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. 1. Formal Matters Claims 1-13 are pending and are the subject of this Office Action. 2. Claim Objections In claim 1, for clarity, it is suggested that the phrase “each monomer” be amended to recite “each targeted monomer”. 3. Claim Rejections - 35 USC § 112(b) 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. Regarding claim 7, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). 4 . 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. 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. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. A. Claims 1- 4 and 6- 9 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Pegram et al. in view of Kazane et al . (cited on the IDS filed 9/28 /23). The claims are essentially drawn to an antibody-drug conjugate (ADC ) based on a complementary and paired nucleic acid skeleton. The skeleton is comprised o f single-stranded antibody-based monomers which form double-stranded tetrameric complexes with single-stranded drug/toxin-based monomers. Regarding claims 1, 2, 4 and 6, Pegram teaches the targeting of a cytotoxic drug (microtubule inhibitor) to HER2-positive breast cancer cells by linking it with a bispecific antibody ( Background ). These antibody drug conjugates (ADCs) , which attach an antibody to a drug via a linker, were well-known in the art at the time of the instant invention. Pegram does not teach the claimed paired nucleic acid skeleton. However, Kazane (Introduction) teaches the limitations of bispecific antibody constriction – these approaches generally require considerable engineering to optimize the biological and biophysical properties of the resulting molecules. For example, bispecific molecules synthesized as genetic fusions require flexible linkers that can lead to instability and aggregate formation, or immunogenicity. Additionally, fusion proteins can only be made in N to C or C to N terminal orientations, severely limiting the relative geometries of the individual antibody fragment subunits; such fusions are also not easily adapted to higher order structures involving three or more antibody combining sites. Chemical methods generally create heterogeneous mixtures with a range of stoichiometries and geometries that are not easily optimized Based on this Kazane concluded that - A synthetic strategy to rapidly self-assemble antibody fragments into multimers with control over composition, valency, and geometry would provide a useful drug discovery tool to test a large number of combinations of antibodies for optimal activity in a given cellular system. As can be seen, Kazane teaches antibody- linked oligonucleotide monomers capable of assembling into tetramers (Abstract; Figure 2 a, b ). This tetrameric structure forms in a predictable manner given complementary base pairing (meeting claim 6 wherein X1, X2 and X3 are 0 ; claim 8 ) . The structure of Kazane mimics that of the instant invention ( instant Figure 1). Claim 7 is taught under “Synthesis of Fab Multimers”. In addition, the last sentence of the paragraph bridging pages 340-341 of Kazane states “that these assemblies can efficiently modulate cell-signaling, kill cancer cells by the recruitment of cytotoxic effector cells, or directly induce cancer cell death, as is the intention of the instant claims (e.g. claim 9). Given this, it would have been obvious at the time of the instant invention to have used the paired nucleic acid construct of Kazane to produce the bispecific-antibody drug conjugate of Pegram in view of the teachings of Kazane that the nucleic acid linker provides a more stable/predictable structure tha n simple bispecific antibody -linked drug conjugates. Kazane teaches that an aminooxy functionality group was coupled to the 5’ end of the oligonucleotide and an HER2 antibody was attached to this group (starting at line 20 of page 342). This construct is similar to that of the instant claims (see the structure of claim 2). This technique could also be used to attach the cytotoxic drug of Pegram to the oligonucleotides since both the toxin and antibodies comprise amino acids (the inhibitor of Pegram is a peptide since it is based on tubulysin) . Regarding claim 3, Xu teaches that HER2-containing ADCs undergo endocytosis (Figure 1). This reference is not being used as part of the rejection, but to show the inherent property of HERs ADCs. Regarding claim 9 , the use of the ADC of Pegram in patients means that pharmaceutical compositions were required. See also the Conclusion of Kazane, which discusses their antibody-nucleic acid structure in the context of clinical medicine. B. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Pegram et al. i n view of Kazane et al . further in view of Eckstein. The teachings of both Pegram and Kazane are seen in paragraph A of this section. Neither teach the modified nucleic acids of claim 5. However, Eckstein (Abstract) teaches – Phosphorothioates have found their usefulness in the general area of oligonucleotide therapeutic applications. Initially this modification was introduced into the antisense methodology because of the nuclease resistance of the phosphorothioate linkage in comparison with that of the phosphate linkage. However, as experimental data accumulated, it was detected that this chemical modification also facilitates cellular uptake and bioavailibity (sic) in vivo. C . Claim s 10 -12 are rejected under 35 U.S.C. 103 as being unpatentable over Pegram et al. i n view of Kazane et al . further in view of Breda Genetics . The teachings of both Pegram and Kazane are seen in paragraph A of this section. Neither teach a nucleic acid sequence library . However, Breda teaches the preparation and use of sequencing libraries. Given this, it would have been obvious to have used any desired sequence in the invention of Pegram and Kazane in order to produce desired complementary nucleic acid strands to hybridize the ADC of Pegram to the skeleton of Kazane . D . Claims 1 - 9 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Pegram et al. in view of Pan and Zhou (CN108866635 - cited on the IDS filed 9/28/23; English translation provided herewith ). This reference is identified as ANSHENG as cited on the PCT/ISA/210 filed 9/28/23 and as discussed in the PCT/ISA/237 filed 9/28/23. The ADC of Pegram is discussed in paragraph A of this section. Briefly, the ADC is a bispecific HER2-coupled oligonucleotide conjugated to the cytotoxic microtubule inhibitor peptide (instant claim 4). Pegram does not teach a paired nucleic acid skeleton . However, Pan teaches a multispecific antibody based on the self-assembly of levorotary nucleic acid (Figure 1) as well as an L-DNA framework pairing method (Figure 2) essentially as recited in instant claim 1, for the pairing of 4 antibodies. However, regarding bispecific antibodies, paragraph [0007] of Pan teaches that “assembling two antibodies or fragments into a single molecule through protein engineering can easily lead to a decrease or loss of antibody affinity” and can “face the problem of light chain mismatch” and that solutions “add[s] more design and screening steps and cannot be directly applied to other bispecific antibody combinations as a universal technology”. In addition, multispecific full-length antibodies can “only be mass-produced in mammalian cell expression systems (such as CHO and HEK293). The process is more complex and the preparation cost is higher than that of antibody fragments (scFv, Fab)”. Therefore, the invention of Pan (paragraph [0010]) “provides a platform technology for linking multiple antibody drugs using a left-handed nucleic acid chain framework to form bispecific or multispecific drugs, which can conveniently and effectively conjugate multiple antibody drugs together to form an antibody drug library”. Furthermore, paragraph [0101] of Pan teaches that “[t]he nucleic acid element portion is a nucleic acid resistant to degradation by nucleases in vivo (e.g., levorotatory nucleic acid). Furthermore, the nucleic acid element portion of one protein drug monomer can complementarily form a double-stranded pairing structure with the nucleic acid element portion of at least one different protein drug monomer. Based on the needs (e.g., an individual's condition and diagnostic results), appropriate protein drug monomers can be selected from the protein drug library to rapidly (within 1 minute), efficiently, cost-effectively, and with high yield assemble multi-target, in vivo stable, multi-specific protein drugs (e.g., multi-specific antibodies) ” . Figures 1 and 2 meet Formula s I and II, respectively, of claim 2. It is noted that D1 and D2 can be 0. Regarding claim 6, X1, X2 and X3 can be 0. Claim 8 is met by Figu re 2. In addition, t he protein-drug library comprises “C” monomers, wherein C ≥ 2 as required by instant claim 1 (C = m) . Claim 1 (translated) of Pan teaches – A protein drug library, characterized in that the protein drug library comprises C different protein drug monomers, wherein the protein drug monomer comprises a protein drug element portion and a nucleic acid linked to the protein drug element portion a component part, and a nucleic acid element portion of one of the protein drug monomers and a nucleic acid element portion of at least one different protein drug monomer may form a double-stranded pairing structure by complementation, thereby constituting a multimeric protein drug Furthermore, regarding instant claim s 2, claim 3 of Pan teach es – A protein drug library according to claim 1 wherein said protein drug monomer has the structure of formula I: P-X-L-Y-A-Z (I) In the formula, P is a protein drug molecule (ie, a protein drug component part); X is a no or redundant peptide; L is a linker molecule; Y and Z are no or redundant nucleic acids; A is a nucleic acid sequence selected from the group consisting of a lefthanded nucleic acid, a peptide nucleic acid, a locked nucleic acid, a thio - modified nucleic acid, a 2'-fluoro-modified nucleic acid, a 5- hydroxymethylcytosine nucleic acid, or a combination thereof; "-" is a covalent bond; Nucleic acid A of any of the protein drug monomers has at least one complementary pairing region that is partially or fully complementary to the complementary pairing region of nucleic acid A of at least one protein drug monomer in the protein drug library. Liqiang teaches that the drug can be an antibody and that the antibody can be HER2 (claim 4; paragraph [0043]), which, as discussed in paragraph A of this section regarding Xu et al., undergoes endocytosis. Claim 5 (locked nucleic acid; 2’-fluoro-modified nucleic acid) is also met in claim 3 of Pan . Claim 7 is taught in paragraph [0058]. Claim 9 is met by claim 3 E. Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Pegram et al. in view of Pan and Zhou further in view of Breda Genetics. The teachings of both Pegram and Pan are seen in paragraph s A and D, respectively, of this section. Neither teach a nucleic acid sequence library . However, Breda teaches the preparation and use of sequencing libraries. Given this, it would have been obvious to have used any desired sequence in the invention of Pegram and Pan in order to produce desired complementary nucleic acid strands to hybridize the ADC of Pegram to the skeleton of Pan . 5 . Conclusion No claim is allowable. Advisory information Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ROBERT S LANDSMAN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT 571-272-0888 . The examiner can normally be reached M-F 8 AM – 6 PM (eastern). 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, Joanne Hama, can be reached at 571-272-2911 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). /ROBERT S LANDSMAN/ Primary Examiner, Art Unit 1647