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 .
Applicant’s amendment and response filed on 4/23/2026 has been received and entered into the case.
Claims 2, 17 and 24 have been canceled, claims 26-27 and 31 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1, 3-13, 15-16, 18-23 and 25 have been considered on the merits. All arguments have been considered.
It is noted that applicant has elected Group I (claims 1, 3-13, 15-16, 18-23 and 25-26) an engineered feeder cell, SEQ ID NO:4, and cancer for the elected species in the reply filed on 10/13/2025.
Response to Amendment
The claim rejection under 35 USC 112 has been withdrawn due to the instant amendment.
The claim rejection under 35 USC 103 has been withdrawn due to the instant amendment. A new rejection is presented below to address the newly added limitation in claim 1.
Claim Rejections - 35 USC § 112 (New Rejection)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-13, 15-16, 18-23 and 25 are rejected 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.
Claim 1 discloses “at least about” in the 2nd line from the bottom. The term “at least” which requires a number for the lower end, i.e. at the minimum requirement, and the term “about” does not provide clear boundary of the range. Thus, one cannot determine what the minimum number of the claimed range, and thus, it is indefinite by using “at least” and “about” together in defining the range in the claims.
In determining the range encompassed by the term "about", one must consider the context of the term as it is used in the specification and claims of the application. Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir. 2007). In< W.L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983), the court held that a limitation defining the stretch rate of a plastic as "exceeding about 10% per second" is definite because infringement could clearly be assessed through the use of a stopwatch. However, the court held that claims reciting "at least about" were invalid for indefiniteness where there was close prior art and there was nothing in the specification, prosecution history, or the prior art to provide any indication as to what range of specific activity is covered by the term "about." Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991).
Applicant is advised to delete the term “about”.
Claim Rejections - 35 USC § 103 (New Rejection)
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.
Claim(s) 1, 9-13, 15-16, 18-23 and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jakobovits et al. (US 2019/0119634 A1; IDS ref.) in view of Xiao et al. (2018, Cytotherapy).
Regarding claims 1 and 9, Jakobovits et al. teach a method of activating and expanding gd T cells by using engineered antigen presenting cells (APCs) expressing an Fc receptor including CD16 (para. 39-40). Jakobovits et al. teach that the APCs are PBMCs or an immortalized cell line (para. 40).
Regarding the engineered feeder cells, Jakobovits et al. do not particularly teach the use of feeder cells for activating and/or expanding gd T cells, however, they teach the use of irradiated PBMC feeder cells for expansion of Vd1 T cells (Example 45) or irradiated K562 cells (Example 47) as an enriched subpopulation of gd T cells. Jakobovits et al. teach the irradiated PBMCs or K562 cells for expanding the enriched gd T cells, and the irradiated cells being APCs (para. 39).
However, Jakobovits et al. do not teach the use of the feeder cells for expanding gd T cells and the expansion including Vd2 subtype.
Xiao et al. teach the use of engineered K562 feeder cells to expand Vg9Vd2 T cells (see entire document).
It would have been obvious to a person skilled in the art to use the engineered APCs as feeder cells taught by Jakobovits et al. to activate and expand the gd T cells with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because the feeder cells can be used T cell activation and expansion because the feeder cells are known to be used for both Vd1 and Vd2 subtypes of gd T cells according to the teachings of Jakobovits et al. and Xiao et al., respectively. As Vd1 and Vd2 subtypes are main subsets in human gd T cells according to Jakobovits et al. (para. 4), and the irradiated K562 feeder cells are capable of being used in expanding both subtypes of Vd1 and Vd2, and thus, one skilled in the art would recognize that the feeder cells can be used to expand gd T cells which contains both Vd1 and Vd2 subtypes.
Regarding the duration of expansion being at least 14 days, Jakobovits et al. teach that gd T cells are expanded within 19 days and less then 30 days (para. 50) or at least 19 or 21 contiguous days (para. 63).
Regarding the at least about 5, 10, 20, 30, 40, 50 or 60% of the cells in the expanded gdT cells being Vd2 subtype, the limitation is a result of the expansion of gd T cells in the presence of an engineered feeder comprising a Fc domain competent for agonizing an Fc receptor as claimed. The combined teachings of Jakobovits et al. in view of Xiao et al. meet the claimed method steps, and thus, the results obtainable from the method would be substantially similar, if not identical. Furthermore, Jakobovits et al. teach an embodiment directed to one-step expansion of Vd1 and Vd2 T cells from human PBMC using specific MAbs (Example 43). After 21 days of expansion, the number of d1 and d2 T cells were significantly increased according to Fig. 40. Considering that the feeder cells can be used for expansion of both subtypes as discussed above, one skilled in the art would expect the increased percentage of both d1 and d2 subpopulations after the expansion for at least 14 days of culturing in the presence of the feeder cells.
Regarding claim 10 directed to the feeder cell being PBMC or an antigen-presenting cell, Jakobovits et al. teach the irradiated PBMC feeder cells for expansion of Vd1 T cells (Example 45) or irradiated K562 cells (Example 47), and Xiao et al. teach K562 artificial antigen-presenting cells (K562-aAPCs) (Abstract; p.421).
Regarding claim 11, Jakobovits et al. teach that the irradiated APCs can be engineered K562 (para. 34).
Regarding claim 12, Jakobovits et al. teach that the APCs express adhesion or co-stimulatory molecules or one or more Fc receptors that is specific for an isotype of an activation agent used in a gd T cell expansion method in addition to CD16A and CD16B (para. 39), and one or more agents that selectively expand d1, d2, d1/d4 or d1/d3/d4/d5 T cells (para. 40). These teachings are considered to meet the at least one gd T cell effector agent.
Regarding claim 13, Jakobovits et al. teach that one or more agents that selectively expand d1, d2, d1/d4 or d1/d3/d4/d5 T cells are expressed on the cell surface (para. 40), and this meets the effector agent being expressed on the external surface of the engineered feeder cells.
Regarding claims 15-16, Jakobovits et al. teach that the APCs express 4-1BBL, CD80, CD86, etc. (para. 39).
Regarding claim 18, Jakobovits et al. teach that the Vd1+ or Vd2+ T cell population would be expanded (para. 225).
Regarding claim 19, Jakobovits et al. teach that the expanded gd T-cell population is allogeneic with respect to the MHC loci of the subject (para. 74).
Regarding claim 20, Jakobovits et al. teach that the gdT cells are stimulated in vitro with at least one antigen for about 5-15 days (para. 210) or gdT cell population can be expanded in vitro in fewer than 36 days (para. 226), and this teaching would be overlapping with the claimed “at least 14 days”.
Regarding claim 21, the wherein clause is directed to the result of method disclosed in claim 20. As Jakobovits et al. teach the limitation of claim 20 as discussed above, the results derived from the method of Jakobovits et al. would be identical to the claimed method.
Regarding claim 22, the wherein clause is directed to the result of the method of claim 1. As Jakobovits et al. in view of Suhoski et al. teach the identical method, the results of the method taught by Jakobovits et al. in view of Suhoski et al. is expected the same as the claimed results.
Regarding claim 23, Jakobovits et al. teach that gdT cells comprised in a whole PBMC population, without prior depletion of one or more specific cell populations
such as one or more or all of the following non-gdT cell monocytes: ab T-cells, B-cells, and NK cells, can be activated and expanded, resulting in an enriched gdT-cell
population (para. 188). Jakobovits et al. also teach that NK cells are not depleted before or after the first and/or second gdT cell expansion (para. 206).
Regarding claim 25, Jakobovits et al. teach that the enriched gd T cell population(s) may be depleted of NK cells (para. 192 and 208). This teaching would meet the depletion of NK cells after activation and expansion of the gdT cells.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 3-4 and 7-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jakobovits et al. in view of Xiao et al. as applied to claim 1 above, and further in view of Parks et al. (WO2018/218151 A1; published on 11/29/2018).
Regarding claim 3 directed to the transmembrane domain being a signal-anchor sequence from influenza virus neuraminidase (NA); claim 4 directed to the transmembrane domain comprising NA peptide sequence.
Parks et al. teach a method of expanding NK cells using feeder cells, and the feeder cells express NK cell activating agents for activating and/or expanding NK cells (p.26-27). the exogenous membrane bound immune cell targeting ligands, i.e. the fusion proteins and the membrane targeting domain from the well characterized influenza virus neuraminidase protein (NA) can be used which consists of the N-terminal cytoplasmic tail, an uncleaved signal-anchor which serves as a transmembrane domain, and a stalk region which extends from the plasma membrane (p.30, lines 7-10). Parks et al. exemplify the structure of NA-Fc in Fig. 3D. The IgG1 Fc region can be IgFc domains that are ligands for CD16 (p.11, lines 32-34).
It would have been obvious to a person skilled in the art to utilize the fusion protein comprising NA fusion peptide and Fc domain targeting CD16 taught by Parks et al. for the method of Jakobovits et al. in view of Xiao et al. A person of ordinary skilled in the art would have been motivated to do so because while Parks et al. teach the use of the fusion protein to be expressed on stimulator cells (such as PBMC as a feeder cells) for stimulating NK cells and their expansion (p.27, lines 1-7), one skilled in the art would recognize that the fusion protein of Parks et al. can be used and expressed on the APCs or feeder cells in a method of Jakobovits et al. in view of Xiao et al. as Parks et al. teach that the feeder cells expressing one or more activating agents, stimulatory peptides, cytokines, and/or adhesion molecules including but not limited to 41BBL, IL-2, IL-12, IL-18, MICA, etc. Furthermore, Parks et al. teach that the NK feeder cells can be K562 cells (p.28, lines 9-15), and this teaching is consistent with the feeder cells taught by Jakobovits et al. (see para. 34, 39 and 171). Thus, the feeder cells taught by Parks et al. expressing immune cell binding ligands via the fusion protein (i.e. NA protein) would be utilized not only the NK cell activating but other immune cell including T cells (p.8, #41), and can be utilized for the method of Jakobovits et al. in view of Xiao et al.
Regarding claim 7, Jakobovits et al. in view of Xiao et al. do not particularly teach that the transmembrane domain and the Fc domain being linked via a peptide linker. However, Parks et al. teach that the fusion of the two polypeptides is with a short polypeptide linker or a peptide linker (p.8, lines 1-3 and 26-29).
Regarding claim 8, Jakobovits et al. in view of Xiao et al. do not particularly teach that the Fc domain being IgG1, IgG2, IgG3 or IgG4, however, Parks et al. teach that the immune cell targeting ligand comprises an immunoglobulin Fc domain selected from the group consisting of IgG1, IgG2, IgG3, and IgG4 (p.27, lines 23-27; p.32, claim 7; p.35, claim 33).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 5-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jakobovits et al. in view of Xiao et al. in view of Parks et al. as applied to claim 4 above, and further in view of A0A1D8EMR4_9INFA (influenza A virus neuraminidase submitted Sep-2016 to EMBL shown below)
As discussed above, Parks et al. teach that to get the Fe domain on the plasma membrane, membrane targeting domain from the well characterized influenza virus neuraminidase protein (NA) can be used which consists of the N-terminal cytoplasmic tail, an uncleaved signal-anchor which serves as a transmembrane domain, and a stalk region which extends from the plasma membrane (p.30, lines 7-10). However, Jakobovits et al. in view of Xiao et al. and Parks et al. do not teach a sequence at least 81% or 95% identical to the sequence of SEQ ID NO:4.
The sequence of influenza virus NA peptide is known according to A0A1D8EMR4_9INFA as shown the alignment below (100% identity), it would have been obvious to a person skilled in the art to utilize the known influenza virus NA peptide for presenting the Fc domain targeting CD16 or any other effector agents to be expressed on the surface of the APCs taught by Jakobovits et al. in view of Xiao et al. and Parks et al. with a reasonable expectation of success.
A0A1D8EMR4_9INFA
(NOTE: this sequence has 8 duplicates in the database searched)
ID A0A1D8EMR4_9INFA Unreviewed; 454 AA.
AC A0A1D8EMR4;
DT 18-JAN-2017, integrated into UniProtKB/TrEMBL.
DT 18-JAN-2017, sequence version 1.
DT 18-JUN-2025, entry version 44.
DE RecName: Full=Neuraminidase {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252};
DE EC=3.2.1.18 {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252};
GN Name=NA {ECO:0000256|HAMAP-Rule:MF_04071,
GN ECO:0000256|RuleBase:RU361252, ECO:0000313|EMBL:AOT22329.1};
GN ORFNames=A9C07_AO03_S21_NA {ECO:0000313|EMBL:AOT22329.1},
GN A9C07_AO04_S22_NA {ECO:0000313|EMBL:AOT22303.1}, A9C07_AO06_S24_NA
GN {ECO:0000313|EMBL:AOT22295.1}, A9C07_AO09_S3_NA
GN {ECO:0000313|EMBL:AOT22229.1};
OS Influenza A virus (A/guineafowl/Hong Kong/WF10_CIP046_RGAO032/1999(H9N1)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus;
OC Alphainfluenzavirus influenzae; Influenza A virus.
OX NCBI_TaxID=1902774 {ECO:0000313|EMBL:AOT22329.1};
RN [1] {ECO:0000313|EMBL:AOT22329.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=A/guineafowl/Hong Kong/WF10_CIP046_RGAO032/1999
RC {ECO:0000313|EMBL:AOT22329.1};
RG Centers of Excellence for Influenza Research and Surveillance (CEIRS);
RA Topham D.J.;
RL Submitted (SEP-2016) to the EMBL/GenBank/DDBJ databases.
Query Match 100.0%; Score 631; Length 454;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNPNQKITTIGSICLVVGLISLILQIGNIISIWISHSIQTGSQNHTGICNQNIITYKNST 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNPNQKITTIGSICLVVGLISLILQIGNIISIWISHSIQTGSQNHTGICNQNIITYKNST 60
Qy 61 WVKDTTSVILTGNSSLCPIRGWAIYSKDNSIRIGSKGDVFVIREPFISCSHLECRTFFLT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 WVKDTTSVILTGNSSLCPIRGWAIYSKDNSIRIGSKGDVFVIREPFISCSHLECRTFFLT 120
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments with regard to the 112 rejections have been fully considered and they are persuasive based on the instant amendment. As indicated above, the 112 rejections have been withdrawn.
Regarding the 103 rejections, the instant amendment necessitated a new ground of rejection and thus, the previously presented 103 rejections have been withdrawn and replaced with the new rejections above. However, it is noted that the new rejections recite the teaching of Jakobovits et al. which has been discussed in the previous rejections and the new reference, Xiao et al., is cited to address the new limitation directed to the expansion of Vd2 subtype of gd T cells.
Regarding the teaching of Jakobovits, applicant asserted that Jakobovits is directed to selective expansion of gd T-cell populations. This is incorrect analysis of the teachings of Jakobovits. While there are teachings directed to selective expansion utilizing enriched subpopulation of subtypes of gd T cells, however, Jakkobovits also teach gd T cell expansion comprising both Vd1 and Vd2 (Example 43).
Regarding the argument that the secondary reference, Parks et al. (WO2018/218151A1) in the rejection to claims 3-4 and 7-8, and subsequently to the rejection to claims 5-6, cannot be relied upon for the present 103 rejection as it is used as an 102(a)(2) art, and the exception under 102(b)(2)(c) applies to subject matter otherwise available only under 102(a)(2). The Examiner respectfully disagrees with the allegation. The Parks reference has a publication date of 11/29/2018, and the earliest filing date of the instant application is 8/12/2020. The publication date of Parks et al. is more than 1 year before the effective filing date of the claimed invention. Thus, the Parks reference is an 102(a)(1) art and the 102(b)(2)(c) exception does not apply to the 102(a)(1) prior art.
Applicant argued that Parks does not teach or suggest the presently claimed engineered immune-cell construct nor the particular neuraminidase peptide limitations recited in claims 3-4 and 7-8. The examiner respectfully disagrees with this argument. It is acknowledged that Parks do not disclose the expansion of gd T cells, and the method of expanding gd T cells is addressed by the teaching of Jakobovits. As the instant claim rejection is under 103 and based on the combination of teachings, a single reference does not need to teach all the limitations disclosed in the claims. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding the particular neuraminidase peptide disclosed in claims 3-4 and 7-8, Parks teach the identical fusion protein comprising a transmembrane domain as claimed as discussed in the claim rejection above. The fusion protein expressed in the feeder cells taught by Parks can be used for a method of activating and/or stimulating target cells, and one skilled in the art would recognize that the feeder cells of Parks can be used for activating and/or expanding gd T cells taught by Jacobovits as they utilize the same feeder cells or aAPCs. Particularly Parks et al. teach that the immune cell targeting ligand of the fusion protein utilizing a transmembrane region comprising neuraminidase can be NK cells, B cell, T cells and/or CAR-T cells (p.8, lines 29-31) as discussed in the claim rejection.
For the reasons as discussed above, it is the Examiner’s position that the teachings of Jakobovits in view of Xiao et al. and Parks et al. along with the EMBL sequence render the claimed invention obvious.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES 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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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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