teach oligonucleotide or probe conjugated antibodies comprising target binding moiety and address tag /identity tag that uniquely identifies target sites in a biological sample and as discussed in the rejection it would be obvious to modify the teaching of Chee et al. with detectably labeled imager oligonucleotides of Desai et al. to detect a biological sample. With reference to the Applicant’s arguments drawn to the purpose of identity tag of Chee et al. and imager oligonucleotides of Desai is different and would not be obvious to combine the teachings to arrive at the claimed system, the arguments were found unpersuasive because as noted in MPEP 2144-IV the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). In the instant context, as discussed in the rejection it would be obvious to modify the teachings of Chee et al. with the detectably labeled oligonucleotides of Desai et al. to derive at the claimed system. For all the above the rejection has been maintained and restated to address the amendment.
Conclusion
No claims are allowed.
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.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
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