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 response filed on 03/11/2026 is acknowledged and has been entered into the application file.
Claims 1, 4, 9-11, 13, 21, 23-24, 26, 28-29, 31, 34, 36-37, 40-42, and 52 are pending and under examination in the instant application.
Status of Prior Rejections/Response to Arguments
RE: Nucleotide and/or Amino Acid Sequence Disclosures:
As requested, applicant has submitted a replacement sequence listing herewith.
RE: Rejection of claims 1, 4, 9-11, 13, 21, 23-24, 26, 28-29, 31, 34, 36-37, 40-42, and 52 under 35
U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph:
Applicants’ amendments filed 03/11/2026 overcome the indefiniteness rejection. Applicants have specifically amended claim 1 to remove the recitation “ex vivo and/or in vivo”. Also, Applicants have specifically amended claim 37 to depend from claim 36 so that there is sufficient antecedent basis for “disease” in the claim.
The rejection is therefore withdrawn.
RE: Rejection of claims 1, 4, and 9-11 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Seidel et al. (US20180282392A1):
Applicants have traversed the rejection asserting that Seidel (1) does not teach genetically modified cells that express both a CAR and a receptor that recognizes the cognate peptide. This is not persuasive since Seidel (1) teaches these genetically modified cells by specifically teaching that CD8+ splenocytes were purified from a nonobese diabetic mouse transgenic for the 8.3 T cell receptor, which contains primarily CD8+ T cells which were then cultured in the presence of immobilized anti-CD3 antibody, a treatment known to stimulate polyclonal T cell activation, and treated stimulated cultures with soluble versions of synTac fusion protein to examine the antigen specificity of any suppressive effect (See Seidel (1) teachings on paragraph 0360, lines 5-12). The rejection is therefore maintained.
RE: Rejection of claims 1, 4, 9-11, 13, 21, 23-24, 26, 28-29, 31, 34, 36-37, 40-42, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Seidel et al. (1) (US20180282392A1), in view of Seidell et al. (2) (US20170176435A1):
Applicants have traversed the rejection asserting that Seidell (1) does not disclose "transducing the plurality of cells with a polynucleotide encoding a chimeric antigen receptor (CAR) to generate a plurality of CAR- expressing T cells or NK cells having both the receptor that recognizes the cognate peptide and the CAR" as recited in claim 1. Seidell (2) does not cure the deficiencies of Seidell (1). This is not persuasive because Seidell (2) was only used to cure the deficiencies of Seidell (1) of the amino acid sequence of the cognate peptide of at least 75%, at least 80%, at least85%, at least 90%, or at least 95% identical to the sequence of CMV pp65 as set forth in instant SEQ ID NO: 6. The rejection is therefore maintained.
New/Maintained Rejections
Claim Rejections - 35 USC § 102
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 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
Claim(s) 1, 4, and 9-11 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Seidel et al. (US20180282392A1, filed on 06/06/2018, and published on 10/04/2018).
Regarding claim 1, Seidel et al. teaches a method of inhibiting a T cell clone which recognizes an epitope peptide comprising contacting a T cell of the clone with a recombinant peptide, wherein the recombinant peptide comprises the epitope peptide and comprises a T cell modulatory domain which is an inhibitory domain, in an amount effective to inhibit a T cell clone (paragraph 0012). Seidel et al. specifically teaches that an inhibitory synTac fusion protein was tested in a T cell suppression assay. It was hypothesized that a light chain version of synTac IGRP fused to PD-L1 would specifically suppress T cells (paragraph 0360, lines 1-4). Seidel et al. also teaches that the recombinant polypeptide construct comprising (i) a candidate epitope peptide bound by a first amino acid linker sequence contiguous with a sequence of amino acids comprising a sequence identical to a human native B2M peptide sequence contiguous with a second amino acid linker sequence contiguous with a T cell modulatory domain peptide, wherein (i) is bound by one, or more than one, disulfide bond to (ii) a sequence of amino acids having the sequence of a MHC heavy chain (paragraph 0016). CD8+ splenocytes were purified from a nonobese diabetic mouse transgenic for the 8.3 T cell receptor. This splenocyte subset contains primarily CD8+ T cells which are specific for the IGRP206-214 peptide in the context of H-2Kd. These CD8+ T cells were then cultured in the presence of immobilized anti-CD3 antibody, a treatment known to stimulate polyclonal T cell activation, and treated stimulated cultures with soluble versions of synTac fusion protein to examine the antigen specificity of any suppressive effect. All CD8+ T cell activation parameters examined were suppressed in an antigen-specific and effector (i.e. MOD) domain-dependent manner (paragraph 0360, lines 5-12).
Regarding claim 4: Following discussion of claim 1 above, Seidel et al. teaches multi-dose in vivo T cell stimulation assays. NOD mice were injected intraperitoneally with synTac fusion protein. Seven days post injection, the mice were sacrificed and PBMC's (from blood) were examined via flow cytometry for relative frequencies of IGRP-specific CD8 T cells. IGRP-41BBL treatment was associated with a higher frequency of IGRP-specific CD8 T cells versus controls, supporting a significant in vivo expansion from a multiple dose (paragraph 0059).
Regarding claim 9: Following discussion of claim 4 above, claim 9 recites wherein the CAR-expressing cell T cell is stimulated to induce cytotoxic effects in a target cell and … secretes a molecule selected from the following: a granzyme, a perforin, a cytokine, a Fas Ligand (FasL). Since the steps of the claimed method of modulating genetically modified cells and the method steps taught by Seidel et al. are the same, the claimed
functional property of the claimed CAR-T cells of having the ability to induce cytotoxic effects in a target cell and secreting a molecule selected from the following: a granzyme, a perforin, a cytokine, a FasL upon stimulation is inherently and necessarily present in Seidel et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. “When the prior art method is the same as a method described in the specification for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) See MPEP 2112.02.
Regarding claim 10: Following discussion of claim 9 above, Seidel et al. teaches that targets of T cells include cancer cells (paragraph 0165).
Regarding claim 11: Following discussion of claim 10 above, Seidel et al. teaches that the fusion protein is specific for a eukaryotic pathogen, wherein pathogens include viruses, bacteria, protozoans, and the like (paragraph 0257, last 2 lines, paragraph 0324, last 2 lines).
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.
Claim(s) 1, 4, 9-11, 13, 21, 23-24, 26, 28-29, 31, 34, 36-37, 40-42, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Seidel et al. (1) (US20180282392A1, filed on 06/06/2018, and published on 10/04/2018), in view of Seidell et al. (2) (US20170176435A1, filed on 01/21/2015, published on 06/22/2017).
Regarding claim 1, 4, 9-11, the teachings of Seidel et al. (1) are set for in details above.
Regarding claim 13: Following discussion of claim 11 above, Seidel et al. (1) teaches that the fusion protein is specific for a eukaryotic pathogen, wherein the pathogen is a virus (e.g., CMV) (paragraph 0150, last 2 lines).
However, Seidel et al. (1) fails to teach that the cognate peptide comprises an amino acid sequence at least 75%, at least 80%, at least85%, at least 90%, or at least 95% identical to the sequence of CMV pp65 as set forth in instant SEQ ID NO: 6.
However, Seidell et al. (2) teaches a peptide epitope was the NLVPMVATV peptide epitope from human cytomegalovirus (CMV) (paragraph 0059), which is identical to instant SEQ ID NO: 6.
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have used the amino acid sequence of the CMV peptide epitope taught by Seidell et al. (2) as the CMV pp65 cognate peptide taught by Seidel et al. (1) as the use of the Seidel et al. (1)’s sequence represents nothing more than the substitution of one CMV peptide epitope amino acid sequence for another with predictable results. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Regarding claim 21: Following discussion of claim 13 above, Seidel et al. (1) teaches that after a 5-day culture period, cells were harvested and examined using flow cytometry for viability and proliferation (paragraph 0360). Seidel et al. (1) further teaches that NOD mice were previously injected intraperitoneally with the synTac fusion protein (paragraph 0372). This reads on vaccinating the subject with a vaccine containing the cognate peptide recognized by the receptor prior to harvesting the cells.
Regarding claim 23: Following discussion of claim 21 above, Seidel et al. (1) teaches that the CD8 splenocytes were first purified from 8.3 TCR transgenic NOD mice (paragraph 0370).
Regarding claims 24, 26: Following discussion of claim 23 above, Seidel et al. (1) teaches administering to the patient an effective amount of a pharmaceutical composition comprising a multimeric polypeptide comprising the peptide epitope (claims 79 and 107 of Seidel et al. (1)), wherein said administering effective to selectively modulate the activity of a pathogen-associated epitope-specific T cell in an individual (paragraph 0042). The treatment was associated with a higher frequency of CD8 T cells versus controls, supporting a significant in vivo expansion from a multiple dose (paragraph 0059).
Regarding claims 28 and 29: Following discussion of claim 26 above, Seidel et al. (1) teaches that the fusion protein further comprises at least one immunomodulatory polypeptide that is selected from the group consisting of a cytokine, co-stimulatory ligand, which includes, but is not limited to, CD7, B7-1 (CD80), B7-2 (CD86), PD-L1, PD-L2, 4-1BBL, OX40L, Fas ligand (FasL), inducible costimulatory ligand (ICOS-L) (claim 89 of Seidel et al. (1) and paragraph 0093).
Regarding claim 31: Following discussion of claim 28 above, Seidel et al. (1) teaches that the fusion protein further comprises at least one immunomodulatory polypeptide that is selected from the group consisting of a cytokine, co-stimulatory ligand (paragraph 0093).
Regarding claim 34: Following discussion of claim 31 above, Seidel et al. (1) teaches specific binding of the synTac fusion protein to the receptor expressed on the T cells (paragraph 0056).
Regarding claim 36: Following discussion of claim 34 above, Seidel et al. (1) teaches that the recombinant peptide comprises the epitope peptide and comprises a T cell modulatory domain which is an inhibitory domain, in an amount effective to treat an autoimmune disorder (paragraph 0314).
Regarding claim 37: Following discussion of claim 26 above, Seidel et al. (1) teaches that the recombinant peptide comprises the epitope peptide and comprises a T cell modulatory domain which is a stimulatory domain, in an amount effective to treat the cancer (paragraph 0315).
Regarding claim 40: Following discussion of claim 37 above, Seidel et al. (1) teaches that the recombinant peptide comprises the epitope peptide and comprises a T cell modulatory domain which is a stimulatory domain, in an amount effective to treat the cancer (paragraph 0315). Although Seidel et al. (1) fails to specifically teach that the cancer is leukemia or lymphoma as recited in claim 40 and wherein the lymphoma is lymphoblastic lymphoma or B-cell Non-Hodgkin's lymphoma as recited in claim 42, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have used the treatment method of Seidel et al. (1) to treat lymphoblastic lymphoma or B-cell Non-Hodgkin's lymphoma with a reasonable expectation of success. One would have been motivated to have done so because the syntac fusion protein of Seidel et al. (1) can be used in the treatment of different diseases that are not limited to autoimmune disorders and cancer.
Regarding claim 52: Following discussion of claim 42 above, claim 52 recites wherein the subject experiences a reduction or elimination in an inflammatory response, a cytokine storm, or at least one off-target effect… or experiences a reduction in a symptom or a side effect thereof as compared to a control subject. Since the steps of the claimed method of modulating genetically modified cells and the method steps taught by Seidel et al. are the same, the claimed functional property of the claimed CAR-T cells of having the ability to experience a reduction or elimination in an inflammatory response, a cytokine storm, or at least one off-target effect or experience a reduction in a symptom or a side effect thereof as compared to a control subject is inherently and necessarily present in Seidel et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. “When the prior art method is the same as a method described in the specification for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) See MPEP 2112.02.
Conclusion
THIS ACTION IS MADE FINAL. 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 HANAN ISAM ABUZEINEH whose telephone number is (571)272-9596. The examiner can normally be reached Mon- Fri 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Hanan Isam Abuzeineh
/H.I.A./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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