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. Application Status The amended claims filed October 29, 2023 are acknowledged. Claims 7 and 9 are amended. Claims 1-14 are pending and under examination herein. Specification The disclosure is objected to for the following informalities: The specification recites “diffuse large cell lymphoma” at ¶ 0022 and ¶ 00108. This type of cancer appears to be referred to in the art as “diffuse large B- cell lymphoma”. Consider, for example , Durani ( Leukemia & Lymphoma (2021) 62(13): 3078-3086; see abstract and title) and Klitgaard (US 2011/0250203 A1; cited in IDS; see ¶ 0122). Appropriate correction is required. Claim Objections Claim s 10 and 13 are objected to because of the following informalities: Claim 10 recites that the immune cell ( singular ) of claim 9 is “at least one” selected from several possible immune cell types . For clarity, it is suggested that “at least one” be removed since the earlier claim refers to a single cell , which cannot be more than one immune cell type simultaneously. By way of example, a natural killer (NK) cell cannot simultaneously be a T cell. Claim 13 recites “diffuse large cell lymphoma”. For the reasons set forth in the objection to the specification above, it is suggested that this be amended to “diffuse large B- cell lymphoma.” Appropriate correction is required. Claim Rejections - 35 USC § 112 (a) 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. (1) Claim s 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. “[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co. , 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) ( en banc) (quoting Univ. of Rochester v. G.D. Searle & Co. , 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar , 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). 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). For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly , 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad , 598 F.3d at 1350 (quoting Eli Lilly , 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech , 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs. , 97 USPQ2d 1870, 1875 (Fed. Cir. 2011). Amgen Inc. v. Sanofi, Aventisub LLC, 872 F.3d 1367 (Fed. Cir. 2017) supported previous decisions ( Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011); AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. , 759 F.3d 1285 (Fed. Cir. 2014)) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. Thus, claiming an antibody by describing the invention by what it does (function) rather than what it is (structure) is invalid. This can be overcome if a relevant number of species with structure/function correlation is known to the art or present in the specification. The claimed invention . The nature and scope of the claimed invention at issue is an antibody or antigen-binding fragment thereof specifically binding to CD5 (as in claim 1 and its dependent claims 2-3) or a chimeric antigen receptor comprising an anti-CD5 antigen-binding site (as in claim 4 and its dependent claims 5-14), wherein the heavy chain variable region (VH) comprises a heavy chain CDR1 having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 10, 18, and 26, a heavy chain CDR2 having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 3, 11, 19, and 27, and heavy chain CDR3 having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 12, 20 and 28, and a light chain variable region (VL) comprises a light chain CDR1 having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 14, 22, and 30, a light chain CDR2 having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 7, 15, 23, and 31, and a light chain CDR3 having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 8, 16, 24, and 32. This claim language fails to satisfy the written description requirement because the respective CDRs in heavy chain and the light chain may be “mixed and matched” to form up to 64 combinations each of heavy chain CDRs (4×4×4) and light chain CDRs (4×4×4), totaling up to 4096 unique combinations of heavy and light chain CDRs in the claimed anti-CD5 antibody or antigen-binding site. As set forth below, Applicant's disclosure and the state of the prior art do not support that Applicant is in possession of all possible combinations of heavy chain and light chain CDR pairings as presently claimed. State of the prior art . It is well established in the art that the formation of an intact antigen-binding site in an antibody usually 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) that provide the majority of the contact residues for the binding of the antibody to its target epitope. See Almagro ( Frontiers in Immunology (2018) 8: 1751) at “The IgG Molecule” ( page 3 ) and Figure 1. Sela- Culang ( Frontiers in Immunology (2013) 4: 302) further teaches, “A major focus in analyzing the structural basis for [antigen] recognition has been in identifying the exact boundaries of the CDRs in a given [antibody]. It is a common practice to identify paratopes through the identification of CDRs” (page 3). Harris ( Trends in Pharmacological Sciences (2016) 37(3): 220-230) teach es that CARs are synthetic constructs typically comprising a single-chain antibody fragment ( scFv , VH-linker-VL, or VL-linker-VH), an extracellular stalk (hinge) region, a transmembrane domain, and one or more intracellular signaling domains (page 223, “Chimeric Antigen Receptor: Structure and Signaling”). The scFv comprises antibody heavy- and light-chain variable fragments, connected by a long flexible peptide linker, that form the antigen-binding domain of the CAR construct. CAR scFvs likewise comprise CDRs that are critical for imparting their antigen recognition properties. Although the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. Ni ( The Protein Journal (2024) 43: 683-696) teaches, “Mutations, even one mutation, introduced in the CDRs through [somatic hypermutation] can change the binding properties and repertoire of antibodies. However, how just one-point mutation can dramatically change the recognition profiles of the antibody is still unclear” (Introduction). Furthermore, while affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody, those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori (Almagro, pages 3 and 6-7). Accordingly, one of ordinary skill in the art would be unable to predict whether a n antibody for which any one of the CDR sequences is substituted for another, such as presented in the instant claims, would retain the function of binding to CD5 as required by the instant claims. Exemplary anti-CD5 antibodies and/or CARs having a specific and defined combination of heavy chain and light chain CDRs have previously been set forth in the art. See , for example, Wada ( Stem Cell Reviews and Reports (2020) 16: 369-384; cited in IDS), Mamonkin (US 2020/0405811 A1; cited in IDS), Klitgaard (US 2011/0250203 A1; cited in IDS), Brenner (WO 2016/172606 A1), and Rezvani (WO 2022/ 221548 A1). Scope of species disclosed in original specification . Example 1 (pages 38- 44 ) sets forth the preparation of four scFvs (clones #1, #4, #11, and #14) specifically binding to CD5, the CDR sequences of which are summarized in Table 1 (pages 40-41) and reproduced below. CD5#1-CAR comprises three heavy chain CDRs comprising the amino acid sequences of SEQ ID NOs: 2-4, respectively, and three light chain CDRs comprising the amino acid sequences of SEQ ID NOs: 6-8, respectively; CD5#4-CAR comprises three heavy chain CDRs comprising the amino acid sequences of SEQ ID NOs: 10-12, respectively, and three light chain CDRs comprising the amino acid sequences of SEQ ID NOs: 14-16, respectively ; CD5#11-CAR comprises three heavy chain CDRs comprising the amino acid sequences of SEQ ID NOs: 18-20, respectively, and three light chain CDRs comprising the amino acid sequences of SEQ ID NOs: 22-24, respectively; and CD5#14-CAR comprises three heavy chain CDRs comprising the amino acid sequences of SEQ ID NOs: 26-28, respectively, and three light chain CDRs comprising the amino acid sequences of SEQ ID NOs: 30-32, respectively. The scFv constructs above were integrated into CARs that were expressed in natural killer (NK) cells (e.g., Example 1.3 at page 42). Example 2 discloses that the four CAR constructs exhibited specificity for and cytotoxic activity against CD5-expressing cancer cell lines (e.g., Example 2; Figures 3-4). The CAR constructs showed decreased cytotoxicity against normal T cells expressing CD5 (e.g., Example 2; Figure 6). 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 sets forth four specific anti-CD5 antibody clones, each having a specific combination of three heavy chain CDRs and three light chain CDRs as enumerated above , which have demonstrated binding activity against CD5. 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. As demonstrated by the state of the art, a full complement of heavy chain and light chain CDRs together confer the antigen-binding properties of an antibody, but it is not possible to reliably predict how mutations (even those conferred through affinity maturation) or substitutions may affect binding of the complete antibody (comprising a VH and a VL). Accordingly, one cannot “mix and match” CDRs as set forth by the present claims absent a clear showing that a relationship between the specifically claimed structures and function of CD5 binding exists. Conclusion . For all of the reasons presented above, one of skill in the art would not know which of the countless other antibodies encompassed by the highly general structural requirements of the claims would also possess the required functional activity of specifically binding to CD5 . 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, the Applicant did not possess the full genus of anti-CD5 antibodies as broadly claimed at the time the application was fi led . (2) Claim s 11-14 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 providing a pharmaceutical composition for treating a CD5-expressing cancer , does not reasonably provide enablement for a pharmaceutical composition used for preventing cancer . 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 amount of guidance, direction, and exemplification disclosed in the specification, as filed, would not be sufficient to enable the skilled artisan to use the claimed invention at the time the application was filed without undue experimentation. MPEP § 2164.01 states: “The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde , 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. In re Wands , 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. In re Wands , 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).” There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors, which have been outlined in the Federal Circuit decision of In re Wands , 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), include, but are not limited to, the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed. See also Ex parte Forman , 230 USPQ 546 (BPAI 1986). Nature of the invention / Breadth of the claims . The nature of the invention at issue is a pharmaceutical composition for preventing cancer (as recited in claims 11-14 ), which comprises an immune cell comprising the CAR of claim 4. The instantly claimed CARs recited in claim 4 are further discussed in the 35 U.S.C. § 112(a) written description rejection above. State of the prior art / Predictability of the prior art . Debela ( SAGE Open Medicine (2021) 9: 20503121211034366) teaches that treating cancer has been a highly complex process, but that some therapeutic strategies have shown promise in patients. Conventional treatment approaches known in the field include surgery, chemotherapy, and radiotherapy (Abstract; page 2). More recent efforts have focused on the use of stem cell therapy, targeted drug therapy (e.g., monoclonal antibodies or small molecule inhibitors), gene therapy, and others (e.g., Abstract; pages 2-5). At the time of filing of the instantly claimed invention, it was understood in the art that CD5 is expressed in malignancies such as T-cell acute lymphoblastic leukemia (ALL), thymic carcinoma, and a small subset of diffuse large B-cell lymphoma (DLBCL) , as well as in normal T cells . See, e.g., Wada ( Stem Cell Reviews and Reports (2020) 16: 369-384; cited in IDS), Durani ( Leukemia & Lymphoma (2021) 62(13): 3078-3086; supra ), and Hishima ( The American Journal of Pathology (1994) 145(2): 268-275). Clinical trials aimed at proving preventative cancer activity by a specific intervention are largely infeasible, due to the impossibly large number of subjects and an equally impossibly long timeframe. Although cancer is a common disease, specific types of cancer are still relatively infrequent events in an otherwise healthy population. Therefore, trials with cancer incidence as endpoints would necessarily involve several thousands of subjects followed for several decades. Such logistic difficulties have precluded cancer prevention trials with cancer incidence as an endpoint in all but a select few malignancies with treatments such as tamoxifen and finasteride . See review by Lee ( Nature Reviews Cancer ( 2011 ) 11: 211-218 ) at page 211; Cancer Prevention Overview (PDQ®)–Patient Version, National Cancer Institute. Working examples / Guidance in the specification . As set forth in the 35 U.S.C. § 112(a) written description rejection above, the four CAR constructs of the invention display cytotoxic activity (i.e., are capable of being used as a treatment) against CD5-expressing cancer cells (e.g., Example 2) . However, the specification does not provide a showing that a pharmaceutical composition comprising the CARs of the invention can be effectively used as a preventative agent against cancer. Conclusion . Upon careful consideration of the factors used to determine whether undue experimentation is required, the amount of guidance, direction, and exemplification disclosed in the specification, as filed, is not deemed sufficient to have enable the skilled artisan to use the claimed pharmaceutical composition at the time the application was filed for prevent ing cancer without undue and/or unreasonable experimentation. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Elizabeth A Shupe whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703) 756-1420 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday to Friday, 9:30am - 6:00pm EST . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. 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