DETAILED ACTION
Applicant is notified that the examiner for this action has changed.
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 claims 9-12 in the reply filed on 6 May 2026 is acknowledged.
Claims 1- withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 6 May 2026.
Information Disclosure Statement
The information disclosure statement (IDS) filed 11 December 2023 is considered, initialed, and attached hereto.
Preliminary Amendment and Claim Status
Applicant filed a preliminary amendment on 11 April 2024, in which claim 6 was canceled and claims 11-12 were amended. Applicant subsequently filed a substitute specification on 24 April 2024, which included the original version of the claims (i.e., including claim 6 and the previous versions of claims 11-12). This Office Action is based on the amended claims filed 11 April 2024 (i.e., original claims 1-5 and 7-10, and amended claims 11-12).
Claim 6 is canceled.
Claims 1-5 and 7-12 are pending.
Claims 1-5 and 7-8 are withdrawn.
Claims 9-12 are under examination.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2). No petition for acceptance of color drawings has been received.
Claim Objections
Claims 9 and 11-12 are objected to because of the following informalities:
Claim 9 in lines 2-3 and line 5 recites “nanopore detectable barcode” and claims 10 and 11 in lines 1-2 of each recite “nanopore-detectable barcode”. Both “nanopore detectable barcode” and “nanopore-detectable barcode” are interpreted as referring to the same limitation, a single spelling should be used consistently for all instances referring to this limitation.
Claim 9 in lines 2, 4, and 5 recites “a. Contacting”, “b. Isolating”, and “c. Detecting”, respectively. MPEP §608.01(m) states: “Each claim begins with a capital letter and ends with a period”. Applicant is suggested to use the lower-case letter instead of the capital letter and to replace the period used to distinguish the steps with another marker such as (a) or a).
Appropriate correction is required.
Claim Interpretation
The instant specification provides a limiting definition for the “nanopore detectable barcode” recited claims 9 and 11-12. Paragraph [0048] recites: “Nanopore-detectable barcode” or “Nanopore-detectable modified nucleotide polymer” as used interchangeably herein, refers to a complete structure of Formula(I), which is capable of being positioned in, captured by, translocated through, and/or traverse a nanopore and thereby result in a detectable change in current through the nanopore. In paragraph [0056], the instant specification recites “a modified nucleotide polymer structure of formula (I):
PNG
media_image1.png
44
119
media_image1.png
Greyscale
wherein, B is a bulky structure; R is a reporter unit, and the superscript i is the reporter unit identifier; X is a spacer unit, and the portion of the polymer comprising B, R, and X, is a barcode unit; n is the number of barcode units, and n is from 2 to 8; and Y is a tail unit comprising 20 to 100 monomer units”. Within the limiting definition of “nanopore detectable barcode”, the recitation of a “bulky structure” has a limiting definition in paragraph [0040] of the instant specification: ““Bulky structure” as used herein refers to a moiety having a structure that is unable to pass through a nanopore. The inability of the bulky structure to pass through a nanopore can be permanent or it can be transient”. Within the limiting definition of “nanopore detectable barcode”, the recitation of a “reporter unit” has a limiting definition in paragraph [0039] of the instant specification: ““Reporter unit” as used herein refers to a portion of a modified nucleotide polymer that includes from 4 to 10 nucleotides or from 4 to 25 nucleotide analogs (or other monomer units) and produces a detectable current level and/or dwell time upon entering, residing in, and/or translocating a nanopore under an applied voltage potential” (emphasis added). Due to the open nature of the word ‘includes’, the broadest reasonable interpretation of reporter unit encompasses portions of a modified nucleotide polymer with >10 nucleotides or >25 nucleotide analogs or other monomer units so long as it includes 4+ nucleotides, 4+ nucleotide analogs, or 4+ of other monomer units. “Spacer unit” does not have a limiting definition in the specification, so the spacer unit of a nanopore detectable barcode it is given a broadest reasonable interpretation encompassing any portion of a nucleotide polymer that is between a reporter unit of one barcode unit and the next barcode unit.
Therefore, the broadest reasonable interpretation of “nanopore detectable barcode” as limited by the specification is a nucleotide polymer of formula (I) as recited in [0056] wherein the bulky structures are either permanently or transiently unable to pass through a nanopore and the reporter units include 4+ nucleotides, 4+ nucleotide analogs, or 4+ of other monomer units.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Akeson et al. (US 2002/0142344, published 3 October 2002), herein Akeson.
Regarding claim 9, Akeson teaches a method of detecting an analyte in a sample (“the subject methods of analyte detection” [0063]), comprising the steps of: (a) contacting the sample with a specific binding protein comprising a barcode to produce an analyte-binding protein complex (“the first step is to contact the sample suspected of comprising the analyte of interest with a targeted molecular bar code having a specific binding pair member specific for the analyte of interest” [0063]; “The subject targeted molecular bar codes include a molecular bar code stably associated with, e.g. covalently attached, typically through a linking group, to a member of a specific binding pair (see FIG. 1)” [0035]; FIG. 1; “the specific binding pair member of the targeted molecular bar code may be a ligand or receptor, an antibody or binding fragment thereof” [0059] because the receptor or antibody are proteins and are options for the specific binding pair member of the targeted molecular bar code, the targeted molecular barcode is equivalent to a specific binding protein comprising a barcode); (b) isolating the analyte-binding protein complex (“Following complex formation, any unbound targeted molecular bar code is separated from the analyte/targeted molecular bar code complexes, i.e. the bound targeted molecular bar codes” [0065]); (c) detecting the barcode using a nanopore (“Following separation of the targeted molecular bar code/analyte complexes from the unbound or free targeted molecular bar codes, as well as any other sample constituents, the molecular bar code of the analyte/targeted molecular bar code complex is separated from the remainder of the complex […] This cleavage step results in the production of a cleavage product mixture comprising free molecular bar code and analyte/specific binding member complex” [0066]; “Following the production of the cleavage product mixture, the free molecular bar codes present therein, if any, are detected and related to the presence of the analyte(s) of interest in the sample” [0067]; “A particularly preferred means of detecting the molecular bar code is to translocate the molecular bar code through a nanopore under the influence of an applied electric field and observe the effect over time of the translocation on a measurable signal” [0068]).
However, in this method recited by Akeson, the molecular bar code does not meet all of the limitations of the claimed nanopore detectable barcode as limited by paragraphs [0048, 0056, 0039, and 0040] of the instant specification (see Claim Interpretation section above). This deficiency is made up for by combining various options taught by Akeson regarding the molecular bar code to obtain their respective advantages.
Akeson teaches that the molecular bar code is made of at least 2 blocks (“In many embodiments of interest, the molecular bar code is a block copolymer in which a plurality of blocks are covalently bonded to each other in sequential fashion. By plurality of blocks is meant at least 2” [0042]); the blocks are of the structure
PNG
media_image2.png
170
358
media_image2.png
Greyscale
wherein m is 10 to 80 and the structure encompasses ribonucleotides and deoxyribonucleotides (see [0046-0052]) and example blocks include oligonucleotides (see [0053]); and that hairpins (a bulky structure) can be introduced adjacent to encoding sections of the molecular bar code to allow the bar codes to be distinguished unambiguously with high sensitivity and to improve signal-to-noise ratio ([0055]; “introduction of a hairpin into a synthetic DNA strand provides an unambiguous means to distinguish between two `bar code` populations at high sensitivity based on residence time in the nanopore” [0123]; “The base pairing structure also acts as a built-in pause to provide a better signal-to-noise ratio for distinct portions of an encoded polymer” [0124]). See also FIG. 14 including a 5’ hairpin bulky structure, followed by an abasic region (20 nucleotides by counting the black squares) equivalent to the reporter unit of 4+ nucleotides and a spacer unit, and at the 3’ having 20 C nucleotides equivalent to the tail unit of 20 to 100 monomer units. Therefore, it would be obvious to one of ordinary skill in the art to use in the above method a targeted molecular barcode as modeled in FIG. 14 would be expanded to include 2+ blocks of encoding polymer equivalent to the reporter and spacer units, each adjacent to hairpins that are bulky structures for improving the detection of the encoding polymer, and with the 20 C nucleotide tail, which is equivalent to the claimed nanopore detectable barcode as limited by the instant specification.
Regarding claim 10, Akeson teaches the method of claim 9 (see 35 U.S.C. 103 rejection of claim 9 above) wherein the specific binding protein is an antibody (“the specific binding pair member of the targeted molecular bar code may be […] an antibody” [0059]).
Therefore, the invention as a whole of claims 9-10 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Akeson et al. (US 2002/0142344, published 3 October 2002), herein Akeson as applied to claims 9-10 above, and further in view of Gong et al. (“Simple Method To Prepare Oligonucleotide-Conjugated Antibodies and Its Application in Multiplex Protein Detection in Single Cells” Bioconj Chem 27(1), pages 217-225 (2015)), herein Gong.
Regarding claim 11, Akeson teaches the method of claim 9 (see 35 U.S.C. 103 rejection of claim 9 above). However, Akeson does not teach that the nanopore detectable barcode is attached to the specific binding protein using click chemistry. This deficiency is made up for in the teachings of Gong.
Regarding claim 11, Gong teaches that many methods for conjugating oligonucleotides (such as the molecular bar code of Akeson, equivalent to the claimed nanopore detectable barcode) to binding proteins such as antibodies are labor intensive or costly (“However, these methods are either too labor intensive or too costly, and are not suitable for large-scale production of oligonucleotide-conjugated antibodies” page 217 right column paragraph 2), which can be improved by using click chemistry to more simply and cheaply conjugate oligonucleotides to antibodies (“The SPAAC-based conjugation method is simple and cost-effective and is well-suited for the preparation of oligonucleotide-conjugated antibodies” page 219 left column paragraph 1).
Regarding claim 12, Akeson teaches the method of claim 10 (see 35 U.S.C. rejection of claim 10 above) and Gong teaches using click chemistry to conjugate oligonucleotides to binding proteins such as antibodies (see 35 U.S.C. 103 rejection of claim 11 above).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to perform the simple substitution of using click chemistry to conjugate an oligonucleotide to an antibody as taught by Gong for the covalent attachment of the molecular bar code of the targeted molecular bar code to the member of a specific binding pair of the method of Akeson (MPEP §2143 I. B.). One of ordinary skill in the art would also be motivated to perform this substitution because Gong teaches that the click chemistry method of conjugation has the advantage of being simple and cheaper than comparable methods (MPEP §2143 I. G.). Importantly, to maintain the predictable functioning of the method of Akeson, this substitution is merely for the bonding of the molecular bar code to the member of a specific binding pair and does not replace the cleavable site of the targeted molecular bar code. As an example, the recited restriction site option of a cleavable linker recited in [0058] of Akeson would be part of the molecular bar code and linked to the member of a specific binding pair via the click chemistry reaction taught by Gong. Therefore, the invention as a whole of claims 11-12 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 9-12 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 9-12 of prior U.S. Patent No. 11,041,845, herein ‘845. This is a statutory double patenting rejection.
Instant claims 9-12 recite identical language to claims 9-12, respectively, of ‘845 except that instant claim 9 does not recite the limitation “wherein the nanopore detectable barcode comprises a modified nucleic acid polymer comprising at least two bulky structures, and wherein each bulky structure is adjacent to a reporter sequence” of claim 9 of ‘845. However, in col 5 lines 31-33 of ‘845, a limiting definition of “nanopore detectable barcode” as being a structure of formula (I), which is given on col 6 lines 43-52 as having 2-8 barcode units comprising a bulky structure shown adjacent to a reporter sequence. Therefore, the quoted limitation of claim 9 of ‘845 above falls entirely within the limiting definition of “nanopore detectable barcode” in the specification of ‘845 and does not change the scope of the claim. As the specification of ‘845 and the instant specification provide identical limiting definitions of “nanopore detectable barcode”, instant claims 9-12 and claims 9-12 of ‘845 have identical scope. Therefore, claims 9-12 are rejected for statutory double patenting with claims 9-12, respectively, of ‘845.
Conclusion
Claims 9-12 are rejected. Claims 1-5 and 7-8 are withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jeffrey Lawrence Bellah whose telephone number is (571)272-1024. The examiner can normally be reached M-Th, 7:30-5 ET.
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.
/JEFFREY BELLAH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
Prosecution Insights