Prosecution Insights
Last updated: April 18, 2026
Application No. 18/279,778

COMPOSITIONS AND METHODS FOR TRACING CELL NETWORKS

Non-Final OA §103§112
Filed
Aug 31, 2023
Examiner
ALAM, DANYAL HASSAN
Art Unit
1672
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The Brigham And Women`S Hospital Inc.
OA Round
1 (Non-Final)
100%
Grant Probability
Favorable
1-2
OA Rounds
3y 2m
To Grant
0%
With Interview

Examiner Intelligence

Grants 100% — above average
100%
Career Allow Rate
1 granted / 1 resolved
+40.0% vs TC avg
Minimal -100% lift
Without
With
+-100.0%
Interview Lift
resolved cases with interview
Typical timeline
3y 2m
Avg Prosecution
21 currently pending
Career history
22
Total Applications
across all art units

Statute-Specific Performance

§101
9.1%
-30.9% vs TC avg
§103
43.9%
+3.9% vs TC avg
§102
10.6%
-29.4% vs TC avg
§112
30.3%
-9.7% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1 resolved cases

Office Action

§103 §112
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. Election/Restrictions Applicant's election without traverse of c laims 1-4,6-7,10,12-13,15-16,19,22,24-25 and 32-36 in the reply filed on 01/30/2026 is acknowledged. Claims 13, 15-16, 19, 22, 24-25 , and 32-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/05/2026 . Claims 1-4, 6-7, 10 , and 12 are under examination. Priority This is a National Stage Entry under 35 U.S.C. 371 of International Patent Application No. PCT/ US202 2 / 018296 , filed March 01 , 2022 . This application also claims priority to US Provisional Application No. 63155067 , filed on March 0 1, 202 1 . 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 appl icant regards as his invention. Claim 6 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. The term “ about ” in claim 6 is a relative term which renders the claim indefinite. The term “ about ” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claim 6 recites “about 15 to about 38 nucleotides long” Claim Rejections - 35 USC § 103 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. Claims 1-4, 6-7, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over McCarroll et al ( WO2020092797A1 , hereinafter, “ McCarroll ”), and in view of Suzuki et al ( Front. Neural Circuits, 2022 , hereinafter, “ Suzuki ”). McCarroll teaches a method tracing neuronal networks using the synapse specific spread of a Rabies Virus (RV) (¶0008). McCarroll teaches a rabies virus encoding a polynucleotide encoding a foreign envelope protein ( pseudotyped rabies virus has envelope gene from another species; ¶0064); and a polynucleotide encoding: a fluorescent protein (rabies virus has fluorescent protein; ¶0094); a barcode sequence flanked by a first common sequence and a second common sequence (barcode sequence fixed to flanking sequences; ¶ 0153; figure 1B); a 3' poly(A) tail (poly(A) signal sequence; ¶ 0019, 0 059; Figure 1B); and a does not encode a functional G protein (glycoprotein (G)-deleted Rabies Virus; ¶0068). McCarroll teaches this virus can e used to specifically delineate neural circuits (¶0108). Regarding claim 1, McCarroll teaches a fluorescent protein, a barcode sequence flanked by common sequences, and a 3’ poly(A) tail and a does not encode a functional G protein ( ¶0094 , 0153, 0019, 0059, 0068 Figure 1B ) . Regarding claim 4, McCarroll teaches a fluorescent protein can be a red, blue, or yellow fluorescent protein (Claim 7). Regarding claim s 6 , 7, and 10 , McCarroll teaches the barcode sequence can be 20 nucleotides long which can be comprised of two sequences of 10 bp each which can be repeats (¶0019, Figure 1B). Furthermore, McCarroll teaches that the two 10bp barcode sequences can be separated by a restriction site region (¶0019, Figure 1B). McCarroll does not teach a foreign virus envelope protein. However, Suzuki teaches an RV which does not encode a functional G protein that is pseudo typed with a foreign envelope EnvA protein (Abstract). This EnvA protein is an avian sarcoma leukosis virus derived protein (Introduction ¶2). Suzuki further teaches, the use of this virus to trace cells by including a fluorescent protein (Figure 1). Regarding claims 2 and 3 , Suzuki teaches the use of avian sarcoma leukosis virus, which is a type of retrovirus, EnvA protein to pseudotype the RV (Introduction ¶2, Figure 1). McCarroll and Suzuki are considered to be analogous to the claim invention because they both aim to label cells using RV . McCarroll teaches a method of using a method tracing neuronal networks using the synapse specific spread of a Rabies Virus (RV) (¶0008). This RV encodes a fluorescent protein as well as a barcode sequence flanked by common sequences and a 3’ poly(A) tail and a does not encode a functional G protein ( ¶0094 , 0153, 0019, 0059, 0068 Figure 1B ) . Suzuki teaches the use of a ASLV envelope protein to pse u dotype the RV (Introduction ¶2, Figure 1). Together , the prior art teaches that ASLV EnvA pseudotyped RV can be used to label cells . Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to have a ASLV EnvA pseudotyped RV encoding a fluorescent protein as well as a barcode sequence flanked by common sequences and a 3’ poly(A) tail and not encode a functional G protein because doing so would enable a tight selection of cells, thereby enabling the mapping of distinct cellular connectomes . One of ordinary skill in the art would have had a reasonable expectation of success in creating a ASLV EnvA pseudotyped RV encoding a fluorescent protein as well as a barcode sequence flanked by common sequences and a 3’ poly(A) tail and not encode a functional G protein given that EnvA from E. coli has been used to pseudotype RV before and that using a virus based EnvA is well known, has been successfully demonstrated, and commonly used in the prior art. Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary. Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over McCarroll and Suzuki as applied to claim s 1-4, 6-7, and 10 above, and further in view of David s son et al ( Scientific reports , 2016 , hereinafter, “ Davidsson ”) , Kebschull et al ( Neuron , 20 16 , hereinafter, “ Kebschull ”) and Kebschull et al ( Nature methods , 20 1 8, hereinafter, “ Kebschull 2 ”) . As discussed above, c laims 1-4, 6-7, and 10 were rendered prima facie obvious by McCarroll and Suzuki. While t he reference s teach a barcode to track cells, the references fail to teach a barcode comprised of VHDBVHDBATVHDBVHDBATVHDBVHDB (SEQ ID NO: 1) . However, Davidsson teaches a method of generating viral vector s with embedded barcoding to enable cell labeling (Abstract). Davidsson teaches barcodes within viral vectors can be designed with a “ VHDB ” nucleotide sequence that is repeated five times to avoid homopolymer sequences which allows for high diversi ty while reducing sequencing errors such as insertion/deletion errors (Section: Barcode Characterization). It is noted that SEQ ID NO: 1 is: VHDB VHDB AT VHDB VHDB AT VHDB VHDB Kebschull teaches a high throughput method for mapping single neuron projections using barcoded RNA (Summary) . Kebschull teaches that by using a virus with barcoded RNA, they were able to identify individual cells with high fidelity (Section: Using RNA to Trace Neurons). Kebschull teaches, the “advantage of using barcodes is that their diversity grows exponentially with the length of the sequence, overcoming the limited diversity ” and that the amount of “ unique barcode identifiers is effectively infinite; even a 30-nt sequence has a potential diversity of 4 30 ≈10 18 barcodes, far surpassing the ∼ 10 8 neurons in the mouse brain ” (Introduction ¶ 5). It is noted that SEQ ID NO: 1 VHDBVHDBATVHDBVHDBATVHDBVHDB is comprised of one additional VHDB motif and 4 additional nucleotides compared to the teachings of Davidsson which would result in a 10 2 increase in the amount of unique barcode identifiers and therefore increasing the likelihood that each neuron would have an individual barcode . Kebschull 2 teaches the use and history of cellular barcoding for spatiotemporal tracking (Abstract). Kebschull 2 teaches that barcodes can be random sequences but can also be composed of semi-random nucleic acid sequences, where some positions are constrained to one or more specific nucleotides , which would include A and T (Section: Labeling cells with nucleic acid sequences , Figure 2 ). It is noted that SEQ ID NO: 1 is: VHDBVHDB AT VHDBVHDB AT VHDBVHDB . McCarroll , Suzuki, Davidsson , Kebschull , and Kebschull 2 are considered to be analogous to the claim invention because they aim to label cells . McCarroll teaches a method of using a method tracing neuronal networks using the synapse specific spread of a Rabies Virus (RV) (¶0008). This RV encodes a fluorescent protein as well as a barcode sequence flanked by common sequences and a 3’ poly(A) tail and a does not encode a functional G protein ( ¶0094 , 0153, 0019, 0059, 0068 Figure 1B ) . Suzuki teaches the use of a ASLV envelope protein to psuedotype the RV (Introduction ¶2, Figure 1). Davidsson teaches that a cell labeling barcode can be composed of repeats of VHDB to lesson errors (Section: Barcode Characterization). Kebschull teaches that increasing the length of the barcode allows for the labeling of more cells (Introduction ¶ 5). Kebschull 2 teaches that the barcode can have positions constrained to specific nucleotides, resulting in a semi-random barcode (Section: Labeling cells with nucleic acid sequences, Figure 2 ). Together , the prior art teaches that ASLV EnvA pseudotyped RV can encode barcodes that are comprised of VHDB repeats and with nucleotide locked positions such as A and T Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to use a EnvA pseudotyped RV, as taught by McCarroll and Suzuki, encoding a VHDB repeat with nucleotide locked position, as taught by Davidsson , Kebschull , and Kebschull 2, because doing so would enable fewer sequencing errors and easier downstream bioinformatic identification, thereby increasing the chance of cell characterization. One of ordinary skill in the art would have had a reasonable expectation of success in creating a semi random barcode comprised of VHDB repeats with locked nucleotide spacers in conjunction with a RV delivery scheme given that use of at least 5 VHDB repeats, increased length, and nucleotide locked spacers is well known, has been successfully demonstrated, and commonly used in the prior art. Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary. Conclusion NO CLAIMS ARE ALLOWED Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Danyal H Alam whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-1102 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M - F 9am - 5pm . 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, FILLIN "SPE Name?" \* MERGEFORMAT Thomas J. Visone can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-270-0684 . 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. /DANYAL HASSAN ALAM/ Examiner, Art Unit 1672 /THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
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Prosecution Timeline

Aug 31, 2023
Application Filed
Apr 01, 2026
Non-Final Rejection — §103, §112 (current)

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Prosecution Projections

1-2
Expected OA Rounds
100%
Grant Probability
0%
With Interview (-100.0%)
3y 2m
Median Time to Grant
Low
PTA Risk
Based on 1 resolved cases by this examiner. Grant probability derived from career allow rate.

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