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 .
Claim Status
Claims 2,3,5, and 33-34 are amended.
Claim 21 is cancelled.
Claims 28-31 and 33-38 are withdrawn.
Claims 1-20,22,24-27 are Pending.
Withdrawn Objections
The objection raised against claim 3 because it improperly refers to table 1 from the specification is withdrawn in view of claim amendment.
Withdrawn Rejections
Claim Rejections - 35 USC § 112
The rejection of claims 2,3,5, and 21 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of claim amendment.
Maintained Rejections
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-22, and 24-27 are rejected under 35 U.S.C. 103 as being unpatentable over Valamehr et al (WO 2017 /079673 A1) in view of Ma et al (CA 3078735 A 1), Wang et al (Translational Cancer Mechanisms and Therapy, 2018), and Rehm et al (WO 2017/211900 A1).
Regarding claims 1,6,11 and 19, Valamehr et al teach methods for obtaining genome-engineered iPSCs with stable and functional genome editing at selected sites. Valamehr et al also teach cell populations derived from the genome-engineered iPSCs. According to Valamehr et al, the genome-engineered iPSCs comprise targeted integration of one or more exogenous polynucleotides, wherein at least one exogenous polynucleotide encodes for a CAR and another encoding for the high affinity and non-cleavable CD16 receptor (hnCD16).(See abstract, paragraph [10], [17], and [18]). Valamehr et al also disclose that the CAR and hnCD16 expressing cells can further contain genomic modifications including deletion of genes or insertion of genes in order to increase resistance to immune detection; however Valamehr et al do not specifically teach modified cell population comprising a CD38 knockout. (See paragraph [00017]). In addition, while Valamehr et al teach to genetically modify iPSCs to express a CAR, Valamehr et al do not teach that the CAR is an anti-BCMA CAR nor do they teach a modified cell population comprising full length of a cytokine and a cytokine receptor.
Ma et al supplement Valamehr et al by teaching a modified cell population comprising of human NK cells transduced to express a BCMA CAR and the soluble IL-15/IL-15 sushi.(See Fig. 50A and 53). Ma et al demonstrate that the produced NK cells expressing the BCMA-CAR and soluble IL-15/IL-15 sushi show anti-leukemic effects in mouse model of multiple myeloma (MM). ( See page 140 Iine 15, page141 line 30, and Fig. 51 ).According to Ma et al, the soluble IL-15/IL-15sushi fusion are stable and enhances CAR T/NK cell persistency, stimulate tumor infiltrate lymphocyte proliferation, and anti-tumor activity. (See page 51, lines 28-31, and page 61, lines 28-31). Ma et al disclose that the NK cells used in the examples are derived from cord blood. (See page 138 lines 29-30, and page 139 lines 1-29, and page140 lines 1-15). Ma et al also state that the source of the modified cell population may be obtained from “human peripheral blood mononuclear cells (PBMC), leukapheresis products (PBSC), human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), bone marrow, or umbilical cord blood”. (See page 5 lines 14-16).
As discussed above, Valamehr et al disclose that the modified cell population may further contain genomic modification such as gene deletion in order to increase resistance to immune detection; however, Valamehr does not specifically teach modified cell population that is a CD38 knockout. Ma et al do not cure such deficiency.
Wang et al supplement Valamehr and Ma by teaching that treatment of multiple myeloma with daratumumab, an anti-CD38 antibody, has unwelcome side effect of killing NK cells, including adoptively transferred NK cells. (See abstract). Wang et al., however, teach that adoptive transfer of CD38-/low NK cells prevents their "fratricide" by daratumumab induced ADCC (See Fig.3, and pages 4008-4011). Wang et al also demonstrate that CD38-/low NK cells exhibited increased cytotoxicity against multiple myeloma cells (See Fig.4). Therefore, in view of the specific teachings of Valamehr to make and use genetically modified iPSCs expressing a CAR and hnCD16, as well as Valamehr teachings to delete genes in iPSCs in order to improve immune effector activity, then the motivation provided by Ma et al to make and use a genetically modified cells expressing BCMA-CAR and IL15/IL15 sushi to improve anti-tumor activity and CAR/cells persistency, and the further teachings of Wang et al that daratumumab "fratricide" CD38+ NK cells while CD38 negative NK show increased cytotoxicity on multiple myeloma, it would have been prima facie obvious to one with ordinary skill in the art at the time the invention was filed to further genetically modify Valamehr cells to express BCMA-CAR and IL15/IL15 sushi in order to improve survival/persistency and anti-tumor activity, and to delete CD38 in order to produce a derivative cell capable of generating CD38 negative NK cells with increased therapeutic potential in combination with daratumumab and with a reasonable expectation of success. Some Teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143 (I)(G).
Regarding claim 2, Valamehr et al teach that iNK cells derived from the genome engineered iPSC have longer telomere length relative to NK cells obtained from adult peripheral blood. (See Fig.31, and paragraph [32]).
Regarding claims 3 , Valamehr et al teach that the genome-engineered iPSCs are HLA class I and/or II deficient. (See paragraph [22], and claims 45-47).
Regarding claims 4 and 20, Valamehr et al in view of Ma et al render obvious a modified cells expressing BCMA-CAR, hnCD16, and IL15/IL15 sushi. However, neither Valamehr nor Ma disclose sequences corresponding to the antigen recognition regions of the BCMA-CAR.
Rehm et al disclose an isolated chimeric antigen receptor polypeptide (CAR) with an extracellular antigen-binding domain that binds a B Cell Maturation Antigen (BCMA) polypeptide. Rehm et al also disclose a genetically modified immune cells expressing the BCMA-CAR and the use of said cell in the treatment of a medical disorder associated with the presence of pathogenic B cells, such as multiple myeloma, and non-Hodgkin's lymphoma. (See abstract). Rehm et al show a proof- of-concept evidence that modified CAR T cells equipped with the isolated BCMA-CAR of the invention mediate strong and efficient in vivo antitumor activity in mouse models of multiple myeloma (MM) and B-cell non-Hodgkin's lymphoma.(See Fig.16). According to Rehm et al, the inventions BCMA-CAR differs from BCMA-CAR of prior arts in that it can react against both B-NHL and MM, while others can only react with MM cells only. (See page 34 lines 18-21). Rehm et al disclose SEQ ID No.11 and 12, which represents the full length of the VH and VL domain of the BCMA-CAR . It is noted that SEQ ID NO 11 and 12 share 100% sequence identity to SEQ ID NO:33 and 34 of instant application. Therefore, it is prima facie obvious to one with ordinary skill in the art at the time the invention was filed to combine the teachings of Valamehr, MA, and Rehm to generate a modified effector cells expressing BCMA-CAR comprising the VH and VL domain represented by SEQ ID NO 33 and 34 and use that to treat patients with B-NHL and MM with a reasonable expectation of success. Some Teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143 (I)(G).
Regarding claims 5 and 21, According to Valamehr et al, the genome-engineered iPSCs or derivatives, such as an NK or T derivative, would have improved persistency and/or survival, increased resistance to native immune cells, and so on. (See claims 38-41).
Regrading claim 6-7, Following the discussion of claim 1 above, Valamehr teaches modified effector cells expressing CD16 that include a high affinity non-cleavable CD16 (hnCD16). Valamehr et al further suggest a CD16 variant comprising F176V and S197P as an exemplary CD16 variant having high affinity and non-cleavable version. (See paragraph [148] ).
Regarding claim 8, Valamehr et al teach genetically-engineered iPSCs comprising at least one exogenous polynucleotide encoding hnCD16 that is resistant to proteolytic cleavage and ectodomain shedding. (See paragraph [48]). However, Valamehr et al do not teach the construction of a chimeric CD16 comprising a non-native transmembrane domain derived from CD28 or a non-native signaling domain derived from CD3ζ.
Chen et al disclose that a chimeric CD16 comprising exogenously expressed FcγRs and T-cell–signaling components can exert enhanced antitumor activity in combination with therapeutic antibodies through ADCC or ADCP. Specifically, Chen’s construct comprises of
CD16 ectodomain, CD8a extracellular domain, CD28 transmembrane domains, two costimulatory domains (CD28 and 4-1BB), and the signaling domain from CD3ζ. Chen et al demonstrate that modified cells expressing the chimeric receptor possess improved cytotoxicity against CD20-positive non-Hodgkin’s lymphoma cells in the presence of rituximab. Thus, in view of Valamehr teachings to make CD16 variant with F158V and S197P that is resistant to ectodomain shedding and proteolytic cleavage, and Chen’s teachings to make a CD16 fusion receptor with the transmembrane domain of CD28 and the signaling domain of CD3ζ that provides enhanced antitumor activity when administered in combination with therapeutic antibodies, would motivate one with ordinary skill in the art to combine both teachings. One would have been motivated to make and use a fusion hnCD16 receptor combining the extracellular domain of Valamehr and the non-native domains taught by Chen because such construct, as taught by Chen, is effective for treating cancer/ tumor. Some Teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143 (I)(G).
Regarding claim 9, Following the discussion of claim 1 above, the combined teachings of Valamehr and Ma render obvious the modified cell population of claim 1. Valamehr et al teach how to make genome-engineered iPSCs comprising targeted integration of one or more exogenous polynucleotides. Valamehr et al suggest that the exogenous polynucleotides can encode a CAR, specifically CD19. However, Valamehr does not teach making a modified cells expressing two CARs. Ma et al teach how to make modified cells comprising two CARs. Ma et al teach that Multiple Myeloma tumors comprises both a stem cell population expressing CD19 and a bulky population expressing BCMA. To prevent relapse and to target the two populations, Ma et al suggest to make and use modified NK cells expressing both BCMA and CD19 CARs for treating patients with MM cancer. ( See Ma et al page 86, lines 3-31). Therefore, it would have been prima facie obvious to one with ordinary skill in the art to modify the teachings of Valamehr et al to make a genetically modified effector cells expressing two CARs. One would have been motivated by the suggestions of Ma et al to make and use modified cells expressing two CARS when the particular disease in question, such as MM, consists of heterogenous cell population expressing various antigens. Because doing so would provide an effective targeting strategy for eradicating all diseased cells. Some Teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143 (I)(G).
Regarding claim 10 and 16-18, Valamehr et al teach that the one or more exogenous gene(s) can be inserted into a safe harbor locus such as the AAVSl, CCR5, ROSA26, collagen, HTRP,Hll, B2M, GADPH, TCR, or RUNXI loci. Valamehr et al teach that the locus specific insertion of CAR can take place at the iPSC level, with the CAR inserted in the constant region of TCR. According to Valamehr, the truncation of TCR constant region leads to TCR knock-out. ( See paragraph [164] and [319]).
Regarding claim 12 and 13-14, The combined teachings of Valamehr, Ma, and Wang render obvious the generation of the modified cell population of claim 1. To get a better therapeutic outcome for cancer patients, Ma et al suggest supplementing the administration of the modified cells with the co-administration of a CAR enhancing agent such as PD-L1 (i.e. atezolizumab), a checkpoint inhibitor.(See Ma et al page 95 lines 10-21, and page 100, lines 10-17). Therefore, it would have been prima facie obvious to the ordinary skill in the art at the time the invention was filed to combine the teachings of Valamehr and Ma and supplement the genetically modified cell population of Valamehr with a checkpoint inhibitor to treat patients with cancer. One would have been motivated to supplement the cells of Valamehr with a checkpoint inhibitor because doing so would improve the therapeutic outcome for cancer patients. Some Teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143 (I)(G).
Regarding claims 15 and 22, Valamehr et al state that “the generated genome-engineered iPSCs are capable of differentiating into hematopoietic lineage cells, including mesodermal cells, CD34 cells, hemogenic endothelium cells, hematopoietic stem and progenitor cells, hematopoietic multipotent progenitor cells, T cell progenitors, NK cell progenitors; T cells, NKT cells, NK cells, or B cells”. ( See page 9, 1st paragraph, and paragraph [28]).
Regarding claims 24-27, Valamehr et al also teach pharmaceutical compositions comprising the genome modified iPSCs or their NK cell derivatives for use in adoptive cell therapy of autoimmune disorders, hematological malignancies such as leukemias, solid tumors, or virus infection. (See Valamehr paragraph [44]). Valamehr et al do not teach a composition comprising the modified cell and one more agent.
Following the discussion of claim 12, the combined teaching of Valamehr and Ma render obvious supplementing the modified cells with a therapeutic agent such as a checkpoint inhibitor to improve the therapeutic outcome. Ma et al further suggest that the combined administration of the modified cells and anti-PD1 provides synergistic efficacy of the CAR polypeptide. ( See page 93 lines 8-10). Therefore, it is a prima facie obvious to one with ordinary skill in the art to supplement the composition of Valamehr containing the modified cells with checkpoint inhibitor/modulator, such as anti-PD1, in order to treat patients with cancer. One would be motivated to do this knowing that it will improve the therapeutic outcome for patients with cancer. Some Teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143 (I)(G).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3,5-19,21-22,24-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, and 17-22 of U.S. Patent No.10927346 (Valamehr et al.February.23.2021). In view of Ma et al (WO 2019/075395 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because
Valamehr et al teach a cell population and a composition comprising NK cells derived from differentiating iPSCs. The derived cell population of Valamehr et al comprises a CD38 deletion, a CAR, hnCD16, a partial or full-length cytokine, and a cytokine receptor. Valamehr et al also teach a composition comprising the NK derivatives and one or more therapeutic agent comprising a peptide, a cytokine, a checkpoint inhibitor, and so forth.
While Valamehr et al teach an NK derivative expressing a CAR; however, Valamehr et al do not specify the CAR is a BCMA-CAR. The teachings of Ma et al are set forth above.
Therefore, it would have been prima facie obvious to one with ordinary skill in the art to modify the teachings of Valamehr et al to make and use NK derivatives that express BCMA-CAR to treat patients with disease/disorder, such as multiple myeloma, where the diseased cell expresses the targeting moiety (i.e. BCMA). Combining prior art elements according to known methods to yield predictable results. See MPEP 2143 (I)(A).
Claims 1-3,5-19,21-22,24-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14,17-19,22 of copending Application No. 18575734. Although the claims at issue are not identical, they are not patentably distinct from each other because 18575734 teach cell population derived from genome-engineered iPSCs comprising a CD38 deletion, exogenous nucleotides encoding a CAR such as BCMA-CAR, hnCD16, and a partial or full-length cytokine and a cytokine receptor. The copending application also teach a composition comprising the iPSCs-derived cell population and one or more therapeutic agent selected from a peptide, a cytokine, a checkpoint inhibitor, and so on.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3,5-19,21-22,24-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21,30-32 of copending Application No. 16765369. In view of Wang et al (Translational Cancer Mechanisms and Therapy, 2018).
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claims teach a cell population derived from genome-engineered iPSCs comprising exogenous nucleotides encoding a CAR such as BCMA-CAR, hnCD16, and a partial or full-length cytokine and a cytokine receptor. The copending claims also teach a composition comprising the iPSCs-derived cell population and one or more therapeutic agent selected from a peptide, a cytokine, a checkpoint inhibitor, and so on.
The copending claims do not teach a genome-engineered iPSCs or derivative that is also a CD38 knockout. The teachings of Wang et al are set forth above.
Therefore, it would have been prima facie obvious to one with ordinary skill in the art to modify the teachings of copending claims to make and use genome-engineered iPSCs or derivative that is also a CD38 knockout. One would have been motivated to do so to produce a derivative cell capable of producing CD38 negative NK cells with increased therapeutic potential when administered in combination with daratumumab. Some Teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143 (I)(G).
Combining prior art elements according to known methods to yield predictable results. See MPEP 2143 (I)(A).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 10/01/2025 have been fully considered but they are not persuasive.
Applicants argue none of the references disclose a CD38 knockout. Applicants also argue that there is no basis in Wang ( or any of the other cited references) for concluding that an NK cell that is merely "negative" for CD38 expression under some circumstances would behave the same as an NK cell in which CD38 is knocked out. This is because CD38-/lowNK cells can at some timepoint reactivate CD38 expression while a knockout NK cell cannot.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive. While the office agrees with Applicant that the naturally occurring effector cells taught by Wang et al express a very low level of CD38 expression (i.e. merely negative, see Fig.4C) and are not a complete knockout; the office nevertheless maintains that Wang et al provide strong motivation and guidance to the ordinary skill in the art to use genetic approaches, such as knockout techniques, to delete CD38 in effector cells. This conclusion is based on Wang et al’s teachings, which clearly show that CD38-targeted therapies are complicated by the presence of effector cells, such as NK cells, that themselves express CD38. Wang et al, for example, demonstrate that CD38 expression could lead to NK-cell being fratricidal in the presence of daratumumab. This is evidenced by Wang’s teachings showing that blocking CD38 with daratumumab F(ab)2 prevents daratumumab-induced apoptosis in CD38+ NK cells. ( See Fig.4D-E). Accordingly, an ordinary skill in the art would be motivated to eliminate CD38 expression in effector cells, such as NK cells, in order to avoid daratumumab’s fratricidal effect on CD38-expressing immune cells. In other words, the office’s projected view that CD38 knockout effector cells are expected to behave similarly to NK cells that merely negative for the expression of CD38 is a valid assumption, given Wang et al’s clear demonstration of the advantage of protecting NK cells from fratricide when CD38 expression is merely negative.
The office also agrees with Applicant that Wang et al show that the naturally occurring NK CD38-/low , which are initially negative for CD38 expression, may activate CD38 expression during in vitro expansion, as shown by Wang et al in Fig.4C. However, the possibility of recovering expression, further support the conclusion that, when effector cells that express CD38 (e.g. NK cells) are used in combination with anti-CD38 therapy to treat melanoma, genetically modified cells that completely lack CD38 would be preferred over the naturally occurring CD38-/lowNK. An ordinary skill in the art can easily extract such understanding from Wang et al’s statement that “ If this occurs in vivo (i.e. acquisition of CD38 expression), it may explain why CD38-/lowNK cells, with greater proliferative ability, do not expand in vivo in daratumumab-treated patients with multiple myeloma to reconstitute the NK-cell compartment after depletion of CD38-/lowNK cells by daratumumab, namely because the acquisition of CD38 expression might result in daratumumab-induced apoptosis of these cells”. ( See 1st column, 2nd paragraph, page 4016). Furthermore, although Wang et al suggest the sequential administration of daratumumab and CD38-/lowNK in combination with pretreatment with F(ab)2 fragments of daratumumab prior to administration to prevent the fratricidal effect; however, Wang et al caution that this approach may also result in the emergence of multiple myeloma cells that are resistant to daratumumab. ( See 1st column, 2nd paragraph, page 4016). Therefore, an ordinary skill in the art ,upon reading Wang et al, would be motivated to turn away from the proposed approaches, which provide only temporary solutions, and instead turn to a more promising and well-established strategies available in the art-such as genetic knockout technique-to completely eliminate CD38 expression in effector cells.
Applicant also argue that because Wang et al’s teachings are solely based on NK cells, there is no basis for making any prediction about the effect of such modification (i.e. deleting CD38) on an iPSC or the ability to derive a desired type of cell therefrom.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive. This is because, at the time the invention was filed, a mouse model of Cd38-/- had already been generated, demonstrating viability and relevance. ( See Kato et al,1998). For example, CD38-knockout mice were shown to be viable, fertile, and develop normally. In other words, no cases of embryonic lethality or global failure of development were reported at the time the invention was filed. Hence, there is no teaching away exists that would discourage PHOSITA to create CD38-KO stem cells. Therefore, an ordinary skill in the art would reasonably conclude that CD38 is not essential for cell survival or development, and would be motivated to isolate stem cells from CD38 knockout mice, or generate CD38 knockout stem cells.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 FATIMAH KHALAF MATALKAH whose telephone number is (703)756-5652. The examiner can normally be reached Monday-Friday,7:30 am-4:30 pm EST.
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/FATIMAH KHALAF MATALKAH/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638