Prosecution Insights
Last updated: April 19, 2026
Application No. 18/452,628

MARKER AND METHOD FOR ANALYSING BIOLOGICAL SAMPLES

Non-Final OA §102§112§DP
Filed
Aug 21, 2023
Examiner
KIM, YOUNG J
Art Unit
1681
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Leica Microsystems Cms GmbH
OA Round
1 (Non-Final)
65%
Grant Probability
Moderate
1-2
OA Rounds
3y 4m
To Grant
82%
With Interview

Examiner Intelligence

Grants 65% of resolved cases
65%
Career Allow Rate
711 granted / 1098 resolved
+4.8% vs TC avg
Strong +18% interview lift
Without
With
+17.7%
Interview Lift
resolved cases with interview
Typical timeline
3y 4m
Avg Prosecution
61 currently pending
Career history
1159
Total Applications
across all art units

Statute-Specific Performance

§101
5.0%
-35.0% vs TC avg
§103
32.5%
-7.5% vs TC avg
§102
16.6%
-23.4% vs TC avg
§112
33.6%
-6.4% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1098 resolved cases

Office Action

§102 §112 §DP
DETAILED ACTION 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 . Priority Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Information Disclosure Statement The IDS received on November 13, 2023 and December 4, 2024 are proper and are being considered by the Examiner. Drawings The drawings received on August 21, 2023 are acceptable. Claim Observation The term, “oligonucleotide nanostructure backbone” is referred by an alternate term, “nanostructure backbone” in dependent claims (see claim 2, 10, 11, and 13, for example). While it is clear that the alternate term is referring to “oligonucleotide nanostructure backbone” as there are no other terms in the claims to which it can be construed, usage of a consistent claim language is preferred. 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. Claim 12 is 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. Claim 12 begins with the phrase, “The method for analyzing a biological sample …” However, there is an insufficient antecedent basis for this “method”. The Office suggests beginning this claim with the article, “A”. Claim Rejections - 35 USC § 102 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. Claims 1, 4-10, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dunaway et al. (WO 2019/222178 A1, published November 2019; IDS ref). As pointed out in In re Mott, 190 U.S.P.Q. 536 (CCPA 1975), "Claims must be given broadest reasonable construction their language will permit in ex parte prosecution, and applicant who uses broad language runs the risk that others may be able to support the same claim with a different disclosure." With regard to claim 1, Dunaway et al. teach a marker comprising the configuration reproduce herein (from Fig. 10): PNG media_image1.png 329 397 media_image1.png Greyscale As seen, the marker comprises: a) an oligonucleotide nanostructure backbone with a plurality of attachment sites at a predetermined positions (see R1, R2, and R3); PNG media_image2.png 242 445 media_image2.png Greyscale b) a plurality of labels for attachment to at least one of the attachment sites (see left, where labels are respectively bound to their respective regions on the backbone R1, and R2); c) at least first orientation indicator and a second orientation indicator (the orientation of oligonucleotide backbone structure is identifiable by their 5’ terminal has a natural DNA base and the 3’ terminal is made of L-DNA, see “wherein at least six nucleotides in the target binding domain identify a corresponding nucleotide in the target nucleic acid molecule and wherein at least two nucleotides in the target binding domain do not identify a corresponding nucleotide in the target nucleic acid molecule; wherein the barcode domain comprises a synthetic backbone, the barcode domain comprising at least three attachment positions … wherein the synthetic backbone comprises L-DNA), wherein each label comprise at least one dye (see two dyes per label molecule, also “first pool of reporter probes that is hybridized to attachment position R1, the dual color combination Yellow-Red can correspond to the dinucleotide Adenine-Thymine”, section [00386]), an encoding oligonucleotide portion configured to encode characteristics of the at least one dye and an attachment oligonucleotide portion configured to reversibly attach to one of the attachment sites1, and wherein the attachment oligonucleotide portion of each label comprises a unique oligonucleotide sequence configured to bind to a complementary sequence of one of the attachment sites (i.e., the sequence of oligonucleotide comprising a dye for R1 is unique, the sequence of oligonucleotide comprising a dye for R2 is unique, etc., see “each attachment position of the at least three attachment positions correspond to two nucleotides of the at least six nucleotides in the target binding domain and each of the at least three attachment positions have a different nucleic acid sequence …”, section [0005]). With regard to claims 4 and 13, the oligonucleotide nanostructure backbone is in a linear fashion and therefore within the range of 10 nm to 10,000 nm2 as the structure as claimed is identical if not highly similar. With regard to claim 5, the attachment sites are spaced apart from each other in a range from 1 nm to 2000 nm.3 With regard to claim 6, because the oligonucleotide comprising the label is made up of a string of bases, such sequences can be considered a “primer sequence” as a primer can be designed to anneal thereto and commence sequencing. With regard to claim 7, the oligonucleotide comprising the label comprises a cleavage site that can separate the label from the oligonucleotide (see section [00387], “detectable label attributed to the reporter probe hybridized to attachment position R1 is removed. To remove the detectable label, the reporter probe can include a cleavable linker”). With regard to claim 8, the at least one dye is a fluorophore (see section [00215], “dual combination of fluorescent dyes… such as ALEXA FLUOR™ 532”). With regard to claim 9, an anchor portion configured to attach the marker to a specific biological feature of the biological sample (see Figure 11, also the target binding region (of Fig. 11) anneals to a target nucleic acid (or biological sample), “sequencing domain of the sequencing probe is hybridized to the target nucleic acid”, section [00393]). With regard to claims 10 and 11, the nanostructure backbone is linear and the first and second orientation indicator are spaced apart from each other (see orientation of Fig. 11 above). Therefore, the invention as claimed is anticipated by Dunaway et al. 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 1-6, 8-11, and 13-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,347,527 (herein, “the ‘527 patent”). 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 ‘527 patent claims a composition comprising: “an oligonucleotide nanostructure backbone with a plurality of attachment sites at predetermined positions” (see claim 1); a plurality of labels for attachment of at least one attachment sites (“a plurality of labels … to be attached to a respective attachment site of the plurality of attachment sites”, see claim 1); and at least a first orientation and a second orientation indicator (“at least a first orientation indicator and a second orientation indicator”, see claim 1), wherein each label comprises at least one dye, an encoding oligonucleotide portion configured to encode characteristics of the at least one dye, and an attachment oligonucleotide portion configured to reversibly attach to one of the attachment sites; and wherein the attachment oligonucleotide portion of each label comprises a unique oligonucleotide sequence configured to bind to a complementary sequence of one of the attachment sits (“a plurality of labels, each respective label to be attached to a respective attachment site of the plurality of attachment sites, each respective label comprising … at least one dye … an attachment oligonucleotide portion comprising a respective oligonucleotide sequence configured to bind to a complementary sequence of the respective attachment site, and an encoding oligonucleotide portion comprising a respective oligonucleotide sequence that is unique to the at least one dye, the encoding oligonucleotide portion facilitating identifying the respective label”, see claim 1). With regard to instant claim 2, the nanostructure backbone comprises scaffold strands and staple strands configured to bind to the scaffold strands at predetermined staple strand positions to fold the scaffold strands into a predetermined shape (“oligonucleotide nanostructure backbone comprises scaffold strands, and staple strands configured to bind to the scaffold strands at the predetermined positions to fold the scaffold strands into a predetermined shape”, see claim 2). With regard to instant claim 3, the staple strands comprise the plurality of attachment sites (“the staple strands comprise the attachment sites”, see claim 3). With regard to instant claim 4, a largest spatial extent of the nanostructure backbone is in a range of 10 nm to 10000 nm (“a largest spatial extent of the oligonucleotide nanostructure backbone is in a range of 10 nm to 10000 nm”, see claim 4). With regard to instant claim 5, the attachment sites are spaced apart from each other in a range from 1nm to 2000 nm (see claim 5, verbatim). With regard to instant claim 6, the plurality of labels comprise primer sequences configured to enable sequencing of at least the attachment oligonucleotide portion and the encoding oligonucleotide portion (see claim 9, “the labels comprise rimer sequences configured to enable sequencing of at least the encoding oligonucleotide portion”, and in view of the configuration of the label shows that the primer sequence allows the sequencing of attachment site and encoding site, see column 4, lines 18-20). With regard to instant claim 8, the at least one dye is a fluorophore (see claim 6, “the at least one dye is a fluorophore”). With regard to instant claim 9, because the claims of the ‘527 patent and instant claim are directed to a product, which is an oligonucleotide sequence, such sequence is capable of annealing to a complementary strand of any source based on their complementarity4. With regard to instant claim 10, the nanostructure backbone extends linearly in one dimension and the first orientation indicator and the second orientation indicator are spaced apart from each other, or arranged on opposite ends of the nanostructure backbone (see claim 7, “the oligonucleotide nanostructure backbone extends linearly in one dimension and the first orientation indicator and the second orientation indicator are spaced apart from each other, or arranged on opposite ends of the oligonucleotide nanostructure backbone”). With regard to instant claim 11, the nanostructure backbone extends in two dimension or three dimensions and the nanostructure backbone comprises at least a third orientation indicator (see claim 8, “the oligonucleotide nanostructure backbone extends in two dimensions or three dimensions, and the oligonucleotide nanostructure backbone comprises at least a third orientation indicator”). With regard to instant claims 13 and 14, the ranges are explicitly embraced by the ranges of claims 4 and 5 of the ‘527 patent. With regard to instant claim 15, the all labels of the plurality of labels comprise the same primer sequences (see claim 10, “all the labels comprise same primer sequences”. Claims of the instant application and those of the ‘527 patent differ in that the instant claims are directed to a “marker” comprising the discussed above, whereas the claims of the ‘527 patent are directed to a “data storage device”. However, these differences are not deemed to be patentably distinct and are obvious over each other because the actual elements defining that “data storage device” or the “marker” are virtually identical, and the term, “marker” is strictly defined by the elements it is comprised of, which, as discussed above, are identical. As well, the ‘527 patent broadly defines “data storage device” as an “organic” data storage device (see column 2, lines 32-33) that embraces an oligonucleotide nanostructure backbone, further confirming the above conclusion: “The data storage device includes an oligonucleotide nanostructure backbone with a plurality of attachment sites …” (column 1, lines 45-55) Therefore, invention as claimed is comprised by the claims of the ‘527 patent and therefore, obvious. Conclusion No claims are allowable. Claims 7 and 12 are deemed unobvious over the claims of the ‘527 patent. With regard to claim 7, there is no reason to place a cleavable site into the label structure of the ‘527 patent. With regard to claim 12, claims of the ‘527 patent is directed to a particular application of providing a structure that contains information. It is not claimed in context of annealing the construct to a biological sample for determining the information of the biological sample and there is no reasonable motivation to apply the claims of the ‘527 patent to such an embodiment. Claims 2, 3, 12, 14, and 15 are free of prior art. Claims 2 and 3 are free of prior art because the closest prior art (Dunaway et al., of record) do not teach an additional oligonucleotide (i.e., staple strand) that binds to a region of the oligonucleotide nanostructure backbone at a predetermined position that results in “folding” of the scaffold strands of the oligonucleotide nanostructure backbone. Claims 14 and 15 are free of prior art because the attachment sites of Dunaway et al. are not each separated from one another by 200 nm to 1000 nm distance and there is no motivation to do so as the R1, R2, and R3 regions are only discussed as being close in proximity. Claim 12 is free of prior art because the products of Dunaway et al. are employed in determining a sequence of a target nucleic acid by successive hybridization of labeled oligonucleotides, which does not require that the target nucleic acid (or biological sample) be dissociated into dissociated sample parts. Rather, the target nucleic acid must remain in the locality on which reporter probes are flowed in for the sequencing reaction to occur. 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. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /YOUNG J KIM/Primary Examiner Art Unit 1637 January 12, 2026 /YJK/ 1 The sequence of the label oligonucleotide annealing to, for example R1, is unique and associated with its own unique dye(s). Therefore, any portion of this sequence can be considered an attachment portion as well as the encoding portion. 2 This assertion is made because the invention of the instant application encompasses a linear oligonucleotide structure, or its folded structure configuration. 3 There is a gap of at least 3 bases between the region where oligonucleotide labels hybridize on R1, R2, and R3. each nucleotide sequence spans approximately 0.34 nm (see Alberts, Molecular Biology of the Cell, 4th edition, 2002, enclosed) and therefore, a gap of at least three or more would result in 1 nm between regions where the label oligonucleotides anneal. 4 The ‘527 patent also confirms this property: “oligonucleotide is, for example, a single stranded DNA or RNA molecule, that may be sequenced to determine its sequence of nucleotides. Complementary parts of oligonucleotides may hybridise or bind to each other”, see column 2, lines 53-57.
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Prosecution Timeline

Aug 21, 2023
Application Filed
Jan 10, 2026
Non-Final Rejection — §102, §112, §DP
Apr 07, 2026
Examiner Interview Summary
Apr 07, 2026
Applicant Interview (Telephonic)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
65%
Grant Probability
82%
With Interview (+17.7%)
3y 4m
Median Time to Grant
Low
PTA Risk
Based on 1098 resolved cases by this examiner. Grant probability derived from career allow rate.

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