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. Information Disclosure Statement Information Disclosure Statement has not been provided. Status of Claims Claims 1-20 are examined herein. Claim Interpretation Claims 1-20 recite amino acid binding protein. In the art of protein structure and protein chemistry the term amino acid refers to a free, unincorporated amino acid. An amino acid incorporated in a peptide or a protein is referred to as an amino acid residue. Throughout the specification Applicant uses the term amino acid when referring to an amino acid residue. Therefore, the claims reciting amino acid will be interpreted as referring to amino acid residue. Claim Objections Claims 1-14, 16, and 19 are objected to because: Claims 1-14 and 19 contain abbreviation FRET. It should be completely spelled out in its first occurrence. Claim 16 recites “naturally occurring amino acids of a different type”, should be “naturally occurring amino acids of [[a]] different type s ”. Appropriate correction is required. Claim Rejections - 35 USC § 112 The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL. —The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims 1-18 and 20 recite a composition comprising amino acid binding proteins. Claim 19 recites a labeled amino acid recognition molecule comprising at least one amino acid binding protein. The claims are broadly drawn to a composition comprising amino acid binding proteins capable of recognizing amino acids in polypeptides. An original claim may lack written description support when a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) ( en banc) (MPEP §2163.03.V). “[T]he disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." (MPEP § 2163.II.A). A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.") (MPEP § 2163). In the instant case, claims 1-20 are directed to a broad genus of amino acid binding proteins capable of recognizing amino acids in polypeptides. The instant specification fails to disclose any amino acid binding protein by structure and binding specificity. The amino acid binding proteins are disclosed in very general terms. For example, “the amino acid binding protein is a Gid protein, a UBR-box protein or UBR-box domain-containing fragment thereof, a p62 protein or ZZ domain-containing fragment thereof, or a ClpS protein” ([0045]). The disclosed proteins are not known in the art for their amino acid specific binding properties. Additionally, there are 20 naturally occurring canonical amino acids, but the number of the disclosed proteins is significantly smaller. Therefore, the specification fails to disclose amino acid binding proteins capable of recognizing any amino acid. No protein structures and binding specificities are disclosed. Another paragraph disclosing the amino acid binding proteins of instant invention - “a recognition molecule of the disclosure is a degradation pathway protein. Examples of degradation pathway proteins suitable for use as recognition molecules include, without limitation, N-end rule pathway proteins, such as Arg/N-end rule pathway proteins, Ac/N-end rule pathway proteins, and Pro/N-end rule pathway proteins. In some embodiments, a recognition molecule is an N-end rule pathway protein selected from a Gid protein (e.g., Gid4 or GidlO protein), a UBR-box protein (e.g., UBRl , UBR2) or UBR-box domain-containing protein fragment thereof, a p62 protein or ZZ domain-containing fragment thereof, and a ClpS protein (e.g., ClpSl , ClpS2). Accordingly, in some embodiments, a labeled recognition molecule comprises a degradation pathway protein. In some embodiments, a labeled recognition molecule comprises a ClpS protein” ([0133]). Again, no protein structures and binding specificities are disclosed. Next paragraph provides “a recognition molecule of the disclosure is a ClpS protein, such as Agrobacterium tumifaciens ClpSl , Agrobacterium tumifaciens ClpS2, Synechococcus elongatus ClpS1, Synechococcus elongatus ClpS2, Thermosynechococcus elongatus ClpS , Escherichia coli ClpS , or Plasmodiumfalciparum ClpS . In some embodiments, the recognition molecule is an L/F transferase, such as Escherichia coli leucyl/phenylalanyl-tRNA-protein transferase…” ([0134]). No protein structures and binding specificities are disclosed. For some proteins specificities are disclosed, but these are mixed specificities and they cannot be used for definitive amino acid identification, such as leucyl/phenylalanyl-tRNA-protein transferase, which has dual leucyl/phenylalanyl specificity. Identification of types of amino acids recited in claims 15-17 is not disclosed in the specification. There are different overlapping types of amino acids: charged, uncharged, hydrophobic, hydrophilic, branched, aromatic etc. The specification fails to disclose or identify the types of amino acids and specific proteins binding to these types and their structures. Finally, the specification discloses the amino acid binding proteins through their desirable properties “an amino acid recognition molecule may be engineered by one skilled in the art using conventionally known techniques”, “desirable properties may include an ability to bind selectively and with high affinity to one type of amino acid only when it is located at a terminus (e.g., an N-terminus or a C-terminus) of a polypeptide”, and “desirable properties include an ability to bind selectively and with low affinity” ([0123]). No protein structures and binding specificities are disclosed. Paragraph [0144] discloses that “Examples of amino acid recognition molecules (e.g., amino acid binding proteins) for use in accordance with the disclosure are described more fully in PCT International Application No. PCT/US2019/061831, filed November 15, 2019, and PCT International Application No. PCT/US2021/033493, filed May 20, 2021, the relevant content of which is incorporated herein by reference in its entirety.” However, PCT/US2019/061831 (WO 2020102741) discloses limited number of amino acid binding proteins with single amino acid binding specificities: A, G, and P (Table 1). The remaining examples have mixed binding specificities: such as D/E, K/R, F/W/Y, K/R/H, P/M/V. As such, PCT/US2019/061831 fails to disclose a broad range of amino acid binding proteins recited in claim 1. Another application PCT/US2021/033493 (WO 2021236983) discloses limited number of amino acid binding proteins with single amino acid binding specificities: W, F, and M (Table 1) and P, A, and G (Table 2). Thus, failing to support the full breadth of claims of instant disclosure. Prior art is silent on a broad range of amino acid binding proteins with single amino acid residue binding specificities. Regarding the structure of an amino acid binding protein - FRET conjugate, the specification fails to provide any information about the structure of such conjugates. No information is provided for the first and second configurations of claims 5 and 6 or structural elements having these configurations. Figures 1-3 of the specification fail to address the FRET labels because they illustrate amino acid recognition molecules labeled with a shielding element, which is not relevant to the claimed matter. The specification fails to provide any examples of the amino acid binding proteins conjugated to their FRET labels and capable of binding to amino acid residues. Additionally, the specification fails to disclose how a FRET label attached to an amino acid binding protein can function in identifying the bound amino acid - prior art is silent on FRET mechanism working with a single binding molecule. Paragraph [0097] discloses “observing different association events, e.g., association events between an amino acid recognition molecule and an amino acid at a terminal end of a peptide, can be performed during a peptide degradation process. In some embodiments, a transition from one characteristic signal pattern to another is indicative of amino acid cleavage (e.g., amino acid cleavage resulting from peptide degradation). In some embodiments, amino acid cleavage refers to the removal of at least one amino acid from a terminus of a polypeptide (e.g., the removal of at least one terminal amino acid from the polypeptide)”, but this fails to address how the FRET label can function in this process. Prior art recognizes a FRET label with the donor and acceptor moieties attached to different binding proteins. However, prior art is silent on FRET donor and acceptor moieties attached to the same amino acid binding protein. The role of FRET labels in identifying amino acids is unclear. Therefore, claims 1-20 are rejected under 35 U.S.C. 112(a) for failure to describe a sufficient number of different amino acid binding proteins and their binding specificities to claim a broad genus of amino acid binding proteins. Based on the above findings, one of ordinary skill in the art would conclude that Applicant did not have possession of the claimed invention. 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 5-7 and 15-17 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 5 recites “at least about”. The metes and bounds of the invention are not clear. As the CAFC noted, and affirmed, regarding the district court determination of this phrase in Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (CA FC) 18 USPQ2d 1016 at page 1031 "the court held the "at least about" claims to be invalid for indefiniteness." Claims 6-7 recite first and second configurations. It is unclear what configurations the claims refer to. Claims 15-17 recite type(s) of amino acid. Types of amino acids are not strictly defined in the art. There are different types of amino acids depending on the specific property in question: charged, uncharged, hydrophobic, hydrophilic, branched, aromatic etc. The specification fails to disclose the types of amino acids recited in the claims. The metes and bounds of this limitation are unclear. Subject Matter Free of the Prior Art Claims 1-20 are free of the prior art. The prior art neither teaches nor suggests a composition comprising an amino acid binding protein comprising a FRET label. The prior art is silent on proteins capable of specific binding to any natural amino acid residue and generating a FRET-dependent signal for identification of these amino acids. The closest prior art teaches: Reed et al. (WO 2020102741) teach in Table 1 amino acid binding proteins with specificities toward P (SEQ ID NO:19 and 20), G (SEQ ID NO:34 and 35), and A (SEQ ID NO:36) amino acids, but fail to teach amino acid binding proteins with specificities toward remaining 17 canonical amino acids. Reed et al. (WO 2021236983) teach in Table 1 amino acid binding proteins with specificities toward W (SEQ ID NO:10), F (SEQ ID NO:51), and M (SEQ ID NO:96 and 97) amino acid; and in Table 2 – P (SEQ ID NO:113 and 114), G (SEQ ID NO:126 and 127), and A (SEQ ID NO:128), but fail to teach amino acid binding proteins with specificities toward remaining 14 canonical amino acids. Rodriques et al. ( PLoS One. 2019 Mar 28;14(3): e0212868) teach single molecule sequencing using fluorescence-based approach (Abstract and Fig. 1A), but fail to teach FRET-based identification. van Ginkel et al. (Proc Natl Acad Sci U S A. 2018 Mar 27;115(13):3338-3343) teach single-molecule peptide fingerprinting using FRET detection (Fig. 1), but fails to teach specific amino acid binding proteins of instant disclosure. Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.” Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571) 272-1899 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 9:00AM-5:00PM (EST) . If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Bao-Thuy Nguyen can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-0824 . 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 Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form. /ALEXANDER ALEXANDROVIC VOLKOV/ Examiner, Art Unit 1677 /REBECCA M GIERE/ Primary Examiner, Art Unit 1677