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 .
Application Status
The amended claims filed June 15, 2026, with the Response to the non-final Office Action are acknowledged. Claims 1-14, 16-25, 28-33, 35-42, and 45 are pending. Claims 1, 21-22, 28, and 31-32 are amended. Claims 35-42 and 45 remain withdrawn from consideration pursuant to a Restriction Requirement.
Claims 1-14, 16-25, and 28-33 are under examination herein.
WITHDRAWN REJECTIONS
All prior rejections of claims 1-14, 16-25, and 28-33 under 35 U.S.C. § 103 are withdrawn in view of Applicant's amendments to claims 1 and 28 to recite “an apoptosis inhibitor” in place of “IL-21 and/or an apoptosis inhibitor”.
NEW REJECTIONS NECESSITATED BY CLAIM AMENDMENT
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.
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.
(1)
Claims 1, 5-7, 9-10, 12-14, 16-19, 21, 23-25, 28-31, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Enoki (US 2010/0068192 A1; cited in PTO-892) in view of Podack (Annals New York Academy of Sciences (2002) 975: 101-113; cited in IDS), Kennedy (Immunology (2006) 118(2): 143-152; cited in PTO-892), and Kaur (Cytokine (2011) 55(2): 307-317).
Enoki discloses a method for preparing a T cell population expressing CD45RA and CCR7 (also known as CD197), wherein the method includes the step of culturing a T cell population in the presence of fibronectin or a fragment thereof and an anti-CD3 antibody (e.g., Abstract; ¶ 0017; claims 1-2 and 5-6), relevant to claims 1, 24, and 28. Enoki teaches that CD45RA and CCR7 are cell surface antigen markers of lymphocytes known to be expressed in undifferentiated cells, e.g., naïve T cells (e.g., ¶ 0072). Such CD45RA+/CCR7+ T cells can be classified into undifferentiated cells, i.e., naïve T-like cells, before differentiation into memory T cells. Naïve T-like cells have increased survival, proliferation, and tumor accumulation and are useful for cell therapy (e.g., ¶ 0072). The anti-CD3 antibody (at a final concentration of 5 μg/mL or 5,000 ng/mL) and fibronectin fragment (CH-296; at a concentration of 25 μg/mL) are immobilized on the culture container (e.g., Example 1, ¶ 0137-0139; ¶ 0087), relevant to claims 10, 13-14, and 16-17. RetroNectin® can be used to improve gene-transducing efficiency (e.g., ¶ 0100). Enoki discloses, “In the present invention, it is preferable that the culture in the presence of fibronectin, a fragment thereof or a mixture thereof is carried out in the presence of a CD3 ligand, from the viewpoint of effectively stimulating a TCR-CD3 complex with T cells to proliferate the cells” (¶ 0080).
CD8+/CD4- T cells are produced in the method (e.g., Examples 1 and 7; Tables 4-5), relevant to claims 6-7. The method disclosed by Enoki further comprises the step of transducing a foreign gene encoding a T-cell receptor (TCR) or a chimeric antigen receptor (CAR) into the cell population (e.g., claims 10-11; ¶ 0098, 0107), such that the cell expresses a CAR or TCR, relevant to claim 5.
Enoki discloses culturing the cells in a medium containing melanoma antigen MART-1-derived HLA-A2.1 binding peptide (i.e., an HLA/peptide complex; e.g., Example 5, ¶ 0191), relevant to claims 9 and 12.
Relevant to claims 21, 23, 31, and 33, Enoki discloses that the medium used in the method for preparing a T cell population of the present invention is not particularly limited, and known media prepared by mixing components necessary for expanding T cells (e.g., a medium containing cytokines such as IL-12 or IL-7) can be used (e.g., ¶ 0083).
Enoki additionally teaches that expansion of T cells is carried out in the presence of fibronectin, a fragment thereof, or a mixture thereof (e.g., ¶ 0075). Enoki discloses a method in which a T cell population is expanded in a plate immobilized with an anti-human CD3 antibody or a plate immobilized with an anti-human CD3 antibody and fibronectin (e.g., Example 1 (3), ¶ 0140-0142; Example 9). The expansion folds of the T cell population resulting from the culture equipment immobilized with fibronectin were consistently higher than that resulting from culture equipment without fibronectin (e.g., Tables 1, 28-29; ¶ 0142, 0248). Enoki further tested the viability of T cell populations expanded using anti-CD3 and CH-296 and observed that 44.9% of cells underwent apoptosis in the CH-296 group compared to 57.6% of the T cell population cultured without immobilization of CH-296 (e.g., Example 9, ¶ 0243-0253; Table 30), suggesting that CH-296 at least partially inhibits apoptosis in this cell population.
Enoki further teaches a CD3+ T cell population obtained by the methods of the invention (e.g., claims 16-17), relevant to claim 25.
However, Enoki does not disclose culturing a CD3+ cell in the presence of a CD30 agonist or an apoptosis inhibitor.
Regarding CD30, Podack teaches that CD30 regulates CD8 cytotoxic T lymphocyte function and survival during memory responses and is important for proliferation and clonal expansion (e.g., Abstract; Figure 1; pages 101-102), relevant to the methods of claims 1 and 28. Using CD30-Ligand (CD30-L) knockout mice, Podack illustrates that CD30 plays a role in primary clonal expansion of CD8 cytotoxic T lymphocytes (e.g., Figure 11; page 109-110, text), relevant to claims 6-7 and 28-30. Using an NK like lymphoma line YT that is a useful model for cytotoxic cells, Podack also illustrates that an agonistic anti-CD30 antibody (“C10”) upregulates CCR7 (also called CD197; e.g., pages 103-107; Figure 7), relevant to claims 1, 18-19, and 24.
Podack further teaches that CD30 can convert effector memory cells into central memory cells, a process accompanied by increased pro-apoptotic molecules that make the cells more vulnerable to apoptosis as well as upregulation of anti-apoptotic molecules that protect the cells from apoptosis (e.g., page 108).
Further regarding CD30, Kennedy teaches: “Early in vitro studies led to the classification of CD30 as a T-cell ‘costimulatory receptor’ based on observations that immobilized CD30-specific antibodies or CD30L-transfected cells enhance the proliferation of human T cells in response to suboptimal stimulation via the TCR. The physiological relevance of these early findings is not clear, because anti-human or anti-mouse CD30L mAb do not appear to block antigen-presenting cell-dependent T-cell proliferation and/or function in a variety of in vitro systems. As CD30 is expressed on T cells rather late after in vitro activation, it is possible that CD30/CD30L interactions occurring relatively late after antigen encounter promote T-cell survival and/or establishment of strong memory responses” (page 145, right column). Thus, continued stimulation with a CD30 agonist would serve to maintain a population of T cells and to generate memory responses in the T cells, the latter of which could be advantageous for adoptive T cell therapy.
Kaur teaches that IL-15 induces T cell proliferation, inhibits apoptosis1, and helps maintain a CD8+ T cell population (e.g., Abstract), relevant to claims 1, 6, 21, 28-29, and 31. Kaur discloses, “An important aspect of increased efficacy of IL-15 as compared to IL-2 is attributed to its anti-apoptotic activity, enhancing the survival of effector and memory CD8+ CTLs. Earlier studies suggest that despite the differences in anti-apoptotic protein bcl-xl expression IL-15 equally promotes the survival of CD8+ T cells with both naïve and activated phenotype as determined by expression of CD44 – an adhesion molecule that is expressed at low levels in naïve and at high levels in activated T cells” (Introduction). Kaur states that the findings of their study suggest that “T cells cultured in IL-15 show increased persistence not only due to levels of anti-apoptotic proteins, but also due to increased anti-oxidant levels, which is complimented by increased cytolytic effector functions” (Abstract; see also Results; Figures 1-4).
In view of these teachings, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to carry out a method of enhancing survival of or maintaining enhanced survival of CD3+/CD8+ cells, comprising the steps of culturing the CD3+/CD8+ cell in the presence of a CD3/TCR agonist (e.g., anti-CD3 antibody) and fibronectin (as taught by Enoki), further in the presence of a CD30 agonist (as taught by Podack and Kennedy) and an apoptosis inhibitor (as taught by Kaur). The skilled artisan would have been motivated to do so because:
Culturing CD8+ cells in the presence of an anti-CD3 antibody and fibronectin stimulates cell proliferation and expansion (as taught by Enoki);
Agonism of CD30, e.g., by an anti-CD30 agonist antibody, upregulates CCR7 (CD197) expression (as taught by Podack), which was desired by Enoki, and promotes the proliferation and survival of T cells (as taught by Kennedy), and further, CCR7-expressing TSCM show increased proliferation, self-renewal, persistence, and anti-tumor effect relative to other more differentiated T cell subsets, which is advantageous for adoptive T cell immunotherapies (as taught by Alvarez-Fernández); and
The presence of the apoptosis inhibitor IL-15 further induces T cell proliferation and helps maintain a memory CD8+ T-cell population (as taught by Kaur).
There would have been a reasonable expectation of success because the prior art recognized the suitability of each of agonism of the CD3/TCR complex (via an anti-CD3 antibody), fibronectin, CD30 agonism (via an anti-CD30 antibody), and the apoptosis inhibitor IL-15 for the purposes of promoting proliferation and survival of CD3+/CD8+ memory T cells, and because combining equivalents known for the same purpose to be used for the same purpose naturally flows from their having been individually taught in the prior art. See MPEP § 2144.06 and § 2144.07.
(2)
Claims 1-2, 21-22, 28-32 are rejected under 35 U.S.C. 103 as being unpatentable over Enoki (US 2010/0068192 A1; supra) in view of Podack (Annals New York Academy of Sciences (2002) 975: 101-113; supra), Kennedy (Immunology (2006) 118(2): 143-152; supra), and Kaur (Cytokine (2011) 55(2): 307-317; supra) as applied to claims 1, 5-7, 9-10, 12-14, 16-19, 21, 23-25, 28-31, and 33, further in view of Alvarez-Fernández (Journal of Translational Medicine (2016) 14: 214; cited in IDS), Zeng (Journal of Experimental Medicine (2005) 201(1): 139-148; cited in PTO-892), and Li (Journal of Leukocyte Biology (2007) 82: 142-151; cited in PTO-892).
The teachings of Enoki are recited in the 35 U.S.C. § 103 rejection above. In addition, Enoki teaches that the methods of the invention comprise a subsequent step in which the cell is cultured in the absence of the CD3/TCR complex agonist and fibronectin fragment (e.g., ¶ 0139), relevant to claim 2.
However, Enoki does not expressly teach that said subsequent step further comprises culturing the CD3+ cell in the presence of a CD30 agonist. Further, although Enoki recites production and expansion methods in which the culture medium comprises IL-7, Enoki does not teach that the medium used in the methods of the invention further comprises each of IL-15, IL-18, and IL-21.
The teachings of Podack, Kennedy, and Kaur are recited above.
Alvarez-Fernández discloses that a short CD3/CD28 costimulation combined with IL-21 enhances the generation of human memory stem T cells for adoptive immunotherapy. Alvarez-Fernández teaches that the use of less differentiated T cells with extensive replicative capacity, in particular, memory stem T cells (TSCM) that are CCR7+ and CD45RA+, show increased proliferation, self-renewal, persistence, and anti-tumor effect relative to other more differentiated T cell subsets (e.g., Background, pages 1-2). Alvarez-Fernández further teaches, “…studies demonstrated the generation and expansion of CD8+ TSCM from naïve T cells through CD3/CD28 costimulation in combination with IL-7 and IL-15 cytokines. However, prolonged in vitro costimulation decrease the expression of memory markers substantially (e.g., CD62L, CCR7 or CD27) leading to a swift [sic] to more differentiated T cells. For these reasons, identification of reproducible methods to generate and expand large numbers of TSCM for [adoptive T cell therapy] of cancer remains a clinical priority” (Background, page 2). To this end, Alvarez-Fernández cultured naïve CD8+ TSCM with IL-7/IL-15 and altered the length of CD3/CD28 costimulation on the maintenance of the TSCM phenotype in vitro, and observed that a short CD3/CD28 costimulation (48h) resulted in significantly greater frequencies of CD8+ TSCM compared with long costimulation (10 days) (e.g., Results, page 3; Figure 2b), relevant to claims 2, 21, 28, and 31.
Alvarez-Fernández also analyzed the effect of IL-21 on in vitro generation and maintenance of TSCM and observed that IL-21 significantly increased the percentage of CD8+ TSCM cultured under short CD3/CD28 costimulation conditions relative to the long costimulation condition (e.g., Results, page 3; Figure 3b), relevant to claims 1-2. Alvarez-Fernández also demonstrated that the addition of IL-21 to naïve T cell culture under both CD3/CD28 costimulation conditions (48h and long) significantly increased TSCM expansion, with the combination of short costimulation and IL-21 leading to the greatest expansion of total CD8+ TSCM (e.g., Results, page 5; Figure b).
Zeng teaches that IL-21 was originally implicated as a regulator of T and B cell proliferation (e.g., Introduction, page 139), and that “IL-21 was initially reported to costimulate anti-CD3–activated murine thymocytes and mature murine T cells in vitro and to enhance the proliferative effects of IL-2, IL-7, and IL-15 even without the addition of anti-CD3” (Results, page 140). Zeng presents data illustrating that IL-21 acts synergistically with IL-15 to potently promote the proliferation of CD8+ T cells and augment interferon (IFN)-γ production in vitro (e.g., Abstract). Specifically, a marked increase in the proliferation and expansion of T cells is observed after culture with both IL-21 and IL-15 as compared to IL-15 alone, with the majority of expanded cells being CD8+ T cells (e.g., Figure 1; Results, page 140-141). By contrast, a similar synergistic effect on CD4+ T cells was not evident (e.g., Results, page 141; Figure 1D). Zeng additionally shows that IL-21 acts synergistically with IL-7 in CD8+ T cells but not in CD4+ T cells (e.g., Results, page 141; Figure 2). The teachings of Zeng further relate to claims 1, 21, and 28-31.
Li examined the role of IL-18 on proliferation and survival of CD8+ T cells. Li teaches that stimulation of T cells through CD3/TCR in the presence of cytokines such as IL-7 results in clonal expansion (e.g., Introduction, page 142). Li additionally teaches that IL-18 was previously shown to be involved in the activation, differentiation, and clonal expansion of CD4+ T cells (e.g., Introduction, page 142). Li illustrates that IL-18 increases proliferation and survival of CD8+ T cells that have been activated by immobilized anti-CD3 antibody in vitro (e.g., Abstract; Figure 2), relevant to claims 22 and 32.
Based on the further teachings of Alvarez-Fernández, Zeng, and Li, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to carry out a method of enhancing or maintaining in vivo survival of a CD3+/CD8+ cell by culturing the cell in the presence of a CD3/TCR agonist (e.g., anti-CD3 antibody) and fibronectin (as taught by Enoki), a CD30 agonist (as taught by Podack and Kennedy), and the apoptosis inhibitor IL-15 (as taught by Kaur), wherein the medium further comprises IL-7, IL-18, and IL-21. The skilled artisan would have been motivated to include each of IL-7, IL-15, and IL-21 in the culture medium because these cytokines exert synergistic effects on the proliferation and expansion of CD8+ T cells (as taught by Zeng). The skill artisan would have been motivated to further incorporate IL-18 because IL-18 increases proliferation and survival of CD8+ T cells that have been activated by an immobilized anti-CD3 antibody in vitro (as taught by Li), thus demonstrating an advantage in methods of proliferation and maintenance when compared to incubation without IL-18. There would have been a reasonable expectation of success because the art recognized the suitability of each of IL-7, IL-15, IL-18, and IL-21 for the instantly claimed purpose of increasing proliferation and expansion of CD8+ T cells.
Further, the skilled artisan would have been motivated to perform a short co-stimulation period with the anti-CD3 antibody (instead of a long co-stimulation period) because shorter CD3 co-stimulation resulted in increased proliferation and expansion of T cells (as taught by Alvarez-Fernández), especially when combined with IL-21. Continued CD30 agonism, e.g., with an anti-CD30 antibody, would serve to promote expansion and maintenance of the T cells.
(3)
Claims 1, 3-5, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Enoki (US 2010/0068192 A1; supra) in view of Podack (Annals New York Academy of Sciences (2002) 975: 101-113; supra), Kennedy (Immunology (2006) 118(2): 143-152; supra), and Kaur (Cytokine (2011) 55(2): 307-317; supra) as applied to claims 1, 5-7, 9-10, 12-14, 16-19, 21, 23-25, 28-31, and 33, further in view of Chang (PLOS One (2014) 9(5): e97335; cited in PTO-892).
The teachings of Enoki are recited in the 35 U.S.C. § 103 rejections above.
However, Enoki does not explicitly teach that the CD3+ cell is derived from an induced pluripotent stem (iPS) cell.
The teachings of Podack, Kennedy, and Kaur are recited in the 35 U.S.C. § 103 rejection above.
Chang discloses antigen-specific T lymphocytes derived from human iPS cells that have a broad TCR repertoire (e.g., Abstract). Using in vitro methods, Chang produced mature T cells, derived from human iPS cells, that express CD3, CD8, and TCR-γδ (e.g., Abstract; Results, pages 3-5; Figure 2). Chang additionally teaches, “Genetic modification of patient-specific [human iPS cells] followed by differentiation to mature T lymphocytes may provide new treatment options for patients with inherited or acquired immune deficiencies. Also, the addition of chimeric antigen receptor sequences (CARs) to patient-specific [human iPS cells] may provide a method to produce virtually unlimited numbers of T lymphocytes designed to target specific tumor types” (Discussion, page 9).
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to use a CD3+ cell derived from an iPS cell (as taught by Chang) in a method of enhancing in vivo survival that comprises culturing a CD3+ cell in the presence of a CD3/TCR complex agonist, fibronectin, a CD30 agonist, and the apoptosis inhibitor IL-15. The skilled artisan would have been motivated to do so because Chang teaches that patient-specific iPS cells, once further differentiated into mature T lymphocytes, may provide new treatment options for patients with inherited or acquired immune deficiencies. It would be further obvious that some CD3+ cells used in the method, derived from an iPS cell, express TCR-γδ, based on the observations of Chang. There would have been a reasonable expectation of success because the skilled artisan would have recognized the suitability of an iPS cell for carrying out the instantly claimed method of producing a CD3+ cell because iPS cells express CD3.
(4)
Claims 1 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Enoki (US 2010/0068192 A1; supra) in view of Podack (Annals New York Academy of Sciences (2002) 975: 101-113; supra), Kennedy (Immunology (2006) 118(2): 143-152; supra), and Kaur (Cytokine (2011) 55(2): 307-317; supra) as applied to claims 1, 5-7, 9-10, 12-14, 16-19, 21, 23-25, 28-31, and 33, further in view of Van Wauwe (The Journal of Immunology (1984) 133(1): 129-132; cited in PTO-892).
The teachings of Enoki are recited in the 35 U.S.C. § 103 rejection above. Enoki further teaches that the CD3 ligand is not particularly limited, and may be exemplified by, for example, an anti-CD3 antibody such as OKT3 (e.g., ¶ 0081).
However, Enoki does not explicitly teach that the anti-CD3 antibody used in the method of the invention is produced from an UCHT1 clone.
The teachings of Podack, Kennedy, and Kaur are recited in the 35 U.S.C. § 103 rejection above.
Van Wauwe teaches that OKT3 and UCHT1 monoclonal antibodies recognize the same human T cell surface antigen and induce proliferation in T lymphocytes (e.g., Abstract). Van Wauwe additionally teaches, “We have previously described that OKT3 and UCHT1 monoclonal antibodies exert mitogenic effects on human blood T cells. The antibodies trigger mitogenesis by interaction with the same antigenic structure on the T cell surface, as evidenced by two-directional co-capping, competitive binding, and immunoprecipitation experiments” (Introduction).
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an OKT3-derived anti-CD3 antibody with a UCHT1-derived anti-CD3 antibody (as taught by Van Vauwe) in a method of enhancing in vivo survival of a CD3+ cell that comprises culturing a CD3+ cell in the presence of a CD3/TCR complex agonist, fibronectin, a CD30 agonist, and the apoptosis inhibitor IL-15. The skilled artisan would have been motivated to do so because of the teachings of Van Vauwe, who discloses that anti-CD3 antibodies derived from OKT3 and UCHT1 both exert mitogenic effects on human blood T cells through their recognition of the same antigenic structure on the T cell surface. There would have been a reasonable expectation of success because both antibodies are in effect functional equivalents being used for the same purpose.
(5)
Claims 1 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Enoki (US 2010/0068192 A1; supra) in view of Podack (Annals New York Academy of Sciences (2002) 975: 101-113; supra), Kennedy (Immunology (2006) 118(2): 143-152; supra), and Kaur (Cytokine (2011) 55(2): 307-317; supra) as applied to claims 1, 5-7, 9-10, 12-14, 16-19, 21, 23-25, 28-31, and 33, further in view of Bowen (The Journal of Immunology (1993) 151(11): 5896-5906; cited in PTO-892).
The teachings of Enoki are recited in the 35 U.S.C. § 103 rejection above.
However, Enoki does not explicitly teach that a concentration of CD30 agonist antibody or binding fragment thereof of 1-1000 ng/mL is contained in the medium in the methods of the invention.
The teachings of Podack, Kennedy, and Kaur are recited in the 35 U.S.C. § 103 rejection above.
Bowen recites culturing YT cells under normal culture conditions in the anti-CD30 monoclonal antibody “C10” at concentrations of 1 ng/mL, 10 ng/mL, 100 ng/mL, and 1 μg/mL (e.g., Figure 1). The C10 antibody inhibits YT cytotoxicity for Raji target cells (e.g., Abstract; Results; Figure 1).
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to prepare a medium comprising an anti-CD30 agonist antibody at a concentration of 1-1000 ng/mL (based on the teachings of Podack and Bowen) in a method of enhancing in vivo survival of a CD3+ cell that comprises culturing the CD3+ cell in the presence of a CD3/TCR complex agonist, fibronectin, a CD30 agonist, and the apoptosis inhibitor IL-15. The skilled artisan would have been motivated to do so because Bowen teaches that various concentrations of an agonistic anti-CD30 monoclonal antibody (“C10”) inhibit cytotoxicity in a cell line (“YT”) that is a useful model for cytotoxic cells. There would have been a reasonable expectation of success because CD30 regulates cytotoxicity and facilitates clonal expansion of CD8+ cells. Furthermore, MPEP § 2144.05 (II)(A) sets forth, "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989).
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Rajah (Toxicology and Applied Pharmacology (2014) 278: 100-106) teaches that z-VAD-FMK inhibits anti-CD3-mediated T cell proliferation and activation in primary T cells due to oxidative stress mediated by depletion of intracellular glutathione (GSH) (see whole document).
Conclusion
No claims are 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.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
1 By virtue of its ability to inhibit apoptosis, IL-15 reads on “an apoptosis inhibitor” as required by claims 1 and 28.
Prosecution Insights