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 .
Status of Application/Amendments/Claims
Applicant’s response filed on 4/22/2026 has been considered. Claims 144-161 are pending. Claims 147, 151 and 153 have been amended. Claims 151 and 155-160 are withdrawn without traverse from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking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. Claims 144-150, 152-154 and 161 examined.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 63/056,293 and 371 of PCT/EP2021/070684 filed on 7/24/2020 and 7/23/2021, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 11/4/2020.
Withdrawn Rejections
The objection to claim 147 is withdrawn in light of applicants claim amendments which sell out the acronym BiTE.
The 112b rejection of claim 147 is withdrawn in light of applicants claim amendments which spell out Bi-specific T-cell engager rather than refer to the trademarked acronym BiTE.
Claim Interpretation
Claim 144 part iii describes optionally isolating T cells that do not express TCR alpha at their cell surface. It is emphasized that claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure, see MPEP 2111.04.
Applicant describes introducing mutations in TCRA or TCRB genes with a “rare-cutting endonuclease or base editor”. According to applicants’ specification, this reads broadly on any TALE-nuclease or any base editing technique (Specification, background).
“BiTe” as described in claim 147 is a bi-specific T-cell engager that simultaneously binds to CD19 and CD3 proteins (Specification, example 1).
Maintained 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 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.
Claims 144-150, 152-154 and 161 stand rejected under 35 U.S.C. 103 as being unpatentable over Duchateau et al. WO 2018/073393, published 4/26/2018 (hereinafter Duchateau, reference of record) in view of Goebeler et al. "Blinatumomab: a CD19/CD3 bispecific T cell engager (BiTE) with unique anti-tumor efficacy." Leukemia & lymphoma 57.5 (2016): 1021-1032 (hereinafter Goebeler, reference of record). This rejection is repeated for the same reasons as outlined in the Office Action mailed on 2/2/2026. A reply to applicant’s arguments is found below.
Claim 144: Duchateau describes a method for producing therapeutic CAR-T cells for use in allogenic therapy (Duchateau, pg 2). Duchateau achieves this by using TALEN-modified endogenous αβ TCR negative T cells comprising an inactivated genomic TCRA gene (Duchateau, pg 27). Duchateau explains that by inactivating the TCRA or TCRB genes it is possible to prevent graft-versus-host disease to achieve “off the shelf” allogenic treatments (Duchateau, pg 2 and 181-182). Duchateau describes expressing at least one exogenous polynucleotide encoding a soluble immune cell engager (antigen binding domain) like IL-12 or IL-15 (Duchateau, pg 35). Duchateau does not specifically list CD3 as the IC engager that binds a component of TCR and binds to a tumor antigen.
Claim 145: Duchateau describes engineered T cells with at least 95% mutated TCRA alleles (Duchateau, pg 61 and claim 9).
Claim 150 and 152-153: Duchateau describes expression of a chimeric antigen receptor (CAR) in the endogenous αβ TCR negative T cells, including CARs that target CD22 (Duchateau, pg 19).
Although Duchateau describes expressing an exogenous IL-12 or IL-15 soluble IC engager, Duchateau does not specifically describe expressing CD3 and CD19 as IC engagers.
Claim 146-148, 154 and 161: Goebeler describes how CD19/CD3 bispecific T cell engagers (BiTES) like Blinatumomab can redirect T cells to cancer cells in an active MHC-independent and targeted manner to effectively treat patient’s refractory to conventional therapies (Goebeler, conclusion para 1). Goebeler outlines the mechanism of action in Fig 1, wherein Blinatumomab recruits a patients T cell directly to CD19 expressing tumor cells (Goebeler, Fig 1).
It would have been prima facie obvious to one of ordinary skill in the art to express an exogenous polynucleotide encoding a CD19/CD3 bispecific T cell engagers (BiTES) like Blinatumomab as described by Goebeler in the TCRA negative CD22 expressing CAR-T cells described by Duchateau as an allogenic CAR-T therapy. It would have been a matter of combining prior art elements according to known methods to yield predictable results since Goebeler shows that CD19/CD3 bispecific T cell engagers like Blinatumomab can redirect T cells to cancer cells in an active MHC-independent and targeted manner to effectively treat patient’s refractory to conventional therapies (Goebeler, conclusion para 1). Furthermore, combining CD19 with CD3 generates a dual targeting mechanism that minimizes antigen escape when tumors stop expressing the target antigen. One would have a reasonable expectation of success given that Duchateau describes expressing similar exogenous polynucleotides like IL-12 using the engineered T cells and one of ordinary skill could readily transduce the same T cells to express both CD3 and CD19 via viral transduction. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Response to Traversal
Applicant argues that Duchateau only discloses IL-12 and IL-15 cytokines and not immune cell engagers. Applicant argues that Duchateau does not disclose two binding domains, much less one that binds to a component of TCR and another that binds to a tumor antigen. Consequently, applicant argues that Duchateau does not teach an immune cell engager as presently claimed.
This argument has been fully considered, but was not found persuasive since Duchateau provides embodiments for expressing at least one exogenous polynucleotide encoding a soluble immune cell engager (antigen binding domain) like IL-12 or IL-15 (Duchateau, pg 35). Duchateau states “In an even more specific aspect, it is herein described engineered immune cells, and preferably primary immune cells for infusion into patients, comprising exogenous sequences encoding IL-15 or IL-12 polypeptide(s), which are integrated at the PDl, CD25 or CD69 endogenous locus for their expression under the control of the endogenous promoters present at these loci” (Duchateau, pg 35). Although it is acknowledged that Duchateau does not specifically describe expressing CD3 and CD19 as IC engagers, one cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references, see MPEP 2145. The rejection argues that it would have been prima facie obvious to one of ordinary skill in the art to express an exogenous polynucleotide encoding a CD19/CD3 bispecific T cell engagers (BiTES) like Blinatumomab as described by Goebeler in the TCRA negative CD22 expressing CAR-T cells described by Duchateau as an allogenic CAR-T therapy.
Applicant argues that Goebeler does not remedy the deficiencies of Duchateau and simply describes the administration of a specific IC engager for CD3 and CD19. Applicant argues that Goebeler does not disclose the expression of Blinatumomab in a T cell.
This argument has been fully considered, but was not found persuasive since Goebeler describes how CD19/CD3 bispecific T cell engagers (BiTES) like Blinatumomab can redirect T cells to cancer cells in an active MHC-independent and targeted manner to effectively treat patient’s refractory to conventional therapies (Goebeler, conclusion para 1) which would lead one of ordinary skill to combine CD19 with CD3 to generate a dual targeting mechanism that minimizes antigen escape when tumors stop expressing the target antigen. One would have a reasonable expectation of success given that Duchateau describes expressing similar exogenous polynucleotides like IL-12 using the engineered T cells and one of ordinary skill could readily transduce the same T cells to express both CD3 and CD19 via viral transduction.
Conclusion
No claims allowed.
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 extension fee 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.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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