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. The preliminary amendments of 03/14/2024 have been entered in full. Claims 1, 6-9, 14-16, 21-29, and 39-41 are pending . 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 appl icant regards as his invention. Claims 1, 6-9, 14-16, 21-29, and 39-41 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. The claims require knowledge of the sequences of all CDRs in the recited amino acid sequences of antibody variable regions. The CDR sequences are not explicitly identified in the claims. The specification provides sequence information for some heavy and light chain CDR3 s (Table2, Table 3), but the relationships of these to the sequences recited in the claims is not clear. The determination of CDR sequences can yield differing results depending on the numbering scheme (e.g. Kabat, Clothia, IMGT) applied to sequences. No numbering scheme is recited . Therefore, the metes and bounds of the claims are unclear. 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, 7-9, 14-16, 21-29, and 39-41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for antibodies or antigen-binding fragments thereof comprising a heavy chain variable region and the light chain variable region each derived from a single functional antibody , does not reasonably provide enablement for antibodies or antigen-binding fragments thereof comprising a heavy chain variable region and the light chain variable region each derived from different antibodies . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The claims are drawn to an isolated antibody or antigen-binding fragment thereof that binds specifically to a TBEV antigen comprising a lateral ridge of domain III of the E protein . As recited, the antibod y or antigen-binding fragment thereof compris es three heavy chain CDRs from any of 59 recited heavy chain variable region sequences paired with three light chain CDRs from any of 59 recited light chain variable region sequences . Thus, the claims require that the CDRs from the heavy and light chains of 59 distinct antibody isolates can be paired in any combination to form a functional antibody. Enablement of the broadly claimed invention is limited by the nature of the heavy and light chain interactions in antibodies. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function. As early as 1987, i t was known that the pairing of polypeptides encoded by different V H and V L genes contributes to antibody diversity and specificity (Smith-Gill et al. (J. Immunol. 139:4135-4144 (1987)) . Antibodies having different combinations of a given VH or VL can fail to bind a particular antigen (Smith-Gill et al. p. 4135, paragraph bridging the columns). Smith-Gill et al. assessed the role of the H and L chains and of specific sequence variation within closely related chains by preparing recombinant antibodies with chains from different source antibodies. When heterologous L chains were combined with specific H chains, the resulting antibody usually retained some affinity for the same protein antigen, but binding to specific domains of the antigen varied: some L chains conferred specific domain binding to the combination, others did not, and generally interaction between both chains determined domain localization of the epitope ((Smith-Gill et al., paragraph bridging pp. 4137-4138). Therefore, the functionality of antibodies formed by heterologous heavy and light chains is varied and unpredictable, and can only be known through experimentation. This example is particularly relevant to the instant case, in which the claimed antibody is required to specifically bind to a specific domain of a protein antigen. The problem of identifying correct VL-VH pairs has remained an important consideration in state-of-the-art methods for cloning antibody sequences (see US 1236204 2). The specification teaches that f ifty-nine antibodies (46 from convalescent and 13 from vaccinated donors, Table 4) were cloned ; the sequences are recited in claims 1 and 6. All but one of the 59 antibodies were shown to bind 3 TBEV subtypes with similar half-maximal effective concentrations . The binding antibodies meet the limitation of binding to a TBEV antigen comprising a lateral ridge of domain III of the E pro tein even though the precise epitope was not determined. Specificity for the lateral ridge of EDIII was demonstrated only for a single isolate: antibody T025, which comprises heavy variable domain SEQ ID NO:19 and light variable domain SEQ ID NO:20. The specification teaches that antibody T025 binds near the lateral ridge of EDIII, making both heavy and light chain contacts to the EDI-EDIII hinge and the BC loop, and light chain contacts to the DE loop of the EDIII (FIG. 9 A). The antibody contacts EDIII using CDRH2, CDRH3, CDRL1, and CDRL3 . T 025 inserts Asp100 HC and Trp94 LC into a cleft in the EDIII, making a salt bridge (Asp100 HC -Lys311 EDIII ) and hydrogen bonds to the EDIII (FIG. 9 B) ([0349] in publication US 20240002480 ). These results are consistent the expectation that CDRs of each immunoglobulin chain provide the majority of the contact residues for the binding of the antibody to its target epitope. The specification does not show that any antibody or fragment comprising less than a full complement of VH/VL CDRs from a single isolate would be capable of binding to a TBEV antigen at all, and binding to a lateral ridge of domain III of the E pro tein was demonstrated only for antibody T025 . In view of the unpredictability of the functionality of antibodies formed by heterologous heavy and light chains, and the lack of evidence in the specification for such functionality, the enabled scope is limited to antibodies or antigen-binding fragments thereof comprising a heavy chain variable region and the light chain variable region each derived from a single functional antibody. Claims 1, 6-9, 14-16, 21-29, and 39-41 are rejected 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification is not enabling for embodiments of the invention comprising the heavy and light chain variable domain sequences of SEQ ID NO: 33 and SEQ ID NO:34. SEQ ID NO: 33 and SEQ ID NO:34 define the respective heavy and light chain variable domains of antibody T036 (Table 4). The specification teaches that , i n contrast to the other antibodies, T036 displayed dose-dependent enhancement of TBEV and POWV-LB RVP infection [0346]. The specification does not teach how to use an antibody having this deleterious functionality in any form (e.g. bispecific, monoclonal) , in any pharmaceutical composition, or for any method of prophylaxis or treatment. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT DANIEL C GAMETT , Ph.D., whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-1853 . The examiner can normally be reached on FILLIN "Work schedule?" \* MERGEFORMAT M-W 9:00 am-5:30pm, EST . Please note the examiner’s part-time schedule . 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