DETAILED ACTION
Claim Status
In Applicant's Response filed on 5/26/2026, claims 44-45 and 65 were amended and claim 66 was newly added.
As such, claims 44-48,54,57,59 and 64-66 are pending and have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of claims 44-48, 54, 57, 59, and 64-65 under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s amendments to claims 44 and 65.
The 103 rejection of record previously casted against claims 44-47, 54, 57, 59, and 64-65 over Duchateau et al (WO 2018206791 A1, 11 May 2018) has been recast below and amended to incorporate teachings related to newly added limitation 66.
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 (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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 44-47, 54, 57, 59, and 64-65 is/are rejected under 35 U.S.C. 103 as being unpatentable over Duchateau et al (WO 2018206791 A1, 11 May 2018; Published 15 Nov 2018; Ref. 1 of Foreign Patent Documents in IDS filed 4/28/2022; previously cited).
Regarding claim 44, Duchateau teaches protease based switch CARs for cell immunotherapy (title and abstract).
Duchateau continues to teach that the binding moiety of a CAR consists of an antigen-binding domain of a single-chain antibody (scFv), comprising the light and heavy variable fragments of a monoclonal antibody joined by a flexible linker. It also teaches the chimeric polypeptides can comprise both a degron and a protease domain to enhance control on the CAR polypeptide, where the degron is included into a self-excision domain that encodes a protease such as nonstructural protein 3 (NS3) protease (Background of the Invention, para 9; see also claim 8 of Duchateau). The CAR can also comprise a hinge such as a CD8a hinge, lgG1 hinge or FcYRIIIa hinge (see claim 15 of Duchateau). It can also contain a transmembrane domain such as CD8a (see claims 12-13 of Duchateau) and a cytoplasmic domain including a CD3 zeta signaling domain and 4-1 BB costimulatory domain (see claim 14 of Duchateau).
Regarding claim 45, Duchateau further teaches that hepatitis C virus NS3 can be used and that the invention thereby provides with various CAR architectures sensitive to small molecules that can easily penetrate cells.
Regarding claim 48, Duchateau teaches A polynucleotide encoding a chimeric polypeptide (see claim 18 of Duchateau).
Regarding claims 54 and 59, Duchateau teaches an engineered immune cell transformed with a polynucleotide encoding a chimeric polypeptide wherein the cell is a T cell and that the protease inhibitor can be introduced to switch on or off the CAR (claim 26, 28, and 34 of Duchateau).
Regarding claim 57, Duchateau teaches that the invention is also drawn to a pharmaceutical composition comprising an engineered primary immune cell or immune cell population.
Regarding claim 65 in-part, Duchateau teaches that a linker can be used that is suitable to link the heavy variable chain to the light variable chain.
Duchateau does not explicitly teach that “the NS3 protease domain is located between: the single light and heavy chain variable fragments and the hinge region; or between the hinge region and the transmembrane region” as in instant claim 44, “wherein the NS3 protease domain is located between the single light and heavy chain variable fragments and the hinge region” as in instant claim 46, or “wherein the NS3 protease domain is located between the hinge region and the transmembrane region” as in instant claims 64-66 in-part. However, rearrangement of parts generally have limited impact on patentability unless they produce unexpected results or solve a specific problem. In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950) (Claims to a hydraulic power press which read on the prior art except with regard to the position of the starting switch were held unpatentable because shifting the position of the starting switch would not have modified the operation of the device.); In re Kuhle, 526 F.2d 553, 188 USPQ 7 (CCPA 1975) (the particular placement of a contact in a conductivity measuring device was held to be an obvious matter of design choice) (see MPEP 2144.04). The cited art taken as a whole demonstrates a reasonable probability that the CAR of Duchateau is either identical or sufficiently similar to the claimed CAR that whatever differences exist, they are not patentably significant. Therefore, the burden of establishing novelty or nonobviousness by objective evidence is shifted to applicants. See MPEP § 2112(v). Clear evidence that the CAR of the cited prior art does not possess a critical characteristic that is possessed by the claimed CAR would advance prosecution and might permit allowance of claims. Applicant is requested to specifically point out the support for any amendments made to the disclosure and arguments in response to this Office Action, including the claims. See MPEP §§ 714.02 and 2163.06. Applicant is also requested to refer to pages and line numbers in the as-filed specification. It is noted that other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a CAR as taught by Duchateau to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill to use the CAR of Duchateau to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to use the CAR of Duchateau with the reasonable expectation of advantageously having CAR architectures sensitive to small molecules that can easily penetrate cells for safer therapeutic use as taught by the prior art.
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive.
On p. 6-10 of Remarks, Applicant argues, in sum, that Duchateau does not teach the NS3 protease domain is located between: the antigen binding fragment comprising a single light and a single heavy chain variable fragment and the hinge region; or between the hinge region and the transmembrane region. Applicant argues that the claimed CAR is “fine tunable” and the claimed CAR is able to be “turned on and off prior to and after membrane insertion with the addition or withholding of protease inhibitors” and this feature is absent in the Duchateau reference.
While Applicant’s arguments have been fully considered, it has not been found persuasive. While Duchateau does not explicitly teach that the NS3 protease is located either between scFv and hinge OR between hinge and transmembrane region, as per MPEP 2144.04, the rearrangement of parts generally have limited impact on patentability unless they produce unexpected results or solve a specific problem. In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950). Fig. 5 of Duchateau demonstrates the variability in the position of the protease (reproduced below). While it only contemplates 3 configurations of the protease's position, one of ordinary skill would have readily understood that they would not be limited to these specific embodiments and that the position of the protease is not static and would be a matter of routine optimization. An argument by the applicant is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection (see MPEP 2145(I)). Absent empirical evidence to the contrary, a reconfiguration of an obvious CAR is not sufficient to sustain patentability. Again, the examiner requests clear evidence that the CAR of the cited prior art does not possess a critical characteristic that is possessed by the claimed CAR. This would advance prosecution and might permit allowance of claims. See MPEP § 2112(v). Thus, Applicant’s arguments are not persuasive.
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Conclusion
No claim is allowed.
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.
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/G.R./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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