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 .
Priority
This application was filed Oct. 19, 2022, and is a 371 application of PCT/KR2021/007091 filed on June 7, 2021, which claims benefit to the foreign application KR10-2021-0046107 filed on April 8, 2021, and foreign application KR10-2020-0069854 filed on June 9, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in foreign Application KR10-2021-0046107 and KR10-2020-0069854, filed on Oct. 19, 2022.
Claim Status
In the response filed Feb. 23, 2026, Applicant has amended claims 1-3 and added new claims 13-14.
On Sept. 2, 2025, Applicant elected, with traverse, Group I (drawn to a feeder cell for culturing natural killer (NK) cells. Claims 5-12 are directed to Group II drawn to a method of proliferating NK cells are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Currently, claims 1-14 are pending and claims 5-12 are withdrawn.
Claims 1-4 and 13-14 are under examination in this office action.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Specification
The objection to the disclosure because of the following informalities: incorrect acronym of “EBV_LCL” (see e.g. page 3), which should recite “EBV-LCL”, and The sequence disclosures located in Table 1 (page 15) is withdrawn due to the substitution specification and sequence listing filed Feb. 23, 2026.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Kamiya, Takahiro and Campana, Darlo, (WO2018/182511, published 2018, hereinafter as “Kamiya”, cited IDS 2/01/2024, prior art of record) in view of David Wald (WO2018/213828, published 2018, hereinafter as “Wald”, prior art of record).
This rejection is a new rejection necessitated by amendments to the claims. However, since it is substantially similar to a rejection set forth in the non-final Official action mailed on Oct. 21, 2025, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
Regarding claim 1, and 3-4, Kamiya discloses a feeder cell (i.e. stimulatory cells)(e.g. K526 cell lines) for culturing natural killer (NK) cells (see e.g. abstract, para. 3, 8, 21, 42, 61-62, and 72, claims 1-36, fig. 1, 3-4, page 14-25), wherein the feeder cell is genetically engineered to express membrane bound interleukin-18 (mbIL-18)(see e.g. claims 1, 14-17, and 33-36). (see e.g. para. 8, 21, 42, and 61; page 14, claim 6). Further, Kamiya discloses K562 variants that are generated by transducing the K562-mb15-41BBL cells with a retroviral vector containing the cDNA sequence encoding membrane bound interleukin (IL)-12, IL-18, or both, and further discloses genetically engineering a cell to express membrane bound IL21 (mbIL21)(i.e. SEQ ID NO. 10)(see e.g. page 37-38, claims 1-16). Further, Kamiya discloses a nucleic acid encoding mbIL-18 (SEQ ID NO: 8) (see e.g. claims 33-34) and mbIL-21 (SEQ ID NO: 36)(see e.g. claims 35-36).
Kamiya does not explicitly teach wherein the feeder cell is genetically engineered to express membrane bound interleukin-18 (mbIL-18) and membrane bound interleukin-21 (mbIL-21).
However, the prior art of Wald discloses a feeder cell (i.e. myeloid leukemia cells) for culturing natural killer (NK) cells (see e.g. abstract) that is genetically engineered to express membrane bound interleukin-21 (i.e. mbIL-21)(i.e. SEQ ID 2)(see e.g. abstract, para. 1-21, 116 claims 1-5, 10, 30 and SEQ ID No: 1-2).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Kamiya and incorporate membrane bound interleukin-21 (mbIL-21) as taught by Wald because Kamiya suggests that the co-expression of co-stimulatory molecules such as mbIL-21 has a synergistic stimulation effect for NK cell expansion (see e.g. paras 43, 48, 50-51, and 79; Example 2). Further, Wald discloses that the genetically manipulated feeder cell line provides robust expansion of NK cells (see e.g. page 2). Thus, the use of the membrane-bound interleukins such as those discloses by Kamiya (e.g. mbIL-15, mbIL-18, and mbIL-21) with the membrane-bound interleukins as discloses by Wald (e.g. mbIL-15 and mbIL-21) would be considered obvious since it is prima facie obvious to substitute one known element (i.e. membrane bound interleukin) for another to obtain predictable results. In the instant case, both Wald and Kamiya disclose feeder cells for culturing natural killer (NK) cells, wherein the feeder cell is genetically engineered to express more than one membrane bound interleukin. Thus, one of ordinary skill could have substituted one element for another with predictable results, since both are readily available and are deliverable using similar techniques. Moreover, an artisan of ordinary skill in the art of (i.e. genetically engineered feeder cells) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 2, Kamiya discloses wherein the feeder cell is selected from the group consisting of K562, EBV transformed B cell line (i.e. EBV-LCL), 721.221, HFWT (see e.g. para. 8, 21, 42, and 61; page 14, claim 6).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant argues that neither the prior art of Kamiya nor Wald anticipate the amended claim 1 of a feeder cell that is genetically engineered to express membrane bound interleukin-18 (mbIL-18) and membrane bound interleukin-21 (mbIL-21) (Remarks, page 7-8).
Applicant’s arguments with respect to the previous rejection of claims 1-4 as rejected as being anticipated over Kamiya and Wald have been fully considered and are persuasive in view of the amendments to the claims. Therefore, the rejection has been withdrawn.
However, upon further consideration, a new grounds of rejection is made in view of Kamiya, Takahiro and Campana, Darlo, (WO2018/182511, published 2018, hereinafter as “Kamiya”, cited IDS 2/01/2024, prior art of record) in view of David Wald (WO2018/213828, published 2018, hereinafter as “Wald”, prior art of record), due to the amendment to the claims.
Applicant argues that neither Kamiya does not disclose evaluation of K562 cell lines for their ability to expand NK cells by comparing a K562-mbIL15-41BBL cell line against cell lines additionally co-expressing mbIL-21 and does not provide specific guidance for co-express mbIL-21 and mbIL-18 (Remarks, page 10).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to applicant's argument that Kamiya does not disclose evaluation of K562 cell lines, it not persuasive because the claim is directed to a composition and not a method. Further, there is not a claim limitation directed to “evaluation of K562 cell lines” compared to other cell lines.
In response to applicant's argument that Kamiya does not provide specific guidance for co-express mbIL-21 and mbIL-18, 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). As discussed above, Kamiya discloses expressing one or more membrane bound interleukin (see e.g. page 37-38, claims 1-16), and Ward discloses NK cells that are genetically modified to express one or more membrane bound interleukin (see e.g. page 3). Thus, a person of ordinary skill in the art would know how co-express one or more membrane bound interleukin such as mbIL-21 and mbIL-18.
Applicant argues that Wald (i.e. Ward) does not provide a reasonable expectation of success to modify the feeder cell co-expressing mbIL-21 and mbIL-18 (Remarks, page 8 and 10).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
It is noted that Applicants arguments correctly cite the prior art of Wald (see Remarks, page 8) but then address the prior art of Wald as the prior art of “Ward” through the response (see Remarks, page 8-10). It appears that “Ward” is a typo, and Applicants meant the prior art of “Wald.” Thus, Applicants remarks will interpret as referring to the cited prior art of Wald.
In response to applicant's argument that Wald does not provide a reasonable expectation of success, 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). In the instant case, Wald discloses genetically modified feeder cell line and NK cells that are able to express one or more proteins capable of providing cytokine support (see e.g. page 3 and 21). Contrary to Applicants assertion an artisan of ordinary skill in the art of (i.e. genetically engineered feeder cells) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
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.
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JOSEPHINE GONZALES
Examiner
Art Unit 1631
/JOSEPHINE GONZALES/ Examiner, Art Unit 1631
/JAMES D SCHULTZ/ Supervisory Patent Examiner, Art Unit 1631