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 .
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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 7/31/2026 has been entered.
Status of Claims
Claims 6-13, 15-17, 19-20 and 23-26 are pending. Claim 7 is rejoined. Claims 8 is withdrawn. Claims 6-7, 9-13, 15-17, 19-20 and 23-26 are currently under examination.
Election/Restrictions
In view of the prior art search the species of “an uncharged DNA” is rejoined for prosecution. In view of the withdrawal of the species “an uncharged DNA”, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Withdrawn Objections
The objection to the Specification is hereby withdrawn. The sequence filed 08/03/2026 which contains no error found.
In view of the amendments, the 35 U.S.C. 102(a)(1) over claim 26 under Leonidova is hereby withdrawn.
In view of the amendments, the 35 U.S.C. 102(a)(1) over claim 26 under Lohse is hereby withdrawn.
In view of the arguments, the 35 U.S.C. 103 rejection over Rogers is hereby withdrawn.
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 6-7, 9-13, 15-17, 19-20 and 23-26 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 6 recites the limitation of ‘Linker’ optionally having one or more heteroatoms selected from O, N, S and further recites the limitation of wherein ‘Linker’ includes one or more photocleavable groups are unclear to the metes and bounds of what is required in the claimed Linker, as the photocleavable groups contain O, N, S heteroatoms. Even though the claim recites the wherein clauses, it is unclear whether the wherein clause is required within the Linker or optional, as recited in the claim. Also, the claim is unclear to the relationship between the hydrocarbon chain of the Linker and the rest of the limitation to the linker. Because the cleavable groups require O, N, S heteroatoms, the claim is unclear to whether the elements are separate Linkers or they are one linking group? Claims 9-13, 15-17, 19-20, 24-25 are rejected as being dependent on claim 6.
Claim 23 recites the limitation of ‘Linker’ optionally having one or more heteroatoms selected from O, N, S and further recites the limitation of wherein ‘Linker’ includes at least one chemically cleavable group are unclear to the metes and bounds of what is required in the claimed Linker, as the cleavable groups contain O, N, S heteroatoms. Even though the claim recites the wherein clauses, it is unclear whether the wherein clause is required within the Linker or optional, as recited in the claim. Also, the claim is unclear to the relationship between the hydrocarbon chain of the Linker and the rest of the limitation to the linker. Because the cleavable groups require O, N, S heteroatoms, the claim is unclear to whether the elements are separate Linkers or they are one linking group?
Claim 26 recites the limitation of ‘Linker’ optionally having one or more heteroatoms selected from O, N, S and “A and B” are optionally having one or more O, N, S, heteroatoms, but further recites the limitation of wherein A or B includes at least S-S bond are unclear to the metes and bounds of what is required in the claimed Linker, as the S-S group contains at least S heteroatoms. Even though the claim recites the wherein clauses, it is unclear whether the wherein clause is required within the Linker or optional, as recited in the claim. Also, the claim is unclear to the relationship between the hydrocarbon chain of the Linker and the rest of the limitation to the linker. Because the S-S group require S heteroatoms, the claim is unclear to whether the elements are separate Linkers or they are one linking group?
Additionally, claims 6, 23 and 26 recite an open-ended recitation of “A conjugate having the structure of Formula (I)” but Formula (I) contains Y and X, which are only zero by z and m. Because m and z are only zero integers without other integers and the preamble recites “a conjugate having”, the claim is unclear to why the formula requires Y and X in the chemical structure. Also, because n is represented from 1 to 12, it is unclear to the chemical conjugation when n is between 2-12.
Furthermore, claims 6-7, 23 and 26 recite “uncharged DNA sequence” is unclear to the structure limitation of what is an uncharged DNA sequence. PNA mimics DNA without the backbone, but it is not considered DNA. The claims are unclear because the person would not recognize the phrase “DNA” without the structure of the charged backbone. The phrase “uncharged DNA” requires an absent backbone, which produces unattached single bases (i.e. individual bases that are separated). Therefore, it is unclear to what is the general structure representing uncharged DNA?
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.
Claim 23 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Leonidova et al. (“In vivo demonstration of an active tumor pretargeting approach with peptide nucleic acid bioconjugates as complementary system”, Chem. Sci., 2015, vol. 6, pgs. 5601-5616, of record 892 dated 12/18/2025), as evidenced by Bollu et al. (“Cleavable Amide Bond: Mechanistic Insight into Cleavable 4‑Aminopyrazolyloxy Acetamide at Low pH”, J. Org. Chem. 2019, vol. 84, pgs. 5596-5602, of record 892 dated 12/18/2025).
Leonidova teaches a highly specific antibody-PNA conjugate has sufficient time to target a tumor (see abstract). Scheme 1D shows the claimed conjugate having Formula I.
PNG
media_image1.png
354
972
media_image1.png
Greyscale
Scheme 1D shows an antibody conjugated to a linker having (spacer)2 wherein the spacer is –NH(CH2)2O(CH2)2OCH2CO–, which would read on the claimed Formula IIIa (e.g., PEG, also see Table 1). Scheme 1D shows amide bonds as part of the linker. The evidentiary teachings of Bollu et al. indicate the cleavage of amide bonds under mild acidic conditions (see abstract and Fig. 1). Fig. 1 also shows that when a mild H+ was added the cyclic amide was cleaved. Similarly, the linker of Leonidova contains a cyclic amide and other amide groups, which would read on the structure of a linker includes an acid sensitive group. Note that the phrase sensitive includes any sensitivity to acid and the phrase “acid-sensitive groups” have not been defined in the specification.
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 6-7, 9-13, 15-16, 19-20 and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Agasti et al. (“Photocleavable DNA Barcode−Antibody Conjugates Allow Sensitive and Multiplexed Protein Analysis in Single Cells”, J. Am. Chem. Soc., 2012, vol. 134, pgs. 18499-18502, published 10/23/2012) in view of Lieber et al. (US20220146714A1, published 10/10/2002), as evidenced by Bollu et al. (“Cleavable Amide Bond: Mechanistic Insight into Cleavable 4‑Aminopyrazolyloxy Acetamide at Low pH”, J. Org. Chem. 2019, vol. 84, pgs. 5596-5602, of record 892 dated 12/18/2025).
With respect to claims 6-7, 12 and 23, Agasti teaches DNA barcoding is an attractive technology, as it allows sensitive and multiplexed target analysis and a photocleavable DNA barcode-antibody conjugate method for rapid, quantitative and multiplexed detection of proteins in single live cancer cells (abstract). Agasti teaches the structure of the antibody-DNA conjugate in Scheme 2 (see below).
PNG
media_image2.png
433
604
media_image2.png
Greyscale
The final structure of the conjugate reads on Formula (I) wherein antibody-DNA wherein the Linker is a carbon chain with formula IIIa wherein Q is a bond and Linker includes an arylmethyl or O-nitobenzyl photocleavable group.
However, Agasti does not teach PNA or uncharged DNA sequence (claim 6) and PNA or single stranded uncharged DNA sequence (claim 23).
Lieber teaches multiplexed detection with DNA (see abstract). Lieber teaches PNAs have shown great potential for use as probes to study base mismatches in DNA as PNAs bind to dsDNA with high affinity, stability, and single base specific and PNA is a DNA mimic in which the negatively charged sugar backbone of DNA is replaced with uncharged pseudo-peptide backbone (see para. [0100]). Lieber teaches ssDNA template (see para. [0031] and para. [0073]). Lieber teaches the direct interaction of PNA labels with double stranded DNA (dsDNA) (see para. [0103]). Lieber teaches biotinylated PNA tag (see para. [0134]).
Thus, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have formed the conjugate as taught by Agasti with PNA or uncharged DNA sequence as taught by Lieber because Lieber teaches PNAs have shown great potential for use as probes as PNAs bind to dsDNA with high affinity, stability. Additionally, it would have been obvious to have used PNA as barcodes for specific highly charged cancer cell regions because PNA provides structural characteristics that do not contain negatively charged sugar backbone.
The person would have a reasonable expectation of success in using the conjugate of Agasti with PNA because it was well understood in the art to use PNA as labels, as taught by Lieber.
With respect to claim 7, see above.
With respect to claim 9, Agasti teaches in Scheme 1 that the antibody is a primary antibody.
With respect to claim 10, as stated above, Agasti does not teach PNA. Lieber teaches PNA sequence comprises between about 5 to 30 bases (see Fig. 16).
With respect to claim 11, as stated above, Agasti does not teach PNA. Lieber teaches PNA sequence comprises about 10 bases (see Fig. 16).
With respect to claim 12, see above.
With respect to claim 13, Agasti teaches in Scheme 2 the linker is a multi-functional linker.
With respect to claim 15, Agasti’s conjugate a hydrocarbon chain (Q is a bond in Formula IIIa) wherein d and e are integer between 2 to 6 (Scheme 2).
With respect to claim 16, Agasti’s conjugate is at least one of A or B comprises the one or more photocleavable groups (Scheme 2). Note that the claim recites a “wherein” clause that does not explicitly limit to these structures. Also, the claim directly reciting an optional limitation of the Linker (i.e., optionally containing O, N, S). These limitations contain optional limitations of O, N, and S groups and have not defined to that these are required elements of the Linker.
With respect to claim 19, Agasti’s conjugate is a hydrocarbon chain (Q is a bond in Formula IIIa) wherein the linker comprises a length ranging between about 0.5 nm to 20 nm (Scheme 2).
With respect to claim 20, Agasti’s conjugate is a hydrocarbon chain (Q is a bond in Formula IIIa) wherein the mw ranging from 1g/mol to 3000g/mol (Scheme 2).
With respect to claim 23, see above Scheme 2 of Agasti which contains an amide bond. The evidentiary teachings of Bollu et al. indicate the cleavage of amide bonds under mild acidic conditions (see abstract and Fig. 1).
With respect to claims 24-25, the claim recites a “wherein” clause that does not explicitly limit to these structures. Also, the claim directly reciting an optional limitation of the Linker (i.e., optionally containing O, N, S). These limitations contain optional limitations of O, N, and S groups and have not defined to that these are required elements of the Linker.
Claims 17 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Agasti et al. and Lieber et al. (US20220146714A1, published 10/10/2002), as applied to claim 6 above, and further in view of Buggenum et al. (“A covalent and cleavable antibody-DNA conjugation strategy for sensitive protein detection via immuno-PCR”, Scientific Reports, vol. 6:22675, pgs. 1-12, published 03/07/2016).
Agasti and Lieber have been discussed in the above rejection, but the reference does not teach linker comprising PEG (claim 17) or at least one of A or B includes disulfide group having an S-S bond (claim 26).
Buggenum teaches cleavable antibody-DNA conjugates, and the chemically cleavable disulphide linker facilitates release and sensitive detection of the dsDNA after immune-staining (see abstract). Buggenum teaches PEG is for coupling (see abstract). Buggenum teaches thiol-maleimide chemistry (see pg. 1, bottom of para. 1). Fig. 1 shows the antibody-DNA conjugate contains a S-S-tetrazine conjugate. Fig. 3 shows the structure of NHS-S-S-PEG4-tetrazine (see below):
PNG
media_image3.png
197
774
media_image3.png
Greyscale
Thus, it would have been obvious to the person to have incorporated the conjugate of Agasti with PEG of Buggenum because Buggenum teaches that PEG has been recognized as spacer for linkages between groups for antibody detection. Additionally, it would have been obvious to have used disulphide linker of Buggenum with to conjugate the maleimide group to the conjugate of Agasti because Buggenum teaches the chemically cleavable disulphide linker facilitates release and sensitive detection of the dsDNA.
The person would have a reasonable expectation of success in using PEG and disulphide linker with the conjugate of Agasti because it has been well understood in the art to conjugate PEG and disulphide linkers to antibodies for attachment of DNA.
Response to Arguments
Applicant's arguments filed 07/31/2026 have been fully considered but they are not persuasive with respect to claim 23 over 35 U.S.C. 102 with Leonidova, as evidenced by Bollu.
First, Applicant argues pgs. 12-13 that the construction of the term “optional” in the claimed invention. In particular, the word “optionally” modifies whether the generally defined carbon containing group also includes one or more identified heteroatoms. It does not modify and cannot eliminate the separate clauses that follow and expressly required the linker to have the structure of Formula IIIa and include a specified cleavable group or disulphide linker.
The arguments are not found persuasive with the arguments to the recited term “optionally”. It is noted that the claims are directed to product claims that are defined by structural limitations. In this case, the phrase “optionally” having one or more O, N, S, heteroatoms conflicts with the overall structure of the formulas which require O, N, S heteroatoms to contain the cleavable groups and S-S groups. For example, the phrase “Linker” encompasses the cleavable groups (claims 6 ad 23) and S-S groups (claim 26) and cleavable groups and S-S groups contain O, N, S. How can the overall Linker be optional to O, N, S heteroatoms when it clearly requires it? Thus, the claims are unclear to the metes and bounds of what is required in the claimed invention.
With respect to the 35 U.S.C. 102 rejection, Applicant argues on pgs. 14-15 that Leonidova does not describe cleavage of that spacer. The evidentiary teachings of Bollu also states that cleavage of amide bonds under mild acidic conditions is a “rare chemical event”.
The arguments are not found persuasive for the following reasons. For claim 23, the phrase “acid-sensitive groups” does not contain any structural features to represent the difference in chemical structure between the claimed acid-sensitive groups vs Leonidova’s amide group. Because no structural feature is provided with the phrase “acid-sensitive groups” and Bollu provides evidence that amide bond are cleavable through acid, Leonidova’s amide group reads on the structure of phrase “acid-sensitive groups”. Thus, the rejection is maintained for claim 23.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NAM P NGUYEN whose telephone number is (571)270-0287. The examiner can normally be reached Monday-Friday (8-4).
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, Gregory Emch can be reached at (571)272-8149. 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.
/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
