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 .
Priority
This application is a U.S. national phase of International Application No. PCT/CN2020/073017, filed on 01/19/2020.
Claim Status
The Amendment, filed on 11/25/2025, is acknowledged in which:
Claims 3-7 and 21 are canceled.
Claims 1, 8, 10, 13-14, and 18 are currently amended.
Claims 9, 11-12, 15-17, and 19-20 were previously presented.
Claims 1-2 and 8-20 are pending in the instant application and are examined on the merits herein.
Withdrawn Objections and Rejections
In the office action dated 08/25/2025,
The specification was objected to for missing page numbers, informalities in the text, and missing symbols to indicate trade names or marks used in commerce. Applicant’s submission of an amended specification with appropriate corrections has overcome the objections and the objections are withdrawn.
All previous rejections of claims 3-7 are moot in view of claim cancellations.
Claims 10 and 18 were rejected under 35 USC 112(b) for reciting a relative limitation without sufficient clarity on the scope of the metes and bounds of said limitation. Applicant’s amendment to specify 1-12 or more weeks has overcome the rejections and the rejections are withdrawn.
Claim 13 was rejected under 35 USC 112(b) for reciting an ICD without clarifying the receptor of origin. Applicant’s amendment of the claim to recite “..of the enhanced receptor..” has overcome the rejection and the rejection is withdrawn.
Claims 1-2, 8-15, and 20 were rejected under 35 USC 102(a)(2) as being anticipated by US 2022/0144960 A1 (herein Yang) and claims 16 and 17 were rejected under 35 USC 102(a)(2) as being anticipated by Yang as evidenced by Miltenyi. Applicant’s amendments to the claims to reduce claim scope to enhanced receptors with anti-PDL1 antibody ECD has overcome the rejections and the rejections as previously stated are withdrawn. However, upon further consideration, new grounds of rejection are made in view of newly found prior art, necessitated by applicant’s amendment.
Claims 18 and 19 are rejected under 35 USC 103 as being unpatentable over Yang and further in view of Tang. Applicant’s amendments to the claims to reduce claim scope to enhanced receptors with anti-PDL1 antibody ECD has overcome the rejections and the rejections as previously stated are withdrawn. However, upon further consideration, new grounds of rejection are made in view of newly found prior art, necessitated by applicant’s amendment.
Claims 1-9, 12-14 and 17 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 18/033,483; and claims 1-8, 12-13 and 20 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 19/107,364. Applicant’s amendment to the base claim to recite an anti-PDL1 antibody ECD has overcome the rejection and the rejection is withdrawn.
The following grounds of objections and/or rejections are either maintained or necessitated by applicant’s amendment to the claims.
New Claim Objections
Claims 11, 12, and 15 are objected to because of the following informalities:
Claim 11 - “claims 1” should read “claim 1” as presented in previous claim amendment.
Claim 12 - the conjunction “or” in the following: “…unmodified TCR or, an artificially modified TCR…” (line 2) has been reintroduced, though previously deleted, creating a grammatical error.
Claim 15 - “characterized by a the naturally modified TCR” (line 2); current amendment reintroduces a grammatical error where “a” was previously deleted.
Appropriate correction is required.
New Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 9-15, and 17-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 12,281,164 B2 (herein Wang; filed Nov 12, 2019).
Regarding claims 1-2, 9-14, 18-20, Wang teaches a vector comprising two transmembrane chimeric antigen receptors separated by a self-cleaving Fur-P2A linker, wherein receptor 1 encodes a HER2 or VEGFR1 (tumor associated antigens - column 4, lines 58-61) targeting CAR and receptor 2 encodes an anti-PD-L1 scFv extracellular domain, a CD8 transmembrane domain (TMD), and a 4-1BB costimulatory intracellular domain (ICD) (Claim 1; Figures 1-2 shown below). Wang teaches the PD-L1 CAR competitively binds to PD-L1 expressed on tumor cells (i.e. cell harmful to a human body) and immunosuppressive immune cells in serosal cavity environment (i.e. cell harmless in a short period of time) to transform a natural immune checkpoint (inhibitory signal) into an activation signal to enhance the tumor killing activity of T cells (in comparison to HER2 targeting CARs alone), while 4-1BB induced downstream signaling promotes proliferation and survival of T cells (Abstract; Figs 7 and 8).
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Regarding claim 15 and 17, Wang teaches T cells derived from PBMCs via CD3/CD28 magnetic bead separation (i.e. isolated T cells positive for these markers) are used for CAR-T experiments (column 15, ¶ 4). As T cell inherently express naturally unmodified TCRs, by broadest reasonable interpretation, T cells isolated from PBMCs would be heterogeneous and capable of recognizing other target molecules, such as those presented by antigen presenting cells within scope of the instant claim.
Response to Arguments - 35 USC § 102
Applicant's arguments filed 11/25/2025 have been fully considered but they are not persuasive.
Applicant states:
“Yang fails to disclose an enhanced receptor comprising an anti-PDL1 monoclonal antibody. Amended claim 1 is novel over Yang or Yang as evidenced by Miltenyi. Moreover, no other cited reference anticipates amended claim 1. The remaining claims, being either directly
or indirectly dependent on claim 1, are consequently novel over Yang or Yang as evidenced by Miltenyi.” (Remarks, page 3-4, page spanning ¶)
Applicant’s arguments regarding an enhanced receptor with an anti-PDL1 antibody ECD is not persuasive because the scope of claim 1 has been amended to exclude previous embodiments referenced in the prior art of record. As Applicant has altered the scope of the claims, new grounds of rejection are made in view of newly found prior art references that teaches an anti-PD-L1 scFv CAR and other features within scope of the instant claims are known in the art.
New Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Wang as applied to claim 12 above, and further in view of WO 2019/241334 A1 (herein Mulé).
Wang teaches claim 12 as discussed above.
Wang does not teach PD-L1 CAR-T cells derived from TILs.
Mulé teaches that, unlike peripheral blood lymphocytes, tumor infiltrating lymphocytes are capable of penetrating tumor masses (pg 1, lines 24-27). Mulé further teaches TILs can be isolated and transduced with vector for expression of a chimeric antigen receptor (Example 3).
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention that the PD-L1 CAR-T cell as taught by Wang using T cells derived from PBMC could be modified to use a TIL derived T cell, and a skilled artisan would be motivated to do to improve therapy penetrance in solid tumors.
Allowable Subject Matter
Claim 8 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, as receptors with 100% identity to SEQ ID NOs: 4, 5, and 6 are free from prior art.
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 HANNAH SUNSHINE whose telephone number is (571)270-7417. The examiner can normally be reached M-Th & Second Friday 8:30am-5pm EST.
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/HANNAH SUNSHINE/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647