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 .
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 21, 2026 has been entered.
Claims 1, 2, 4, 5, 8, 12, 13, 15, 17-19, 21, 23, 25, 27, 29, and 33 are now pending. All claims are amended. Claims 17, 19 and 25 remain withdrawn. Claims 1, 2, 4, 5, 8, 12, 13, 15, 18, 21, 23, 27, 29, and 33 are currently being examined as drawn to the elected species of:
(A) antigen binding regions that comprise an scFv;
(B) antigen binding molecule is scFv-Fc;
(C) immune cells that are Vδ2+ ɣδ T cells;
(D) specificity of the antigen binding region for GD2; and
(E) immune cells containing only one encoded antigen binding molecule.
The claims are amended and limited in scope to ɣδ T cells.
Maintained Objection
Claim Objections
2. Claim 23 is free of the art but is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Each of the VH and VL sequences, SEQ ID NOs: 20 and 18, and SEQ ID NO:17 are novel.
Maintained Rejections
(addressing amendments)
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
3. Claim(s) 1, 2, 4, 5, 12, 13, 15, 18, 27, 29, and 33 remain rejected under 35 U.S.C. 102(a)(2) as being anticipated by US Patent 12,042,515, Qian et al, claiming priority to 2017.
Qian teaches transgenic or engineered immune killer cells, including a γδ T cell, that comprises a nucleic acid sequence encoding and expressing a secretable antibody;
wherein the secretable antibody comprises an Fc region that is capable of binding to a Fc receptor, and comprises an scFv binding region (scFv-Fc) (Figures 1, 11, 19, and 27; col. 3, lines 5-46; col. 4, lines 9-37; col. 6, lines 24-43; col. 9, lines 3-25; col. 9, lines 34-41; col. 9, lines 52-60; col. 13-17; col. 19, lines 4-28; Examples 13-20);
wherein the secretable antibody binds to a tumor antigen that is GD2 (col. 3, lines 47-51; col. 8, lines31-42; col. 9, lines 3-11; claims 1-8);
wherein immune cell can also express a chimeric antigen receptor (CAR) and/or express a protein that acts as a molecular brake and is targeted by known antibody therapeutics, thereby encompassing immune cells that do not express a CAR (Figures 1, 11, 19, and 27; col. 4, lines 9-37; col. 13, lines 7 to col. 14, line 36).
Qian teaches a method of producing the immune cell by introducing nucleic acid sequence encoding the antibody into the immune cell, wherein the nucleic acid sequence is comprised in a recombinant expression vector or viral vector (col. 4, lines 38-42; col. 14, lines 21-46; col. 18, lines 1-28; Examples 13-24).
Qian teaches a method of treating cancer in an individual, comprising administering to the individual a therapeutically effective number of the immune cells, wherein the cancer is a solid tumor (col. 4, lines 47-61; col. 7, lines 32-34; col. 17, lines 47-59; claims 9-14; Example 19; Figure 17).
Quian teaches the advantage of immune cells expressing anti-tumor antibody (col. 2, lines 23-43):
Therefore, if the cellular immunity effector cells keep the cell killing toxicity while being able to efficiently express antibody with anti-tumor activity, the problems that the immune treatment effect of cells is insufficient and a macromolecular antibody is difficult to enter into solid tumors will be simultaneously overcome, with the treatment cost reduced. Under the effect of chemokines, the cells with both cell killing toxicity and high-level expression of antibodies can actively enter into tumor tissue via cytomorphosis, so that local high-level expression of antibody in the tumor tissue can be achieved, and the side effects caused by systemic administration can be avoided. Meanwhile, due to the co-existence of the antibody and the cytotoxic cell killing immune cells, the antibody acting on the immune cells (such as HER2 antibody Herceptin) can induce strong ADCC effect and CDC effect to efficiently kill tumor cells. Moreover, the antibody acting on T cells (such as PD1 antibody Keytruda) can prevent the inhibitory effects of tumor microenvironment on the re-infused effector T cells, making them continuously exert a therapeutic effect.
Qian teaches: (col. 19, lines 4-28):
The present invention overcomes the deficiencies of the present commonly used gene transfection vector system (low transfection efficiency for killer cells, and low expression level of antibody), so that the immune killer cells can stably express high level of antibodies comprising full-length human Fc segment. The present invention overcomes the difficulty of insufficient cellular immune-therapy effect and the difficulty of macromolecular antibodies entering into solid tumors. In addition, the present killer cells can remain the cytotoxic while they can also stably express antibodies comprising human Fc segment at high levels, or stably express antibodies comprising human Fc segment, or stably express the antigen-binding fragment of the antibodies of interest and CAR. In addition, in order to prevent the proliferation of immune cells stably expressing antibodies in vivo which may lead to over-expression of the antibodies and in turn systemic toxicity and autoimmune disease, a molecular brake system (such as a CD20-Rituxan molecular brake system, CD20BR) is introduced. Using the commercially available monoclonal antibody (such as Rituxan), killing cells integrated with antibody expression cassette will be rapidly removed via the ADCC effect and CDC effect mediated by the monoclonal antibody, and thus the safety for therapy is effectively improved.
Qian patented the claims:
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SEQ ID NO:11 encodes an EGFR CAR + CD20 Rituxan molecular brake + secretable anti-PD1 scFv-Fc antibody (see Example 21, col. 29-33).
Response to Arguments
4. Applicants argue that Qian exemplifies NK cells expressing a secretable antibody comprising an Fc region in Examples 13-19, but does not exemplify γδ T cells. Applicants argue although Qian discloses γδ T cells in a list of other cells, Qian does not disclose engineering γδ T cells to secrete antibodies as they disclose for NK cells. Applicants argue that Qian teaches modifying T cells is difficult and cite:
"The integration of an exogenous gene into NK cell or T cell genome can be mediated by a retrovirus or a lentivirus, for which stable expression can be realized theoretically. However, an antibody contains both light chains and heavy chains with long coding sequences and large molecular weight, making it very difficult to package and prepare retrovirus or lentivirus with full-length antibody expression cassette and to express the antibody efficiently. They can only be used to express the structurally simple single-chain antibody (lacking Fc segment, incomplete in function and short in half-life)."
Applicants argue that disclosure of the modification of NK cells in this way does not, therefore, disclose that γδ T cells may be modified in this way. Applicants argue that the NK cell modifications exemplified in Qian cannot be extrapolated to γδ T cells. Applicants argue there is no enabling disclosure of γδ T cells comprising a nucleic acid sequence encoding a secretable antigen binding molecule that comprises an antigen binding region, wherein the antigen binding molecule is capable of binding to a Fc receptor.
5. The arguments have been considered but are not persuasive. As admitted by Applicants, Qian teaches γδ T cells are included in the immune cells taught to be engineered to secrete antibodies comprising an Fc region. As admitted by Applicants, Qian successfully demonstrates engineering another immune cell, NK cell, to express secretable antibodies, therefore demonstrates enabling technology. Qian also demonstrates successfully engineering T cells to express a secretable antibody with Fc region (see examples 21-24).
Applicants have taken the section of Qian cited out of context to argue that modifying γδ T is unpredictable. The section cited by Applicants is in the Background of Technology summarizing problems in the art to be solved. The entire Qian patent is devoted to disclosing the invention that successfully overcomes the problems contemplated by Qian for stable antibody expression in immune cells. Therefore, Applicant’s arguments are not persuasive.
Finally, Qian patented γδ T cells stably integrated with an expression cassette comprising a nucleotide sequence encoding a secretable anti-PD-1 antibody with an Fc region (scFv-Fc) (represented at least by SEQ ID NO:11). See claims 1 and 4. US Patent claims are presumed enabled (35 USC 282).
New Rejection
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.
6. Claim(s) 1, 2, 4, 5, 12, 13, 15, 18, 27, 29, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent 12,042,515, Qian et al, claiming priority to 2017.
Qian teaches and claims as set forth above regarding claims 1, 2, 4, 5, 12, 13, 15, 18, 27, 29, and 33.
Although Qian teaches, suggests, and patented a γδ T cell comprising a nucleic aid sequence encoding a secretable antigen binding molecule that comprises an scFv antigen binding region and an Fc region (scFv-Fc), Qian does not provide a working example of making the modified γδ T cell.
Qian provides successful working examples of modifying related immune cells: NK cells and T cells, to comprise a nucleic acid sequence encoding a secretable antigen binding molecule that comprises an scFv antigen binding region and an Fc region (scFv-Fc) (see Examples 13-19 and 21-24).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to make and use a γδ T cell comprising a nucleic acid sequence encoding a secretable antigen binding molecule that comprises an scFv antigen binding region and an Fc region (scFv-Fc) as taught and suggested by Qian. One would have been m motivated to, and have a reasonable expectation of success to, because: (1) Qian suggests making and patented such γδ T cells, and (2) Qian provides detailed examples demonstrating successfully modifying related immune cells, including T cells, to comprise a nucleic acid sequence encoding a secretable antigen binding molecule that comprises an scFv antigen binding region and an Fc region (scFv-Fc).
Maintained Rejections
7. Claim(s) 1 and 8 remain rejected under 35 U.S.C. 103 as being unpatentable over US Patent 12,042,515, Qian et al, claiming priority to 2017; in view of WO 2020/021045, Quintarelli et al, claiming priority to 2018.
Quian teaches modified immune killer cells, including NK and γδ T cells, comprising a nucleic acid sequence encoding and expressing a secretable antibody; wherein the secretable antibody comprises an Fc region, wherein the secretable antibody binds GD2, and methods of administering the cells to treat cancer, as set forth above and previously of record.
Qian does not teach the γδ T cells comprise Vδ2+ cells.
Quintarelli also teaches modified NK or γδ T cells for the treatment of cancer, and teaches γδ T cells can comprise Vδ2+ cells and methods of isolating the cells to make a therapeutic composition (p. 8, 11, 13, 15, 22-23, 31-33, 35, 43-44; Examples; claims 70, 72, 93-95, 139, 149-150), wherein the NK or γδ T cells can be engineered to comprise a nucleic acid encoding an antibody that binds a tumor antigen such as dinutuximab (anti-GD2), or encoding a CAR targeting GD2 (p. 12-13, 16-17, 39).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize Vδ2+ cells as the γδ T immune cell of Qian. One would have been motivated to and have a reasonable expectation of success to because: (1) both Qian and Quintarelli teach modifying γδ T cells to express an anti-tumor antibody, including anti-GD2 antibody, and to administer the modified γδ T cells for cancer therapy; (2) Quintarelli teaches these γδ T cells include Vδ2+ cells; and (3) Quintarelli teaches known methods for isolating and modifying Vδ2+ cells.
Response to Arguments
8. Applicants argue that while Quintarelli does contain some general statements about modifying gamma delta T cells, and modifying cells to express an antibody, there is no specific teaching or even a suggestion in Quintarelli about expressing an antibody (or any other antigen-binding molecule that is capable of binding to a Fc receptor) in a gamma delta T cell. Rather, Quintarelli in the combination only concerns expression of a chimeric antigen receptor (CAR) in gamma delta T cells.
9. The arguments have been considered but are not persuasive. The limitation of modifying γδ T cells to express a secretable antibody comprising an Fc region is not a deficiency of Qian and does not need to be remedied by Quintarelli. Quintarelli addresses the limitation of using Vδ2+ cells as the modified γδ T cells for the same therapeutic purpose as Qian. Contrary to arguments, Quintarelli does suggest engineering their immune cells to express an antibody that binds to a cancer-associated antigen, including GD2 on p. 16:
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Continued on p. 17:
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10. Claim(s) 1 and 21 remain rejected under 35 U.S.C. 103 as being unpatentable over US Patent 12,042,515, Qian et al, claiming priority to 2017; in view of WO 2018/183888, Lynn et al; and US Patent Application Publication 2018/0100016, Song.
Quian teaches immune killer cells, NK cells or γδ T cells, comprising a nucleic acid sequence encoding and expressing a secretable antibody; wherein the secretable antibody comprises an scFv and Fc region, and binds to tumor antigen GD2, for the treatment of cancer, as set forth above and previously of record.
Qian does not teach the sequences of the anti-GD2 antibody comprise instant VH and VL SEQ ID NOs:4 and 5.
Lynn teaches an anti-GD2 scFv antibody comprising SEQ ID NO:44 that comprises 100% of instant SEQ ID NOs:4 and 5 (p. 29 and 38) (see sequence alignments below). Lynn teaches the antibody can be expressed by an immune cell in a CAR construct and used for the treatment of cancer (p. 6, Figure 1; p. 14, 32, 44, 58-60).
Song teaches transfecting an NK immune killer cell to express a CAR (NK-CAR) comprising an anti-tumor scFv antibody, such as an anti-GD2 scFv antibody comprising variable heavy chain region SEQ ID NO:16 that is 100% identical to instant SEQ ID NO:4, and comprising variable light chain region SEQ ID NO:14 that comprises 100% of instant SEQ ID NO:5 (see sequence alignment in previous office action), and wherein the anti-tumor scFv is fused to an IgG CH2-CH3 Fc region (claims 5-12; [17]; [20]; [37-38]; Figure 3; [59-60]; Example 1). Song teaches administering the transformed NK cell to a patient to treat cancer or a tumor, wherein the anti-GD2 antibody of the NK cell binds to tumor cells expressing GD2 (claims 13-15; [10];[22]; [32]; [88-90]). Song teaches NK cells are naturally capable of ADCC ([6]; [11]).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize the anti-GD2 scFv antibody of Lynn and Song as the anti-GD-2 scFv-Fc antibody expressed by the γδ T cell of Qian. One would have been motivated to and have a reasonable expectation of success to because Qian, Lynn, and Song teach utilizing anti-GD2 antibody for the same purpose of targeting and treating cancer (functionally equivalent); and Lynn and Song teach the known sequences of the anti-GD2 antibody for recombinant expression in an immune cell.
Instant anti-GD2 VH domain SEQ ID NO:4 aligned with Lynn SEQ ID NO:44:
RESULT 3
BFS45894
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BFS45894 standard; protein; 244 AA.
XX
AC BFS45894;
XX
DT 29-NOV-2018 (first entry)
XX
DE Anti-GD2 scFv antibody (14G2a), SEQ 44.
XX
KW GD2 protein; acute lymphoblastic leukemia; cancer; cell exhaustion;
KW cell signaling; cell therapy; cytostatic; expression; glioblastoma;
KW glioma; hodgkins disease; immune stimulation; neuroblastoma;
KW osteosarcoma; sarcoma; single chain antibody; t-lymphocyte; therapeutic.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2018183888-A2.
XX
CC PD 04-OCT-2018.
XX
CC PF 30-MAR-2018; 2018WO-US025459.
XX
PR 31-MAR-2017; 2017US-0479930P.
XX
CC PA (STRD ) UNIV LELAND STANFORD JUNIOR.
XX
CC PI Lynn R, Mackall C, Wandless TJ, Weber E;
XX
DR WPI; 2018-77552Y/71.
DR N-PSDB; BFS45893.
XX
CC PT New chimeric antigen receptor (CAR) comprises extracellular ligand-
CC PT binding domain, transmembrane domain, cytoplasmic domain, and regulatable
CC PT destabilization domain, for treating or delaying the progression of
CC PT cancer in patient.
XX
CC PS Disclosure; SEQ ID NO 44; 126pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR),
CC useful for treating cancer. The CAR comprises an extracellular ligand-
CC binding domain, transmembrane domain, cytoplasmic domain having signaling
CC domains, and regulatable destabilization domain (RDD). The invention
CC further claims: (1) a genetically modified T cell comprising an isolated
CC nucleic acid sequence encoding the CAR; (2) a method for improving and/or
CC prolonging a T lymphocyte cell (T cell) effector function in a mammal;
CC (3) a method for treating a mammal suffering from cancer by introducing a
CC T cell comprising the CAR into the mammal; (4) a method for stimulating a
CC T cell-mediated immune response to a target cell population or tissue in
CC a mammal; (5) a method for providing an anti-cancer immune response in a
CC mammal; (6) a method for treating or delaying the progression of cancer
CC in a patient; and (7) a therapeutically effective amount of a composition
CC comprising genetically modified T cells for expressing CAR. The CAR is
CC useful for preparing a composition for treating or delaying the
CC progression of cancer in the patient; improving and/or prolonging T cell
CC effector function in the mammal; treating mammal suffering from cancer;
CC stimulating T cell-mediated immune response to the target cell population
CC or tissue in the mammal; and providing the anti-cancer immune response in
CC the mammal, where cancer is selected from neuroblastoma, glioblastoma,
CC midline glioma, osteosarcomas, sarcoma, B lineage acute lymphoblastic
CC leukemia, B-cell chronic lymphocytic leukemia, B-cell non-Hodgkin's
CC lymphoma, leukemia and lymphoma, acute lymphoblastic leukemia, Hodgkin's
CC lymphoma, and childhood acute lymphoblastic leukemia. The CAR is useful
CC for maintaining the functionality under conditions in which unmodified
CC CAR T cells display exhaustion; and inhibiting or reversing CAR T cells
CC exhaustion by modulating CAR surface expression for enhancing CAR T cell
CC function. The invention is useful for treating T cell exhaustion by
CC inhibiting or modulating T cell receptor signaling. The present sequence
CC is a anti-GD2 single chain variable fragment (scFv) antibody, which can
CC be useful for preparing a CAR construct for treating cancer in the method
CC of the present invention.
XX
SQ Sequence 244 AA;
Query Match 100.0%; Score 593; Length 244;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVKLQQSGPSLVEPGASVMISCKASGSSFTGYNMNWVRQNIGKSLEWIGAIDPYYGGTSY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 132 EVKLQQSGPSLVEPGASVMISCKASGSSFTGYNMNWVRQNIGKSLEWIGAIDPYYGGTSY 191
Qy 61 NQKFKGRATLTVDKSSSTAYMHLKSLTSEDSAVYYCVSGMEYWGQGTSVTVSS 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 192 NQKFKGRATLTVDKSSSTAYMHLKSLTSEDSAVYYCVSGMEYWGQGTSVTVSS 244
Instant anti-GD2 VL domain SEQ ID NO:5 aligned with Lynn SEQ ID NO:44:
RESULT 6
BFS45894
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BFS45894 standard; protein; 244 AA.
XX
AC BFS45894;
XX
DT 29-NOV-2018 (first entry)
XX
DE Anti-GD2 scFv antibody (14G2a), SEQ 44.
XX
KW GD2 protein; acute lymphoblastic leukemia; cancer; cell exhaustion;
KW cell signaling; cell therapy; cytostatic; expression; glioblastoma;
KW glioma; hodgkins disease; immune stimulation; neuroblastoma;
KW osteosarcoma; sarcoma; single chain antibody; t-lymphocyte; therapeutic.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2018183888-A2.
XX
CC PD 04-OCT-2018.
XX
CC PF 30-MAR-2018; 2018WO-US025459.
XX
PR 31-MAR-2017; 2017US-0479930P.
XX
CC PA (STRD ) UNIV LELAND STANFORD JUNIOR.
XX
CC PI Lynn R, Mackall C, Wandless TJ, Weber E;
XX
DR WPI; 2018-77552Y/71.
DR N-PSDB; BFS45893.
XX
CC PT New chimeric antigen receptor (CAR) comprises extracellular ligand-
CC PT binding domain, transmembrane domain, cytoplasmic domain, and regulatable
CC PT destabilization domain, for treating or delaying the progression of
CC PT cancer in patient.
XX
CC PS Disclosure; SEQ ID NO 44; 126pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR),
CC useful for treating cancer. The CAR comprises an extracellular ligand-
CC binding domain, transmembrane domain, cytoplasmic domain having signaling
CC domains, and regulatable destabilization domain (RDD). The invention
CC further claims: (1) a genetically modified T cell comprising an isolated
CC nucleic acid sequence encoding the CAR; (2) a method for improving and/or
CC prolonging a T lymphocyte cell (T cell) effector function in a mammal;
CC (3) a method for treating a mammal suffering from cancer by introducing a
CC T cell comprising the CAR into the mammal; (4) a method for stimulating a
CC T cell-mediated immune response to a target cell population or tissue in
CC a mammal; (5) a method for providing an anti-cancer immune response in a
CC mammal; (6) a method for treating or delaying the progression of cancer
CC in a patient; and (7) a therapeutically effective amount of a composition
CC comprising genetically modified T cells for expressing CAR. The CAR is
CC useful for preparing a composition for treating or delaying the
CC progression of cancer in the patient; improving and/or prolonging T cell
CC effector function in the mammal; treating mammal suffering from cancer;
CC stimulating T cell-mediated immune response to the target cell population
CC or tissue in the mammal; and providing the anti-cancer immune response in
CC the mammal, where cancer is selected from neuroblastoma, glioblastoma,
CC midline glioma, osteosarcomas, sarcoma, B lineage acute lymphoblastic
CC leukemia, B-cell chronic lymphocytic leukemia, B-cell non-Hodgkin's
CC lymphoma, leukemia and lymphoma, acute lymphoblastic leukemia, Hodgkin's
CC lymphoma, and childhood acute lymphoblastic leukemia. The CAR is useful
CC for maintaining the functionality under conditions in which unmodified
CC CAR T cells display exhaustion; and inhibiting or reversing CAR T cells
CC exhaustion by modulating CAR surface expression for enhancing CAR T cell
CC function. The invention is useful for treating T cell exhaustion by
CC inhibiting or modulating T cell receptor signaling. The present sequence
CC is a anti-GD2 single chain variable fragment (scFv) antibody, which can
CC be useful for preparing a CAR construct for treating cancer in the method
CC of the present invention.
XX
SQ Sequence 244 AA;
Query Match 100.0%; Score 589; Length 244;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DILLTQTPLSLPVSLGDQASISCRSSQSLVHRNGNTYLHWYLQKPGQSPKLLIHKVSNRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DILLTQTPLSLPVSLGDQASISCRSSQSLVHRNGNTYLHWYLQKPGQSPKLLIHKVSNRF 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPPLTFGAGTKLELK 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPPLTFGAGTKLELK 113
Response to Arguments
11. Applicants argue that Song is directed to NK cells and not γδ T cells so there is no motivation to combine Song with Qian. Applicants state that Lynn does teach γδ T cells as a variety of T cell and argue that γδ T cells are not exemplified. Applicants argue they demonstrate for the first time that γδ T cells can be modified to stably encode a sequence encoding a secretable antigen-binding molecule that is capable of binding to an Fc receptor. Applicants argue this is surprising given the challenges associated with stable expression of such antigen molecules set out in Qian in the combination.
12. The arguments have been considered but are not persuasive. Qian teaches and both NK and γδ T cells are immune killer cells that can be modified to express the secretable scFv-Fc that binds to GD2. Qian successfully exemplifies modifying both NK and T cells to comprise a nucleotide sequence encoding a secretable scFv-Fc antibody that binds to a tumor-associated antigen. Qian also patented NK and γδ T cells that comprise a nucleotide sequence encoding a secretable scFv-Fc antibody that binds to a tumor-associated antigen. Therefore, Qian provides a reasonable expectation of success to make their claimed γδ T cells by demonstrating the success of modifying both NK cells and T cells to stably express secretable scFv-Fc. Therefore, arguments that such methods are challenging and unpredictable are not persuasive. Lynn and song teach the known sequences of a GD2 antibody used for the same therapeutic purpose taught by Qian. It is well within the level of the ordinary skilled artisan to substitute the known GD2 antibody sequences of Lynn and Song into the GD2 antibody of Qian for the same purpose of therapeutically targeting the GD2 antigen as taught by the combined references. Applicants have not provided persuasive evidence to support their arguments of surprising results for stably modifying a γδ T cell. MPEP 716.01(c) states: The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). The stable integration and expression of a nucleic acid encoding a secretable antibody into γδ T cells is expected based on the disclosure and examples of the cited combined references.
13. All other objections recited in the Office Action mailed February 23, 2026 are hereby withdrawn in view of amendments.
14. Conclusion: Claims 1, 2, 4, 5, 8, 12, 13, 15, 18, 21, 27, 29, 33 are rejected. Claim 23 is objected to.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Laura B Goddard/Primary Examiner, Art Unit 1642
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