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 .
Election/Restrictions
This action is in response to the papers filed on 03/20/2026. Claims 1-5, 7, 9, 12, 15, 18, 25, 33, 38, 40, 42, 50, 53, 55, 57, and 59 are currently pending as per claims filed on 12/29/2023. Claims 4, 5, 7, 9, 12, 15, 18, 25, 33, 38, 40, 42, 50, 53, 55, 57, and 59 have been amended and claims 6, 8, 10-11, 13-14, 16-17, 19-24, 26-32, 34-37, 41, 43-49, 51-52, 54, 58, and 60 have been canceled by Applicants’ amendment filed on 12/29/2023. No claims were added. Claim 1 is an independent claim.
Applicant’s election without traverse of Group 1, claims 1, 4, 5, 7, 9, 12, 15, 18, 25, 33, 38, 40, 42, 50, 53, 55, 57, and 59 in the reply filed on 03/20/2026 is acknowledged.
Claims 2 and 3 are withdrawn from further consideration by Applicants pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
In addition, the examiner required species election between the following species:
1. A CAR encoding an antigen-binding domain that binds to STEAP2 (from claim 38).
2. A CAR encoding an antigen-binding domain that binds to GPC3 (from claim 40).
It is noted that applicant’s response to restriction filed 03/20/26 is incomplete as no election of species was indicated. Upon further review and to further prosecution, examiner has withdrawn the requirement for election of species of claim 38 and 40. Examiner called attorneys listed by applicant to select species and expedite prosecution, however no response was received. Therefore, claim 38 and 40 have been rejoined as examination of both species together does not represent undue burden.
The requirement is still deemed proper and is therefore made FINAL.
Therefore, claims 1, 4, 5, 7, 9, 12, 15, 18, 25, 33, 38, 40, 42, 50, 53, 55, 57, and 59 are subject to examination to which the following grounds of rejection are applicable. Claim 1 is an independent claim.
Priority
The instant application claims domestic benefit to US provisional patent
application number 63/368,550 filed on 07/15/2022. Thus, the earliest possible priority
for the instant application is 07/15/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/29/2023, 09/09/2025, and 03/20/2026 were filed after the mailing date of the current office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 38 and 40 are objected to because abbreviations such as STEAP2, VL-CDR and VH-CDR should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim 50 is objected to because abbreviations such as TCM and TSCM should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim 59 is objected to because abbreviations such as mpH/min should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim Interpretation
Claim 18 recites the units “U/mL” and “IU/mL”. The specification fails to define what “U” and “IU” indicate. The examiner interprets U/mL to mean “units/mL” and can be broadly read as any unit of measurement. The examiner interprets IU/m to mean “international units/mL”, wherein “international units” is defined as a standardized measure of biological activity.
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 1, 4, 5, 7, 9, 12, 15, 18, 25, 33, 38, 40, 42, 50, 53, 55, 57, and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Alizadeh et al (WO 2018102761 A1), and further in view of Aftab et al (WO 2020055862 A1), Bosco et al (US Patent Application Pub 20230192803; as cited in IDS), Gilbreth et al (WO 2021126672 A1), Millipore Sigma (Successful Transduction Using Lentivirus, pages 1-7, downloaded 4/15/2026), and Moody et al (WO 2021214270 A1; as cited in IDS).
The applied Moody and Gilbreth reference have a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1). The publication date for Moody is 28 October 2021. The publication date for Gilbreth is 24 June 2021. The earliest effective filing date of the instant application is July 15, 2022.
Therefore rejection under 35 U.S.C. 103 CANNOT be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(c) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. Because the reference qualifies as prior art under 102(a)(1), the provisions of MPEP 717.02 do not apply.
The applied Bosco reference has a common inventor with the instant application
Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). The publication date for Bosco is 22 June 2023 and the earliest filing date is 15 October 2021. The earliest effective filing date of the instant application is July 15, 2022.
This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding claim 1, Alizadeh teaches a method for expanding T cells in culture media, wherein:
the culture media comprises optionally added IL-21 (para 0010);
a method for introducing a vector, e.g. a lentiviral vector, expressing a T cell receptor (e.g., a CAR) into a population of T cells that have been activated and the expanding the cells in said culture media (para 0010);
that the CAR can be produced by any means known in the art, preferably recombinant DNA techniques, and nucleic acid encoding regions of the chimeric receptor can be prepared, inserted into an expression vector, and used to transform a cell line such as T lymphocytes (para 0035),
and the collection of prepared cells described above for injection into mice engrafted with Raji tumor cells,
rendering obvious:
(b) culturing the T cells in a culture media that comprises human interleukin 21 (IL-2 1);
(c) activating the T cells
(d) transducing the T cells with a vector comprising a nucleic acid encoding a chimeric antigen receptor (CAR) or a T-Cell Receptor (TCR) to produce CAR-T cells or T-cell Receptor (TCR) cells;
(e) culturing the CAR-T cells in a medium;
And (f) harvesting the CAR-T cells or T-cell Receptor (TCR) cells.
Alizadeh does not teach (a) isolating CD3+ T cells from a sample and that the cells of steps (b), (c), and (d) are CD3+.
Aftab teaches manufacturing processes for antigen-stimulated T cells that express CARs and “the process may comprise an initial T-cell enrichment step, wherein CD3+ T cells are enriched/purified from a more heterogeneous mixture of cells (e.g., from whole blood, from PBMCs, and the like); stimulated to recognize and respond to pre- selected antigens (e.g., viral antigens or other tumor/disease-associated antigens, etc.); and transduced with one or more CAR constructs. (page 6, detailed description, line 26-30).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of a method for expanding a population of T cells comprising culturing T cells in media with IL-21, activating cells, transducing with a vector encoding a CAR, and culturing and harvesting the CAR-T cells from Alizadeh with the teachings of isolating CD3+ T cells from a more heterogeneous mixture of cells at step (a) and then subsequently activating and transducing with a CAR-vector to respond to pre- selected antigens from Aftab to have a method for expanding a population of T cells that are enriched for CD3+ cells. One would be motivated to do so to increase efficiency of the methods process such that only CD3+ cells of interested are subjected to expansion. Since isolating, expanding, and culturing of CD3+ cells is known in the art, one would have a reasonable expectation of success.
Regarding claim 4, the teachings of Alizadeh and Aftab render obvious claim 1. Moreover, Alizadeh teaches the culture media comprises optionally added IL-21 (para 0010).
Regarding claim 5, the teachings of Alizadeh and Aftab render obvious claim 1. Moreover, Alizadeh teaches a method for introducing a vector, e.g. a lentiviral vector, expressing a T cell receptor (e.g., a CAR) into a population of T cells that have been activated and the expanding the cells in said culture media (para 0010);
culture media comprises optionally added IL-21 (para 0010), rendering transducing the CD3*I cells with a vector comprising a nucleic acid encoding a CAR to produce CAR-T cells.
Regarding claim 7, the teachings of Alizadeh and Aftab render obvious claim 1. Moreover, Alizadeh teaches “cultures are then maintained at 37°C, 5% CO2 with addition of X-Vivol5 10% FCS as required to keep cell density between 3x105 and 2x106 viable cells/mL, rendering obvious wherein from about l x106 to about 1 x 109 CD3+T cells are cultured in the culture media in (b).
Regarding claim 9, the teachings of Alizadeh and Aftab render obvious claim 1 and 7. Moreover, Alizadeh teaches culturing the population of human T cells for at least one day in a culture medium (page 23-24, claim 1 (b) – claim 15), rendering obvious wherein the CD3+ T cells in (c) are cultured for about one day or about two days.
Regarding claim 12, the teachings of Alizadeh and Aftab render obvious claim 1, 7, and 9. Moreover, Alizadeh teaches the activating step comprises exposing the cells to an anti-CD3 antibody and an anti-CD28 antibody (para 0011), rendering obvious wherein the CD3+ T cells in (c) are activated with an anti-CD3 antibody or CD3-binding fragment thereof, and an anti-CD28 antibody or a CD28-binding fragment thereof.
Regarding claim 15, the teachings of Alizadeh and Aftab render obvious claim 1, 7, 9, and 12. Moreover, Alizadeh teaches wherein the population of cells is cultured in the culture medium for at least five days and less than 40 days, rendering obvious wherein the CAR-T cells or TCR cells are cultured in (e) from about four to about six days.
Regarding claim 18, the teachings of Alizadeh and Aftab render obvious claim 1, 7, 9, 12, and 15. Moreover, Alizadeh teaches “all exogenously added interleukins other than IL-15 (e.g., IL-7, IL-21, IL-4 and IL-9) are present at less than 10 ng/ml (less than 8 ng/ml, less than 6 ng/ml, less than 5 ng/ml, 3 ng/ml or even less than 1 ng/ml) and exogenously added IL-2 is present at less than 50 U/ml (less than 40 U/ml, less than 30 U/ml, less than 20 U/ml, less than 10 U/ml, less than 5 U/ml or even less than 1 U/ml) (para 0003), rendering obvious wherein the concentration of human IL-21 is from about 0.01 U/mL to about 0.3 U/mL, and the concentration of human IL-2 is from about 5 IU/mL to about 100 IU/mL absent any evidence to the contrary.
Moreover, in relation to the claimed concentration of human IL-21 and human IL-2 in claim 18, With respect to modification of the variables in claims 8-12, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since the prior art teaches exogenously added IL-2 and IL-21 in culture for transfection and proliferation of CD3+ T cells, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the biotech art.
Further, Applicant is reminded that differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II. A.
Regarding claim 25, the teachings of Alizadeh and Aftab render obvious claim 1, 7, 9, 12, 15, and 18. However, the combined teachings do not teach the lentivirus is added at a multiplicity of infection (MOI of about 0.25 to about 20.
Millipore Sigma teaches “It is highly recommended that for each new cell type to be transduced, a range of MOI be tested” and “For most cell types, a range of 0.1 - 10 MOI is suitable.” (page 2, Recommendations and steps to optimize your experiment setup).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of a method for expanding a population of CD3+ T cells comprising culturing T cells in media with IL-21, activating cells, transducing with a vector encoding a CAR, and culturing and harvesting the CAR-T cells from Alizadeh and Aftab with the teachings of testing and optimizing the MOI to be between 0.1 and 10 from Millipore Sigma to use a range of 0.1 and 10 MOI for lentivirus transduction in the instantly claimed methods . One would be motivated to do so to efficiently transduce the cells with the optimal level of CAR lentivirus and, since lentivirus transduction in T cells is known in the art, one would have a reasonable expectation of success.
Regarding claim 33, the teachings of Alizadeh, Aftab, and Millipore Sigma render obvious claim 1, 7, 9, 12, 15, 18, and 25. Moreover, Alizadeh teaches the population of cells is cultured for a period of time sufficient to expand the population less than 100-fold (claim 21, page 24), rendering obvious herein the CAR-T cells or TCR cells are expanded from at least about 1 fold to about 5 fold during (e).
Regarding claim 38, the teachings of Alizadeh and Aftab render obvious claim 1. However, the combined teachings do not teach the CAR encodes an antigen-binding domain that binds to STEAP2 and wherein the antigen-binding domain comprises the amino acid sequences recited in (a), (b), (c), (d), or (e).
Bosco teaches a polynucleotide encoding a CAR comprising an antigen-binding domain that binds to STEAP2 and wherein the antigen-binding domain comprises a VL-CDR1 comprising SEQ ID: 1 having 100% similarity to SEQ ID NO: 1 of instant application claim 38 (a), VL-CDR2 comprising SEQ ID: 2 having 100% similarity to SEQ ID NO: 2 of instant application claim 38 (a), VL-CDR3 comprising SEQ ID: 3 having 100% similarity to SEQ ID NO: 3 of instant application claim 38 (a), VH-CDR1 comprising SEQ ID: 4 having 100% similarity to SEQ ID NO: 4 of instant application claim 38 (a), VH-CDR2 comprising SEQ ID: 5 having 100% similarity to SEQ ID NO: 5 of instant application claim 38 (a), and VH-CDR3 comprising SEQ ID: 6 having 100% similarity to SEQ ID NO: 6 of instant application claim 38 (a) (para 0010). Therefore, SEQ ID: 1-6 of Bosco renders obvious SEQ ID: 1-6 of the instant application, respectively. See sequence alignment below.
Qy = instant application sequence, Db = Bosco sequence
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SEQ ID NO: 1 Instant Application vs SEQ ID NO: 1 Bosco Reference
SEQ ID NO: 2 Instant Application vs SEQ ID NO: 2 Bosco Reference
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201
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SEQ ID NO: 3 Instant Application vs SEQ ID NO: 3 Bosco Reference
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83
218
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SEQ ID NO: 4 Instant Application vs SEQ ID NO: 4 Bosco Reference
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70
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SEQ ID NO: 5 Instant Application vs SEQ ID NO: 5 Bosco Reference
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290
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SEQ ID NO: 6 Instant Application vs SEQ ID NO: 6 Bosco Reference
Regarding claim 40, the teachings of Alizadeh and Aftab render obvious claim 1. However, the combined teachings do not teach the CAR encodes an antigen-binding domain that binds to GPC3 and wherein the antigen-binding domain comprises a VH and VL comprising the amino acid sequences recited.
Gilbreth teaches a polynucleotide encoding a CAR comprising an antigen-binding domain that binds to GPC3 and wherein the antigen-binding domain comprises a VL-CDR1 comprising SEQ ID: 40 having 100% similarity to SEQ ID NO: 115 of instant application claim 40, VL-CDR2 comprising SEQ ID: 41 having 100% similarity to SEQ ID NO: 116 of instant application claim 40, VL-CDR3 comprising SEQ ID: 42 having 100% similarity to SEQ ID NO: 117 of instant application claim 40, VH-CDR1 comprising SEQ ID: 37 having 100% similarity to SEQ ID NO: 112 of instant application claim 40, VH-CDR2 comprising SEQ ID: 38 having 100% similarity to SEQ ID NO: 113 of instant application claim 40, and VH-CDR3 comprising SEQ ID: 39 having 100% similarity to SEQ ID NO: 114 of instant application claim 40. Therefore, SEQ ID: 37-42 of Bosco renders obvious SEQ ID: 112-117 of the instant application. See sequence alignment below.
Qy = instant application sequence, Db = Gilbreth sequence
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SEQ ID NO: 112 Instant Application vs SEQ ID NO: 37 Gilbreth Reference
SEQ ID NO: 113 Instant Application vs SEQ ID NO: 38 Gilbreth Reference
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SEQ ID NO: 114 Instant Application vs SEQ ID NO: 39 Gilbreth Reference
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SEQ ID NO: 115 Instant Application vs SEQ ID NO: 40 Gilbreth Reference
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SEQ ID NO: 116 Instant Application vs SEQ ID NO: 41 Gilbreth Reference
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SEQ ID NO: 117 Instant Application vs SEQ ID NO: 42 Gilbreth Reference
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Regarding claim 42, the teachings of Alizadeh and Aftab render obvious claim 1. However, the combined teachings do not teach the nucleic acid also encodes an armoring molecule and wherein the armoring molecule comprises a dominant-negative TGFβ receptor type 2 (TGFβRIIDN).
Moody teaches methods for using CAR-T cells to treat cancer and “an isolated nucleic acid sequence encoding (a) a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen-binding domain specific for a cell surface antigen; and (b) an armoring molecule, wherein the armoring molecule counters immunosuppression of a cell in a tumor microenvironment when expressed on a surface of the cell” (para 0011). Moody also teaches “a TGFβRIIDN armoring molecule expressed on a surface of the cell.” (para 0012).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of a method for expanding a population of CD3+ T cells comprising culturing T cells in media with IL-21, activating cells, transducing with a vector encoding a CAR, and culturing and harvesting the CAR-T cells from Alizadeh and Aftab with the teachings of an armoring molecule, specifically being TGFβRIIDN, being expressed on the surface of a CAR-T cell to generate a nucleic acid that encodes a CAR and also encodes the armoring molecule TGFβRIIDN. One would be motivated to do so to counter immunosuppression of a cell in a tumor microenvironment and by having both the CAR and armoring molecule sequence on the same nucleic acid construct, it would eliminate the needing to use two constructs/molecules and, instead, increase efficiency of expression by only using one construct with both CAR and armoring molecule sequences.
Regarding claim 50, the teachings of Alizadeh and Aftab render obvious claim 1. Moreover, Alizadeh teaches “a population of T cells expressing a CAR and comprising central memory T cells; memory stem T cells, and naive T cells (TCM/SCM/N CAR expressing cells)” (claim 38, page 26), “wherein greater than 40% of the TCM/SCM/N CAR expressing cells are CD45RA+” (claim 39, page 26), cells cultured in IL21 have 7 +/- 5% CCR7+ cells (Example 7, para 0057, page 18; Figure 7A and B), and “the High IL-15/Low IL-2 culture conditions (i.e. optionally with IL-21) described herein result in a higher proportion of desirable CD45RA+ CD45RO- T cells (para 005).
Regarding the recitations of “ wherein from about 15% to about 50% of the CAR-T cells” (claim 50), “wherein more than 50% of the CAR-T cells express a chimeric antigen receptor” (claim 53) “wherein more than 50% of the CAR-T cells express CD8” (claim 55), “wherein the CAR-T cells or TCR cells have an oxygen consumption rate (OCR) above I00pmol/min” (claim 57), and “wherein the CAR-T cells or TCR cells have an extracellular acidification rate (ECAR) above 30mpH/min” (claim 59), do not provide an active step, and appears to be an inherent effect of the methodology of claim 1. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Provisional Rejection, Obviousness Type Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 5, 7, 9, 12, 15, 18, 25, 33, 38, 40, 42, 50, 53, 55, 57, and 59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 91, and 102 of copending Application No. 17/271,430 as per claims filed on 12/23/2025, in view of Aftab et al (WO 2020055862 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over the cited claims of Application No. 17/271,430. It is noted that copending application has received a notice of allowance, but has not yet issued. Upon issuance as a US Patent, this rejection will become non-provisional.
The claims of co-pending application 17/271,430 are drawn to a method of making a population of cells that express a CAR by contacting the T cells with an agent that stimulates a co-stimulatory molecule (i.e. activating the cells), contacting the cells with a nucleic acid that encodes a CAR, and harvesting the cells (claim 1 and 91). Moreover, the method comprises culturing the cell in culture media comprising IL-21 (claim 102).
The instant application differs from claims 1, 91, and 102 by requiring isolation of CD3+ T cells from a sample.
However, at the time the invention was made, Aftab teaches that manufacturing processes for antigen-stimulated T cells that express CARs and “the process may comprise an initial T-cell enrichment step, wherein CD3+ T cells are enriched/purified from a more heterogeneous mixture of cells (e.g., from whole blood, from PBMCs, and the like); stimulated to recognize and respond to pre- selected antigens (e.g., viral antigens or other tumor/disease-associated antigens, etc.); and transduced with one or more CAR constructs. (page 6, detailed description, line 26-30).
Therefore, in view of the teachings of Aftab for enriching CD3+ T cells for subsequent activation and transduction of a CAR nucleic acid, it would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the instantly claimed method to include a step of isolating CD3+ T cells as taught by Aftab to enrich for the cell type/population of interest (CD3+) for subsequent activation and CAR nucleic acid transduction.
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Claims 1, 4, 5, 7, 9, 12, 15, 18, 25, 33, 38, 40, 42, 50, 53, 55, 57, and 59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 91, and 102 of copending Application No. 17/271,430 as per claims filed on 12/23/2025, in view of Aftab et al (WO 2020055862 A1), Bosco et al (US Patent Application Pub 20230192803; as cited in IDS), and Gilbreth et al (WO 2021126672 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over the cited claims of Application No. 17/271,430. It is noted that copending application has received a notice of allowance, but has not yet issued. Upon issuance as a US Patent, this rejection will become non-provisional.
Copending Application No. 17/271,430 and Aftab teaches the method of expanding a population of T cells of claim 1 as discussed above, the contents of which is incorporated herein in its entirety.
Regarding claim 38, the claims of Bosco are drawn to a nucleotide sequence encoding a CAR wherein the CAR comprises an antigen-binding domain that binds to STEAP2 and wherein the antigen-binding domain comprises variable heavy chain and light chain regions which comprise amino acid sequences that are 100% identical to the sequences recited in claim 38 (a) of the instant application (claim 1 and 12 of Bosco).
Regarding claim 40, the claims of Gilbreth are drawn to a nucleotide sequence encoding a CAR wherein the CAR comprises an antigen-binding domain that binds to GPC3 and wherein the antigen-binding domain comprises variable heavy chain and light chain regions which comprise amino acid sequences that are 100% identical to the sequences recited in claim 40 of the instant application (claim 13 of Gilbreth).
Thus it would have been obvious for one of ordinary skill in the art to select the CDRs for the VH and VL according to Bosco and Gilbreth to render obvious the six complementarity determining regions (CDR) of a heavy chain variable region and a light chain variable region for STEAP2 and GPC3 with a reasonable expectation of success.
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Conclusion
Claims 1, 4, 5, 7, 9, 12, 15, 18, 25, 33, 38, 40, 42, 50, 53, 55, 57, and 59 are rejected.
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/JULIANA IRENE CANDELARIA/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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