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 .
Status of the Claims
Applicant’s submission filed 28 August 2025 has been entered. Claims 1-3 and 154-177 are pending. Claims 165-170 and 172 have been amended, while claims 173-177 have been newly added. Therefore, claims 165-173 and 176 are examined on the merits as being drawn to the elected invention and species, with claims 1-3, 154-164, and 177 withdrawn for failing to read on the elected invention and claims 174-175 withdrawn for failing to read on the elected species of a CXCR4 antagonist, as there are other non-elected species required within the recited claims. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Nucleotide and/or amino acid sequence disclosures
The substitute Specification filed 09 September 2025 is acknowledged and entered into the application file. With that, Applicant has added an Incorporation by Reference paragraph, thus obviating the objection of record.
Therefore, the objection is withdrawn.
RE: Objection to the Specification
The substitute Specification filed 09 September 2025 is acknowledged and entered into the application file. With that, Applicant has failed to remove all prefixes or other browser-executable code
within Paragraph [0260] of the Specification.
Therefore, the objection is maintained. The Examiner suggests either deleting the browser-executable code in its entirety, or modifying the recitation to “(idtdna[dot]com)”.
RE: Claim Interpretation
Applicant has traversed the Examiner’s interpretation of the claims, asserting in Pages 20-21 of the Remarks filed 28 August 2025 that the use of a mobilization agent (e.g., CXCR4 antagonist) imparts measurable, structural/phenotypic differences in both (i) the starting population that is collected and (ii) the resulting cell-therapy product. More specifically, Applicant points to Paragraphs [00228]-[00241] of the Specification, which state that the mobilization of immune cells affects the cytotoxicity of the immune cells against target cells, as well as the ability of the mobilized immune cells to produce target antigen-induced cytokines, and polyfunctionality of the immune cells. See Paragraphs [00228]-[00229] and [00236]of the Specification filed 09 September 2025.
In response, the Examiner has fully considered Applicant’s arguments and finds them persuasive. Therefore, the product-by-process interpretation of instant claim 165 regarding the mobilized immune effector cell is withdrawn. However, the Examiner notes that the amendment to independent claim 165 requiring the cell transformed with a heterologous polynucleotide to now be a mobilized cell, coupled with this interpretation of mobilized cells, narrows the claim scope of independent claim 165.
It is also of note that Applicant has not provided any arguments against the interpretation of instant claims 170-172. Therefore, the product-by-process interpretation of instant claims 170-172 regarding the donor and method in which the blood and/or bone marrow is obtained from the donor is maintained.
RE: Objection to claims 166-167 and 169-172
Applicant’s amendments to each of claims 166-167, 170, and 172 obviate the current objections of record. Therefore, the objections are withdrawn for claims 166-167, 170, and 172.
However, Applicant has failed to fully comply with the objections to instant claims 169 and 171. More specifically, Applicant has failed to remove the repeat of IL13Ra2 in Line 74 of instant claim 169, nor the extraneous space between “and/or” in Line 2 of instant claim 171. Therefore, the objections are maintained for claims 169 and 171.
RE: Rejection of claims 169 and 172 under 35 USC 112(b)
Applicant’s amendments to instant claim 172 clarify the claim scope and thus obviate the rejection of record. Therefore, the rejection is withdrawn for claim 172.
However, Applicant has failed to fully comply with the rejection to instant claim 169. More specifically, Applicant has failed to remove the parenthetical language of “proacrosin binding protein sp32 (OY-TESI) in Line 59, “CD32 (FCGR2A)” in Line 75, and “claudin18.2 (CLD18A2)” in Line 85 of claim 169. Therefore, the rejection is maintained for claim 169.
RE: Rejection of claims 165-172 under 35 USC 102(a)(1) and 35 USC 102(a)(2) over Poznansky et al
The amendments to independent claim 165 and associated claim interpretation discussed above obviate the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 165-172 under 35 USC 102(a)(2) over Motz et al
The amendments to independent claim 165 and associated claim interpretation discussed above obviate the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 165-172 under 35 USC 103 over Poznansky et al in view of Lundqvist et al
Applicant's arguments filed 28 August 2025 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 29-30 of the Remarks filed 28 August 2025 that the disclosure of Lundqvist et al is concerned with the mobilization of CD34+ hematopoietic progenitors for peripheral blood stem cell transplantation, and does not teach administering a mobilizer and collecting T cells for the manufacture of CAR-T cells. In response, the Examiner respectfully submits that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Lundqvist et al was a secondary reference relied upon to teach the isolation of T cells following the administration of Plerixafor to a donor. It is of note that while Lundqvist et al do disclose the isolation of CD34+ cells, the main focus of Lundqvist et al was to better characterize T cells that have been isolated following donor Plerixafor treatment. See, for example, Abstract and Pages 3-4 of Lundqvist et al.
Applicant has further traversed the rejection, asserting in Pages 30-32 that the ordinary artisan would recognize that CD34+ PBSC collection and CAR-T collection undergo different workflows as evidenced by the contemporaneous art, and that the ordinary artisan would not have been motivated to introduce Plerixafor before T cell collection for CAR-T manufacturing based on this art and the disclosure of Lundqvist et al. In response, the Examiner respectfully submits that the disclosure of Lundqvist et al teach that the administration of Plerixafor within healthy subjects prior to T cell collection yielded a median of 264 x 106 CD3+ T cells without altering the cytokine gene expression of the T cells, which is about a 3x-fold increase from baseline. See Page 6 and Figure 1A of Lundqvist et al. Therefore, the ordinary artisan would have been motivated to utilize mobilized T cells from the disclosure of Lundqvist et al, as they increase the yield without impacting the cytokine functionality of the T cells. Furthermore, the Examiner would like to note that it is not required that the expectation of success be a certainty; only one that is reasonable to a person of ordinary skill. In re Longi, 759 F.2d 887, 897 (Fed. Cir. 1985) (“Only a reasonable expectation of success, not absolute predictability, is necessary for a conclusion of obviousness”). Therefore, although PBSC collection and CAR-T cell collection were previously shown in the art to undergo different workflows, the ordinary artisan would have recognized that alternative methods exist, and that the mobilized T cells of Lundqvist et al can serve as the starting material for CAR-T cells.
Applicant has further traversed the rejection, asserting in Pages 32-33 of the Remarks filed 28 August 2025 that contemporaneous art teaches away from the mobilization of T cells for the generation of CAR-T cells. More specifically, Applicant cites that the contemporaneous art teaches that monocytes and other myeloid cells within leukapheresis products inhibit CAR-T cell expansion or pose a toxicity threat to the CAR-T cells via IL-1/IL-6 from the monocytes. In response, the Examiner respectfully submits that Poznansky et al disclose that the immune cells are isolated using apheresis techniques, including a kit that specifically isolates T cells from a whole blood sample. See, for example, Paragraph [0076] of Poznansky et al. Therefore, the ordinary artisan would recognize that the mobilized T cells isolated using apheresis techniques are not in culture with monocytes or other myeloid cells, and consequently are not subject to the expansion and toxicity risks detailed in the contemporaneous art.
Applicant has lastly traversed the rejection, asserting in Pages 34-37 that the instant disclosure provides unexpected results when using leukocytoapheresis products for the manufacture of engineered cell therapy products. More specifically, Applicant asserts that CAR-T cells generated from mobilized T cells are as effective as non-mobilized CAR-T cells in exerting cytotoxicity against cells expressing their target antigen. In addition, Applicant asserts that mobilization results in the increase in percentage of naïve T cells, and that non-transduced T cells in a mobilized CAR-T cell population showed limited ‘bystander’ activation, indicating a potentially favorable clinical toxicity profile. In response, the Examiner respectfully reminds Applicant that, in submitting evidence asserted to establish unobvious results, there is a burden on Applicant to indicate how the examples asserted to represent the claimed invention are considered to relate to the examples intended to represent the prior art and, particularly, to indicate how those latter examples do represent the closest prior art. The evidence relied upon should also be reasonably commensurate in scope with the subject matter claimed and illustrate the claimed subject matter relative to the prior art subject matter. MPEP § 2145. It should also be established that the differences in the results are in fact unexpected and unobvious and of both statistical and practical significance. MPEP § 716.02(b). In the instant case, Applicant has failed to indicate how the alleged unexpected results differ from the closest prior art, and has instead referenced different pieces of art that were published after the effective filing date of the instant invention to supply the “unexpected results”. It is also of note that the instant claims are directed to a mobilized immune effector cell that is transformed with a heterologous polynucleotide expressing an immune receptor, and that comparison to a cell therapy product or CAR-T cells is not commensurate in scope with at least instant claim 165.
Therefore, the rejection is maintained and amended to encompass the claims as currently written.
New/Maintained Grounds of Rejection
Information Disclosure Statement
The information disclosure statement filed 02 September 2025 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
In addition, the information disclosure statement filed 02 September 2025 fails to comply with the provisions of 37 CFR 1.97(a) because it lacks the appropriate size fee set forth in 37 CFR 1.17(v). It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Specification
The substitute Specification filed 09 September 2025 is acknowledged and entered into the application file.
However, the disclosure remains objected to because it contains an embedded hyperlink and/or other form of browser-executable code in Paragraph [0260] of the instant Specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
However, the lengthy Specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which Applicant may become aware in the Specification.
Claim Interpretation
Under the broadest reasonable interpretation of each claim, all of the “optional” limitations are not required.
Instant claims 170-172 are directed to products, which utilize product-by-process language. The limitations of the process of production are considered only in so far as the process of production imparts distinct structural or chemical characteristics or properties to the claimed product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e. is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP § 2113.
Claims 170-171 further define the donor from which the immune effector cells are isolated. When defining the source of cells, the source of the cells is only considered in as far as the source defines the cell as having distinct biochemical or morphological characteristics. In the instant case, the source – or donor – of the immune effector cells does not impart a distinction to the cells, but rather their physical and structural characteristics dictates their classification as a particular cell type.
Claim 172 further defines the method in which the blood and/or bone marrow is obtained from the donor. In the instant case, there is no evidence that the isolation method imparts any particular structure or significance to the claimed immune effector cells.
Therefore, the claims will be interpreted as if the isolation of cells from the blood and/or bone marrow of any donor, wherein the donor has any characteristic and by using any isolation technique, fulfills the limitations detailed in the instant claims.
Claim Objections
Claims 168-169 and 171-173 are objected to because of the following informalities:
Regarding claim 168: The instant claim is objected to for reciting option “(f) a dendritic cell”, followed by option “(g) a natural killer T cell”, which is then followed by option “(f) an immune cell derived from a hematopoietic stem cell.” Instead, the last option must be recited as option “(h) an immune cell derived from a hematopoietic stem cell.”
Appropriate correction is required.
Regarding claim 169: The instant claim is objected to for reciting “glycoprotein 100 (gpI00)” instead of “glycoprotein 100 (gp100)” in Line 25.
In addition, the instant claim comprises a repetition of “IL13Ra2” in Line 74.
Appropriate correction is required.
Regarding claims 171-172: The instant claims each recite the phrase, “and /or” in Line 2. The extraneous space between “and” or “/or” must be deleted such that the phrase instead reads as, “and/or”.
Appropriate correction is required.
Regarding claim 173: The instant requires an “and” following “prior to collection of the cells” in step c), as well as the deletion of the second “Plerixafor” in Line 9.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 169 and 176 are 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.
Regarding claim 169: The instant claim remains rejection for the use of parentheticals “proacrosin binding protein sp32 (OY-TES1)” in Line 59, “CD32 (FCGR2A)” in Line 75, and “claudin18.2 (CLD18A2)” in Line 85. While parentheticals can be used as abbreviations, the use of parentheticals adjacent to terms which recite alternate names or isoforms renders the claim indefinite because it is not clear whether the items within the parentheticals are required or optional. Applicant should review the claim and remove any parentheticals that are not expressly utilized as an abbreviation.
Appropriate correction is required.
Regarding claim 176: The instant claim is a “use” claim that recites a use of the mobilized cell of claim 165 without setting forth any active, positive steps delimiting how this use is actually practiced. See MPEP § 2173.05(q). Therefore, the metes and bounds of the claim cannot be determined, thus rendering the claim indefinite.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 176 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because it is a “use” claim that does not provide any active steps within the claim language. See MPEP § 2173.05(q).
Claim Rejections - 35 USC § 103
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.
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.
Claims 165-173 and 176 are rejected under 35 U.S.C. 103 as being unpatentable over Poznansky et al (WO 2017/083441 A1, of record) in view of Lundqvist et al (J Immunol, 2013, of record). This rejection reflects Applicant’s species election of a CXCR4 antagonist, Plerixafor, and prostate-specific membrane antigen (PSMA). Poznansky et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Lundqvist et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 165-168: Poznansky et al disclose methods and compositions for treating cancer in a patient by administering an effective amount of cytokine receptor modified immune cells to the patient (Abstract).
As such, Poznansky et al disclose the administration of an anti-fugetactic agent prior to the administration of immune cells modified to express a chimeric antigen receptor, wherein the chimeric antigen receptor (CAR) comprises an antigen-binding domain and transmembrane domain (Paragraphs [0031]-[0033], [0060], [0091], [0123], [0132]-[0133], [0171], [0182]-[0187]; Example 1).
Poznansky et al further disclose that the anti-fugetactic agent is a CXCR4 antagonist, such as Plerixafor (Paragraphs [0032], [0137]).
Poznansky et al further disclose that the modification of the immune cells involves the transformation of the cells with a nucleic acid encoding the CAR (Paragraphs [0123], [0125]).
Poznansky et al further disclose that the immune cells – particularly T cells – are isolated from the blood or bone marrow of a donor (Paragraphs [0019], [0075]-[0076], [0090]-[0091]).
Poznansky et al do not disclose the cell isolation timing in relation to the administration of the CXCR4 antagonist, such that the T cells are isolated from the blood or bone marrow of a donor that has undergone treatment with a CXCR4 antagonist – as required by instant claim 165.
Lundqvist et al, however, disclose T cells isolated from a subject that had been previously treated with Plerixafor (Page 3, Study Design; Page 5, Mobilization).
Therefore, it would have been prima facie obvious to modify the teachings of Poznansky et al such that the T cells are isolated after the donor has undergone treatment with a CXCR4 antagonist, or Plerixafor, as is disclosed in Lundqvist et al. One of ordinary skill before the effective filing date of the invention would have been motivated to isolate mobilized T cells that have higher apheresis T cell yield (see Lundqvist et al, Pages 3-4), and would have had a reasonable expectation of success since both Poznansky et al (Paragraphs [0002]-[0003], [0076]) and Lundqvist et al (Page 3) are concerned with the movement of T cells and disclose the isolation of T cells via leukapheresis. See MPEP § 2143(I)(G).
Consequently, Poznansky et al as modified by Lundqvist et al render obvious the isolation of mobilized T cells (claim 168) from the blood and/or bone marrow of a donor that have undergone treatment with the CXCR4 antagonist, Plerixafor (claim 166). As the mobilized T cells are modified ex vivo such that they are transformed with a nucleic acid encoding a chimeric antigen receptor (claim 167) having an antigen binding domain and transmembrane domain, this therefore renders obvious the mobilized immune effector cells of instant claim 165.
Regarding claim 169: Following the discussion of claim 165, Poznansky et al further disclose that the CAR is specific for prostate-specific membrane antigen, or PSMA (Paragraphs [0023], [0126]). This therefore reads on the mobilized cell of the instant claim.
Regarding claim 170-171: The instant claims are a product-by-process limitation further
describing the source – or donor – of the immune effector cells. See Claim Interpretation section above. Accordingly, the source of the cells does not change the cells, per se. Therefore, the instant claims are
rejected for the same reason as instant claim 165.
However, it is of note that Poznansky et al do disclose that the immune cells are isolated from the blood or bone marrow of an autologous or allogeneic donor – which reads on instant claim 170 (Paragraphs [0019], [0076], [0090]).
Regarding claim 172: The instant claim is a product-by-process limitation further
describing the method in which the immune effector cells are isolated. See Claim Interpretation section above. Accordingly, the isolation technique of the cells does not change the cells, per se. Therefore, the instant claim is rejected for the same reason as instant claim 165.
However, it is of note that Poznansky et al do disclose that the immune cells are isolated from the blood or bone marrow of a donor via leukapheresis – which reads on the instant claim (Paragraph [0076]).
Regarding claim 173: Following the discussion of claim 166, Lundqvist et al further disclose that the donors are injected with a single 240 μg/kg injection of Plerixafor (Page 6). As 240 μg/kg – or 0.240 mg/kg – is within the claimed range in part b), this therefore renders obvious the mobilized cell of the instant claim. See MPEP § 2131.03.
Regarding claim 176: Following the discussion of claim 165, Poznansky et al further disclose that the CAR-T cells are comprised within a composition and administered to a subject suffering from cancer (Paragraphs [0159]-[0167]). This therefore reads on the instant claim.
Conclusion
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure. King et al (US 2018/0228871 A1, of record on IDS filed 23 July 2024) disclose (i) the mobilization of T cells with Plerixafor and (ii) the genetic modification of the mobilized T cells into CAR-T cells for use in immunotherapy. See Paragraph [0062] of King et al.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633