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 .
2. Applicant’s response filed on 03/18/2026 is acknowledged.
3. Claims 1-3, 6-7, 9, 12-16, 18, 20-24, 26-30, 33-40, 42, 44-45 and 46 are pending.
4. Applicant’s election without traverse of Group I and the species of a human T cell expressing SEQ ID NO:55 in the reply filed on 03/18/2026 is acknowledged.
5. Claims 21-24, 26-30, 33-40, 42, 44-45 and 46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group and claims 13-16 and 20 are withdrawn for being directed to a non-elected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/18/2020. Applicant did not elect a T cell expressing TCR, self-cleaving peptide sequence(s), or a synthetic antigen receptor, so those claims have been withdrawn
6. Claims 1-3, 6-7, 9 and 12 are under consideration as they read on a human T cell expressing SEQ ID NO:55. The Examiner extended the search to include the art of record set forth below.
7. Applicant’s IDS documents filed on 04/23/2024, 11/01/2024 and 03/18/2026 have been considered.
8. 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.
9. Claim 1-3, 6-7, 9 and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-7, 12, 18, 20, 23-24, 26, 33-37 and 39-40 of copending Application No. 18/837,837 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-3, 5-7, 12, 18, 20, 23-24, 26, 33-37 and 39-40 of copending Application No. 18/837,837 are directed to T cells encompassed by instant claims 1-3, 6-7, 9 and 12.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
10. Claims 1-3, 6-7, 9 and 12-16 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claim 1 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: claim 1 recites a human T cell which comprises 35 different alternatives which do not have a common structure or a common use alone or within the context of expression on a human T cell.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
11. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
12. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
13. Claims 1-2, 6-7, 9 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018/075941 (PTO-892; Reference N) as evidenced by the attached sequence alignment.
WO 2018/075941 teaches a composition, the composition comprising T cells, wherein the T cells express AP4 comprising the sequence set forth in reference SEQ ID NO:1 . (In particular, paragraphs [0033]-[0034]). The T cells may be T helper cells (TH cells), cytotoxic or effector T cells (Tc cells, TE cells, CTLs, CD8+ T cell), memory T cells (TM cells), suppressor T cells (Treg cells), natural killer T cells (NKT cells), mucosal associated invariant T cells, and gamma delta T cells (γδ T cells) (In particular, paragraph [0044], whole document). T cells for use in a composition of the disclosure may be isolated from a subject. The T cells may be obtained from a single subject, or a plurality of subjects. A plurality refers to at least two (e.g., more than one) subjects. When T cells obtained are from a plurality of subjects, their relationships may be autologous, syngeneic, allogeneic, or xenogeneic. In a specific embodiment, the relationship is allogeneic. In another specific embodiment, the relationship is autologous. Methods of collecting/isolating T cells from a subject are standard in the art. For example, several kits are commercially available to isolate T cells from whole blood or peripheral blood mononuclear cells (PBMCs). Additionally, flow cytometry using cell surface markers may be used to isolate/enrich T cells. (In particular, paragraph [0045])
WO 2018/075941 teaches an AP4 construct of the disclosure is a polynucleotide sequence encoding a polypeptide comprising AP4. As used herein, the terms "polynucleotide sequence of the disclosure" and "AP4 construct" are interchangeable. The disclosure also provides isolated polypeptides encoded by AP4 constructs, vectors comprising AP4 constructs, and isolated cells comprising said vectors. (In particular, paragraph [0039]) An AP4 construct of the disclosure is a polynucleotide sequence encoding a polypeptide comprising AP4. (In particular, paragraph [0040]) When more than one polypeptide is encoded by a polynucleotide of the disclosure, the polynucleotide may comprise more than one promoters operably linked to each polynucleotide encoding a polypeptide. By way of non-limiting example, a polynucleotide encoding a polypeptide comprising a first AP4 may be operably linked to a first promoter and a polynucleotide encoding a polypeptide comprising a second AP4 may be operably linked to a second promoter. The first and second promoter may be the same or different. Promoters are described in more detail below. Alternatively, when more than one polypeptide is encoded by a polynucleotide of the disclosure, the polynucleotide may be operably linked to a single promoter. In such an embodiment, several strategies common in the art may be used to generate more than one expression product. By way of non-limiting example, a splicing signal, internal ribosomal entry site (IRES) or proteolytic cleavage site may be inserted between thepolynucleotides encoding the polypeptides. By way of non-limiting example, a polynucleotide encoding a polypeptide comprising a first AP4 and a second AP4 operably linked to a single promoter may further comprise a splicing signal, IRES or proteolytic cleavage site between the coding regions of the first and second AP4. (In particular, paragraph [0040]).
WO 2018/075941 teaches the T cells are transfected with a vector comprising an AP4 construct of the disclosure. An AP4 construct is as described in Section 1(a)i. As used herein, a vector is defined as a nucleic acid molecule used as a vehicle to transfer genetic material. Vectors include but are not limited to, plasmids, phasmids, cosmids, transposable elements, viruses (e.g., bacteriophage, animal viruses, and plant viruses), and artificial chromosomes (e.g., YACs), such as retroviral vectors (e.g., derived from Moloney murine leukemia virus vectors (e.g., MoMLV, MSCV, SFFV, MPSV, SNV, etc), lentiviral vectors (e.g., derived from HIV-1 , HIV-2, SIV, BIV, FIV, etc.), adenoviral (Ad) vectors including replication competent, replication deficient and gutless forms thereof, adeno-associated viral (AAV) vectors, simian virus 40 (SV-40) vectors, bovine papilloma virus vectors, Epstein-Barr virus, herpes virus vectors, vaccinia virus vectors, Harvey murine sarcoma virus vectors, murine mammary tumor virus vectors, and Rous sarcoma virus vectors.(In particular, paragraph [0049], whole document).
WO 2018/075941 teaches a vector encoding an AP4 construct may be delivered to the cell using a viral vector or via a non-viral method of transfer. Viral vectors suitable for introducing nucleic acids into cells include retroviruses, adenoviruses, adeno-associated viruses, rhabdoviruses, and herpes viruses. Non-viral methods of nucleic acid transfer include naked nucleic acid, liposomes, and protein/nucleic acid conjugates. A vector encoding an AP4 construct that is introduced to the cell may be linear or circular, may be single-stranded or double-stranded, and may be DNA, RNA, or any modification or combination thereof. .(In particular, paragraph [0050], whole document).
WO 2018/075941 teaches a vector encoding an AP4 construct may be introduced into the cell by transfection. Methods for transfecting nucleic acids are well known to persons skilled in the art. Transfection methods include, but are not limited to, viral transduction, cationic transfection, liposome transfection, dendrimer transfection, electroporation, heat shock, nucleofection transfection, magnetofection, nanoparticles, biolistic particle delivery (gene gun), and proprietary transfection reagents such as LIPOFECTAMINE, DOJINDO HILYMAX, FUGENE, JETPEI, EFFECTENE, or DREAMFECT. .(In particular, paragraph [0051], whole document).
WO 2018/075941 teaches that upon introduction into the cell, a vector encoding an AP4 construct may be integrated into a chromosome. In some embodiments, integration of the vector encoding an AP4 construct into a cellular chromosome may be achieved with a mobile element. The mobile element may be a transposon or a retroelement. A variety of transposons are suitable for use in the disclosure. Examples of DNA transposons that may be used include the Mu transposon, the P element transposons from Drosophila, and members of the Tc1 /Mariner superfamily of transposons such as the sleeping beauty transposon from fish. A variety of retroelements are suitable for use in the disclosure and include LTR-containing retrotransposons and non-LTR retrotransposons. Non-limiting examples of retrotransposons include Copia and gypsy from Drosophila melanogaster, the Ty elements from Saccharomyces cerevisiae, the long interspersed elements (LINEs), and the short interspersed elements (SINEs) from eukaryotes. Suitable examples of LINEs include L1 from mammals and R2Bm from silkworm. (In particular, paragraph [0052], whole document).
WO 2018/075941 teaches the basal medium may contain antigen. The antigen may be included to generate antigen-specific T cells. For example, a tumor-associated antigen or a viral antigen may be used to generate antigen-specific T cells. A skilled artisan would be able to select the antigen based on the desired disease or disorder to be treated. In certain embodiments, when antigen is present T cells should be co-cultured with autologous dendritic cells derived from bone marrow cells or blood-derived monocytes and irradiated tumor cells. If the basal medium contains tumor-associated antigens, the tumor-associated antigen may be added prior to transduction of the vector comprising an AP4 of the disclosure, after transduction of the vector comprising an AP4 of the disclosure, or both before and after transduction of the vector comprising an AP4 of the disclosure. (In particular, paragraph [0059])
Claim 6 is included in this rejection because instant SEQ ID NO:55 is encoded by SEQ ID NO:23 as taught in the instant specification. As such, this limitation is inherent in the reference T cell expressing SEQ ID NO:55.
The reference teachings anticipate the claimed invention.
14. Claims 1-2, 7, 9 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2020/163755 (IDS filed on 04/23/2024; Reference 2).
WO 2020/163755 teaches a human T cell that heterologously expresses a polypeptide comprising a human Fas extracellular domain or portion thereof linked to a human OX40 intracellular domain and optionally, 1-10, e.g., 7 amino acids of the Fas intracellular domain via a transmembrane domain (a modified human T cell that heterologously expresses an enhanced signaling receptor (polypeptide) comprising an extracellular domain of an inhibitory receptor, such as Fas, fused (linked) to the intracellular domain of a co-stimulatory receptor, such as OX40, via a transmembrane domain; paragraphs [0011], [0012], [0014], [0015], [0017], (0031), [0055], [0058], [0064), [0065], [00111], (00121), [00123]), wherein the polypeptide is encoded by a heterologous nucleic acid construct inserted into a target genomic locus of the cell (the enhanced signaling receptor or ESR is encoded by a heterologous polynucleotide sequence (nucleic acid construct) that is provided to the T cell using a transposon vector which inserts the heterologous polynucleotide encoding the ESR at a target site in the target DNA of the T cell (target genomic locus of the cell); paragraphs [001 1], [0012], [0014], [0015], (0031), (0044), [0050}, [0051], [0055], [0058], [0064], [0065)), optionally wherein the target genomic locus is the T-cell receptor or TCR locus of the cell, optionally wherein the heterologous nucleic acid construct is non-virally inserted (the enhanced signaling receptor or ESR is encoded by a heterologous polynucleotide sequence (nucleic acid construct) that is provided to the T cell using a transposon vector (non-virally inserted); (In particular, paragraphs (0011], [0012], [0014], [0015], [0064), [0065], whole document). T lymphocytes include killer T cells, helper T cells and gamma delta T cells. Immune cells can be primary cells isolated from a subject or can be the result of further culturing including in the form of a cell line. Immune cells can be the subject of genetic engineering in addition to that described herein, e.g., expression of a CAR-T receptor. (In particular, paragraph [0058])
The reference teachings anticipate the claimed invention.
15. 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.
16. Claims 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over each of WO 2018/075941 (PTO-892; Reference N) and WO 2020/163755 (IDS filed on 04/23/2024; Reference 2) in view of Eyquem et al. (PTO-892; Reference U).
WO 2018/075941 and WO 2020/163755 have been discussed supra.
The claimed invention differs from the prior art in the recitation of “wherein the target insertion site is in exon 1 of a TCR-alpha subunit constant gene (TRAC) or in exon 1 of a TCR-beta subunit constant gene (TRBC)” of claim 3.
Eyquem et al teaches that targeting gene delivery to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia. The reference further teaches that targeting the CAR to the TRAC locus averts tonic CAR signalling and establishes effective internalization and re-expression of the CAR following single or repeated exposure to antigen, delaying effector T-cell differentiation and exhaustion. (In particular, abstract, whole document).
The reference teaches that TRAC has a role in control of CAR expression in two critical ways. One is to promote optimal baseline expression, which prevented tonic signalling in the absence of antigen and allowed effective CAR internalization upon single or multiple contacts with antigen. The other is to direct a balanced transcriptional response resulting in a kinetically optimal recovery of baseline CAR expression after antigen engagement. In contrast to T cells with higher CAR expression, the TRAC-CAR profile correlated with decreased T-cell differentiation and exhaustion, resulting in superior tumour eradication. The reference teaches that targeting a CAR coding sequence to the TCR locus, placing it under the control of endogenous regulatory elements, reduces tonic signalling, averts accelerated T-cell differentiation and exhaustion, and increases the therapeutic potency of engineered T cells. The targeting of CARs to a TCR locus may thus provide a safer therapeutic T cell (by minimizing the risks of insertional oncogenesis and TCR-induced autoimmunity and alloreactivity), a better defined T-cell product (by yielding constant CAR expression and avoiding position-effect variegation and vector copy number variation) and a more potent T cell (by reducing constitutive signalling and delaying T-cell exhaustion). (In particular, pages 116-117, whole document).
It would have been obvious to one of ordinary skill in the art to have chosen to deliver the genes of WO 2018/075941 and WO 2020/163755 into the T-cell receptor α constant (TRAC) locus of the T cells to provide a safer therapeutic T cell, a better defined T-cell product and a more potent T cell as taught by the art of Eyquem et al were advantages of gene insertion into the TRAC locus.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
17. No claim is allowed.
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. 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 Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
April 4, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641