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 .
Acknowledgement of Receipt
Applicant’s Response, filed 2/13/2026, in reply to the Office Action mailed 11/13/2025, is acknowledged and has been entered. Claims 1, 7, 8 and 10 have been amended. Claims 1, 5, 7, 8, 10, 12-17 are pending, of which claim 17 is withdrawn from consideration at this time as being drawn to a non-elected invention. Claims 1, 5, 7, 8, 10, 12-16 are readable upon the elected invention and are examined herein on the merits for patentability.
Response to Arguments
Applicant’s arguments have been fully considered but are not found to be persuasive. Any rejection not reiterated herein has been withdrawn as being overcome by claim amendment. New grounds for rejection are set forth hereinbelow.
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, 5, 7, 8, 10, 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Shapiro et al. (US 2021/0228746) in view of Hombach et al. (Cancers, 2017, 9, 112, p. 1-13).
Shapiro teaches a method of detecting a cell in a subject, the method including subjecting the subject to magnetic resonance imaging (MRI) or magnetic particle imaging (MPI), visualizing the cell in a resulting MRI scan or MPI scan, and determining a location of the cell in the subject, wherein the cell was previously isolated from the subject, coupled to the nanoparticle construct, and administered back to the subject.
In one aspect, the cell is a T cell, including chimeric antigen receptor, CAR-T cells (paragraph 0023-5).
The nanoparticle construct includes a nanoparticle defining an outer surface, a magnetic nanocrystal carried by the nanoparticle, and a coupling agent extending from the outer surface of the nanoparticle, wherein the coupling agent is configured to couple the nanoparticle construct to a cell (paragraph 0008).
In one aspect, the coupling agent is a maleimide functionality, an antibody, an antibody fragment, or combinations thereof (paragraph 0013).
Shapiro does not specifically teach wherein the antibody or antibody fragment binds to CD25 and/or CD4.
Hombach teaches that T cells can be antigen-specifically redirected by genetic engineering with a chimeric antigen receptor (CAR) that combines the advantages of antibody mediated target recognition with the induction of T cell effector functions. Upon antigen engagement, CAR T cells execute a cellular response in a specific fashion, as indicated by cytokine release, T cell amplification and lysis of cognate target cells. Since the CAR circumvents the MHC (major histocompatibility complex) restriction, both CD8+ and CD4+ T cells can be activated through the same CAR. CD4+ T cells are of particular interest for the use in adoptive cell therapy of cancer because they differentiate into various cell subsets which initiate, modulate, or suppress a cellular and humoral immune response. CD4+ T cells represent the majority in number of the peripheral blood, and, in addition to CD8+ cytotoxic T cells, can exhibit cytolytic capacities. The recently described MHC class II-restricted CD4+ cytotoxic T cells (CD4+ CTLs) emerge during chronic viral infections and during an anti-tumor response. The physiologic function of cytotoxic CD4+ CTLs is not yet completely understood. On the other hand, CD4+ regulatory T (Treg) cells which predominantly display a CD4+CD25high phenotype suppress ongoing immune reactions through multiple mechanisms, potentially also through CTL like properties. The situation raises the question of whether CD4+CD25high Treg cells can mediate MHC unrestricted, but antigen specific cytolysis when redirected by a CAR as do CAR redirected CD4+CD25− T cells. To explore the CD4+ T cell mediated target cell lysis upon CAR activation, we isolated CD4+CD25− and CD4+CD25high T cells from the peripheral blood of healthy donors and engineered the cells with a CD28-CD3ζ signaling CAR with specificity for the carcinoembryonic antigen (CEA) (page 1).
Peripheral blood lymphocytes from healthy donors were isolated by density centrifugation, and monocytes were depleted by plastic adherence. Non-adherent lymphocytes were washed with cold phosphate buffered saline (PBS) containing 0.5% (w/v) BSA, 1% (v/v) FCS and 2 mM EDTA. CD4+CD25+ Treg cells and CD4+CD25− T cells were isolated by magnetic activated cell sorting (MACS) utilizing the CD25 T cell isolation kit (Miltenyi) as recommended by the manufacturer. The number of isolated CD4+CD25+ Treg cells and of CD4+CD25− T cells was determined by flow cytometry. Isolated T cells were washed, counted, and utilized for further experiments. For in vitro amplification of CD4+CD25+ Tcells, Polysorb culture plates were coated with OKT3 and 15E8 mAbs (each 5 µg/mL) over night in PBS, washed twice with PBS and isolated T cells were added in X-Vivo15 medium, 10% (v/v) FCS supplemented with IL-2 and IL-15. CD4+CD25− T cells were initially cultured in RPMI 1640 medium, 10% (v/v) FCS in the presence of OKT3 and 15E8mAb and IL-2. After activation for 48 h CD4+CD25− T cells were further cultivated in RPMI 1640 medium, 10% (v/v) FCS supplemented with IL-2 (400 U/mL) (pages 2-3).
CAR modified Treg cells are suggested to be suitable for auto- or allogeneic cell therapy of autoimmune diseases due to their immune repression without lytic activities (page 11).
It would have been obvious to one of ordinary skill in the art at the time of the invention to provide a CD25 and/or CD4 binding antibody as the antibody coupled to a nanoparticle as taught by Shapiro in which a nanoparticle construct comprising an antibody is coupled to a cell, and cells previously isolated from the subject, coupled to the nanoparticle construct, and administered back to the subject, when the teaching of Shapiro is taken in view of Hambach. One would have been motivated to do so because Hambach teaches that CD4+ T cells are of particular interest for the use in adoptive cell therapy of cancer because they differentiate into various cell subsets which initiate, modulate, or suppress a cellular and humoral immune response, and that CD4+ regulatory T (Treg) cells which predominantly display a CD4+CD25high phenotype suppress ongoing immune reactions through multiple mechanisms. One would have had a reasonable expectation of success in doing so because Hambach teaches that CD4+CD25+ Treg cells and CD4+CD25− T cells were isolated by magnetic activated cell sorting (MACS) a CD25 T cell isolation kit / beads, including use of stimulation by IL-2 agonist. Regarding the temperature at which cells are incubating, it is noted that differences in concentration or temperature will generally 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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; or In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).
Conclusion
No claims are allowed at this time.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/LHS/
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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