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.
Status of Claims
Claims 6-13, 15-17, 19-20 and 23-26 are pending. Claims 7-8 are withdrawn as being the nonelected species. Claims 6, 9-13, 15-17, 19-20, and 23-26 are currently under examination.
Withdrawn Objections
In light of the amendments, the 35 U.S.C. 112(b) rejection is hereby withdrawn.
In view of the amendments, the 35 U.S.C. 102(a)(1) rejection over Lohse of claim 6, 9-13, 15-17, 19, 22 and 24-25 is hereby withdrawn.
In view of the amendments, the 35 U.S.C. 102(a)(1) rejection over Leonidova as evidenced by Bollu of claims 6, 9-10, 12-13, 15-17, 22, 24-25 is hereby withdrawn.
In light of the amendments, the 35 U.S.C. 103 rejection over Leonidova and Erickson is hereby withdrawn.
In light of the amendments, the 35 U.S.C. 103 rejection over Lohse is hereby withdrawn.
In light of the approved terminal disclaimer, the nonstatutory double patenting rejections are hereby withdrawn.
Claim Objections
Claims 6, 23 and 26 are objected to because of the following informalities: Claim 23 appears to invoke the Markush language for “chemically cleavable group selected from the group consisting of….or…” (emphasis added) which a Markush language should recite – and –.
Additionally, claims 6, 23, and 26 recite in the preamble “any of Formulas (I)” should be – Formula (I) – because there is only one general formula.
Appropriate correction is required.
Nucleotide and/or Amino Acid Sequence Disclosures
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located in the amended drawing dated 08/07/2025. Applicant has updated the drawing to add SEQ ID NOs to the drawing, but, for example, SEQ ID NOs: 23, 24, 25, 26, 27 are not in the previous sequence listing. However, Applicant has not updated the sequence listing in XML format with respect to said SEQ ID NOs. Additionally, the automated system for the Sequence listing dated 03/09/2026 has indicated errors found during validation.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Response to Arguments
Currently, the automated system for the Sequence listing dated 03/07/2026 has indicated errors found during validation. For the complete comments, please see sequence listing report dated 03/09/2026.
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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.
Claims 23 and 26 are 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).
With respect to claim 23, 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.
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In particular, 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). Leonidova teaches the PNAs were cleaved using a mixture of trifluoroacetic acid – water—triisopropylsilane (see pg. 5610, right col., bottom of para. 1 of General chemistry). Leonidova further teaches Cys-c-PNA was cleaved off the resin following the general protocol shown above (see pg. 5610, right col., bottom of para. 2 of General chemistry). In particular, 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). Thus, the linker comprising the amide bonds of Leonidova read on the structure of a linker that includes an acidic sensitive group of claim 23. Note that the phrase sensitive would include any sensitivity under mild acidic conditions. Scheme 1D of Leonidova shows amide bonds are connected to (CH2)2O(CH2)2OCH2 (i.e., spacer). The evidentiary teachings of Bollu et al. indicate the cleavage of amide bonds under mild acidic conditions (see abstract and Fig. 1). Thus, the linker comprising the amide bonds of Leonidova read on the structure of a linker comprising one or more chemically cleavable groups. Note that the recitation of “optionally having one or more O, N, or S heteroatoms, and wherein at least one of A or B includes at least one disulfide-based group” would be interpreted as optional because disulfide-based group requires S heteroatoms.
With respect to claim 26, note that the recitation of A and B are “optionally having one or more O, N, or S heteroatoms, and wherein at least one of A or B includes at least one disulfide-based group” would be interpreted as optional limitations because disulfide-based group requires S heteroatoms. Thus, the claim no longer requires a disulfide-based group.
Claim 26 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lohse et al. (WO2007/015168A2, published 02/08/2007, of record 892 dated 09/25/2024).
New grounds of rejection because the recitation of A and B are “optionally having one or more O, N, or S heteroatoms, and wherein at least one of A or B includes at least one disulfide-based group”. This would be interpreted as optional limitations because disulfide-based group requires S heteroatoms. Thus, the claim no longer requires a disulfide-based group.
With respect to claim 26, Lohse teaches monomeric or polymeric linker molecules useful in biological and chemical applications and the linkers may be used in conjugation with fluorescent labels, nucleic acid or nucleic acid analog probes (see abstract). Fig. 2A shows the linker conjugated to an antibody, which would read on ‘Specific binding entity’ is an antibody. Lohse teaches longer linker molecules based upon polyethylene glycol (PEG) (see para. [0005]). Lohse teaches Formula I which reads on the limitations of a ‘Linker’ that is a branched or unbranched or substituted or unsubstituted group having between 2 and 80 carbon atoms with optionally O or N groups wherein the ‘Linker’ has the claimed structure of Formula (IIIa) (i.e., PEG wherein d and e are integers of 2). In particular, Lohse teaches in Formula I that R2 is oxygen (O) (see paras. [025]-[026]). Fig. 1 depicts a synthesis of an exemplary L15 linker unit derived from 3,9, 12-trioxa-6, 15-diaza-5-oxo-pentadecanoic acid (see para. [013]). Lohse teaches [L-15]n-PNA (see para. [0320]; PNA is peptide nucleic acid, para. [067]). Figs. 1-3 depict the claimed Formula (I) wherein specific binding entity is an antibody, Z is a peptide nucleic acid sequence, X and Y are zeros and n is between 1-12.
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, 9-13, 15-17, 19-20, and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Rogers et al. (“Site-directed recombination via bifunctional PNA-DNA conjugates”, PNAS, vol. 99, no. 26, pgs. 16695-16700, published 12/24/2002).
With respect to claims 6, 23, and 26, Rogers teaches site-specific DNA binding molecules offer the potential for genetic manipulation of mammalian cells and peptide nucleic acids (PNAs) are a DNA mimic in which the purine and pyrimidine bases are attached to a polyamide backbone (see abstract). Fig. 1 shows the design and synthesis of a bifunctional PNA-DNA conjugate to produce DNA oligonucleotide-bis-PNA. In particular, Fig. 1C shows a (CH2)3-S spacer for conjugation of PNA-DNA.
Note that the claim recites ‘Linker’ is optionally having one or more heteroatoms selected from O, N, or S, and the recitation of Formula (III) and photocleavable groups require O, N, and/or S heteroatoms; therefore, these recitations are optional limitations to the ‘Linker’. In other words, the ‘Linker’ may contain Formula (III) and photocleavable groups but not required under the claimed conjugate. Although Rogers teaches (CH2)3-S, the reference does not explicitly teach the linker is simply 2 to 80 carbon atoms.
Meanwhile, 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 simply used (CH2)3-S as a linker as taught by Rogers for attachments of nucleic acid group and peptide nucleic acid group because Rogers recognizes the hydrocarbon group of (CH2)3-S as the spacer with the ability to conjugate the peptide nucleic acid group via thiol reaction.
With respect to claim 9, Rogers teach a rabbit polyclonal antibody directed against recombinant human XPA protein (see pg. 16699, left col., para. 1). Rogers does not teach the specific binding entity is a primary antibody. However, it would have been obvious to have conjugated the antibody with PNA because antibodies bind against a specific target.
With respect to claims 10 and 12, Rogers teaches PNA claim comprising between about 5 to about 30 bases (see pg. 16696, left col., para. 3).
With respect to claim 11, Rogers do not teach the PNA sequence comprises about 10 bases. However, it would have been obvious to have used a shorter PNA because the conjugation is not directly from PNA but rather the linker.
With respect to claim 13, Fig. 1C shows that CH2)3-S is bifunctional linker.
With respect to claims 15-17 and 24-25, the claim recites a “wherein” clause that is directly reciting an optional limitation of the Linker (i.e., optionally containing O, N, S). These limitations contain optional limitations of O, N, and/or S groups and have not defined that these are required elements of the Linker. Therefore, the limitations are optional.
With respect to claims 19-20, Rogers teaches PNA claim comprising between about 5 to about 30 bases (see pg. 16696, left col., para. 3), which would fall within the claimed nanometer.
Response to Arguments
Applicant’s arguments filed 03/07/2026 have been considered but are moot because Applicant’s amendments necessitated a new ground of rejection. However, the amendments to claim 23 is maintained in view of Leonidova.
35 U.S.C. 102 Rejection for Claim 23:
Applicant argues on page 11 (last para.) that Leonidova does not disclose a linker that is an acid-sensitive group. Applicant further argues on page 12 that while Leonidova includes ordinary amide bonds as part of a stable spacer, it does not teach designing the linker to include one or the claimed chemical-cleavage modalities. Bollu (evidenced art) explans that cleavage of amide bonds under mild acidic conditions is a rare chemical event.
The arguments are not found persuasive because the claim is directed to a product. Meanwhile, the phrase amide group of Leonidova would read on the structure of “acidic sensitive groups”, which is any chemical structure that is “cleavable” (might be cleaved) by acidic conditions. Thus, the rejection is maintained for claim 23.
35 U.S.C. 103 Rejection for Claim 26:
In light of the amendments of “optionally having one or more O, N, or S heteroatoms, and wherein at least one of A or B includes at least one disulfide-based group”. Because O, N, and S heteroatoms are optional limitations, the interpretation of having the disulfide-based group is optional. Therefore, the claim no longer requires disulfide-based group.
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.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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