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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/8/2026 has been entered.
Claims 1 and 304-312 are pending. Claims 1 and 310 have been amended. The 112(b) rejection cited in Office Action 10/17/2025 is hereby withdrawn in view of amendments.
Claims 1 and 304-312 are currently being examined.
Maintained Rejections
(Arguments Addressed)
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.
Claim(s) 1 and 304-312 remain rejected under 35 U.S.C. 103 as being unpatentable over Crooks et al (WO2017075389 A1; Published 5/4/2017; of record), in view of Purroy, et al. (Erythropoietin Receptor-Mediated Molecular Crosstalk Promotes T Cell Immunoregulation and Transplant Survival. J Am Soc Nephrol. 2017;28(8):2377-2392) and Uguccioni et al (J Exp Med (1996) 183 (5): 2379–2384).
It is noted claim 1 recites a method “comprising” the recited steps. MPEP 2111.03 states: For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, “The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). In the instant case, the claims will be interpreted as methods that comprise any step, in addition to those recited in the claims.
Crooks teaches a method of preparing a population of T cells comprising:
a) selecting stem or progenitor cells; [0006-0007]
b) introducing one or more nucleic acids encoding at least one T-cell receptor (TCR); and [0026, 0036, 0043, 0181]
c) culturing the cells to induce the differentiation of the cells into T cells; [0006, 00029]
wherein a), b), and/or c) exclude contacting the cells with a feeder cell or a population of feeder cells. [0170, 0173, 0174– Crooks teaches that the cells, and culture are free of feeder cells]. Crooks teaches wherein the method: (c) comprises a culture that is feeder-free; the stem or progenitor cells comprise CD34+ cells; and/or cells of a) have been cultured in medium comprising IL-3, IL-7, IL-6, SCF, TPO, FLT3L, and a 574 amino acid recombinant human fibronectin fragment. [see at least 0018, 0170, 0173, 0174; 0219; 0307]
Regarding claim 305: Crooks teaches wherein the TCR comprises an iNKT TCR. [0026, 0042]
Regarding claim 306: Crooks teaches wherein the TCR comprises a TCR that specifically recognizes a NY-ESO-1 antigen. [0058, 0063]
Regarding claims 307 and 309: Crooks teaches, wherein (c) comprises culturing the cells in a differentiation and/or expansion medium; and wherein the method further comprises stimulation and/or expansion of the cells. [see at least 0006, 0067]
Regarding claim 308: Crooks teaches wherein (c) comprises contacting the cells with one or more of DLL1. Crooks teaches that that the cells may express exogeneous “Notch Ligand”, and further states examples of Notch Ligand as DLL-1. [0007; claim 70]
Regarding claim 310: Crooks teaches that the method further comprises activation of the cells by contacting the cells with anti-CD3 and/or anti-CD28-coated beads. [0055, 0102, 0103]
Regarding claim 311: Crooks teaches that the method further comprises transferring a nucleic acid comprising a CAR molecule. [see at least; 00024; 00026]
Regarding claim 312: A cell or population of cells produced by the method of claim 1. [Whole document]
However, Crooks does not teach that the medium comprises MCP-4 and EPO.
Purroy teaches the use of EPO in cell media (Fig 4) for t-cell expansion and differentiation and teaches that EPO induces T-cell differentiation, specifically, Treg induction, in vitro and teaches that EPO signaling axis could be used to treat T-cell mediated pathologies. [Abstract]
Uguccioni teaches that MCP-4 is a chemoattractant with high efficacy for T-lymphocytes, thus marking the importance of adding MCP-4 to cell media to attract and induce migration of lymphocytes.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to culture the cells in a medium comprising IL-3, IL-7, IL-6, SCF, MCP-4, EPO, TPO, FLT3L, and a 574 amino acid recombinant human fibronectin fragment. One would have been motivated to, and have a reasonable expectation of success, because: (1) Crooks teaches the instantly claimed method and teaches that the cells are cultured in medium comprising IL-3, IL-7, IL-6, SCF, TPO, FLT3L, and a 574 amino acid recombinant human fibronectin fragment, (2) Purroy teaches a method of using EPO in cell media to allow for T-cell differentiation, and (3) Uguccioni teaches that MCP-4 is a chemoattractant with high efficacy for T-lymphocytes, thus marking the importance of adding MCP-4 to cell media to attract and induce migration of lymphocytes. Given the known methods of preparing population of T cells by the instantly claimed method, and given the known methods and roles of using EPO and MCP-4 in culture mediums, one of ordinary skill in the art could have pursued adding EPO and MCP-4 in the method of Crooks with a reasonable expectation of success.
Response to Arguments
Applicant argues that there must be some motivation to combine references and that those of skill in the art would not have bene motivated to pick and choose elements from the cited prior art because there was no reasonable expectation that the very specific constellation of growth factors recited in the claims allows stem or progenitor cells to differentiate into T cells as recited in the claims. Applicant argues that is well known in the art that the effects of growth factors on the differentiation of stem or progenitor cells and T cells are highly unpredictable, especially when used in combination with other. Applicant argues that those of skill in the art understand that T cell growth and differentiation is an unpredictable process and that the effects different growth factors and differentiation factors on the growth and differentiation of stem cells, progenitor cells and T cells are highly unpredictable, especially when used in combination with other growth factors and differentiation factors. Applicant cites Coppola et al., Int J Mol Sci. 2020 Oct 22;21(21):7814, and states that this reference teaches that using T cell growth factors (such as IL-7) in combination with other growth and differentiation factors is unpredictable because T cell fates-such as proliferation versus exhaustion, or effector versus regulatory (Treg) development-are highly context-dependent. Slight changes in physiological factors such as receptor expression can completely alter the outcome. Thus, Applicant argues that there was no reasonable expectation that the very constellation of growth factors recited in the claims allows for stem or progenitor cells to differentiate into T cells as recited in the claims.
Applicant’s arguments have been considered but are not persuasive. The claims are drawn to the following: A method of preparing a population of T-cells comprising a) selecting stem or progenitor cells, b) introducing one or more nucleic acids encoding at least one T-cell receptor (TCR), c) culturing the cells to induce differentiation of the cells into T-cells, excluding contacting the cells with a feeder cell or a population of feeder ells, and cells of a) have been cultured in a medium comprising: IL-3, IL-7, IL-6, SCF, MCP-4, EPO, TPO, FLT3L, and a 574 amino acid recombinant human fibronectin fragment. The Examiner relied on the combination of the prior art to render the method obvious. The primary reference, Crooks, teaches this method and teaches that the culture medium comprises: comprising IL-3, IL-7, IL-6, SCF, TPO, FLT3L, and a 574 amino acid recombinant human fibronectin fragment. Crooks does not teach that the medium comprises EPO or MCP-4 (2 out of the 9 components of the cell culture medium). The secondary reference Purroy teaches the known use of EPO in cell media that allows for T-cell differentiation, specifically Treg induction, and Uguccioni teaches the known use of MCP-4, which is a chemoattractant with high efficacy for T-lymphocytes. Ugoccioni teaches the importance of adding this to cell media to induce migration of lymphocytes. Although the primary reference, Crooks, does not teach the use of EPO and MCP-4, the secondary references teach the known roles, mechanism, and importance of EPO and MCP-4 for cell medium. Thus, as noted in the 103 rejection, given the known methods of preparing population of T-cells by the instantly claimed method, and given the known role and methods of using EPO and MCP-4 in cell culture mediums, one of skill in the art could have pursued adding EPO and MCP-4 in the method of Crooks with a reasonable expectation of success.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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, Gregory Emch can be reached at (571) 272-8149. 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.
/SARAH A ALSOMAIRY/ Examiner, Art Unit 1646
/Zachariah Lucas/Supervisory Patent Examiner, Art Unit 1600
Prosecution Insights