DETAILED ACTION
Applicant’s response of 09/02/2025 has been received and entered into the application file.
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
Claims 1-2, 4-16, and 35-39 are pending in the instant application. Applicants have previously elected without traverse Group I, drawn to a modified antigen-specific immune cell comprising on its surface an exogenous CD 160 protein, wherein the exogenous CD 160 protein results in up-modulation of the modified antigen-specific immune cell, in the reply filed on 05/15/2025.
Claims 15-16 and 37-39 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 05/15/2025. Therefore, claims 1-2, 4-14, and 35-36 are under examination in the instant application.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claim(s) 1, 13-14, and 35-36 under 35 U.S.C. 102 (a)(1) as being anticipated by Abate-Daga et al.:
Applicants have traversed the rejection asserting that Abate-Daga does not teach that TCR-engineered T-cells comprising on its surface an exogenous CD 160 protein will have higher IFNy production and improved cytolytic activity in vitro and in vivo as indicated by Figures 2 & 3 of the present application
Applicant's arguments filed 09/02/2025 have been fully considered but they are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., TCR-engineered T-cells comprising on its surface an exogenous CD 160 protein will have higher IFNy production) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The rejection is therefore maintained.
RE: Rejection of claim(s) 1-2, 4-5, 7-14, and 35-36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sako et al.:
Applicants have traversed the rejection asserting that Sako does not teach modified immune cells, much less a modified antigen-specific immune cell comprising on its surface an exogenous CD160 protein.
Applicant's arguments filed 09/02/2025 have been fully considered but they are not persuasive.
In response, Sako et al. does actually teach that CD160 is effectively expressed on the surface of TCRαβ T cells (see Sako et al. teachings on page 870, column 1, paragraph 2, lines 14-16). TCRαβ T cells are the modified immune cells that express CD160 on its surface.
The rejection is therefore maintained.
RE: Rejection of claim(s) 1 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Abate-Daga et al., in view of Swanson et al.:
Applicants have traversed the rejection asserting that Abate-Daga does not teach or suggest modifying an immune cell to comprise exogenous CD160 protein on the cell surface, thus, one skilled in the art reading Abate-Daga would not be motivated to modify the T cells of Abate- Daga to express an exogenous CD160 protein, such as SEQ ID NO: 24 of Swanson.
Applicants further argue that the Examples of the subject application demonstrate the surprising findings that T cells modified with exogenous CD160 have increased IFNy production, results which are not predictable from the teachings of Abate- Daga et al. T cells transduced with exogenous mCD160 increased the inflammatory activity of tumor-specific T cells, demonstrating exogenous expression of CD160 potentiated the intrinsic cytolytic activity, boosted inflammatory function, and enhanced tumor-killing activity of antigen-specific T cells (applicants point to Example 2). Also, applicants point to FIG. 15E, Example 11 to note that TCR-T cells overexpressing huCD160TC also exhibited an elevated level of inflammatory cytokine IFNy as indicated by intracellular staining and FACS analyses.
This is not persuasive because, Abate-Daga et al. does specifically teach expressing CD160 on the surface of TCR-engineered CD8+ lymphocytes (see Abate-Daga et al. teachings on page 1399, column 2, paragraph 1, lines 10-15). TCR-engineered CD8+ lymphocyte is a modified immune T cell. Although Abate-Daga et al does not explicitly teach that the CD160 expression on the surface of TCR-engineered lymphocytes result in up-modulation of the modified immune cell, this functional property is inherently and necessarily present in Abate-Daga et al.
The rejection is therefore maintained.
New/Maintained Grounds of Rejection
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)(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, 13-14, and 35-36 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Abate-Daga et al. (Abate-Daga et al., “Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes”. Blood. 2013 Aug 22;122(8):1399-410).
Regarding claim 1, Abate-Daga et al. teaches that CD160 expression is associated with decreased reactivity of TCR-engineered CD8+ lymphocytes in a ligand-independent manner (page 1399, column 2, paragraph 1, lines 10-15). The TCR-engineered CD8+ lymphocytes expressing CD160 of Abate-Daga et al. reads on the claimed modified antigen-specific immune cell comprising on its surface an exogenous CD160 protein…wherein the immune cell is a T cell.
Claim 1 recites the functional limitation “wherein the exogenous CD 160 protein results in up-modulation of the modified antigen-specific immune cell compared to a precursor antigen-specific immune cell not comprising the exogenous CD160 protein”. Since the structure of the claimed modified immune cell comprising the CD160 protein on its surface and the engineered T-cells of Abate-Daga et al. are the same, the claimed functional property of the claimed modified immune cell of up-modulating the modified immune cell compared to a precursor immune cell not comprising CD160 on its surface is inherently and necessarily present in Abate-Daga 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 structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997).
Regarding claim 13 and 14: Following discussion of claim 1 above, Abate-Daga et al. teaches that CD160 expression is associated with decreased reactivity of TCR-engineered CD8+ lymphocytes in a ligand-independent manner (page 1399, column 2, paragraph 1, lines 10-15). This reads on that the modified antigen-specific immune cell further comprises a functional exogenous receptor as recited in instant claim 13, wherein the functional exogenous receptor is an engineered T cell receptor (TCR) as recited in instant claim 14.
Regarding claim 35, it recites “a modified antigen-specific immune cell obtained by the method of claim 15”. This is a product-by-process limitation that claim a modified antigen-specific immune cell produced by the method of claim 15 by contacting a precursor antigen-specific immune cell with the exogenous CD 160 protein or a first nucleic acid encoding the exogenous CD 160 protein, wherein the exogenous CD 160 protein results in up-modulation of the modified antigen-specific immune cell as compared to the precursor antigen-specific immune cell. MPEP 113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Abate-Daga et al. teaches that CD160 expression is associated with decreased reactivity of TCR-engineered CD8+ lymphocytes in a ligand-independent manner (page 1399, column 2, paragraph 1, lines 10-15). The TCR-engineered CD8+ lymphocytes expressing CD160 of Abate-Daga et al. is comparable to the claimed product modified antigen-specific immune cell comprising on its surface an exogenous CD160 protein…wherein the immune cell is a T cell. So, Abate-Daga et al. actually teaches the product that results from the method of claim 15, which is the same as the product of claim 1.
Regarding claim 36: Following discussion of claim 1 above, Abate-Daga et al. teach “the modified antigen- specific immune cell”. The cells of Abate-Daga et al are in cell culture medium, the cell culture medium reads on a pharmaceutically acceptable carrier. The phrase “A pharmaceutical composition” recited in claim 36 is an intended use and needs not to be taught in prior art. It is noted that the use of a product for a particular purpose is not afforded patentable weight in a product claim where the body of the claim does not depend on the preamble for completeness but, instead, the structural limitations are able to stand alone. The MPEP states that, “.. in apparatus, article, and composition claims, intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.” In re Casey, 152 USPQ 235 (CCPA 1967); In re Otto, 136 USPQ 458, 459 (CCPA 1963) (MPEP 2111.02). In this case, the pharmaceutical composition doesn’t result in any structural difference between the claimed modified antigen- specific immune cell comprising CD160 on its surface of instant claim 1 and the engineered TCR-engineered CD8+ lymphocytes expressing CD160 in cell culture medium of Abate-Daga et al. in order to patentably distinguish the claimed invention from the prior art.
Claim(s) 1-2, 4-5, 7-14, and 35-36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sako et al. (Sako et al., “Membrane expression of NK receptors CD160 and CD158k contributes to delineate a unique CD4+ T-lymphocyte subset in normal and mycosis fungoides skin”. Cytometry. 85, Issue 10, October 2014, Pages 869-882).
Regarding claim 1, Sako et al. teaches that CD160 is effectively expressed on CD4+ T lymphocytes and its engagement in TCRαβ T cells is capable to provide costimulatory signals upon CD3/TCR stimulation (page 870, column 1, paragraph 2, lines 14-16). The TCRαβ T cells expressing CD160 of Sako et al. reads on the claimed modified antigen-specific immune cell comprising on its surface an exogenous CD160 protein…wherein the immune cell is a T cell.
Regarding claim 2: Following discussion of claim 1 above, Sako et al. teaches that CD160 is expressed on the surface of TCRαβ T cells (page 870, column 1, paragraph 2, lines 14-15). This reads on that the modified antigen-specific immune cell is a cytotoxic αβ-T cell.
Regarding claim 4: Following discussion of claim 2 above, Sako et al. teaches that CD160 is expressed on the surface of TCRαβ T cells (page 870, column 1, paragraph 2, lines 14-15). This reads on that the modified antigen-specific immune cell is a Tumor-infiltrating T cell.
Regarding claim 5: Following discussion of claim 1 above, Sako et al. further teaches that CD160 expression is highly restricted to lymphocyte subsets, such that it is found on circulating cytotoxic CD8+ granzyme B+ and perforin+ T cells (page 870, column 1, paragraph 2, lines 10-14). This reads on that the modified antigen-specific immune cell is a cytotoxic T cell.
Regarding claims 7-8: Following discussion of claim 1 above, Sako et al. further teaches that CD160 is a GPI-anchored Ig-like receptor identified by the BY55 mAb on human circulating CD56dim+ NK cells and TCRγδ lymphocytes (Abstract). This reads on that the CD160 protein is membrane bound as recited in instant claim 7, via a GPI linker as recited in instant claim 8.
Regarding claims 9-10: Following discussion of claim 8 above, Sako et al. teaches that CD160 engagement in TCRαβ T cells is capable to provide costimulatory signals upon CD3/TCR stimulation (page 870, column 1, paragraph 2, lines 14-16). Furthermore, Sako et al. teaches that CD160 engagement by its physiological ligand provided costimulation to CD3 signaling, whereas in NK lymphocytes it triggered an autonomous activating signaling (page 880, column 1, paragraph 1, lines 4-8). This reads on that the CD160 protein further comprises an intracellular domain as recited in instant claim 9, wherein the intracellular domain comprises an intracellular signaling domain derived from a signaling subunit of a TCR complex as recited in instant claim 10 since CD3 is a signaling subunit of the TCR complex.
Regarding claims 11-12: Following discussion of claim 7 above, Sako et al. teaches that CD160 engagement by its physiological ligand provided costimulation to CD3 signaling (page 880, column 1, paragraph 1, lines 4-8). Physiological ligand reads on an immune-cell binding moiety that binds to a surface molecule of the immune cell.
Regarding claim 13 and 14: Following discussion of claim 1 above, Sako et al. teaches that CD160 is effectively expressed on CD4+ T lymphocytes and its engagement in TCRαβ T cells is capable to provide costimulatory signals upon CD3/TCR stimulation (page 870, column 1, paragraph 2, lines 14-16). This reads on that the modified antigen-specific immune cell comprises a functional exogenous receptor as recited in instant claim 13, wherein the functional exogenous receptor is an engineered T cell receptor (TCR) as recited in instant claim 14.
Regarding claim 35, it recites “a modified antigen-specific immune cell obtained by the method of claim 15”. This is a product-by-process limitation that claim a modified antigen-specific immune cell produced by the method of claim 15 by contacting a precursor antigen-specific immune cell with the exogenous CD 160 protein or a first nucleic acid encoding the exogenous CD 160 protein, wherein the exogenous CD 160 protein results in up-modulation of the modified antigen-specific immune cell as compared to the precursor antigen-specific immune cell. MPEP 113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Sako et al. teaches that CD160 is effectively expressed on CD4+ T lymphocytes and its engagement in TCRαβ T cells is capable to provide costimulatory signals upon CD3/TCR stimulation (page 870, column 1, paragraph 2, lines 14-16). The TCRαβ T cells expressing CD160 of Sako et al. is comparable to the claimed product modified antigen-specific immune cell comprising on its surface an exogenous CD160 protein…wherein the immune cell is a T cell. So, Sako et al. actually teaches the product that results from the method of claim 15, which is the same as the product of claim 1.
Regarding claim 36: Following discussion of claim 1 above, Sako et al. teaches the “the modified antigen- specific immune cell”. The cells are present in PBS (See Pg 870, col. 2, paragraph 3), PBS reads on a pharmaceutically acceptable carrier. The phrase “A pharmaceutical composition” recited in claim 36 is an intended use and needs not to be taught in prior art. It is noted that the use of a product for a particular purpose is not afforded patentable weight in a product claim where the body of the claim does not depend on the preamble for completeness but, instead, the structural limitations are able to stand alone. The MPEP states that, “.. in apparatus, article, and composition claims, intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.” In re Casey, 152 USPQ 235 (CCPA 1967); In re Otto, 136 USPQ 458, 459 (CCPA 1963) (MPEP 2111.02). In this case, the pharmaceutical composition doesn’t result in any structural difference between the claimed composition and the engineered TCR-engineered CD8+ lymphocytes expressing CD160 in PBS of Sako et al. in order to patentably distinguish the claimed invention from the prior art.
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 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Abate-Daga et al. (Abate-Daga et al., “Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes”. Blood. 2013 Aug 22;122(8):1399-410), in view of Swanson et al. (the US Patent No. 10,882,914 B2, filed on 04/14/2017, and issued on 01/05/2021).
Regarding claim 1, the teachings of Abate-Daga et al. are set forth in detail above
Regarding claim 6: Following discussion of claim 1 above, Abate-Daga et al. fails to teach that the exogenous CD160 protein comprises an amino acid sequence that is identical to any of instant SEQ ID NOs: 1-4.
However, Swanson et al. teaches a CD160 immunoglobulin superfamily (IgSF) protein comprising amino acid sequence as set forth in SEQ ID NO: 24 (TABLE 2), which is at amino acids 1-138, 100% identical to instant SEQ ID NO: 1.
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 acids at positions 1-138 of SEQ ID NO: 24 of the CD160 protein of Swanson et al. as the CD160 protein taught by Abate-Daga et al. as the use of the Swanson et al.’s sequence represents nothing more than the substitution of one CD160 protein amino acid sequence for another
with predictable results.
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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Hanan Isam Abuzeineh
/H.I.A./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633