CTNF 18/042,989 CTNF 80545 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. The amendments of 02/23/2026 have been entered in full. Claims 1, 4, 11, 17, 19, 20, 40, 50, 52, 64, 86, 90, 94, 100, 136, 138, 139, 149, 153, 163, and 292 are pending. Election/Restrictions 08-25-01 AIA Applicant’s election without traverse of claims to compositions comprising a multi-specific chimeric antigen receptor (CAR) comprising an IL13 polypeptide and a TGF- b binding region and methods of making and using the compositions in the reply filed on 02/23/2026 is acknowledged. 08-06 AIA Claim 17 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/23/2026 . Claims 1, 4, 11, 19, 20, 40, 50, 52, 64, 86, 90, 94, 100, 136, 138, 139, 149, 153, 163, and 292 are under consideration . Specification 07-29 AIA The disclosure is objected to because of the following informalities: SEQ ID NO’s 159 and 160 are listed in the Sequence Listing as being short peptides. This conflicts with Table 1 of the specification, which shows SEQ ID NO’s 159 and 160 as full-length CAR sequences (see p.99 of the specification as filed) . Appropriate correction is required. Claim Rejections - 35 USC § 112 07-30-02 AIA 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 applicant regards as his invention. 07-34-01 Claim 90 is 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 90 is unclear because of the conflicting definitions of SEQ ID NO’s 159 and 160 noted above. 07-36 AIA 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. 07-36-01 AIA Claim 90 is 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. Claim 90 is dependent from claim 1, which is drawn to a polypeptide comprising a TGF- b binding region. SEQ ID NO’s 1, 13, 17, 19, 22, 136, 138, 140, and 142 do not comprise a TGF- b binding sequence. Therefore, recitations of these sequences are in claim 90 outside of the scope 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, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Double Patenting 08-33 AIA 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp. Claims 1, 4, 11, 19, 40, 50, 94, 100, 136, 138, 139, 149, 153, 163, and 292 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 10, 18, 58, 88, 111, 132, 133, 143, 147, and 157 of copending Application No. 18042985 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. The respective independent claims are drawn to overlapping subject matter. Copending claim 1ii and pending claim 1 each recite a polypeptide comprising an IL13 polypeptide, a TGF- b binding region, a peptide spacer, a transmembrane domain, and a cytoplasmic region comprising a co-stimulatory region and a primary intracellular signaling domain. Pending claims 4 and 11 recite further inclusion of glioblastoma binding domains. These embodiments are species within the scope of copending claim 1i, 1iii, or 1iv. Overlapping subject matter is also recited in the respective dependent claims. Pending dependent claim 50 recites the same sequences as in copending claim 1i and 1ii. Pending claims 94, 136, 138, 139, 149, 153, and 163, recite the same limitations as in copending claims 88, 111, 132, 133, 143, 147, and 157. Pending claim 292 is within the scope of copending claim 143, as they encompass administering the same polypeptide for the same purpose. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-21-aia AIA Claim s 1, 4,19, 20, 52, 64, 94, 100,136, 138, 139, 149, 153, 163, and 292 are rejected under 35 U.S.C. 103 as being unpatentable over US 20160340649 (Brown), Hou, A.J. et al., "Bioengineering and Translational Medicine, 3(2):75-86, 2018 (‘Hou’; of record), and Burger MC, et al., Front Immunol. 2019 Nov 14;10:2683 (‘Burger’; of record), and US 20210252069 (Kong) . The claims are drawn to compositions comprising a chimeric antigen receptor (CAR) comprising an IL13 polypeptide and a TGF- b binding region and methods of making and using the compositions. Dependent claims recite features common to the art of making and using CARs and to embodiments wherein the CAR further comprises GD2 or EGFRvIII binding regions. Brown teaches chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain that includes IL-13 or a variant thereof that binds interleukin-13Rα2 (IL13Rα2), a transmembrane region, a costimulatory domain and an intracellular signaling domain (Abstract). Brown teaches that T cells expressing a CAR targeting IL13Rα2 can be useful in treatment of glioblastoma [0014]. Brown does not teach a CAR comprising a TGF- b binding region, as required in the instant claims. Hou teaches [Introduction] that one prominent mechanism contributing to the failure of CAR-T cell therapy of solid tumors is immunosuppression caused by the secretion of transforming growth factor beta (TGF‐β) by tumor cells. Hou discloses a CAR comprising a TGF‐β binding domain, (TGF‐β CAR). Expression of TGF‐β CAR in T cells inhibits endogenous TGF‐β signaling and converts TGF‐β into a potent T‐cell stimulant. TGF‐β CAR‐T cells proliferate robustly and secrete Th1 cytokines in the presence of TGF‐β. TGF‐β CAR‐T cells can also protect neighboring immune cells from the suppressive effects of TGF‐β by enabling tumor‐targeted CD8 + T cells to retain cytolytic activity in the presence of TGF‐β, and by discouraging CD4 + T cells from TGF‐β–induced Treg differentiation. Hou teaches that these results suggest that the TGF‐β CAR can safely and effectively boost the anti‐tumor efficacy of T‐cell therapy. Burger teaches that, similar to T cells, specific recognition and elimination of cancer cells by natural killer (NK) cells can be markedly enhanced through expression of chimeric antigen receptors (Abstract). Burger identifies IL-13Rα2, EGFRvIII, and GD2 among potential targets for glioblastoma therapy (p.4, p8). Burger teaches that TGF-β impairs NK cells and that NK cells can be made resistant to TGF-β by expression of a dominant-negative TGF-β receptor (p.3). Kong teaches CAR polypeptides that may be made specific for various cancer antigens, including IL13Rα2 or EGFRvIII ([0053] claim 25). The CAR further comprises TGF-βR2 exodomain engineered to convert the inhibitory signal of TGF-β into an activation signal in CAR-T cells. [0021][0036][0038]. Starting from Kong, one of skill in the art would construct a CAR according to pending claim 1 by choosing IL-13, as taught in Brown, as the means to target IL13Rα2. From Brown, Hou, and Burger it is evident that IL-13Rα2 and TGF- b are each known effective targets for CAR based treatment of glioblastoma and, therefore, it would be obvious to combine the two modalities. The motivation to combine the teachings and to administer cells expressing TGF‐β CARs along with cells expressing other CARs is reinforced in Hou, which teaches that TGF‐β CARs can safely and effectively boost the anti‐tumor efficacy of T‐cell therapy. The construction of CARs having multiple specificities in a single polypeptide is known in the art. The combination of IL13Rα2 or EGFRvIII and a TGF- b binding region in a single CAR is suggested in Kong. Therefore, the pending claims recite a combination of familiar elements according to known methods, which is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc . (KSR), 550 U.S. 398 at, 82 USPQ2d at 1395 . 07-22-aia AIA Claim s 11, 40, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Brown, Hou, Burger, and Kong as applied to claim s 1 and 4 above, and further in view of US 11591407, US 9394368, US 11014980 and US 6576232 . As noted above, Brown, Hou, Burger, and Kong taken together teach or suggest a chimeric antigen receptor (CAR) comprising an IL13 polypeptide and a TGF- b binding region optionally further comprising GD2 or EGFRvIII binding regions. Brown, Hou, Burger, and Kong do not teach the specific sequences recited in claims 11, 40 and 50. US 11591407 teaches an anti-GD2 scFv comprising SEQ ID NOs 46 and 47 (SEQ ID NO: 114). US 9394368 teaches a CAR comprising an anti-EGFRvIII scFv comprising SEQ ID NOs 38 and 39 (SEQ ID NO: 68). US 11014980 teaches an anti-TGF- b scFv comprising all of the CDR sequences recited in claim 40 (SEQ ID NO:97). IL13 having SEG ID NO: 4 was disclosed in US 6576232 (SEQ ID NO:7). Therefore, even when specific sequences are considered, the pending claims are drawn to a combination of familiar elements according to known methods, which is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc . (KSR), 550 U.S. 398 at, 82 USPQ2d at 1395. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL C GAMETT, Ph.D., whose telephone number is (571)272-1853. The examiner can normally be reached on M-W . Please note the examiner’s part-time schedule . 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, Joanne Hama can be reached on 5712722911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /DANIEL C GAMETT/Primary Examiner Art Unit 1647 Application/Control Number: 18/042,989 Page 2 Art Unit: 1647 Application/Control Number: 18/042,989 Page 3 Art Unit: 1647 Application/Control Number: 18/042,989 Page 4 Art Unit: 1647 Application/Control Number: 18/042,989 Page 5 Art Unit: 1647 Application/Control Number: 18/042,989 Page 6 Art Unit: 1647 Application/Control Number: 18/042,989 Page 7 Art Unit: 1647 Application/Control Number: 18/042,989 Page 8 Art Unit: 1647 Application/Control Number: 18/042,989 Page 9 Art Unit: 1647
Prosecution Insights