DETAILED ACTION
Applicant’s amendment and Arguments/Remarks received on 10 October 2025 have been entered. Claims 1-11, 13-14, and 16-29 were previously pending in the application. Claims 1-11, 13-14, and 16-29 are currently pending in the application. Claim 1 is an independent claim.
The following election of species remains in effect in the instant application:
Tumor antigen: MAGE-A4;
Mammalian cells: T cells;
Claims 28-29 remain withdrawn from consideration as being directed to a nonelected species. Claims 1-11, 13-14, and 16-27 are currently pending and under examination in the instant application. An action on the merits follows.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2020/073403, filed August 20, 2020, which claims priority to British Application No. 1911954.4, filed December 18, 2003. Filing of a certified copy of the UNITED KINGDOM 1911954.4, filed 01/27/2022 is acknowledged.
Thus, the earliest possible priority for the instant application is August 20, 2019.
Information Disclosure Statement
The information disclosure statement filed 10 October 2025 has been considered by the Examiner. Examiner notes the filing of IDS Size Fee assertions for the IDS filed 10 October 2025, as required under 37 CFR 1.98, indicating that no IDS size fee is required under 37 CFR 1.17(v) at this time.
Specification
The objection to the specification of the disclosure for Figure 6 not including individual descriptions of panels a or b, is withdrawn in view of the amendment to the specification.
Claim Objections
The objections to amended claims 6 and 17 for an apparent typographical error and reciting abbreviations without first writing out the full term, respectively, are withdrawn in view of the amendments to claims 6 and 17.
Claim Rejections - 35 USC § 112(b)
The rejection of amended and previously presented claims 1-11, 13-14, and 16-27 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for independent claim 1 reciting "the T cells" without antecedent basis and as a narrower range of “mammalian cells” is withdrawn in view of Applicant’s amendments to claim 1 such that claim 1 now recites, “a population of mammalian cells that comprise T cells” and “a transduction-primed mammalian cell population that comprises the T cells”.
Claim Rejections - 35 USC § 103
The rejection of amended and previously presented claims 1-11, 13-14, and 16-27 under 35 U.S.C. 103 as being unpatentable over Bonner et al. (US20190284533A1, published 19 September 2019, filed 10 February 2017, which claims priority to provisional application No. 62/294,615 filed on 12 February 2016); in view of Sun et al. (2019, Cell Death & Disease, 10, 475, 1-10, published 17 June 2019; Boon et al. 1997, Immunology Today, 18(6), 267-268); and Simon et al. (2019, Journal of Immunological Methods, 472, 55-64, published online 14 June 2019), is maintained. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant’s amendments to the claims have addressed issues of indefiniteness and apparent typographical errors. Additionally, Applicant removed a limitation from independent claim 1, thereby broadening the scope of the claim. By not further limiting the scope of the claimed invention, Applicant’s amendments have not overcome a finding of obviousness under 35 U.S.C. 103 over Bonner, Sun, Boon, and Simon.
Applicant argues that A) Bonner and Simon do not exemplify poloxamer pretreatment; B) the prior art teaches away from the claimed invention; C) the instant inventors demonstrated new unexpected mechanisms supporting the claimed pretreatment; and D) there is no teaching or suggestion of pretreatment at “6 hours or more” prior to transduction.
However, this is not agreed.
In response to applicant’s arguments against the references individually, it is noted that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). 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). Further, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In addition, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Specifically, regarding Applicant’s argument A), note that a lack of experimental examples demonstrating the teaching within the prior art does not nullify the teaching itself. As discussed in the prior action, Bonner was cited for teaching exposing a population of mammalian cells to a poloxamer in the absence of a lentiviral vector for 6 hours or more, for 12 hours or more, and for about 24 hours [0668]. As acknowledged by Applicant, Bonner indicates in [0665-0668] that the incubation prior to culture with a retrovirus is contemplated, thereby teaching to perform the step even though Bonner themselves did not perform the step. As such, it would have been obvious to an ordinarily skilled artisan to perform the step as taught by Bonner.
Further, Simon was cited for teaching the motivation to use a poloxamer (e.g., poloxamer 388) in a method of transducing T cells specifically with a lentiviral vector to increase transduction efficiency, wherein the lentiviral vector comprises a nucleic acid encoding a heterologous TCR which binds to a tumor antigen. Simon was not relied upon for teaching the preincubation step, which was already taught by the base reference, Bonner.
Regarding Applicant’s argument B), note that a teaching away from a non-cited reference does not negative a teaching of a cited reference. Additionally, the teaching cited by Applicant that a poloxamer was known to function by promoting improved vector-to-cell contact does not teach away from pre-treatment with the poloxamer, in that an ordinarily skilled artisan could understand from the cited teaching that precoating a cell with a poloxamer could potentially allow a poloxamer-cell interaction which would then allow subsequent cell-poloxamer-vector interactions to form upon treatment with vector. There is no reason that an ordinarily skilled artisan would consider that teaching of a poloxamer promoting improved vector-to-cell contact would be a teaching away from pretreating the cells with the poloxamer or that such a pretreatment would be necessarily meaningless.
Regarding Applicant’s argument C), note that Applicant’s assertions of unexpected results rely on statements in the specification without citing any data or providing any additional evidence. As such, Applicant’s arguments amount to arguments of counsel. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration. Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the applicant. MPEP 716.01(c). Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
The statements in the specification page 35 cited by Applicant refer to data from Figure 6, wherein treatment with the poloxamer F108 (referring to a trade name for poloxamer 338) of increasing doses increases the percentage of CD8 T cells which are LDL-receptor+ by about 40% compared to cells without poloxamer, but does not increase the percentage of LDL-receptor+ cells when combined with CD3/CD28 activation, in that about 95% of cells are LDL-receptor+ independent of poloxamer treatment [Figure 6A]. Additionally, treatment of increasing poloxamer F108 concentrations increased the mean fluorescence intensity of LDL-receptor+ CD8 T cells both in the presence and absence of CD3/CD28 activation [Figure 6B], which the specification teaches is indicative of the amount of LDL-receptor per cell [page 35 ¶ 2]. However, neither the drawings nor the specification teach that the treatment with poloxamer F108 in Figure 6 is a pre-treatment. Neither the drawings nor the specification teach that the duration of pretreatment affects the expression of LDL-receptor. Nor does the data presented in Figure 6 provide any indication of whether the observed changes are statistically significant. Therefore, the disclosure does not provide any evidence that pretreatment of poloxamer, nor any specific duration of pretreatment of poloxamer, will increase the LDL-receptor abundance on the cell surface of T-cells in a way to provide unexpectedly high transduction efficiency.
Further, note that Applicant’s disclosure for increased transduction efficiencies with treatment at day 0 vs day 1 shown in Figures 1 only teaches that the T cells were exposed to the poloxamer “at day 0 or day 1 and then transduced with a lentiviral vector” [page 2 lines 32-33, page 34 liens 27-33], but does not indicate when the cells were transduced with the lentiviral vector. As such, the transduction could have occurred at any time subsequent to the exposure to the poloxamer, including immediately following exposure to the poloxamer, for either the “day 0” or the “day 1” treatment.
The data presented in Figure 2 does not compare pre-treatment to co-treatment.
The data in Figure 3 provides a comparison of day 0 vs day 0+18 hrs (e.g., day 1- 6 hrs) vs day 1 exposure, wherein again the actual transduction timing is not explicitly recited, in that it is not taught whether transduction is at day 0, day 1, or some other time. The specification does not provide a limiting definition of “day 0” or “day 1” which would indicate the transduction timing; nor do the drawings provide a timeline schematic that would indicate the transduction timing relative to the “day 0” or “day 1” indicators.
Figure 5 demonstrates lentiviral transduction of CD34+ hemogenic precursor cells, and is not a transduction of T cells, as required by independent claim 1.
Therefore, Applicant’s data presented in the disclosure has not established evidence of unexpected results for pre-treatment of T-cells with any poloxamer to increase transduction efficiency to unexpected levels.
It is also noted that any evidence of unexpected results must be commensurate in scope with the claimed invention, and that a greater, or greater than additive, effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected MPEP 716.02 (a) and (d). Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).
Specifically, the data referenced by Applicant’s citation of page 35 (e.g., the data in Figure 6A and 6B of the Drawings), along with Applicant’s data in Figures 1-3 and 5, present only a single poloxamer and are not representative of the full genus of poloxamers claimed. Additionally, the data presented in Figure 6 does not indicate any pretreatment, and as such does not encompass the claimed pretreatment scope of 6 hours or more. Nor do any of the other Figures provide evidence of unexpected results for pretreating T cells with poloxamer for at least 6 hours prior to transduction with a viral vector. Therefore, Applicant’s data referenced to support a finding of unexpected results is not commensurate in scope with the claimed invention.
Regarding Applicant’s argument D), Bonner was cited for teaching exposing a population of mammalian cells to a poloxamer in the absence of a lentiviral vector for 6 hours or more, for 12 hours or more, and for about 24 hours [0665-0668]. Specifically, Bonner teaches culturing the cells with a poloxamer prior to culture for any of the “foregoing periods of time disclosed herein” [0668], wherein such “foregoing periods of time” are disclosed in [0665-0666] and include “about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, about 23 hours, about 24 hours, about 48 hours, or about 72 hours, or any intervening duration of time” [0666]. Therefore, the durations taught by Bonner for about 6 hours through about 72 hours are teachings which fall within the claimed range of 6 hours or more.
Therefore, Applicant’s arguments do not overcome a finding of obviousness over Bonner, Sun, Boon, and Simon under 35 U.S.C. 103, and the rejection is maintained.
Conclusion
No claim is allowed.
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 Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634