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 .
1. Claims 14-25, 28, and 28 have been cancelled. Claims 26 and 27 have been amended.
Claims 1-13, 26, 27, and 29-33 are pending and under examination.
Claim Objections
2. Claim 29 is objected to because of the recitation “a step” in second to last line. Correction to “the step” is required.
3. Applicant is advised that should claim 7-9 be found allowable, claim 31-33 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 103
4. 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.
5. Claims 1-9, 26, 27, and 29-33 are rejected under 35 U.S.C. 103 as being unpatentable over Kaiser et al. (U.S. 2017/0037370; priority date 04/24/2024), in view of Flynn et al. (Clin. Transl. Immunol., 2-14, 3: 1-7).
Kaiser et al. teach using Miltenyi CliniMACS in a method for generating an isolated population of T-cells, the method comprising: (1) subjecting human PBMCs (i.e., a sample of human cells comprising T-cells) to negative selection with CD14 and CD25 to deplete the cells expressing CD14 and CD25, followed by positive selection with CD62L to obtain a population of T-cells enriched in naïve and central memory T-cells cells (TNs and TCMs, respectively); and (2) transducing the enriched T-cell population with a viral vector encoding a CAR or a TCR. Kaiser et al. teach achieving a transduction efficiency of about 26% (claims 1, 3-6, 10-13, and 29) (see Abstract; [0017]; [0036]-[0037]; [0050]-[0051]; [0061]; [0075]; [0087]; Fig. 7; Fig. 9).
Although Kaiser et al. do not specifically teach that the enriched T-cell population also comprises stem central memory T-cells (TSCMs), it was known in the prior art that TSMCs express CD62L (see Flynn et al., p. 2, Table 1). Thus, one of skill in the art would have reasonably concluded that that the enriched T-cell population is also enriched in TSMCs (claims 1 and 29).
With respect to claims 2 and 30, Kaiser et al. do not specifically teach that the enriched T-cells comprise less than 15% CD14+ and less than 5% CD25+. However, one of skill in the art would have reasonably expected that the negative selection with CD14 and CD25 would result in very low numbers of CD14+ and CD25+ cells. Conversely, one of skill in the art would have found obvious to continue the negative selection process until achieving very low amounts of CD14+ and CD25+ cells because Kaiser et al. teach that these cells are inhibitory (see [0051]).
Kaiser et al. do not specifically teach the percentages recited in claims 1, 9, 29, and 33. However, these percentages are a result of the enrichment process using negative selection with CD14 and CD25, followed by positive selection with CD62L. The claims do not require more than this and the specification does not teach more than this. These enrichment steps are already taught by Kaiser et al.
Furthermore, Flynn et al. teaches that: (1) all of TNs, TSCMs, and TCMs express CD62L; (2) only TNs and TSCMs express CD45RA; and (3) only TSCMs and TCMs express CD45RO (see p. 2, Table 1).
Since the population taught by Kaiser et al. is enriched in TNs, TSCMs, and TCMs, one of skill in the art would have reasonably expected that the enrichment process would result in: (1) TNs, TSCMs, and TCMs together constituting at least 70% of the population (i.e., at least 70% are CD62L+ T-cells; claims 1 and 29); (2) TNs and TSCMs together constituting less than 70% of the population (i.e., less than 70% are CD45RA+ T-cells; this range overlaps with the recited range of greater than 40%; claims 1 and 29); and (3) TSCMs and TCMs together constituting less than 70% of the population (i.e., less than 70% are CD45RO+ T-cells this range overlaps with the recited ranges of less than 60% and more than 40%; claims 9, 29, and 33).
In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05.
Conversely, one of skill in the art would have found obvious to continue the enrichment steps until obtaining a population comprising a totality of TNs, TSCMs, and TCMs of at least 70%.
With respect to claims 7, 8, 31, and 32, Kaiser et al. teach that the cells could be enriched for either CD4+ or CD8+ T-cells before the negative and positive selection steps with CD14/CD25 and CD62L, respectively (see [0050]). One of skill in the art would have reasonably expected that enriching for either CD4+ or CD8+ T-cells before the selection steps would result in a population of cells comprising at least 40% CD4+CD62L+ or CD8+CD62L+ T-cells.
With respect to claims 26 and 27, Kaiser et al. teach that the enriched population of CAR T-cells could be used as cellular therapy to treat diseases (see [0036]; [0111]). Flynn et al. teach that CAR T-cells could be used to treat cancer, where the CAR T-cells could be autologous (see p. 4, column 1). Thus, using the method of Kaiser et al. with autologous cells and further administering the resultant enriched population of autologous CAR T-cells to subjects affected by cancer would have been obvious to one of skill in the art, to achieve the predictable result of treating the cancer in the subjects.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
6. Claims 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (J. Immunother., 2012, 35: 1-28), in view of both Flynn et al. (Clin. Transl. Immunol., 2-14, 3: 1-7) and Biasco et al. (Science Translation Medicine, February 2015, 7: 1-12). Wang and Biasco are cited on the IDS filed on 01/09/2025.
Wang et al. teach using Miltenyi CliniMACS to isolate a population of cells enriched in central memory CD8+ T-cells cells (TMCs) suitable for cancer therapy, where isolation comprises: (1) subjecting human PBMCs to negative selection with CD4, CD14, and CD45RA to remove the CD4+, CD14+, and CD45RA+ cells, followed by positive selection with CD62L; and (2) transducing the enriched T-cell population with a viral vector encoding a CD19 CAR. Wang et al. teach that several isolation runs using different PBMC samples resulted in an average of 70% enrichment in CD62L+ T-cells as estimated by FACS, with individual runs resulting in 79.6%, 82.5%, and 78.5% enrichment in CD62L+ T-cells. Wang et al. teach that the 70% average estimated by FACS is an underestimation of CD62L-positivity due to the competition between the anti-CD62L antibody used for staining and the biotinylated anti-CD62L antibody used for the positive selection step (claims 10-12) (see Abstract; p. 3-4; paragraph bridging p. 5 and 6; p. 14, Fig. 1; p. 15, Fig. 2C). Wang et al. teach that the population comprising CAR TMCs is being used in clinical trials (see Abstract; p. 23, Fig. 8).
Since it was known in the prior art that TMCs also express CD95 (see Flynn et al., p. 2, Table 1), one of skill in the art would have reasonably concluded that the population of cells taught by Wang et al. comprises an average of 70% enrichment in CD62L+ CD95+ T-cells.
Since it was known in the prior art that CD45RA is expressed by the naïve T-cells (TNs) and stem central memory T-cells (TSCMs) (see Flynn et al., p. 2, Table 1), one of skill in the art would have readily understood that the enriched population of Wang et al. is depleted of TNs and TSCMs.
However, Wang et al. teach that the capacity to engraft is a key property that correlates with therapeutic efficacy. Wang et al. teach that TCMs engraft long-term and reconstitute functional memory following adoptive transfer (see Abstract; paragraph bridging p. 9 and 10; p. 10). Biasco et al. teach that genetically engineered TSCMs have a long-term engrafting capacity and constitute an active reservoir for the generation of TCMs (up to 12 years after infusion). Biasco et al. suggest using TSCMs in clinical trials (see Abstract; p. 6, column 2, last paragraph; p. 9, column 2, third paragraph; p. 9, second full paragraph). Biasco et al. teach that although TNs and TSMCs express both CD45RA and CD62L, only TSCMs express CD95 (see p. 1, column 1).
Based on these teachings, one of skill in the art would have found obvious to modify the method of Wang et al. by omitting the step of negative selection with CD45RA and further adding positive selection for CD95 to achieve the predictable result of obtaining a population of cells enriched in TSMCs and TMCs, exhibiting enhanced therapeutic effect.
The percentages recited in claim 10 are a result of the enrichment process using the selection markers noted above. Since TSMCs and TCMs express both CD62L and CD95, one of skill in the art would have reasonably expected the enriched population to comprise more that 85% of CD62L+CD95+ T-cells, out of which at least 40% would be CD45RA+ TSCMs (i.e., at least 40% CD45RA+ T-cells)
With respect to at least 10% transduction efficiency (claim 10), Kaiser et al. teach that using CliniMACS results in transduction efficiency of about 26% (see [0017]; [0036]; [0061]; Fig. 7). Thus, one of skill in the art would have reasonably expected the method taught by the cited prior art to result in at least 10% transduction efficiency.
With respect to claim 13, Kaiser et al. teach that the T-cells could be genetically engineered to express a TCR instead of a CAR (see [0037]). Using a TCR would have been obvious to one of skill in the art, to achieve the predictable result of obtaining a composition suitable to treat cancer.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
7. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633
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