Prosecution Insights
Last updated: April 19, 2026
Application No. 18/162,118

Oligonucleotide Paints

Non-Final OA §102§112§DP
Filed
Jan 31, 2023
Examiner
FLINDERS, JEREMY C
Art Unit
1684
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
President and Fellows of Harvard College
OA Round
1 (Non-Final)
64%
Grant Probability
Moderate
1-2
OA Rounds
3y 9m
To Grant
80%
With Interview

Examiner Intelligence

Grants 64% of resolved cases
64%
Career Allow Rate
378 granted / 586 resolved
+4.5% vs TC avg
Strong +15% interview lift
Without
With
+15.2%
Interview Lift
resolved cases with interview
Typical timeline
3y 9m
Avg Prosecution
48 currently pending
Career history
634
Total Applications
across all art units

Statute-Specific Performance

§101
8.8%
-31.2% vs TC avg
§103
33.2%
-6.8% vs TC avg
§102
26.1%
-13.9% vs TC avg
§112
21.1%
-18.9% vs TC avg
Black line = Tech Center average estimate • Based on career data from 586 resolved cases

Office Action

§102 §112 §DP
DETAILED ACTION Status of the Claims Claims 1-18 are currently pending and are examined herein. The present application is being examined under the pre-AIA first to invent provisions. Information Disclosure Statement The information disclosure statement (IDS) submitted on 01/31/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Abstract Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as "means" and "said," should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. Currently, the abstract is too short at 18 words and is not descriptive enough to relay the necessary details to the reader. Claim Rejection(s) – 35 USC § 112, 1st Paragraph The following is a quotation of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 5 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. This rejection concerns “new matter.” Claim 5 recites that the target nucleic acid is linked to a protein that comprises an antibody, however, the specification as originally filed does not provide adequate written description support for this limitation. In the context of the target sequence, the disclosure as originally filed states on pp. 13-14 that “in certain aspect, small Oligopaints can pass into a cell, can pass into a nucleus, and/or can hybridize with targets that are partially bound by one or more proteins, etc.”, however, there in no mention that could be found for target sequences linked to antibodies. The only mention of antibodies in the specification appears at pp. 21-22 and is in the context of antibodies which bind to the detectable and/or retrievable label of the Oligopaints. Claim 10 recites detection of a high number of target nucleic sequences that comprises at least one of 50 or more targets, 100 or more targets, 1000 or more targets, 10,000 or more targets, however, the only mention in the specification of multiplex probes recites “the set of oligonucleotide paints provides one spectrally resolvable color, or at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 50, 100, 200, 300, 400, 500 or more spectrally resolvable labels” (e.g., as per p. 4). Applicants are reminded, as per 37 C.F.R. 1.121, that no amendment may introduce new matter into the disclosure of an application, and that in accordance with MPEP § 2163(II)(A)(3)(b), when filing an amendment an applicant should show support in the original disclosure for new or amended claims. MPEP §2163(I) states that to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. MPEP §2163(I)(B) explains the written description matter as it relates to new and amended claims, stating that the written description requirement prevents an applicant from claiming subject matter that was not adequately described in the specification as filed. MPEP 2163.06(I) notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” Claim Rejections - 35 USC § 112, 2nd Paragraph 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 9 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 pre-AIA the applicant regards as the invention. Claim 9 recites the limitation " the protein, the peptide, the DNA sequence, the RNA sequence, and the carbohydrate ". There is insufficient antecedent basis for this limitation in the claim. As per MPEP 2173: It is of utmost importance that patents issue with definite claims that clearly and precisely inform persons skilled in the art of the boundaries of protected subject matter. Therefore, claims that do not meet this standard must be rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph as indefinite. Further, as per MPEP 2173.02: If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. As currently written, the metes and bounds of the rejected claims are unascertainable for the reasons set forth above, thus the above claim(s) and all dependent claims are rejected under 35 USC 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. Claim Rejections – 35 U.S.C. 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 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 pre-AIA 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 – b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States. Dubrowski et al. Claims 1-4, 6-8, and 12-18 are rejected under 35 U.S.C. 102(b) as being anticipated by Dubrowski et al. (SPIE, 2008, Vol. 6859:1605-7422, doi:10.1117/12.763519). Regarding claim 1, Dubrowski discloses a method comprising contacting a plurality of oligopaints to a target nucleic acid sequence (e.g., FISH probes as per the 2.2.2 FISH probe synthesis section on p. 5), wherein contacted oligopaints form a barcode or combinatorial color sequence that enables reading of a high number of target nucleic acid sequences (e.g., as per the 2.2.3 FISH staining on tissue sections on p. 6). Regarding claim 2, Dubrowski discloses the above method, wherein the target nucleic acid sequence comprises a DNA sequence or an RNA sequence (e.g., chromosomal DNA as per the 2.2.3 FISH staining on tissue sections on p. 6). Regarding claim 3, Dubrowski discloses the above method, wherein the target nucleic acid sequence is an oligonucleotide (e.g., chromosomal DNA as per the 2.2.3 FISH staining on tissue sections on p. 6). Note that p. 10 of the specification states “[t]he principles of the present invention may be applied with particular advantage in methods of tagging (i.e., painting with chromosome paints) one or more oligonucleotide sequences, e.g., chromosome regions (e.g., sub-chromosomal regions) and/or one or more entire chromosomes”, which implies that target oligonucleotides can be chromosome or sub-chromosomal regions. Regarding claim 4, Dubrowski discloses the above method, wherein the target nucleic acid sequence is linked to a protein (e.g., chromosomal DNA is linked to histones, etc.). Regarding claims 6-7, Dubrowski discloses the above method, wherein the contacted oligonucleotide paints are in contact with a retrievable label and is configured to be identifiable with a retrievable label (e.g., fluorophore-dUTP as per the 2.2.2 FISH probe synthesis section on p. 5). Regarding claim 8, Dubrowski discloses the above method, wherein the retrievable label is configured to bind a moiety selected from the group consisting of a protein, a peptide, a DNA sequence, an RNA sequence, and a carbohydrate (e.g., fluorophore-dUTP which can inherently be bound by a fluorophore-specific antibody). Regarding claim 12, Dubrowski discloses the above method, wherein the genome comprises a human genome (e.g., as per the 2.2.3 FISH staining on tissue sections on p. 6). Regarding claim 13, Dubrowski discloses the above method, wherein detecting occurs in a cell, and the method further comprising karyotyping the cell (e.g., as per the 2.2.3 FISH staining on tissue sections on p. 6). Regarding claim 14, Dubrowski discloses the above method, wherein detecting occurs in a cell, and the method further comprises detecting a chromosomal aberration in a cell (e.g., as per the 2.2.3 FISH staining on tissue sections on p. 6). Regarding claims 15-18, Dubrowski discloses the above method, wherein the contacting occurs within a human cell in human tissue (e.g., as per the 2.2.3 FISH staining on tissue sections on p. 6). Walter et al. Claims 1-18 are rejected under 35 U.S.C. 102(b) as being anticipated by Walter et al. (Cytogenet. Genome Res., 114:367–378 (2006) DOI: 10.1159/000094227). Regarding claim 1, Walter discloses a method comprising contacting a plurality of oligopaints to a target nucleic acid sequence (e.g., as per the Combinatorial labeling and wide-field epifluorescence microscopy in combination with image deconvolution section on p. 368), wherein contacted oligopaints form a barcode or combinatorial color sequence that enables reading of a high number of target nucleic acid sequences (e.g., as shown in Fig. 1). Regarding claim 2, Walter discloses the above method, wherein the target nucleic acid sequence comprises a DNA sequence or an RNA sequence (e.g., genomic DNA as per genomic DNA as per Fig. 1). Regarding claim 3, Walter discloses the above method, wherein the target nucleic acid sequence is an oligonucleotide (e.g., genomic DNA as per genomic DNA as per Fig. 1). Note that p. 10 of the specification states “[t]he principles of the present invention may be applied with particular advantage in methods of tagging (i.e., painting with chromosome paints) one or more oligonucleotide sequences, e.g., chromosome regions (e.g., sub-chromosomal regions) and/or one or more entire chromosomes”, which implies that target oligonucleotides can be chromosome or sub-chromosomal regions. Regarding claim 4, Walter discloses the above method, wherein the target nucleic acid sequence is linked to a protein (e.g., chromosomal DNA is linked to histones, etc.). Regarding claim 5, Walter discloses the above method, wherein the protein comprises an antibody (e.g., secondary labeling antibodies as per Table 2). Regarding claims 6-7, Walter discloses the above method, wherein the contacted oligonucleotide paints are in contact with a retrievable label and is configured to be identifiable with a retrievable label (e.g., secondary labeling antibodies as per Table 2). Regarding claim 8, Walter discloses the above method, wherein the retrievable label is configured to bind a moiety selected from the group consisting of a protein, a peptide, a DNA sequence, an RNA sequence, and a carbohydrate (e.g., secondary labeling antibodies as per Table 2). Regarding claim 9, Walter discloses the above method, wherein the protein, the peptide, the DNA sequence, the RNA sequence, and the carbohydrate are in a cell (e.g., secondary labeling antibodies as per Table 2). Regarding claim 10, Walter discloses the above method, wherein the high number of target nucleic sequences comprises at least one of 50 or more targets, 100 or more targets, 1000 or more targets, 10,000 or more targets (e.g., staining up to 63 chromosomes as per p. 371, right column and/or up to 127 staining patterns as per p. 368, right column). Regarding claim 11, Walter discloses the above method, wherein the high number of target nucleic acid sequences comprises a number of targets that encode 1-99% of a genome (e.g., as per Fig. 1). Regarding claim 12, Walter discloses the above method, wherein the genome comprises a human genome (e.g., Fig. 1-2). Regarding claim 13, Walter discloses the above method, wherein detecting occurs in a cell, and the method further comprising karyotyping the cell (e.g., karyotyping an interphase nucleus of an MCF-7 breast cancer cell as per Fig. 2B). Regarding claim 14, Walter discloses the above method, wherein detecting occurs in a cell, and the method further comprises detecting a chromosomal aberration in a cell (e.g., karyotyping an interphase nucleus of an MCF-7 breast cancer cell as per Fig. 2B). Regarding claims 15-16, Walter discloses the above method, wherein the contacting occurs within a human cell (e.g., karyotyping an interphase nucleus of an MCF-7 breast cancer cell as per Fig. 2B). Regarding claim 17, Walter discloses the above method, wherein detecting occurs in a biological tissue (e.g., tissue as per Fig. 2A). Regarding claim 18, Walter discloses the above method, wherein the biological tissue is human tissue (e.g., multicolor-FISH of human smooth muscle tissue in a paraffin section as per Fig. 2A). 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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b). U.S. 17/770,943 Claims 1-4, 6-8, and 10-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 264-265, 267-269, 271, 273-280, and 282 of copending Application No. 17/770,943 (the reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. U.S. 17/779,272 Claims 1-4, 6-8, and 10-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 56, 101, and 115 of copending Application No. 17/779,272 (the reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. U.S. 10,844,426 B2 Claims 1-4, 6-8, and 11-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 10,844,426 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent. U.S. 10,501,779 B2 Claims 1-4, 6-8, and 11-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 10,501,779 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEREMY FLINDERS whose telephone number is (571)270-1022. The examiner can normally be reached M-F 10-6:00 EST. 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, Heather Calamita can be reached on (571)272-2876. 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. /JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
Read full office action

Prosecution Timeline

Jan 31, 2023
Application Filed
May 18, 2023
Response after Non-Final Action
Feb 21, 2026
Non-Final Rejection — §102, §112, §DP (current)

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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
64%
Grant Probability
80%
With Interview (+15.2%)
3y 9m
Median Time to Grant
Low
PTA Risk
Based on 586 resolved cases by this examiner. Grant probability derived from career allow rate.

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