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/Restriction/Claims
Applicant’s election without traverse of species CD3 and CD19 (immune cell engagers) and CD22 (CAR) in the reply filed on 12/17/2025 is acknowledged. Claims 144-161 are pending. Claims 151 and 155-160 are currently withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 144-150, 152-154 and 161 are the subject of the present Official action.
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.
Claim Objections
Claim 147 is objected to because of the following informalities: the claims contain the acronym BiTE. While acronyms are permissible shorthand in the claims, the first use should include the full recitation followed by the acronym in parentheses. Appropriate correction is required.
Claim Rejections - 35 USC § 112b
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 147 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 147 describes the soluble immune cell engager as BiTE TM. Trademarks cannot be used to identify any particular material or product in patent claims, see MPEP 2173.05(u). The value of a trademark is lost to the extent that it becomes descriptive of a product rather than used as an identification of a source or origin of a product. Thus, the use of a trademark in a claim to identify or describe a material or product (i.e. Bi-specific T-cell engager) would not only render a claim indefinite, but would also constitute an improper use of the trademark.
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).
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 are rejected under 35 U.S.C. 103 as being unpatentable over Duchateau et al. WO 2018/073393, published 4/26/2018 (hereinafter Duchateau) 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).
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 CD22 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.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571)272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634