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. Claim Objections The examiner objects to claim 13 because it does not end in a period. Specification The disclosure is objected to because of the following informalities: Table 5 at page 44 is illegible. It also does not appear to provide SEQ ID NOs: for each of the sequences that seem to be represented in the leftmost column. Tables 6-9 at pages 46-49 suffer similar deficiencies. Table 15 starting at page 65 does not provide SEQ ID NOs: for the sequences within it. See 37 CFR 1.831(c) and MPEP 2412.02. Appropriate correction is required. Applicant should ensure that all sequences shown in the specification are represented in the sequence listing accompanying this application. A replacement sequence listing may be necessary to accomplish this if the current sequence listing does not account for all of the sequences in the specification . Drawings The drawings are objected to because Figures 35 and 4 5-49 show sequences but do not accompany each one with a SEQ ID NO:. See 37 CFR 1.831(c) and MPEP 2412.02. In addition, the material in the table under Figures 53(a) and 53(b) is illegible; the same is true of Figures 54-56. What appear to be numbers above the amino-acid sequence s in Figures 45-49 are illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Applicant should ensure that all sequences shown in the Figures are represented in the sequence listing accompanying this application. A replacement sequence listing may be necessary to accomplish this if the current sequence listing does not account for all of the sequences in the drawings . 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 1-14 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 1 refers at line 4 to “an amino acid sequence of protein A56 represented by SEQ ID NO:1.” It then goes on to refer generally to “the amino acid sequence of protein A56.” As applicant’s own disclosure shows, the amino acid sequence of protein A56 varies by species. (See Figure 35, e.g.) It is unclear whether the “amino acid sequence of protein A56” at lines 7, 9, 11, and 13 is limited to that set forth in SEQ ID NO:1. The antecedent basis for “protein A56” at lines 7, 9, 11, and 13 is unclear. See MPEP 2173.05(e). Clarification is required. Claims 2-14 depend from claim 1 and do not rectify the indefiniteness, so they must also be rejected under 35 U.S.C. 112(b). Claim 3 requires that the binding molecule or fragment thereof contains certain amino acids in particular regions relative to protein A56. Claim 1, however, describes a binding molecule or fragment thereof that binds to protein A56. It is not clear how the structure of the binding molecule or fragment thereof corresponds to protein A56 per se. Clarification is required. Claim 6 is the binding molecule or fragment thereof, wherein it is “used to” decrease cancer-cell burden. It is unclear whether claim 6 claims the composition of matter or a method of using it. Claim 6 refers to coadministration with an oncolytic virus, but it is unclear whether it refers to a composition comprising the binding molecule or fragment thereof and a virus or to an actual active step of coadministration. See MPEP 2173.05(u) (“use” claims). Clarification is required. Claims 7 and 8 depend from claim 6 and do not rectify the indefiniteness, so they must also be rejected under 35 U.S.C. 112(b). 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 1-14 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. For this rejection, the examiner interprets all instances of “protein A56” as referring to the amino-acid sequence represented by SEQ ID NO:1. Claim 1, from which all claims depend, is drawn to a binding molecule or fragment thereof that specifically binds to a conformational epitope of A56 protein that contains certain amino acids at particular positions. Specifically, relative to SEQ ID NO:1, claim 1 requires a basic or nucleophilic amino acid somewhere at positions 60-63; a nucleophilic amino acid somewhere at positions 44-50 (presumably within SEQ ID NO:1); a nucleophilic amino acid somewhere at positions 53-59 (presumably within SEQ ID NO:1); a nucleophilic amino acid somewhere at positions 85-90 (presumably within SEQ ID NO:1); and a basic or nucleophilic amino acid somewhere at positions 91-94 (presumably within SEQ ID NO:1). Critically, claim 1 is open to all binding molecules and fragments , having any structure, that bind to any of the specified conformational epitope s . The as-filed disclosure does not demonstrate possession of the breadth of the claims in view of the prior and contemporaneous art. First, the claims do not limit the structure of the “binding molecule” or its “fragment.” The specification identifies a “binding molecule” broadly as being “ a biological molecule having capacity to specifically bind to A56 ,” i.e., any molecule of any structure that is capable under some conditions of binding A56 with some specificity. (See page 15, lines 5-6.) As of the effective filing date, skilled artisans understood that A56 binds several proteins as part of its normal function. DeHaven et al. (2011, Journal of General Virology 92: 1971-1980; reference U ) teaches that Vaccinia virus (VACV) A56 protein binds to K2 serine protease and to the VACV complement control protein (VCP) , anchoring them to cell surfaces. (Abstract; page 1791.) DeHaven does not, however, identify the site on A56 where K2 and VCP bind. Skilled artisans were also aware that the A56-K2 complex binds to components of the viral fusion complex. See Hong et al. (2020, Journal of Virology 94: e00093-20 ; reference V ) at abstract and page 1. Hong likewise does not teach which portion of A56 binds to K2, VCP, or the viral fusion complex. The identification of conformational epitopes was likewise unpredictable as of the effective filing date. Sanchez- Trincado et al. (2017, Journal of Immunology Research Article ID 2680160; reference W ) teach that while a linear epitope can be predicted from the primary structure (sequence) of an antigen, prediction of conformational epitopes has “lagged behind” for two practical reasons. (Page 6, column 1; page 8, column 1 ; see Figure 5.) First, identifying a conformational epitope requires knowledge of the three-dimensional structure of an antigen second, isolating conformational B-cell epitopes from their protein context for selective antibody production is a difficult task that requires suitable scaffolds for epitope grafting. (Page 8, column 1.) Sanchez- Trincado writes that “ prediction of conformational B-cell prediction is currently of little relevance for epitope vaccine design and antibody-based technologies .” (Page 8, column 1.) A diligent search of the prior and contemporaneous art revealed no three-dimensional structure for protein A56, so the methods described by Sanchez- Trincado would not have been available as of the effective filing date for the skilled artisan to have predicted the structure of any conformational epitope of A56. Even if the binding molecule were limited to antibodies/CARs or fragments thereof, and even if the conformational epitope of A56 were known, a round the time of the invention, skilled artisans also recognized the unpredictable impact on antibody/CAR binding of changing amino acids within an epitope. See Michieli et al. (US 20200407452; reference A ) at paragraphs 189, 194 (abrogation of antibody binding due to mutation of epitope within MET); Pantaleo et al. (US 20190062431; reference B ) at paragraph 112 (abrogation of antibody binding due to mutation of epitope within PD-1). Indeed, some antibodies can distinguish between epitopes that differ by a single amino acid. See Kornete et al. (2018, Journal of Immunology 200: 2489-2501; reference X ) at page 2493, column 2. Claim 1 permits extensive variability within the conformational epitope. The claim allows that there can be any basic or nucleophilic acid at positions 60-63 in SEQ ID NO:1’s protein A56. T he nucleophilic amino acids are serine (S) , histidine (H) , threonine (T) , and cysteine (C) , while the basic amino acids are lysine (K) and arginine (R). See Horowitz et al., US 20080152657 (reference C ) at paragraph 80. As such, the region of SEQ ID NO:1 at positions 60-63 (which is Ala-Lys-Ser-Asp or AKSD ; see appendix to Office action ) contains just one basic amino acid (K) and one nucleophilic amino acid (S). The sequence H KSD at positions 60-63 would also meet the structural requirements of claim 1 , however, since histidine is a nucleophilic amino acid . A ccording to the above-cited art teachings, though, the skilled artisan would not necessarily have expected that this sequence would bind the same antibody as the native A KSD sequence would. Claim 1 in fact permits variation among six choices (S, H, T, C, K, and R) at any of 28 amino-acid positions (44-50, 53-59, 60-63, 85-90, and 91-94) within protein A56 . This wide variety of permissible A56 variations would have been expected to impact the ability of a given antibody to bind the conformational epitope. For these reasons, skilled artisans did not recognize a structure-function correlation between a binding molecule’s structure and its ability to bind the conformational epitopes encompassed by claim 1. A review of the as-filed disclosure does not reveal such a structure-function correlation either. Applicants acquired antibodies to A56 through a commercial provider, then used phage-library techniques to assess A56 binding profiles. (Page 39, lines 10-24.) The disclosure is not specific about the nature or source of antibodies (e.g., polyclonal vs. monoclonal, source animal, etc.). The specification focuses on ten antibodies that have high specificity for A56. (Page 40, lines 14-21.) The specification explains that five antibodies —Ab13, Ab16, Ab18, Ab01, and Ab19— were used to identify epitopes on A56. (Page 41, lines 16-17.) The drawings show that these five antibodies do not bind the same portion of A56. Figures 45-49 are illustrative: It is clear from Figures 45-49 that the five antibodies applicants tested do not actually share a conformational epitope. The specification also discloses no information about the structure of these antibodies beyond the fact that they are antibodies of some sort. The as-filed disclosure therefore does not supply a sufficient structure - function correlation between a given binding molecule’s structure and its ability to bind the conformational epitope as it is set forth in claim 1. “F or inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. ” MPEP 2163(II)(A)(3)(a)(ii). D isclosure of only a method of making the invention and the function may not be sufficient to support a product claim . Furthermore, the disclosure of a “newly characterized antigen” and a functional genus claim to corresponding binding molecules is insufficient to meet the description requirement. See Amgen Inc. v. Sanofi , 872 F.3d 1367, 1378 (Fed. Cir. 2017) (antibodies) . The fact that making and using binding molecules with the claimed function might have been routine in the art might show an enabling disclosure but does not address possession. Id. (citing Ariad Pharms., Inc. v. Eli Lilly & Co. , 598 F.3d 1336, 1345 (Fed. Cir. 2010) ( en banc) (observing that written description and enablement are separate requirements of 35 U.S.C. 112)). Claim 1 is not supported by adequate written description because the as-filed disclosure does not demonstrate possession of the invention as the claims recite it . Claims 2-14 depend from claim 1 and do not rectify the issue, so they must also be rejected under 35 U.S.C. 112(a) for lack of written description. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of copending Application No. 18/281,870 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The ’870 application claims an immune cell expressing a chimeric antigen receptor (CAR) that specifically binds to a protein antigen; this protein antigen may be a conformational epitope of protein A56. (Claim 3.) Specifically, the conformational epitope of the ’870 application ’s CAR includes a basic or nucleophilic amino acid somewhere at positions 60-63; a nucleophilic amino acid somewhere at positions 44-50 of protein A56 ; a nucleophilic amino acid somewhere at positions 53-59 of protein A56 ; a nucleophilic amino acid somewhere at positions 85-90 of protein A56 ; and a basic or nucleophilic amino acid somewhere at positions 91-94 of protein A56 . (Claim 3.) The broadest reasonable interpretation of examined claim 1’s “binding molecule” includes a CAR, as informed by applicant’s definition at page 15, lines 5-6, of the as-filed specification. As such, the CAR of the ’870 application anticipates the claimed “binding molecule” that binds the same epitope. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT LORA E BARNHART DRISCOLL , whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-1928 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 7:00-4:00 p.m. 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 Patricia Engle , can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-6660 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Lora E Barnhart Driscoll/ Primary Examiner, Art Unit 3991