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 .
Election/Restrictions
Applicant's election with traverse of Group I (claims 1, 3-13, 15-16, 18-23 and 25-26) in the reply filed on 10/13/2025 is acknowledged. Applicant’s election of an engineered feeder cell, SEQ ID NO:4, and cancer for the elected species.
The traversal is on the ground(s) that the groups I and II possesses a common technical feature that makes contribution over the prior art. This is not found persuasive because applicant did not address the examiner’s analysis that the commonly shared technical feature is known in the art as discussed in the restriction requirement.
The requirement is still deemed proper and is therefore made FINAL.
It is noted that claim 26 was inadvertently grouped with Group I instead of Group II in the restriction requirement mailed on 8/13/2025. As claim 26 is directed to the method of treating, decreasing, inhibiting, reducing, ameliorating and/or preventing a cancer as claim 27, claim 26 should have been grouped in Group II. Furthermore, the election of “cancer” as an elected species would be moot as claim 26 is withdrawn being directed to non-elected subject matter. Any inconvenience was regretted.
Claims 2, 17 and 24 have been canceled, claims 26-27 and 31 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1, 3-13, 15-16, 18-23 and 25 have been considered on the merits.
Claim Rejections - 35 USC § 112
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 5-6 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.
Claims 5-6 disclose that the NA peptide of claim 4 comprises a sequence at least 81% or at least 95% identical to SEQ ID NO:4 (elected species). Claim 4 discloses that the NA peptide is from parainfluenza virus. The sequence search of SEQ ID NO:4, however, came up with no identical or close to the sequence of parainfluenza virus hemagglutinin-neuraminidase. Rather SEQ ID NO:4 is up to 100% identical to HN protein of influenza virus (see below sequence alignment). Considering that the parainfluenza virus (Paramyxoviridae family) is different from influenza virus (Orthomyxoviridae family), it is not clear if SEQ ID NO:4 is directed to any part of the parainfluenza virus NA peptide sequence. Clarification is required.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5-6 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As discussed above, the SEQ ID NO: 4 belongs to influenza neuraminidase rather than parainfluenza neuraminidase. As claims 5-6 are dependent on claim 4 which discloses “parainfluenza neuraminidase NA peptide”, the limitation, i.e. SEQ ID NOs, of claims 5-6 do not further limit the subject matter of claim 4. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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 Suhoski et al. (2007, Mol. Ther.).
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), and Vd1 T cells are in a subpopulation of gd T cells. As Jakobovits et al. teach the irradiated PBMCs for expanding the enriched gd T cells, and the irradiated cells being APCs (para. 39), it would have been obvious to a person skilled in the art to use the engineered APCs as feeder cells to activate and expand the gd T cells with a reasonable expectation of success.
Furthermore, Suhoski et al. teach the use of engineered APCs as feeder cells for T-cell activation. Suhoski et al. teach that it would be useful to have off-the-shelf aAPCs that could simply be added as feeder cells to T cell cultures. (Abstract; p.3, 2nd col.).
Thus, it would have been obvious to a person skilled in the art to use the engineered APCs expressing a Fc receptors for CD16 can be used as a feeder cell to activate and expand gdT cells with a reasonable expectation of success. These teachings would meet the limitation of claim 10.
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 Suhoski 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 parainfluenza virus hemagglutinin-neuraminidase (NA); claim 4 directed to the transmembrane domain comprising NA peptide sequence; claim 5-6 directed to the NA peptide sequence comprising a sequence at least 81% or 95% identical to SEQ ID NO:4, Jakobovits et al. in view of Suhoski et al. do not teach the limitations.
Parks et al. teach the use of a fusion protein comprising uncleaved signal anchor domain comprising a signal anchor domain of the signal anchor domain of neuraminidase or parainfluenza virus hemagglutinin-neuraminidase (p.8, lines 18-25), and the Fc domain presented by the NA fusion peptide/protein comprises transmembrane region and an immune cell targeting ligand including CD16 (p.11, lines 16-21 and 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 Suhoski 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) for stimulating NK cells and their expansion (p.27, lines 1-7), however, one skilled in the art would recognize that the fusion protein of Parks et al. can be used and expressed on the APCs in a method of Jakobovits et al. in view of Suhoski 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 Suhoski et al.
Regarding claim 7, Jakobovits et al. in view of Suhoski 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 Suhoski 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 Suhoski 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)
Regarding the SEQ ID NO:4 of claims 5-6, the SEQ ID NO:4 is identical to the neuraminidase of influenza virus rather than the claimed parainfluenza virus. Considering the claimed sequence being influenza virus hemagglutinin-neuraminidase, the claims would be interpreted as using NA sequence from influenza virus.
Regarding the influenza virus neuraminidase protein, 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, Parks et al. do not teach 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 Suhoski 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.
Conclusion
No claims are allowed.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631