DETAILED ACTION
It is noted that this application has been transferred to Examiner Joseph G. Dauner of Art Unit 1682. Please direct all future correspondences to Examiner Dauner. Contact information for Examiner Dauner is provided at the end of this Office action.
Upon further consideration, the finality of the 4/13/2026 Office action is withdrawn.
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 .
The claims filed 6/9/2026 are under consideration.
The amendments and arguments presented in the papers filed 6/9/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 4/13/226 listed below have been reconsidered as indicated.
a) The rejections of claims 1-5 and 7-20 under 35 U.S.C. 103 as being obvious over US 2020/0277664 A1 (Frenz) are withdrawn as the rejection does not adequately address each of the recited limitations of the claimed methods, in particular in regards to element (ii) of step (b), as argued in the Remarks (p. 7-9).
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New grounds of rejection necessitated by amendment are detailed below.
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 1-5 and 7-20 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. Regarding claim 1, the claim recites “the second spatial barcode” in line 1 of step (d). The recitation lacks proper antecedent basis.
Claims 2-5 and 7-20 depend from claim 1 and are rejected for the same reason.
Regarding claim 3, the claim recites “the second nucleic acid analyte” in line 2. The recitation lacks proper antecedent basis.
Regarding claim 5, the claim recites “the second analyte” in line 4. The recitation lacks proper antecedent basis.
Regarding claim 9, the claim recites “the nucleic acid second capture probe” in line 2. The recitation lacks proper antecedent basis.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 3, 5, 7, 8, 9, 10, 11, 12, 15, 16 and 17 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Belhocine (WO 2019/157529 A1).
The following are new rejections.
Regarding claims 1 and 15, Belhocine teaches providing an “array” of beads comprising a plurality of “nucleic acid capture probes” (Fig. 2, beads 214; Fig. 8, oligonucleotides 820, 802 and/or 818). See also, Figs. 10A, 10B and 10D, Fig. 21 and Fig. 87A and 87B. The oligonucleotides include “a first spatial barcode” in the form of barcode sequence 810 of Fig. 8 (para. 229). The oligonucleotides further include oligonucleotide sequences 808 and 816 that are structurally analogous to a “first capture domain”. See e.g., Fig. 21, 22, 87A and 87B. These teaching of Belhocine are relevant to step (a).
Belhocine further teaches contacting “tissue sections” which are portions of cells extracted from tumor sample (para. 1094 and 1098) with:
i) antibodies that bind to proteins that include an oligonucleotide comprising an “antibody barcode” that identifies an “antigen-binding complex” (Fig. 87A and 87B);
ii) a plurality of “capture oligonucleotides” comprising a double stranded barcode sequence 8758, and a first single stranded adaptor sequence 8760a, where sequence 8760a hybridizes with a “antibody barcode” comprising sequences 8706B and 8762; and
iii) a “plurality of first probes” comprising sequences complementary to a nucleic acid analyte and to a GGG portion of a capture probe on a bead (Fig. 11A and/or Fig. 26). See also Fig. 119, oligonucleotides 11904 that hybridize to a target and an oligonucleotide to a bead forming complex 11910.
These teachings of Belhocine are relevant to step (b) based on the broadest reasonable interpretation of the claim. The claim does not limit step (b) to being performed: on an “intact” tissue section; in an in situ manner; on a “fresh frozen tissue section” or a “fixed tissue section”; on a “tissue section disposed on a substrate” or a “tissue section disposed on the array”. The claim does not provide any structural relationship or orientation between the “tissue section” and the “array”, nor does not it limit what a “location” encompasses or what is a relationship between the “array” and a positioning of the “first nucleic acid capture probe” and the “second nucleic acid capture probe”. In view of the full scope of the elements of step (b), the teachings of Belhocine are applicable.
Belhocine teaches determining the sequences of bead bound nucleic acids using sequencing methods (e.g., para. 6, 8, 11, 171, 176 and 256).
Belhocine teaches correlating the “spatial barcodes” and “antibody barcodes” and/or first probe sequences or complements with a “location” of the protein or nucleic acid analyte in the “tissue section”. For example, correlating the presence CD47 proteins to the location of poly-A containing mRNA and correlation the presence of poly-A containing mRNA with the location of CD47 proteins. Alternatively, the presence of the protein and nucleic acid is correlated being “located” within the extracted cells. See, e.g., 1079 or 1109-1110.
These teachings of Belhocine are relevant to steps (c) and (d) based on the broadest reasonable interpretation of the claim. The claim does not limit these steps to identifying the “spatial location” of analytes: within an “intact” tissue section; in a in situ-based manner; within a “tissue section disposed on a substrate”; or within a “tissue section disposed on the array”.
Regarding claim 2, Belhocine teaches first and second probes that are ligated (see, e.g., Fig. 117 or 119) and that are either part of a single oligonucleotide (Fig. 119) or a part of separate oligonucleotides (Fig. 117).
Regarding claim 3, Belhocine teaches releasing a barcoded ligation product using RNase (para. 443, 517, 1042) or heat (para. 245, 455).
Regarding claim 5, Belhocine teaches a plurality of barcoded oligonucleotide “probes” and “correlating” the “location” of plurality of analytes using sequence oligonucleotides from the “array” of beads. See also, Figs. 10A, 10B and 10D and Fig. 21 and 87A and 87B.
Regarding claim 7, Belhocine teaches removing unbound antibodies (para. 854).
Regarding claim 8, Belhocine teaches the “first capture domain” and “second capture domain” have a plurality of possible sequences, including poly(T) sequences (para. 890; and Fig. 10A).
Regarding claim 9, Belhocine teaches the “first nucleic acid capture probe” and “second nucleic acid capture probe” includes a read “primer binding site” (para. 427).
Regarding claims 10 and 11, Belhocine teaches extending “capture probes” using polymerases and templates, including “capture probes” (Fig. 119).
Regarding claim 12, Belhocine teaches permeabilizing “tissue sections” (para. 410), which are portions of cells extracted from tumor sample as described above.
Regarding claim 16, Belhocine teaches oligonucleotides are attached to molecules via cleavable linkers (para. 13).
Regarding claim 17, Belhocine teaches the use of 5’ blocking priming sequence as a “blocking probes” (para. 1038).
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.
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.
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) 1-5 and 7-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Frenz (WO 2020/123316 A1) in view of Belhocine (WO 2019/157529 A1).
The prior art of US 2020/0277664 A1 (Frenz) previously relied upon, claims priority to PCT/US2019/065072, which published as Frenz (WO 2020/123316 A1). The two references have the same disclosure based on their relationship as applications. Furthermore, the two references have identical sets of drawings and the same 4 “Examples”.
Regarding claims 1-5 and 7-20, the Remarks acknowledge the teachings of US 2020/0277664 A1 (Frenz) and argues the reference is only deficiency is in regards to element (ii) of step (b) (p. 7-8). In view of the relationship between US 2020/0277664 A1 (Frenz) and Frenz (WO 2020/123316 A1), Frenz is only deficient regarding the “capture probes” used in part (ii) of step (b) in view the Remarks characterization of US 2020/0277664 A1 (Frenz).
It is noted the Frenz also teaches the use of “splint” oligonucleotides that function similar to the claimed “capture probes” in that they link two oligonucleotides by hybridizing to each of them. See p. 42, 355 and 357. Frenz does not specifically teach what two oligonucleotides are being linked via hybridization.
However, Belhocine teaches a plurality of “capture oligonucleotides” comprising a double stranded barcode sequence 8758, and a first single stranded adaptor sequence 8760a, where sequence 8760a hybridizes with “the antibody barcode” comprising sequences 8706B and 8762. See Figs. 87A and 87B.
It would have been prima facie obvious to the ordinary artisan at the time of filing to have substituted the linkage of the antibody oligonucleotide to the bead via direct hybridization with the indirect linkage through the use of a “capture probe” or bridging oligonucleotide. The modification has a reasonable expectation of success as Belhocine teaches the two approaches are obvious variants of one another (Fig. 87A and 87B).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5 and 6-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-20 of U.S. Patent No. 11,821,035 B1;
claims 1-21 of U.S. Patent No. 12,031,177 B1;
claims 1-24 of U.S. Patent No. 12,275,988 B2;
claims 1-20 of U.S. Patent No. 11,821,035 B1;
claims 1-27 of U.S. Patent No. 11,692,218 B2;
claims 1-30 of U.S. Patent No. 11,845,979 B2;
claims 1-19 of U.S. Patent No. 12,098,417 B2;
claims 1-29 of U.S. Patent No. 11,952,627 B2;
claims 1-30 of U.S. Patent No. 11,519,033 B2;
claims 1-27 of U.S. Patent No. 12,195,790 B2;
claims 1-20 of U.S. Patent No. 12,128,403 B2;
claims 1-19 of U.S. Patent No. 12,545,949 B2;
claims 1-30 of U.S. Patent No. 11,753,673 B2;
claims 1-29 of U.S. Patent No. 11,840,724 B2;
claims 1-47 of U.S. Patent No. 11,788,122 B2;
claims 1-30 of U.S. Patent No. 12,241,060 B2; and
claims 1-24 of U.S. Patent No. 12,571,029 B1,
in view of Frenz (WO 2020/123316 A1) and/or Belhocine (WO 2019/157529 A1).
The above patents are directed to methods of analyzing the location of analytes within tissue sections using arrays, probes and barcodes. The patented claims are analogous to those of the present application. Any of the elements that are lacking within the patented claims are provided in the Frenz and/or Belhocine references.
It would have been prima facie obvious to the ordinary artisan at the time of timing to have modified the patented claims by incorporating the elements of Frenz and/or Belhocine in order to analyze the location of nucleic acid analytes and proteins within a tissue section.
Claims 1-5 and 6-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-20 of copending Application No. 18/804654;
claims 1-20 of copending Application No. 18/936270;
claims 1-20 of copending Application No. 19/228286;
claims 1-160 of copending Application No. 19/121955;
claims 1-20 of copending Application No. 19/179536;
claims 1-30 of copending Application No. 18/927479;
claims 1-30 of copending Application No. 18/074081;
claims 1-20 of copending Application No. 19/447151; and
claims 1-21 of copending Application No. 19/080120,
in view of Frenz (WO 2020/123316 A1) and/or Belhocine (WO 2019/157529 A1).
The above applications are directed to methods of analyzing the location of analytes within tissue sections. The applications’ claims are analogous to those of the present application. Any of the elements that are lacking within the patented claims are provided in the Frenz and/or Belhocine references.
It would have been prima facie obvious to the ordinary artisan at the time of timing to have modified the patented claims by incorporating the elements of Frenz and/or Belhocine in order to analyze the location of nucleic acid analytes and proteins within a tissue section.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682
Prosecution Insights