DETAILED ACTION Status of the Application Claims 1-21 are pending. Claims 1-21 are under examination. The following Office Action is in response to Applicant's communication dated 12/12/2023. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claim Interpretation For purposes of examination, the claims are interpreted according to their plain language as would be understood by one of ordinary skill in the art. Where the claim language is internally inconsistent or unclear, the Office does not infer unstated limitations or supply missing relationships. The interpretations set forth below are adopted solely to permit examination and do not resolve ambiguities in the claim language. Claim 1 recites “ screening for a candidate molecule ” in the preamble, then later in step (1) recites “ plurality of test molecules ”, and finally in step (2) recites “ the candidate molecule ” . The claim does not define w he ther the “ test molecules ” and the “ candidate molecule ” refer to different set of molecules or the same molecules at different stages of the method, thereby creating ambiguity as to the relationship between these terms. For purposes of examination only, and to facilitate a complete analysis of the claim, the Examiner interprets the “ test molecules ” recited in step (1) as corresponding to the molecules being screened in the method, and the “ candidate molecule ” recited in step (2) as a molecule selected from that plurality based on its ability to form the complex with first and second targets. Thus the “ test molecules ” and the “ candidate molecule ” are interpreted as referring to the same set of molecules at different stages of the screening process. This interpretation is adopted solely for examination and does not resolve the lack of clarity in the claim language. 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. Claim 15 and 21 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 15 and 21 recites the limitation “(b) the amino acid sequence represented by SEQ ID NO: 71, 75, 78, or 82 in which one or more amino acids are deleted, inserted, substituted, and/or added” . This language fails to provide any objective boundaries on the extent or nature of permissible modifications. Under broadest reasonable interpretation, the claim encompasses sequences with an indeterminate number and type of modifications, without any limitation on sequence identity, structural constraints, or functional requirement. As a result, it is unclear at what point a modified sequence would no longer be considered within the scope of the claimed sequence, including whether such modified sequences would retain sufficient homology, structural features, or functional characteristics of the referred sequences. Given the highly structure-dependent and unpredictable nature of protein function, the absent of such limiting criteria render the scope of the claim ambiguous. Accordingly, the metes and bounds of the claim are unascertainable. 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. 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. Claim(s) 1-21 is/are rejected unde r 35 U.S.C. 103 as being unpatentable over Cabantous et al. ( Sci Rep 3, 2854 (2013) , disclosed in IDS) in view of Lee et al. ( ACS Cent. Sci. 2016, 2, 8, 506–516) . Regarding claim 1 , Cabantous discloses a system for detecting interactions between biological molecules using complimentary fragments of a split protein, where in the first target molecule is associated with a first fragment of a reporter protein and a second target molecule is associated with a second fragment of the reporter protein. Upon proximity of the first and second target molecules, the fragments associate to reconstitute a functional protein, thereby indicating interaction between the targets [Fig. 1 and abstract] . This corresponded to the claimed first and second target molecules associate with first and second moieties that associate upon proximity. However, Cabantous relies primary on fluorescence-based detection and does not teach isolating the resulting complexes via affinity base methods. Lee discloses a proximity-dependent labeling system in which interacting or proximally located proteins are covalently labeled (e.g. biotinylating) and subsequently isolated using affinity bases techniques such as streptavidin pull-down. Specifically, Lee discloses that proximity labeling generates covalently modified protein that can be enriched and isolated using affinity capture methods, thereby enabling identification of interacting partners with complex mixtures. Additionally, Lee demonstrates that small molecules such as Rapamycin can induce formation of a ternary complex between two target proteins, thereby teaching the use of candidate molecules that mediate or stabilize interaction between multiple targets [Fig. 1 and abstract] . Thus, Lee discloses both ( i ) proximity-dependent detection of interacting proteins and (ii) the use of a third component, namely labeling and capture system, that selectively recognizes and isolates complexes form through proximity-dependent events. Both references are directed to detecting and characterizing protein-protein interactions based on molecular proximity and operate on systems involving interacting inducible protein complex formation. Further, Lee and Cabantous employ the same inducible protein complex, Rapamycin-Induced Heterodimer of FKBP25 and FRB in their studies. As of the application’ s effective filing date, one of ordinary skill in the art would have had a reasonable expectation of success and motivated to combine these teachings to modify Cabantous ’ split-protein interaction detection system to incorporate proximity dependent labeling and affinity-based isolation techniques of Lee to enable recovery and identification of interacting complexes. Lee ’s method allows isolat ion/enrichment of interacting partners by standard pull-down methods using streptavidin (SA) beads , thereby simplify the downstream identification of the interaction events among multiple potential interacting species and conditions. Incorporation of this label and capture system into the split-protein framework would have provided a third detecting component that recognize the proximity induced complex and permit its isolation, while enabling screening or identification of candidate molecules capable of inducing such interactions from plurality of candidates within the mixture. Regarding claim 2 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 1 as discussed fully above and incorporated here. Lee further discloses identifying the candidate molecule [ page 1 ]. Regarding claim 3 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 1 as discussed fully above and incorporated here. Lee and Cabantous further disclose third molecule is a molecule that reacts with the first moiety and/or the second moiety when the first moiety and the second moiety are in proximity or association (e.g. GFP 1-9 in Cabantous [abstract and Fig. 1 ] ) and biotin label in Lee [ Fig. 1]) Regarding claim 4 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 1 as discussed fully above and incorporated here. Cabantous further discloses the third molecule is a molecule that does not substantially react with the first moiety and/or the second moiety when the first moiety and the second moiety are neither in proximity nor in association. (e.g. GFP need s all domains to generate green fluorescent [Fig. 1] ) Regarding claim 5 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 2 as discussed fully above and incorporated here. Cabantous demonstrates rapamycin-induced association of FRB/FKBP12, which is reversible and can be removed out of complex via natural dissociation for later identification steps. Under BRI, “eluting” encompasses removal of the candidate molecule from the complex by disassociation. Regarding claim 6 , Lee and Cabantous discloses a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 5 as discussed fully above and incorporated here. Although Lee and Cabantous do not disclose determining a sequence of a polynucleotide encoding the candidate molecule eluted , Lee teaches proximity-dependent labeling and subsequent affinity-base enrichment of interacting partners from the complex biological mixture, which enable recovery of molecules associate with a proximity-induced interaction . It would have been obvious to one of ordinary skill in the art, when apply Lee and Cabantous ’ method to screen a plurality of candidate molecules in a library format, to include a step of identify which specific candidate is responsible for the interaction . Further, methods for associating candidate molecules with identifying information (e.g. nucleic acid encoding sequence s, barcodes, or known library composition) and determining such identities were well-established in the art, and their implementation would have been a predictable use of prior art techniques depend ing on the nature of the candidate molecules being screened. See KSR International Co. v. Teleflex Inc. , 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) Regarding claim s s 7 and 16 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 1 as discussed fully above and incorporated here. Although Lee and Cabantous do not explicitly disclose repeating steps (1) and (2) a plurality of time , it would have been obvious to one of ordinary skill in the art to perform such steps iteratively to improve detection sensitivity, enrich for interacting complexes, and increase the likelihood of identifying candidate molecules with desired activity. See KSR International Co. v. Teleflex Inc. , 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) . Regarding claim 8 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 1 as discussed fully above and incorporated here. Cabantous further discloses the method is performed in vitro. [abstract] Regarding claim s 9 , 10 , 17 , and 18 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 1 as discussed fully above and incorporated here. Although Lee and Cabantous do not explicitly disclose the chemical structure and classification of candidates or the library size (e.g. 1 x 10 4 or more ) , the selection of the type of library, including display library or a DNA encoding library , would have been dependent on the nature of the target molecules and the intended interaction being screened. For example, therapeutic PROTAC - CREPT uses a peptide warhead from the CREPT dimerization motif to induce proteasome-dependent degradation [Ma et al. Theranostics . 10(8):3708-3721 , published Feb 19 2020] , one of ordinary skill in the art would understand screening for such PROTAC and its analogs would comprise the library for such peptides is a DNA encoding library. Accordingly, selecting an appropriate library type and size (e.g. 1 x 10 4 or more ) based on the characteristics of the target molecule s represents a routine and predictable design choice within the skill of the ordinary artisan. See KSR International Co. v. Teleflex Inc. , 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) and MPEP § 2144.05 (II), 2144.05 (III)(C) In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Regarding claim s 11 and 19 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 1 as discussed fully above and incorporated here. Cabantous further discloses the protein is GFP [abstract]. Regarding claim s 12 and 20 , Lee and Cabantous disclos e a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 1 as discussed fully above and incorporated here. Lee further disclose s the affinity-based method is a pull-down method (e.g. biotin-streptavidin [abstract]) Regarding claim s 13, 14 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 5 as discussed fully above and incorporated here. Lee and Cabantous do not disclose eluting step (2A) is performed with an enzyme or by heat ( claim 13 ) and eluting step (2A) is performed by cleaving a first linker between candidate molecule and first and second moiet ies ( claim 1 4 ). However, Cabantous demonstrates rapamycin-induced association of FRB/FKBP12 , which is reversible and can be removed out of complex via natural dissociation for later identification steps. Under BRI, “eluting encompasses removal of the candidate molecule from the complex by disassociation. Routine condition such as temperature, buffer, or competitive conditioning would achieve such removal. Likewise, cleave linker(s) broadly encompasses separating components of the complex, including via disruption of the interaction that hold the complex together. Accordingly, the prior arts render obvious the claimed elution steps, as they represent conventional and recover components of a protein complex. Regarding claim s 15 and 2 1 , Lee and Cabantous disclose a method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule of claim 1 as discussed fully above and incorporated here. Cabantous further discloses the protein providing the first moiety and the second moiety contains an amino acid sequence selected from the group consisting of (a) to (c) below: (a) an amino acid sequence represented by SEQ ID NO: 71, 75, 78, or 82; (b) the amino acid sequence represented by SEQ ID NO: 71, 75, 78, or 82 in which one or more amino acids are deleted, inserted, substituted, and/or added; and Attorney Docket No. 6663.0254 (c) an amino acid sequence having 80% or more sequence identity to the amino acid sequence represented by SEQ ID NO: 71, 75, 78, or 82. (e.g. GFP [abstract]) . Conclusion No claims are allowed Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Khai Quynh Tien Pham whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-6998 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-T, 9-4 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, FILLIN "SPE Name?" \* MERGEFORMAT Heather Calamita can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-2876 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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