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 .
Election/Restrictions
Applicant’s election without traverse of Group 1 and cancelation of claims in Groups 2-4 in the reply filed on 11/14/2025 is acknowledged.
Claims 44-48, 54, 57, 59 and newly added claims 64-65 are pending and have been examined herein.
Priority
The instant claims herein are examined utilizing the accepted effective filing date of 10/30/2019 for the basis of any prior art rejections.
Claim Objections
Claim 45 is objected to because of the following informalities:
Claim 45 contains the acronyms “HCV”, and “T54A”. The examiner suggests spelling out these acronyms followed by their respective shorthand in parentheses.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 44-48, 54, 57, 59 and 64-65 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 44, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The phrase “optionally” in the recitation of “optionally, an intracellular signaling domain, such as an intracellular signaling domain of CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS (CD278), lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, TNFSF14, NKG2C, B7-H3, CD132, or ILR3 (CD122),wherein 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” in claim 44 renders the claim indefinite because it makes it unclear what is actually required by the claim limitations.
Claim 44 recites the limitation " the single light and heavy chain variable fragments ". There is insufficient antecedent basis for this limitation in the claim as there is no previous recitation of any single light and heavy chain variable fragments in the claim.
Claim 65 recites “wherein the antigen-binding fragment is a scFv comprising a single light chain variable fragment, a single heavy chain variable fragment, and a single chain variable fragment linker between the single light chain variable fragment and the single heavy chain variable fragment and the NS3 protease domain is located between the scFv and the hinge region or between the hinge region and the transmembrane region”. While the claim contains a new limitation to narrow the antigen fragment to be a single light chain variable fragment, the remainder of the claim is a repeat of instant claim 44. It is unclear what Applicant intends to claim in the rest of the claim, rendering the claim indefinite.
Please note that claims 45-48, 54, 57, 59 and 64-65 are included in this rejection for being dependent on indefinite claim 44.
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).
Duchateau teaches protease based switch CARs for cell immunotherapy (title and abstract). It teaches 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) abs a cytoplasmic domain including a CD3 zeta signaling domain and 4-1 BB costimulatory domain (see claim 14 of Duchateau). This reads on “chimeric antigen receptor (CAR) comprising: an antigen binding fragment of an antibody; a single chain variable fragment linker; at least one non-structural protein 3 (NS3) protease domain; at least one cleavage site; a hinge region; a transmembrane region; a CD3-zeta signaling domain; and, optionally, an intracellular signaling domain, such as an intracellular signaling domain of . . . 4-1BB” as in instant claim 44. The reference 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 (“wherein the at least one NS3 protease domain is selected from a wild-type HCV NS3 protease domain . . . a NS3 protease domain sensitive to inhibition by a small molecule inhibitor” as in instant claim 45). The reference teaches A polynucleotide encoding a chimeric polypeptide (see claim 18 of Duchateau) (“A nucleic acid encoding the CAR” as in instant claim 48). The reference also 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) (as in instant claim 54 and “A method of producing a T cell expressing a CAR, said method comprising transforming a T cell with a vector encoding a CAR according to claim 44 and expressing said CAR in said T cell” as in instant claim 59). The invention is also drawn to a pharmaceutical composition comprising an engineered primary immune cell or immune cell population (“a pharmaceutical composition comprising a T cell according to claim 54” as in instant claim 57). Finally the reference teaches that a linker can be used that is suitable to link the heavy variable chain to the light variable chain (“wherein the antigen-binding fragment is a scFv comprising a single light chain variable fragment, a single heavy chain variable fragment, and a single chain variable fragment linker between the single light chain variable fragment and the single heavy chain variable fragment” as in instant claim 65 in-part).
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 claim 64 and 65 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 unobviousness 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.
Conclusion
No claim is allowed.
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/G.R./Examiner, Art Unit 1632 /KARA D JOHNSON/Primary Examiner, Art Unit 1632