DETAILED ACTION
The present Office Action is responsive to the Amendment received on January 16, 2026.
Preliminary Remark
The Office notes that Applicants’ claim set received on January 16, 2026 does not conform to the guidelines set forth in 37 CFR 1.121(c)(4)(i). The claim set cancels claims 7-10 identifying them as being canceled, and then recites the texts of the same claims with strike-through markings. When claims are canceled, the texts are not needed and reciting them again in this manner is not proper.
For the purpose of compact prosecution, non-responsive amendment has not been mailed.
Claims 7-10, and 14 are canceled.
Claim Objections
The objection made to claim 3 for reasons discussed in the Office Action mailed on July 17, 2025 is withdrawn in view of the Amendment received on January 16, 2026.
Claim Rejections - 35 USC § 112
The rejection of claims 3, 8, 9, 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to particularly point out and distinctly claim the subject matter, made in the Office Action mailed on July 17, 2025 is withdrawn in view of the Amendment received on January 16, 2026.
Claim Rejections - 35 USC § 103
The rejection of claims 1-7 and 10-15 under 35 U.S.C. 103 as being unpatentable over Kosmeder et al. (US 2008/0268462 A1, published October 30, 2008) in view of Wallace et al. (U.S. Patent No. 7,494,776, issued February 24, 2009), made in the Office Action mailed on July 17, 2025 is withdrawn in view of the Amendment received on January 16, 2026.
Double Patenting - New Grounds, Necessitated by Amendment
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 1-3, 6, 11-13, and 15-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,920,186 (herein, “the ‘186 patent”) in view of Kosmeder et al. (US 2008/0268462 A1, published October 30, 2008).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
With regard to instant claim 1, claims of the ‘1186 patent also claims a method for imaging a plurality of protein targets (“imaging a sample to detect bound labeled … repeating”, see claim 1, steps (7) and (9)), comprising:
contacting a cell or tissue sample with one or more target-specific binding partners, wherein each target-specific binding partners is linked to an antigen, and wherein target-specific binding partners of different specificity are linked to different antigens (see claim 1(1), “contacting a sample being tested for the presence of one or more targes with one or more target-specific binding partners, wherein the sample is a cell or tissue, wherein each target-specific binding partners of different specificity are linked to different antigens”);
contacting the sample with antigen-binding partners linked to docking strands, wherein different antigen-specific binding partners are linked to different docking strands (see claim 1(3), “providing antigen-specific binding partners linked to docking strands”; also claim 1(4), “wherein the docking strands are nucleic acid strands and different antigen-specific binding partners are linked to different docking strands”);
contacting the sample with labeled imager stands, wherein the labeled imager strands comprise a portion that hybridizes to the docking strand and a fluorescent label (see claim 1(6), “labeling of the docking strand using an optical label”; also claim 4, “wherein the docking strands are labeled using labeled nucleic acids that bind to the docking strand”);
detecting the fluorescent signal from each of the hybridize imager strands (see claim 1(7), “imaging the sample to detect bound labeled antigen-specific binding partners”);
removing the image strands or inactivating the fluorescent signal (see claim 1(8), “extinguishing the signal from the optical label”); and
repeating steps (c) through (e) with multiple sets of differing imager strands to image a plurality of targets in the biological sample (see claim 1(9), “repeating steps (1)-(8), or any subset therefor”).
With regard to instant claim 2, the target-specific binding partner comprises an antibody or antigen-binding fragment thereof (see claim 8, “target-specific binding partner comprises an antibody or antigen-binding fragment thereof”).
With regard to instant claim 3, the target-specific binding partner comprises a known binding partner of a target molecule (see claim 9).
With regard to instant claim 6, the antigen-specific binding partner comprises an antibody or antigen binding fragment thereof that specifically binds the antigen of the target-specific binding partner (see claim 12, “the antigen-specific binding partner comprises an antibody or antigen binding fragment thereof that specifically binds the antigen of the antigen-bound target-specific binding partner”).
With regard to instant claims 16 and 17, the cell or tissue sample is contacted with a circularizable probe that comprises a portion that hybridizes to the docking strand and amplified with a polymerase (see claim 5, “the DNA amplification reaction comprises rolling circle amplification1”).
While claims of the ‘186 patent claim that the target-specific binding partner is a primary antibody and that the antigen-specific binding partner specifically binds to the antigen of the target-specific binding partner) comprising the docking strand, the ‘186 patent claims do not explicitly recite that a secondary antibody is used (claim 11).
Claims of the ‘186 patent do not explicitly claim that multiple antigen-specific binding partners bind to a single antigen (claim 12), or that multiple types of antigen-specific binding partners are used (claim 13).
While claims of the ‘185 patent claim that optical labels are detected and the optical labels are extinguished, the claims do not explicitly recite that photobleaching is employed (claim 15).
While claims of the ‘185 patent claim that docking strands are amplified via RCA, the ‘185 patent does not claim that the circularized probe is combined with the target-specific binding partner linked to a docking strand before contacting the sample (claim 18), or amplification occurs separately from contacting the sample with labeled imager strands (claim 19), during the same step (claim 20), or at least two targets are imaged using at least two labels in the same imaging step (claim 21), and some in succession after extinguishing the previous signal (claim 22).
Kosmeder et al. teach a method of detecting multiple targets in a sample as depicted in the below-reproduced figure (Fig. 7):
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As seen, the artisans teach the steps of: a) contacting a sample being tested for the presence of one or more targets with one or more target-specific binding partners, wherein each target-specific binding partner is linked to an antigen, and wherein target-specific binding partners of different specificity are linked to different antigens (see antibodies 134, 142, 150, 158, 166, and 174, each of which targets a different target Ki-67, CD3, Kappa, CD20, CD-68, and Lamba; each linked to a different antigen (BF, Biotin, DNP, NP, TS, and Rot); see sections [0421]-[0426]); b) contacting the sample with antigen-specific binding partner (see antibodies 138, 146, 154, 162, 170, and 178), which are labeled (see 140, 148, 156, 167, 172, and 180; also sections [0422]-[0426]); c) imaging the sample to detect bound labeled antigen-specific binding partners (“using different signal generating moieties, several different sample targets can be visualized substantially simultaneously, or sequentially, as may be desired”, section [0426]).
The target-specific binding partner comprises an antibody (see above), the target-specific binding partner comprises a known binding partner of a target molecule (see above), and the antigen-specific binding partner comprises an antibody (i.e., secondary antibody, see above).
The multiple antigen-specific binding partners bind to a single antigen (i.e., monoclonal antibody; see section [0045] for example).
Multiple types of antigen-specific binding partners are used (see different antibodies that are specific to different antigens above).
Kosmeder et al. teach that fluorophores can be photo-bleached that permanently covert organic fluorophores into non-fluorescent molecules (see section [0311]).
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 combine the claims of the ‘185 patent with the teachings of Kosmeder et al. and conventional knowledge available to one of ordinary skill in the art, thereby arriving at the invention as claimed for the following reasons.
As discussed above, the claims of the ‘185 patent already claims a method of detecting a plurality of targets from tissues or cell, wherein the target-specific binding partner (e.g., target specific antibody) is labeled with an antigen, the antigen is bound to an antigen-specific binding partner comprising a docking strand. The docking strand is amplified in order to provide a plurality of sites on which imager strands comprising optical labels can bind to in order to generate amplified signal that relate to the target analyte in the sample.
While the claims of the ‘185 patent did not explicitly recite that the antigen-specific binding partner, one of ordinary skill in the art would have recognized that any such recognition partners, such as secondary antibody for that antigen would have yielded the same predictable outcome of producing a detectable complex formed between the target-specific binding partner and the antigen-specific binding partner via the antigen.
Indeed, such a knowledge has been demonstrated by Kosmeder et al. who teach the a target-specific antibody comprising an antigen, and a secondary antibody that specifically binds to that antigen, wherein the antigen of the target-specific antibody is different for different target analytes.
Therefore, one of ordinary skill in the art would have had the motivation to employ conventionally known means of producing the detectable complex involving a secondary antibody but also would have had a clear expectation of success at the combination yielding a successful detection signal.
As to the use of multiple-antigen specific binding partners binding to a sing antigen or multiple types of antigen specific binding partners being used, doing so would have been obvious for reasons already taught by Kosmeder et al.
As to photo-bleaching the optical labels of the claims of the ‘185 patent, doing so would have also been obvious based on the explicit claim (of the ‘185 patent) that recites that the previous optical labels can be “extinguished”, wherein photobleaching would have been a well-known mechanism, as evidenced by Kosmeder et al.
With regard to the various variations of producing and detecting the RCA product, the Office contends that such means would have been an obvious application of the method of the ‘185 patent, regardless of their order or steps being performed in succession or together, yielding the predictable outcome of providing detectable signals of multiple analytes from cells or tissue sample.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 March 30, 2026
/YJK/
1 Parent claim 1 explicitly requires that docking strand is increased by DNA amplification. The dependent claim 15 that recites that this increase of docking strand is via RCE amplification, which would inherently require that a circular probe is annealed to the docking strand, a technique well-established in the art.
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