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 .
Claim Status and Formal Matters
This action is in response to papers filed 5/1/2026.
Claims 1, 9-10, 83-86 have been amended.
Claim 86 has been added by amendment.
Claims 1, 6, 9-10, 12, 14, 83-86 are being examined.
Applicant’s election without traverse of group 1, claims 1, 6, 9-10, 12, 14, 82 in the reply filed on 4/11/2024 is acknowledged.
Applicant elects "the barcodes encode spatial information". At least claims 1, 6, 9-10, 12, 14, and new claim 82 are readable on the elected species. For the species of "a barcode of the first or second nucleic acid", Applicant elects "the first nucleic acid is selected from a library having a minimum Hamming distance of 4". At least claims 1, 6, 9-10, 12, 14, and new claim 82 are readable on the elected species.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 41, 43, 44, 46, 48, 51, 53, 59, 63, 67, 69, 70, 74, and 80, withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/11/2024.
The prior objection to the specification has been withdrawn in view of arguments.
Priority
The instant application was filed 04/29/2021 and is a National Stage entry of PCT/US19/59484 with an International Filing Date: 11/01/2019 and claims priority from provisional application 62754450 , filed 11/01/2018.
Response to Amendment
The Declaration of Yin under 37 CFR 1.132 filed 5/1/2026 is sufficient to overcome the rejection of claims 1, 6, 9-10, 12, 14, 83-86 based upon 112(b).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/1/2026 is being considered by the examiner.
.
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, 6, 9-10, 12, 14, 83-86 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.
Claim 1 has been amended to recite, “1) a first nucleic acid barcode comprising a first barcode strand flanked by a first crosslinking strand and a first complementary strand, and (2) a second nucleic acid barcode comprising a second barcode strand flanked by a second crosslinking strand and a second complementary strand, wherein the first and second nucleic acid barcodes are each a separate single- stranded nucleic acid,.” The metes and bounds are unclear what is required, as the recitation of “first barcode strand,” “first crosslinking strand” and “a first complementary strand,” suggest the each is a separate strand. However, the amendment to recite, “wherein the first and second nucleic acid barcodes are each a separate single- stranded nucleic acid,” it is unclear if the limitation requires “first barcode strand,” “first crosslinking strand” and “a first complementary strand,” is a single strand nucleic acid or encompasses 3 different strands. The same issue relevant to the second nucleic acid barcode.
Claim 1 has further been amended to, “wherein the first and second barcode strands comprise first and second barcode domains, respectively, wherein each barcode domain is are a bit value.” The metes and bounds are unclear and confusing what is required of a first and second barcode domain and how it limits the first and second barcode strands, it is unclear where a domain begins or ends, etc.
Claim 1 has been amended to recite, “wherein the first and second barcode domains are selected from a barcode library having a minimum Hamming distance of 4 between each barcode domain.” The claim is confusing and unclear how the barcode library relates to the providing step as there is no requirement the first and second nucleic acids barcode are from a library. Further it is unclear if a minimum Hamming distance of 4 between each barcode domain limits only the barcode domain, the barcode strand, or both. Thus the metes and bounds are unclear.
Claim 1 has further been amended to recite, “(b} photocrosslinking (1) the first nucleic acid barcode to (2) the second acid barcode to produce thereby producing a concatemer of barcodes.” The metes and bounds are unclear as the claim has also been amended to recite, “herein the first and second crosslinking strands each comprise a photoreactive element, wherein the first complementary strand of the first nucleic acid barcode is complementary to and hybridizes to the second crosslinking strand of the second nucleic acid barcode, or wherein the first crosslinking strand of the first nucleic acid barcode is complementary to and hybridizes to the second complementary strand of the second nucleic acid barcode.” Thus in view of the amendment the metes and bounds are unclear as to what is being crosslinked in view the first 112 (b) rejection with respect to what is required of the first nucleic acid barcode to (2) the second acid barcode as (1) and (2) appear to define the first nucleic acid barcode to (2) the second acid barcode as three different nucleic acid strands. However the wherein clauses require, “wherein the first complementary strand of the first nucleic acid barcode is complementary to and hybridizes to the second crosslinking strand of the second nucleic acid barcode, or wherein the first crosslinking strand of the first nucleic acid barcode is complementary to and hybridizes to the second complementary strand of the second nucleic acid barcode.” Thus the metes and bounds are unclear.
Claim 83 has been amended to recite, “further comprising photocrosslinking to the first or second nucleic acid barcode at least one additional nucleic acid barcode that comprises a barcode strand flanked by a crosslinking strand and a complementary strand, wherein the crosslinking strand comprises a photoreactive element.” The metes and bounds are unclear what is required, as strand suggests separate nucleic acid strands or molecules. It is unclear if this recitation similar to claim 1 is intended to be a single nucleic acid molecule with 3 domains or 3 individual molecules.
Claim 86 has been added by amendment and recites, “a) the first nucleic acid barcode comprises a first barcode strand flanked by a first crosslinking strand and a first complementary strand; (b) the second nucleic acid barcode comprises a second barcode strand flanked by a second crosslinking strand and a second complementary
strand; (c) the third nucleic acid barcode comprises a third barcode strand flanked by a third crosslinking strand and a third complementary strand; (d) the first, second and third crosslinking strands each comprise a photoreactive element,” The metes and bounds are unclear if the first nucleic acid barcode, second nucleic acid barcode, and third nucleic acid barcode each require 3 different strands or 9 separate nucleic acid molecule or are intended to encompass a 3 molecules each comprising a barcode, a crosslinking domain and complementary domain. Further it is unclear what is being photocrosslinked.
Response to Arguments
The previous rejections have been withdrawn in view of the amendments.
These are new grounds of rejection necessitated by amendment.
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.
Claim(s) 1, 14, 83 -86 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee ( Nature Nanotechnology (2009) volume 4, pages 430-436), Bystrykh (PLOS one (2012) volume 7, issue 5 e36852) and Navarro (Bioinformatics, 33(16), 2017, 2591–2593)
As noted in the MPEP 2111.02, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Further, a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951). Accordingly, the claim language of "a method of writing or storing data” merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims.
The active steps of the claim are providing a first and second oligonucleotide each with a barcode and hybridization domains which comprise photoreactive element and photocrosslinking.
The specification teaches, “In some embodiments, the photoreactive element is a photoreactive Nucleotide” (0075), (00191).
The specification teaches in 0057 a preferred embodiment of a nucleic acid barcode, while 0058 teaches, “[00058] As used herein, the term "barcode domain" or "DNA data domain" refers to the part of the barcode strand that comprises a nucleic acid sequence that represents special information, an arbitrary value, or code. The barcode domain sequence can be predetermined by a barcode library. The barcode domain can be a sequence comprising DNA, RNA, synthetic nucleobases, or any combination thereof.”
Thus while the specification provides preferred embodiments of some of the limitations, the specification does not provide limiting definitions and thus are broad.
Further the claims have been amended to provide what the barcode is intended to represent in the wherein clause of the providing step, this does not provide for an active step or explicitly limit the active step.
This rejection is drawn to the interpretation claim 14 requires spatial information.
Lee teaches
PNG
media_image1.png
744
721
media_image1.png
Greyscale
Lee does not specifically teach barcodes. However, Lee teaches, “It is important to note that our ABC monomer system is designed to be modular. The built-in 'plug-and-play' feature coupled with its 'mix-and-match' flexibility makes the ABC monomer a versa- tile platform technology-any other functional groups, both organic and inorganic, that can be conjugated with DNA (or RNA) can be incorporated into the final nanoarchitectures. Thus, we anticipate that our ABC monomers will lead to many possibilities for creating more novel nanostructures and nanomaterials with multiple functionalities.” Further, Lee teaches the nucleic acids have sequences and thus represents the information of the sequence of the nucleic acid.
Therefore it would have been prima facie obvious to one of skill in the art prior to the effective filing date of the claims the art of Lee teachings encompass a first and second oligonucleotide comprising a complementary strand, barcode and crosslinking domain. The artisan would be motivated to recognize the sequence is data as the artisan recognizes the sequences were known as they were synthesize. The artisan would have a reasonable expectation of success as the artisan is merely recognizing the breadth of barcode.
Lee does not specifically teach spatial information, which is bit information
However, Navarro teaches the use of barcodes to provide spatial information (figure 1).
Bystrykh teaches, “Multiplex deep sequencing is a very powerful approach whenever relatively small DNA fragments should be sequenced within a big number of samples. Instead of analyzing those samples one at a time, DNA samples can be mixed together and sequenced in one run using modern high throughput sequencing machines. This approach requires specific sequence tags that allow finding and identifying the address of any sequence in the mixture and assigning it back to the original sample” (page 1, 1st column top)
Bystrykh teaches, “Every tag design relies on the simple combinatorial rule that,
with a given number of bases q and defined length of the sequence d, the total number of combinations is q. This predetermines a minimal required length of the tag and generates enough barcoded primers for all samples. The difference in approaches resides in the way of selecting barcodes out of all possible combinations. A literature search revealed a great diversity of selection approaches. The first DNA barcodes were probably designed by random selection, for instance by Bonaldo et al. [3]. Later the problem was dealt with by introducing thorough selection principles out of all possible sequences of a given length [4–6]. In some cases, unfortunately, selection principles were not revealed [7–9]. Commercially available barcoded primers from Illumina (https://icom.illumina.com/download/summary/ ATZRuMiBPkukcRQOJ792Xg) and Epicentre (http://www. epibio.com/pdftechlit/312pl1110.pdf) belong to this group as well. Finally, some proportion of designs (not all of them were aimed at barcodes generation) used not only well defined strategies for the selection of DNA oligonucleotides, but also used elements of coding theory [10–15]. All those designs appeared several decades after the pioneering works of Shannon [16], Hamming [17], Reed and Solomon [18] and Levenshtein [19], who established the basics of the coding principles as well as correction of errors in corresponding code words. Considering such a variety of approaches, using coding principles or not, one can argue that since code-containing and code –free barcodes are equally popular, it proves that coding theory is not strictly required for such barcode designs. This is partially true: an invariant property of the DNA barcodes is not a coding principle, but sequence difference between those barcodes. Measures of such differences are known in coding theory as either Hamming or Levenshtein distance, and it is a built-in component of error-correcting codes. In the case of code-free designs, this distance must be achieved using an alignment algorithm and by counting mismatches. Although minimal distance can be achieved by various restrictive algorithms or by simple hand-picking, one is never sure that the best solution has been found. An analysis by alignment is computationally intense, and it often requires custom scripts especially for analysis of short tags. As I will demonstrate here, the benefit of using coding theory is that one can achieve a better result with less computational effort. As a bonus it will retain the benefit of error detection and correction without use of alignment. Considering constraints of size and the subject area, I will focus on linear codes, based mostly on the design of Hamming [17], while not discussing edit-metric codes. This paper aims to provide relatively easy and ready-made examples, to be used by molecular biologists whenever they need to select their own list of tags suited to their application in order to achieve the best possible result. “(page 1, 2nd column-page 2). Bystrykh teaches, “Therefore, in order to correct one or more substitution errors the Hamming distance should be 3 or higher.”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use barcode domains with a hamming distance of at least 4 with spatial information which has been assigned an independent value which identifies the value or barcode in a barcode library.. The artisan would be motivated to use spatial barcode domains with a hamming distance of at least 4 to provide information with respect to the location of nucleic acids with little or no ambiguity. The artisan would have a reasonable expectation of success as the artisan is merely using known barcodes in known methods.
Bystrykh teaches, “This coding system is unique in its compactness regarding numbers of possible tags generated with a minimal distance of 3 and higher as well as for its algorithm that corrects substitution errors. Briefly, a Hamming code is a binary code constructed from data bits interrupted by parity bits at every 2n position. Parity bits are used for checksum function over different subsets of the data bits, allowing the identification of substitution errors [17]. Hamming used a rather elaborate checksum scheme: the 1st parity bit checks every odd position of the code word starting from the 1st position, the second parity bit checks consecutive pairs of bits starting with the 2nd position and interval of 2 bits, the 3rd bit will check 4 bits in a row starting from position 4 and interval 4, and so on. The whole reason for this system is to have simple error detection algorithm that operates in a binary code only. The classic version of the Hamming code has a length of 7 bits composed of 4 data and 3 parity bits, denoted as Hamming(7,4) code. In a context of DNA coding we might need a binary code with an even number of bits. For this case Hamming suggested adding extra parity position at the end of the code word to check all bits in the word. From this perspective the Hamming(7,4) code can be extended to Hamming(8,4), consequently Hamming(15,11) will be extended to the Hamming(16,11) code. Details of the code design are provided in the Supplementary File S1) (page 2, 2nd column).
With regards to claims 9-10, Lee teaches the first and second nucleic acid in a predestined polymeric sphere and attached to the slide as they are attached in
With regards to claim 83, 86 the Lee teaches 3 or more concatemerized.
With regards to claim 84, Therefore it would have been prima facie obvious to one of skill in the art prior to the effective filing date of the claims the art of Lee teachings encompass a first and second oligonucleotide comprising a complementary strand, barcode and crosslinking domain in order. The artisan would be motivated to recognize the sequence is data (barcodes) in the middle to allow for hybridization to other domains. The artisan would have a reasonable expectation of success as the artisan is merely recognizing the breadth of barcode.
With regards to claim 85, Lee does not specifically teach the length of the barcode, crosslinking strand and complementary strand.
However it would have been prima facie obvious to one of skill in the art prior to the effective filing date of the claims to use more than 5 nucleotides for barcode, crosslink and hybridization strands. The artisan would be motivated to provide 5 or more nucleotides in each to allow sufficient length to allow strong and specific hybridization. The artisan would have a reasonable expectation of success as the artisan is merely using art accepted methods of designing nucleic acids for hybridization.
Response to Arguments
The response traverses the rejection asserting claim 6 was not rejected over the art and has been amended into the independent claim. This argument has been thoroughly reviewed but is not considered persuasive as claim 1 has been amended to recite, “wherein the first and second barcode domains are selected from a barcode library having a minimum Hamming distance of 4 between each barcode domain.” This has a different scope than claim 6 reciting, “wherein the first and second barcode
The response further traverses the rejection of claim 84, asserting the rejection does not apply specific rationale. This argument has been thoroughly reviewed but is not considered persuasive as the rejection states, “The artisan would be motivated to recognize the sequence is data (barcodes) in the middle to allow for hybridization to other domains.” Further, the claim as amended provides the name of each nucleic acid barcode and provides names for different portions of the barcodes and provides an order to the nucleic acid barcodes. It does not define any specific structure, other than implicated by the functional language of the independent claim.
Thus the rejection as amended is maintained.
Summary
No claims are allowed.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday 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, Anne Gussow can be reached at (571)272-6047. 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.
/Steven Pohnert/Primary Examiner, Art Unit 1683
Prosecution Insights