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 .
Detailed Action
This action is in response to the papers filed August 30, 2026.
Noncompliance with 37 CFR 1.52
Applicant's amendments to the claims filed 08/30/2026 fail to comply with the requirements of 37 CFR 1.52. 37 CFR 1.52(a)(1)(iv-v) states that all papers that are submitted on paper or by facsimile transmission must be plainly and legibly written either by a typewriter or machine printer in permanent dark ink or its equivalent and presented in a form having sufficient clarity and contrast between the paper and the writing thereon to permit the direct reproduction of readily legible copies in any number by use of photographic, electrostatic, photo-offset, and microfilming processes and electronic capture by use of digital imaging and optical character recognition. In this case, Applicant's amendments are presented in a low-resolution, grainy and faint grey-scale ink or type that lacks sufficient clarity and contrast between the paper and the writing thereon so as to render the changes introduced by the amendments difficult to read and understand. If applicable, it is recommended that applicant avoid submitting amendments containing color text that is converted to a lower-resolution, grey-scale upon submission. Applicant is therefore notified that any future submission of an amendment to the application that is too difficult to read so as to raise any degree of uncertainty regarding the specific text or language submitted will delay prosecution of the application.
Claim Amendments
Applicant’s amendment to the claims filed 08/30/2026 is acknowledged.
Claims 5-6 have been cancelled.
Claims 1-3 are amended.
Claims 1-4 and 7-13 are pending.
Claims 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention
Claims 1-4 and 7-10 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the application. See, the Requirement for Restriction/Election mailed 11/28/2025.
In the reply filed 01/28/2026, Applicant elected without traverse Invention I, claims 1-10, drawn to a method of culturing natural killer cells, and the species of ovarian cancer, as the cancer type.
Claims 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/28/2026.
Priority
The instant application 18/300,852 was filed on 04/14/2023. This application is a continuation (CON) of international application PCT/KR2021/014245 filed 10/14/2021, claiming priority based on Korean patent application KR10-2020-0134623 filed 10/16/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. While a certified copy of the foreign patent application is provided with the instant application, a certified English translation of said foreign patent application has not been provided.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 04/01/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Claim Objections
Claim 2 is objected to because of the following informalities:
In claim 2, the phrase “TRAIL (TNFSF10)” should either be (1) “TRAIL” or (2) “TNFSF10” because one of ordinary skill in the art would have recognized TRAIL and TNFSF10 as synonyms for the same gene.
Appropriate action is required.
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.
Claims 1-4, 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Choi et al. (2019) “Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer” BMC cancer, 19:817, 11 pages; in view of KR20190093499A to Woo et al.
KR20190093499A was published in a non-English language. This rejection relies upon a machine translation from Espacenet (European Patent Office), a paper copy of which has been provided.
This rejection is newly applied, necessitated by amendment.
Choi teaches a method of culturing natural killer (NK) cells, the method comprising:
selecting mononuclear cells from human peripheral blood by drawing blood;
obtaining CD3-CD56+ NK cells from the selected mononuclear cells; and
treating the obtained CD3-CD56+ NK cells with IL-2, anti-NKp46 antibody, and plasma, followed by culturing in a feeder cell-free culture medium.
See, Abstract; Methods on pg. 2-3; and Figures 1-2.
Choi teaches that the blood sample containing peripheral blood mononuclear cells (PBMCs) was obtained by drawing blood (pg. 2, right column, first full paragraph).
Choi does not teach that the blood sample containing PBMCs was obtained by leukapheresis, as claimed in claim 1.
Woo is relevant prior art for teaching a method of culturing NK cells obtained from a blood sample containing PBMCs. See, e.g., Abstract; par. 7-13. The “blood sample” is peripheral whole blood or leukocytes isolated by leukapheresis (see, par. 20-21), and leukapheresis is a closed system.
Accordingly, prior to the effective filing date of the instantly claimed invention, one of ordinary skill in the art would have recognized that drawing blood or leukapheresis is a suitable means of obtaining a blood sample containing mononuclear cells, including NK cells, for culture. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to substitute a blood sample obtained by blood drawing, as found in Choi, with a blood sample obtained by leukapheresis, as found in Woo, with a reasonable expectation of success because closed systems, such as leukapheresis, minimize the risk of contamination, and the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Claim 1 further describes the cultured NK cells as possessing increased expression of CCL1 and/or CCR5, and/or decreased expression of KIR3DL2 and/or Siglec9, relative to NK cells before culture.
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). See, MPEP 2112.
In this case, the limitation directed towards increased or reduced expression of one or more markers describes an intended result or functional property of performing the cell culture recited in claim 1. A recitation of an intended result or functional property of the claimed process must result in a manipulative difference between the claimed process and the cited prior art in order to patentably distinguish the claimed process from the cited prior art. If the prior art process is capable of performing the intended result, or if the functional property naturally flows from the prior art process, then the prior art reads on the intended result or functional property recitation. There is no requirement that the cited prior art expressly teach or suggest the intended result or functional property recitation, but only that the subject matter is, in fact, present in the cited prior art. As outlined above, the manipulative actions positively recited by the claims would have been prima facie obvious over the cited prior art. Indeed, Choi teaches the same step of treating CD3-CD56+ NK cells with IL-2, anti-NKp46 antibody and plasma, followed by cell culture in a feeder cell-free medium, as claimed in claim 1. Therefore, the intended result or functional property of cultured NK cells possessing increased or reduced expression of one or more markers, relative to non-cultured NK cells, would have naturally flowed from performing the process steps taught by Choi. Accordingly, absent evidence to the contrary, the intended result or functional property recitations are not found to patentably distinguish the claimed invention from the cited prior art.
For these reasons, claim 1 would have been prima facie obvious over the prior art.
Regarding dependent claims 2-4, the claims further describe the cultured NK cells as possessing increased expression of NKG2D, NKp30, NKp44, NKp46, FASL, TRAIL, Granzyme A, Granzyme K, Perforin, HCST, IL-2RA, CSF2 and/or BCL-2, decreased expression of CXCL8, IL-10 and/or PMAIP1, and/or increased purity, cell proliferation fold and cancer cell killing ability, relative to NK cells before culture.
These limitations describe intended results or functional properties that naturally flow from performing the process steps (manipulative actions) positively recited in claim 1. Therefore, for the same reasons provided above with regards to claim 1, the intended result or functional property recitations of dependent claims 2-4 are not found to patentably distinguish the claimed invention from the cited prior art.
Regarding dependent claim 8, Choi teaches the plasma is separated from human peripheral blood. See, pg. 2, right column, first full paragraph.
Regarding dependent claim 10, Choi teaches culturing is to culture NKs by culturing PBMCs. See, e.g., Abstract; Figure 1.
Dependent claims 7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Choi et al. (2019) “Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer” BMC cancer, 19:817, 11 pages; and KR20190093499A to Woo et al.; as applied to claims 1-4 8, and 10 above; in further view of KR20170000798A to Seok et al.
This rejection is newly applied, necessitated by amendment.
Regarding dependent claim 7, Choi and Woo do not teach that the NK cells are cryopreserved and then thawed, as claimed.
Seok is relevant prior art for teaching a method of culturing NK cells in a medium containing IL-2, anti-NKp46 antibody and plasma. See, e.g., Abstract; par. 9-12. Seok further teaches the PBMCs used for NK cell production may also be cryopreserved and then thawed. See, par. 17.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the process of Choi by having the NK cells cryopreserved and then thawed, as suggested by Seok, with a reasonable expectation of success because cryopreservation enables viable PBMCs to be collected and stored for a period of time for later use, e.g., for shipping from a blood collection center to a clinical setting or laboratory for ex vivo expansion and/or transplantation.
Regarding dependent claim 9, Choi discloses that culturing is performed in the presence of antibodies (i.e., gamma globulin). See, e.g., Abstract; Figure 1. Seok teaches culturing is performed in the presence of gamma globulin (IgG) and fibronectin. See, e.g., par. 12, 18.
Applicant’s remarks filed 08/30/2026 have been carefully considered, but are not found persuasive for the following reasons. The arguments are addressed to the extent found relevant to the new grounds of rejection.
Applicant argues the rejection conflates the leukapheresis recited in step 1 with the closed-system in step 2. See, page 6 of the reply. The argument is not persuasive because leukapheresis is a closed process of both collecting PBMCs from whole blood and obtaining leukocytes (including, NK cells) from PBMCs.
Applicant argues that the working examples in the specification show increased CCL1 and NKp44 expression by the claimed “selection process” (Table 1 vs Table 2). See, pages 6-7 of the reply. The argument is not persuasive because the “selection process” in the working examples is not claimed. See, paragraphs 151 and 175 of the specification, which describes using the CliniMACS Prodigy® system requiring anti-CD3 and anti-CD56 microbeads to enrich for CD3-CD56+ NK cells.
Applicant argues that Woo teaches feeder cells, and importing upstream processing from the feeder cell-dependent system of Woo into a feeder-free system of Choi without expecting altered biological outcomes further underscores the lack of predictability in the art. See, page 7 of the reply. The argument is not persuasive as lacking objective evidence.
Conclusion
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 JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D Schultz can be reached at (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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