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. Claim Status Claim s 1- 20 as filed o n 18 October 2023 are pending and under examination. 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 -3, 5-10, 12-20 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. Claims 1-2, 10, and 18 reference tables in the claim from the specification. MPEP 2173.05 (s) indicates where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). Claims 39 and 42 incorporate these terms by being dependent on claims that include tables and fails to correct the issue. Claims 3, 5-9, 12-17, and 19-20 are included in this rejection as they include the limitation of Table 2 without correction either by not further limiting the CDR sequences or allowing percent identity which would incorporate the sequences of Table 2. Claim s 4 and 11 are not including in the rejection as it is limited to pairs of heavy and light chains with fully defined CDRs. 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 1-3, 5-10, 12-20 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. MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or it may be satisfied by the disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010). Scope of the Claimed Genus Claim 1 is to a nucleic acid encoding a CD19 binding CAR. Subparts (a) and (b) are to specific combinations of six CDRs in the CD19 binding domain. Subpart (c) is to CDRs of Table 2. Table 2 comprises 12 sets of CDRs. The CDR sequences of Table 2 identify LCDR 1, 2, and 3 and HCDR 1, 2, and 3 and the claim only allows the swapping of the 12 LCDR1s with each other, LCDR2s with each other, etc. But this mixing and matching produces numerous combinations of CDRs with unknown binding activity. Claim s 2 , 10, and 18 repeat this limitation and allow for mixing and matching. Claims 3 and 5 allows for percent identity of the light and heavy chains which in combination of the mixing and matching of claim 2 from which it depends allows for variation of the CDRs of the heavy and light chains producing CDR combinations with unknown binding activity. Claims 6-9, 12-17, and 19-20 provide no further limitations to the CDRs of the claims from which they depend. Summary of Species Disclosed in the original specification Applicant discloses 12 CD19 binding domains with fully defined six CDRs in Table 2 pages 33-35 of the instant specification. State of the Relevant Art Cluster of Differentiation 19 (CD19) is a 85-95 kDa transmembrane cell surface glycoprotein receptor. CD19 is a member of the immunoglobulin superfamily of proteins and contains two extracellular Ig-like domains, a transmembrane domain, and an intracellular domain. CD19 modifies B cell receptor signaling by lowering the triggering threshold for B cell receptor for the antigen, it coordinates with additional proteins to regulate essential B cell signaling. CD19 is associated with multiple kinases and pathways. CD19 is relevant as a target in B cell malignancies as its expression is tightly regulated on normal B cells only being expressed on early B cell precursors and mature B cells. It is a known therapeutic target in cancer (Schneider (US 20190106492 A1) (IDS) [0006]-[0007]). A chimeric antigen receptor (CAR) comprise an antibody or antigen-binding fragment, a transmembrane domain, and an intracellular signaling domain which can comprise multiple signaling domains. The extracellular domain of the CAR is the antibody or antigen binding domain that comprises a variable heavy and variable light domain which comprise 3 CDRs in each domain. The six CDRs of the antigen binding domain determine the specific binding domain of the CAR like a traditional antibody (June (WO 2016 /019300 A1) (IDS) (Figure 1A and 1B and page 2 starting in line14 to page 6 line 14) and Schneider (US 20190106492 A1) (IDS) ([005]-[006]). It has been established for decades in the art that the formation of an intact antigen-binding site in a conventional antibody requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro et. al., Front. Immunol. 2018; 8:1751 (PTO-892) (see Section “The IgG Molecule” in paragraph 1 and Figure 1). While affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody (page 3 “The IgG Molecule”, second and third paragraphs), those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori. E.g., id., (page 6 ending paragraph onto page 7). Further, the skilled artisan has long recognized that even minor changes in the amino acid sequences of the VH and VL, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al., Proc. Nat’l Acad. Sci. USA, 79:1979-83 (1982) (PTO-892). Rudikoff teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. E.g., Abstract. Similarly, Brown et al., J. Immunol., 156(9):3285-91 (1996) (PTO-892), teach that although a single amino acid change in CDR2 of heavy chain of a particular antibody was tolerated, the antibody lost binding upon introduction of two amino acid changes in the same region. Brown, p. 3290 and Tables 1 and 2. Table 1 of Brown shows that even a conservative substitution does not ensure that functionality of the antibody is retained. These older citations are supported my more recent discoveries of why these substitutions change antibody activity. Marvin et. al., Biochemistry, 42(23):7077-7083 (2003) (“Marvin” PTO-892) teaches that changes to the heavy and light chains altered binding affinity (Table 2) with changes to the CDR having large impacts but the changes with the largest impact were from residues in the CDR, but not from ones interfacing with the antigen ( Page 7081 in col 1 “Conclusions and Discussion” and Page 7082 in Figure 4). The earlier work of Rudikoff and Brown is confirmed by Chiu et al., Antibodies, 8(55):1-80. (2019) (“Chiu” PTO-892). Chiu teaches that the complementarity - determining regions (HCDRs 1-3 and LCDRs 1-3) determine antigen binding requiring specific sequences and orientation of those sequences to properly form tertiary structures that can recognize and bind antigens (Page 4 in 1.2.2 first and last paragraphs and Figure 3). Chiu teaches that antibody modeling with known LCDRs 1-3, HCDR1 and HCDR2 could not predict HCDR3 In the decades since Rudikoff the field has increased understanding of antibody engineering. Structure-Based antibody engineering is unable to predict antibody sequences (Page 6 in 1.2.6, Pages 10-11 in Section 2 in particular second paragraph of page 11). Chiu notes the advancement in antibody engineering but notes it is still not possible to predict the point mutations that would improve affinity in both antibodies and multispecific molecules (Page 51 in lines 6-12). Chiu teaches that antibody-drug conjugates (ADCs) comprise antibodies that act as binding domains and that being in an ADC does not change the binding expectations of the antibody within the ADC (page 32 in Section 3.3 in particular par 1 and 4). In general, absent at least the conserved structure of the CDRs of the heavy chain and light chain of an antibody or antigen-binding domain , the skilled artisan generally would not be able to visualize or otherwise predict an antibody or antigen-binding domain with a particular set of functional properties would look like structurally. Are the disclosed species representative of the claimed genus? MPEP § 2163 states that 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. The specification disclose s 12 species of antigen binding domains. Given the variability encompassed by the genu s of anti-CD19 binding domains described species therefore cannot be considered representative of the genus. An antibody as defined by its CDRs provides only the binding activity of that antibody not of any variation to those sequences either by changes to amino acids or the mixing and matching of CDRs to produce new combinations./ Identifying characteristics and structure/function correlation In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that the skilled artisan as of the effective filing date would have expected to convey the claimed binding activity. As noted above, the art identifies the CDRs of an antibody as the structure that provides its function. A single change to an amino acid in one CDR changes its binding activi ty . The disclosure does not provide one of skill in the art with structures that provide the function of the claims except for the twelve CD19 binding domains where all six CDRs are fully defined in their sequences. Conclusion: For all of the reasons presented above, one of skill in the art would not know which of the countless other compositions encompassed by the claims that meet the highly general structural requirements of the claims would also possess the required functional activity . Therefore, the skilled artisan would not reasonably conclude that the inventors had full possession of compositions as broadly claimed at the time the application was fi led . Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, Applicant was not in possession of the invention as claimed. This rejection could be overcome by limiting the claims to specific combinations of six CDRs without mixing and matching. Examiner points to subparts (a) and (b) of claim 1 for an example of language that could overcome this rejection. The claims can recite less than 100% identity outside the 6CDRs, which need to be defined with 100% identity as a set. 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 . Claims 1- 13, and 15-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18381258 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The reference application sequence match the instant sequence. The CDRs of instant claim 1 subparts (a) and (b) and of Table 2 match the sequences of claim 1 of the reference application. Regarding claims 1-5 and 10-12, the reference application recites a vector comprising a vector comprising a promoter and a nucleic acid sequence that encodes the CAR of the instant application wherein the CAR comprises an scFV (claims 1 and 15). Regarding claims 6-9, the reference application recites a CD28 transmembrane domain, a signaling domain of OX40 and CD3 zeta (claims 1-7 and 16). Regarding claim 13, the reference application recites a modified cell comprising the vector encoding the CAR (claim 17). Regarding claims 14-15, the reference application recites a switch receptor comprising a first polypeptide of PD1 and a dominant negative receptor comprising a truncated variant of TIM-2, and a polypeptide that enhances an immune cell function of IL-7 (claim 17). Regarding claim 16, the reference application recites a population of modified cells (claim 19). Regarding claims 17-18, the reference application recites a method of treating a mammal having a disease associated with CD19 expression by administering the modified cells of the instant claims (claims 19-20). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claims 1-2, 13-14, 17, and 19-20 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18381258 in view of Schneider (US 20190106492 A1) (IDS). The recitations of the reference application from the previous double patenting rejection are incorporated here in full. The reference application does not recite the modified cell is a modified immune cell of NK cells, a modified NK T cell, or a modified T cell. The reference application does not recite an autologous o allogenic modified T cell. The reference application does not recite the disease associated with CD19 expression is cancer. These deficiencies are filled by Schneider. Schneider teaches the use of CD19 binding CAR T cells (abstract and Figure 1) wherein the T cells are allogenic or autologous ([0262]). Schneider further teaches the sue of the CAR T cells in a method of treating cancer ([0260] and claim 45). It would have been obvious at the time the application was filed to substitute the generic modified cells and generic disease of the reference claim with the modified autologous T cells for use in a method of treating cancer taught by Schneider. These substitutions would have been obvious as substitution of specific species of cells and disease to be treated with generic cells and disease of the reference claims. One of skill in the art would have been motivated to use art taught working autologous T cells in the art taught working method of treating cancer with a CD19 binding CAR T cell taught by Schneider. There would have been reasonable expectation of success as Schneider teaches the use of modified cells that express a CAR that binds CD19 in autologous T cells for use in a method of treating cancer. This is a provisional nonstatutory double patenting rejection. Conclusion No claims allowable. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT FRANCESCA EDGINGTON-GIORDANO whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-8232 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon - Fri 8:00 - 5:00 . 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 Julie Wu can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-5205 . 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. /F.E./ Examiner, Art Unit 1643 /Meera Natarajan/ Primary Examiner, Art Unit 1643