CTNF 18/290,259 CTNF 101424 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. DETAILED ACTION Claim Status 2. Claims 1-15 are under consideration. Information Disclosure Statement 06-52 AIA 3. The information disclosure statement (IDS) submitted on 31 October 2024 was filed after the mailing date of the Instant Application on 10 November 2023 . The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. 06-49-06 AIA 4. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Specification 06-16 AIA 5. Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided. 6. The use of the terms “Stemspan” on page 9 (lines 11 and 16) and page 35 (lines 17 and 22); “Vi-Cell” on page 36, line 11; “CryoStor” on page 36, line 29; “OpTmizer” on page 37, line 23; and “ImmunoCult” on page 38, lines 24 and 30, which is a trade name or a mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Note that “Stemspan”, “CryoStor”, “OpTmizer”, and “ImmunoCult” are merely examples and all improper uses of trademarks in the specification should be identified by Applicant and properly addressed. Claim Objections 07-29-01 AIA 7. Claim s 1, 3, 5, and 11 are objected to because of the following informalities: Regarding claim 1, the abbreviation “iNKT” should appear after the first instance of the word in line 1. Regarding claim 3, “comprises” should be replaced with “is” as it refers to only one vector. Regarding claim 5, “district” appears to be a typo and should be replaced with “distinct”. Regarding claim 11, the comma before “or” should be removed . Appropriate correction is required. Claim Rejections - 35 USC § 112(a) 07-30-01 AIA 8. 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. 07-31-03 AIA 9. Claim s 1-15 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 isolated transgenes, vectors, and cells, and methods of using the same , does not reasonably provide enablement for unisolated transgenes, vectors, and cells or methods of their use in producing a transgenic animal . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. In making a determination as to whether an application has met the requirements forenablement under 35 U.S.C. 112 ¶ 1, the courts have put forth a series of factors. See, In reWands , 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include: (1) the breadth of the claims, (2) the nature of the invention, (3) the relative skill of those in the art, (4) the presence or absence of working examples, (5) the amount of direction or guidance provided, (6) the state of the prior art, (7) the level of predictability in the art, and (8) the quantity of experimentation necessary. The claims recite methods for using vectors and cells, which includes transgenes and transgenic animals respectively, since they are not isolated; the claims can further read on the production of a transgenic animal. The additional transgene(s) could be a CAR, which comprises antibody binding domains, or an antibody. The nature of the invention are methods of producing an iNKT cell. The level of skill of one of ordinary skill in this art is high. The specification does not indicate that the vectors and host cells are isolated. Therefore, these words will be given their broadest reasonable interpretation to one of ordinary skill in the art as discussed above. With respect to transgenes within animals and transgenic animals themselves, none were made here. With respect to the unisolated host cells and vectors as transgenes, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall et Al., Theriogenology, 1996, 45: 57-68). The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine et Al., J. Biotechnol., 1994, 34: 269- 287). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et Al., Current Opinions in Biotechnology, 1992, 3: 548-553). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, 2009, 32: 107-121) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (Pg. 116, Paragraph, second). Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the CAR, antibody, and antibody fragments of the instant claims. The Examiner notes here, in addition to these issues, even assuming arguendo PHOSITA could make a host organism with functional transgene that encodes the instantly recited antibody, there is no predictability that the host will survive its expression. The transgene depends on the host for function and harm to the host, including death, renders the transgene nonfunctional and thus not enabled. The art is well-aware of side effects caused by therapeutic antibodies or antigen binding domains of the CAR(s), such as the ones instantly recited. In a transgenic cell or animal that expresses the same, the antibody or binding domain will exert any possible side effect it can. It is not administered but chronically present and so such side effects are chronic and potentially more serious than any from an administered antibody. Hansel (Nat. Rev. Drug. Discov., 2010, 9: 325-337) teaches in their table 1 on page 328 numerous exemplary side effects from licensed monoclonal antibodies to include: increased bleeding risk, infection, heart failure, cancer, thyroid disorder, autoimmune reactions, and cytokine release syndrome (CRS) to name only a few. One or more such effects, or similar, may occur with the therapeutic antibody instantly recited when administered and indeed be exacerbated by chronic exposure due to internal expression. The instantly encoded antibody or antigen binding domain may very well target related or unrelated proteins in the transgenic host, leading to such side effects. For all these reasons, transgenes in transgenic animals and the animals themselves are not enabled. At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the cell, vector, polynucleotide, and transgene claims to specify they are not in a transgenic animal using, for example, “isolated”. Applicant may consider using “purified” in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above. For methods claims, Applicant may also consider adding “ in vitro ” before method in line 1. In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use functional transgenes and transgenic animals encompassed by the instant claims. Claim Rejections - 35 USC § 112(d) 07-36 AIA 10. The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. 11. Claims 7-8 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The claims recite that the HSC is derived from a pluripotent stem cell. However, Examiner is unaware of any other cell sources for HSC thus making it the only option and therefore, claims 7-8 are not further limiting. Said another way, they only recite inherent features of the HSC of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form so long as no duplicates are made, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 103 07-20-aia AIA 12. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. 07-23-aia AIA 13. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 07-21-aia AIA 14. Claim s 1-5, 7-8 ,and 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Smith (PNAS, 20 January 2015, 11(2): 1523-1528) in view of Xiao (US 20220000921 A1; CON to 19 June 2019) . Regarding claims 1-2, 4, and 12-13, Smith teaches “a new method to generate large numbers of iNKT cells in mice through T-cell receptor (TCR) gene engineering of hematopoietic stem cells (HSCs)” (¶ 1), thus showing that differentiation of HSCs into iNKT cells is possible with just TCRs (Figure 2A). Smith does not teach adding a chimeric antigen receptor (CAR) or transgenes to the HSCs. However, Xiao teaches a method of making a variety of cells derived from stem cells: “Embodiments include a modified cell comprising an isolated nucleic acid comprising a first nucleic acid and second nucleic acid, the first nucleic acid encoding a chimeric antigen receptor (CAR), the second nucleic acid encoding a therapeutic agent…” (Abstract) and “The stem cells can be adult stem cells, embryonic stem cells, more particularly non-human stem cells, cord blood stem cells, progenitor cells, bone marrow stem cells, induced pluripotent stem cells, totipotent stem cells or hematopoietic stem cells. A modified cell can also be a dendritic cell, a NK-cell, a B-cell or a T cell selected from the group consisting of inflammatory T-lymphocytes, cytotoxic T-lymphocytes, regulatory T-lymphocytes or helper T-lymphocytes.” (¶ [0151]). Therefore, Xiao’s method would have been predictably useable to make an iNKT cell, which is a cell type derived from stem cells and similar to the immune cells made in Xiao above. A reasonable expectation of success would have been had by a person of ordinary skill in the art. Xiao also teaches “In embodiments, a single vector contains the isolated nucleic acid encoding the first CAR, the therapeutic agent, and the second CAR or TCR. In embodiments, a first vector contains the first nucleic acid encoding a first CAR and a nucleic acid encoding one or more therapeutic agents, and a second vector contains the nucleic acid encoding the second CAR or TCR.” (¶ [0131]) and “In embodiments, the therapeutic agent includes a cytokine. […] In embodiments, the cytokines include proinflammatory cytokines such as … IL-15…” (¶ [0147]). Adding a proinflammatory cytokine would result in a better immune response. Xiao further teaches why one would include both a CAR molecule and a TCR molecule: “In embodiments, methods for enhancing T cell response in a subject include administering a T cell including a CAR molecule and a TCR molecule. The CAR molecule targets or binds a surface marker of a white blood cell, and the TCR molecule binds a marker or an antigen of the tumor that is expressed on the surface or inside the tumor cell.” (¶ [0203]). The CAR and TCR molecules are thus demonstrated to target different markers, allowing the iNKT to have more specificity by increasing avidity to a cell type with the antigens of both CAR and TCR. In summary, Xiao teaches a method of deriving cells from stem cells, wherein a CAR molecule, TCR molecule, and “therapeutic agent” (transgene) which can include the proinflammatory cytokine IL-15. Xiao further details that the nucleic acids can be on one or two vectors. Therefore, it would have been obvious to one of ordinary skill before the time of filing to take the method of Smith, wherein iNKT cells are made from HSCs with only the addition of TCRs, and further include the methods of Xiao to add a CAR molecule and cytokine IL-15 in order to increase marker recognition (specificity) and immune response, respectively. A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc ., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02). Regarding claims 3 and 5, Xiao teaches that the isolated polynucleotides can be placed into vectors, for example, a lentiviral vector (¶ [0168]). Therefore, it would be obvious to have multiple vectors and for those vectors to be lentiviral vectors. Regarding claims 7-8, Xiao teaches “stem cell may include embryonic stem (ES) cells (i.e., pluripotent stem cells)” (¶ [0152]) and “embryonic stem cells may be differentiated into blood stem cells (e.g., Hematopoietic stem cells (HSCs)), which may be further differentiated into various blood cells (e.g., red blood cells, platelets, white blood cells).” (¶ [0154]). Therefore, Xiao teaches that ES cells are also known as pluripotent stem cells and can be differentiated into HSCs, which can be further differentiated. Regarding claim 11, Smith teaches an alpha/beta iNKT cell by showing that the HSCs are infected with a vector that has both TCR α and TCR β and are further differentiated into iNKT cells (Figure 2A). Regarding claims 14-15, Xiao teaches “In embodiments, the extracellular antigen binding domain of a CAR includes at least one scFv or at least a single domain antibody. As an example, there can be two scFvs on a CAR. The scFv includes a light chain variable (VL) region and a heavy chain variable (VH) region of a target antigen-specific monoclonal antibody joined by a flexible linker.” (¶ [0116]) and gives a camelid antibody as an example of a single domain antibody (¶ [0147]). Such a camelid antibody is a heavy chain antibody called VHH . 07-22-aia AIA 15. Claim s 1-8 and 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Smith ( Supra ) and Xiao ( Supra ) as applied to claim s 1-5, 7-8, and 11-15 above, and further in view of Li (Experimental Hematology, 2003, 31: 1206-1214) . Regarding claim 6, Smith and Xiao make claim 4 obvious as seen above in section 14. All discussions thereon above incorporated here. Xiao further teaches “On Day 1, the cells were infected with lentiviral vectors.” (¶ [0356]). Xiao does not teach whether the vectors are introduced sequentially or simultaneously. However, Li discusses “Current protocols of retroviral gene transfer into murine hematopoietic stem cells (HSC)” (Objective), one of which includes “We observed that two rounds of infection with mixed supernatants pooled from two vectors were superior to infecting target cells with supernatants from only one vector followed by a second round infection with the other vector” (Efficient gene transfer by double infection with two vectors). Therefore, it would have been obvious to one of ordinary skill before the time of filing to take the obvious method of claim 4 and further infect the HSCs with the vectors simultaneously as it proved advantageous over sequential infection. A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc ., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02). That being said, sequential infection also worked in Li above and so is predictably functional and obvious here as well. Claims 1-5, 7-8, and 11-15 further in view of Li would still be obvious . 07-22-aia AIA 16. Claim s 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Smith ( Supra ), Xiao ( Supra ), and Li ( Supra ) as applied to claim s 1-8 and 11-15 above, and further in view of Liu (Nature, Scientific Reports, 19 May 2017, 7: 2193) . Regarding claims 9 and 10, Smith and Xiao make claim 1 obvious as seen above in section 14. All discussions thereon above incorporated here. Xiao further teaches “ In embodiments, the polyprotein comprises a cleavable moiety between the CAR and the therapeutic agent, and the cleavable moiety comprises a 2A peptide” (¶ [0169]). Neither Smith nor Xiao explicitly states that the 2A peptide induces ribosomal skipping. However, Liu teaches “The mechanism of 2A-mediated “self-cleavage” was recently discovered to be ribosome skipping the formation of a glycyl-prolyl peptide bond at the C-terminus of the 2A” (Page 1, ¶ 2). Therefore, it would have been obvious to one of ordinary skill before the time of filing to include a 2A sequence in the nucleic acid encoding the CAR and therapeutic agent in order to induce ribosomal skipping for self-cleavage. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc. , 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc. , 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02) . Double Patenting 08-33 AIA 17. 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. 08-37 AIA 18. Claim s 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 3-4, 6, 9-11, and 21 of copending Application No. 17/965,377 in view of Smith (PNAS, 20 January 2015, 11(2): 1523-1528), Xiao (US 20220000921 A1; CON to 19 June 2019), Li (Experimental Hematology, 2003, 31: 1206-1214), and Liu (Nature, Scientific Reports, 19 May 2017, 7: 2193). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘377 recites a method of producing a T cell by transducing a HSC with one or more nucleic acids encoding an iNKT TCR and a different second TCR, then differentiating the HSC into an iNKT cell. Claims 3-4 and 6 of ‘377 state that the TCRs can be alpha beta TCRs, indicating that the resulting iNKT cell will be an alpha beta iNKT cell. Claim 9 of ‘377 recites that one or more nucleic acids encoding a CAR and one or more transgene may be introduced. Claim 10 of ‘377 that the transgene may be a cytokine, a checkpoint inhibitor, an inhibitor of transforming growth beta signaling, an inhibitor of cytokine release syndrome, or an inhibitor of neurotoxicity. Claim 11 of ‘377 states that the TCRs are engineered, which would thereby result in an engineered iNKT cell. Claim 21 of ‘377 states that introducing the second TCR comprises inserting one of more nucleic acids into the HSC via lentiviral transduction. In summary, ‘377 claims a method of producing an engineered alpha beta iNKT cell, wherein an HSC is given a TCR, CAR, and transgene. Wherein the transgene is selected from the same group as recited in the instant claims and lentiviral transduction can be used. Therefore, these claims are not patentably distinct from claims 1 and 11-12 of the Instant Application. The claims of ‘377 do not further discuss if the nucleic acids are on one or more vectors, if the HSC is derived from a progenitor cell that is a pluripotent cell, if the nucleic acids encode a sequence to induce ribosomal skipping, if that sequence is 2A, the specific cytokine, or if the CAR comprises a single domain antibody or a variable region of a heavy-chain antibody. However, the aforementioned claims of ‘377 in view of Smith, Xiao, Li, and Liu make claims 1-15 obvious, as discussed above in sections 14-16 . This is a provisional nonstatutory double patenting rejection. 08-37 AIA 19. Claim 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 5-7, 15-16, and 18-20 of copending Application No. 18/290,257 in view of Smith (PNAS, 20 January 2015, 11(2): 1523-1528), Xiao (US 20220000921 A1; CON to 19 June 2019), Li (Experimental Hematology, 2003, 31: 1206-1214), and Liu (Nature, Scientific Reports, 19 May 2017, 7: 2193). Claim 1 of ‘257 recites a method of producing a T cell by differentiating and maturation of an HSC. Claim 5 of ‘257 states that the HSC may express at least one TCR or CAR. Claims 6-7 of ‘257 state that the HSC is derived from a progenitor cell that is a pluripotent stem cell. Claims 15-16 of ‘257 state that the T cell is an iNKT cell, more specifically an alpha beta iNKT cell. Claims 18-20 of ‘257 state that the HSC can comprise one or more additional transgene, with that transgene being a cytokine, a checkpoint inhibitor, an inhibitor of transforming growth factor beta signaling, an inhibitor of cytokine release syndrome, or an inhibitor of neurotoxicity; and that the cytokine may be IL2, 7, 15, 12, 18, or 21. In summary, ‘257 claims a method of producing an alpha beta iNKT cell from a HSC that is given a TCR, CAR, and transgene. Wherein the transgene is selected from the same group as recited in the instant claims and can be the same cytokine as well. Additionally, the HSC is derived from a pluripotent stem cell. These claims are not patentably distinct from claims 1, 7-8, and 11-13 of the Instant Application. The claims of ‘257 do not further discuss if the nucleic acids are on one or more vectors, specifically lentiviral vectors, , if the nucleic acids encode a sequence to induce ribosomal skipping, if that sequence is 2A, or if the CAR comprises a single domain antibody or a variable region of a heavy-chain antibody. However, the aforementioned claims of ‘257 in view of Smith, Xiao, Li, and Liu make claims 1-15 obvious, as discussed above in sections 14-16 . This is a provisional nonstatutory double patenting rejection. Conclusion 20. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA E LY whose telephone number is (571)272-5169. The examiner can normally be reached Monday - Thursday, 8:00 am - 5:00 pm EST. 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, Michael Allen can be reached at (571) 270-3497. 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. /KRISTINA E. LY/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671 Application/Control Number: 18/290,259 Page 2 Art Unit: 1671 Application/Control Number: 18/290,259 Page 3 Art Unit: 1671 Application/Control Number: 18/290,259 Page 4 Art Unit: 1671 Application/Control Number: 18/290,259 Page 5 Art Unit: 1671 Application/Control Number: 18/290,259 Page 6 Art Unit: 1671 Application/Control Number: 18/290,259 Page 7 Art Unit: 1671 Application/Control Number: 18/290,259 Page 8 Art Unit: 1671 Application/Control Number: 18/290,259 Page 9 Art Unit: 1671 Application/Control Number: 18/290,259 Page 10 Art Unit: 1671 Application/Control Number: 18/290,259 Page 11 Art Unit: 1671 Application/Control Number: 18/290,259 Page 12 Art Unit: 1671 Application/Control Number: 18/290,259 Page 13 Art Unit: 1671 Application/Control Number: 18/290,259 Page 14 Art Unit: 1671 Application/Control Number: 18/290,259 Page 15 Art Unit: 1671 Application/Control Number: 18/290,259 Page 16 Art Unit: 1671 Application/Control Number: 18/290,259 Page 17 Art Unit: 1671
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