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 reply to the Restriction Requirement, dated January 23, 2026, has been received. By way of this reply, Applicant has elected, without traverse, Group I: claims 1-11 and 15-18, drawn to fusion proteins, and the species of LG112: SP-OKT3 scFv-CHIP.dTPR-CD8alpha hinge/TM-P2A-eGFP.
Claims 1-20 are pending in the application. Claims 12-14 and 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 23, 2026.
Claims 1-11 and 15-18 are under examination before the Office.
Claim Rejections - 35 USC § 112
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 1-11 and 15-18 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.
Claims 1-4, 7, 9-10, and 15-16 recite the term "preferably". Examples and preferences create confusion over the intended scope of a claim. It is not readily apparent if the preferred species recited are intended as limitations that narrow the scope of the claims. Description of examples or preferences is properly set forth in the specification rather than the claims. MPEP 2173.05(d).
For the purpose of claim construction, it is assumed that these "preferred" limitations are optional.
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.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6-11 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Delisa (WO2019178604A1) in view of Kamiya (WO2019032916A1, cited in IDS).
Delisa teaches a fusion protein comprising E3 ubiquitin ligase (i.e., a degradation tag protein) fused to a protein that binds the target of interest, wherein the fusion protein recruits the E3 to the target protein, leading to its polyubiquitination and subsequent degradation by the proteasome (para. 0006).
Delisa further teaches a linker coupling the E3 and the targeting domain (para. 0009).
Delisa further teaches that the targeting domain may be an antibody, including an scFv (para. 0042).
Delisa further teaches that the E3 ubiquitin ligase may be the carboxyl terminus of Hsc70-interacting protein (CHIP) (para. 0007), which is pertinent to claim 2.
Delisa further teaches a polynucleotide encoding the above fusion protein (para. 0010), which is pertinent to claim 6.
Delisa further teaches vectors for expression of the above fusion protein and cells comprising such (para. 0074), which is pertinent to claims 7 and 10.
Delisa further teaches pharmaceutical compositions of the above (para. 0017), which is pertinent to claims 8, 11, and 15-18.
Delisa also teaches inclusion of eGFP into a vector comprising the above fusion protein (para. 0021).
However, Delisa does not teach an antibody that binds CD3, a CD8-alpha domain, or a chimeric antigen receptor (CAR).
Kamiya teaches that it is useful to knockdown TCRs in CAR-T cells to reduce risk of graft-versus-host disease (para. 00242). Kamiya also teaches that downregulation of TCRs and CD3 can be accomplished by targeting the molecules for degradation (para. 0098).
Kamiya further teaches a fusion protein, comprising a signal peptide, a target-binding domain, a linker, and a localization domain (e.g., para. 0057). Kamiya further teaches the target-binding molecule comprises an antibody that binds CD3/TCR, and may be an scFv, and may also comprise CD8a hinge domain (para. 0010-0012).
Kamiya further teaches a cell comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), which comprises an scFv (para. 0066) that binds CEA (para. 0061), a CD8a alpha transmembrane domain, and a 4-1BB-CD3ζ ytoplasmic domain (para. 00253), which is pertinent to claim 9.
Kamiya also teaches the anti-CD3 antibody OKT3 (para. 00270).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Delisa and Kamiya to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Delisa and Kamiya are concerned with in vivo protein knockdown. Starting from the E3 ubiquitin ligase system taught by Delisa, one of skill in the art would be informed to target CD3/TCR by the use of an scFv that binds CD3 based upon the suggestion of Kamiya. Doing so would solve the known problem in the art taught by Kamiya of TCRs on CAR-T cells causing graft-versus-host disease. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Delisa and Kamiya as applied to claim 1 above, and further in view of Zhang (US20140186958A1).
The teachings of Delisa and Kamiya have been discussed supra. However, Delisa and Kamiya do not teach P2A-eGFP.
Zhang teaches that P2A-eGFP is useful as an easy visual method for detecting expression of recombinant protein in mammalian cells (para. 0274). Zhang also teaches that the P2A sequence causes a ribosomal skip resulting in two mature proteins from the same transcript (para. 0269).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Delisa, Kamiya, and Zhang to arrive at the claimed invention. Starting with the fusion peptide of Delisa and Kamiya, the ordinary artisan would appreciate that the addition of a P2A-eGFP sequence would be useful to visualize expression of the fusion protein in vivo, especially since Delisa teaches vectors comprising eGFP. Each component of the claimed fusion protein is taught by the references, and one of ordinary skill could readily assemble the claimed fusion protein by known methods, given guidance found in Delisa, with each component of the combination performing its known, usual function, leading to a predictable result.
All the claimed elements were known in the prior art and one of ordinary skill in the art could have arrived at the claimed invention by using known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results. Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Qasim (US20200087681A1) teaches a cell comprising nucleic acid sequence encoding a chimeric antigen receptor (CAR), which comprises an scFv that binds CEA, a transmembrane domain, and a cytoplasmic domain (para. 0132).
Qasim further teaches that it is useful to disrupt TCR expression in CAR-T cells in order to make said cells more universal and reduce the capability of said cell to produce graft-versus-host disease, and that this disruption may be done by any means known in the art (para. 0136).
Crew (US20180193470A1) teaches that proteolysis targeting chimeric (PROTAC) proteins, which rely upon targeted ubiquitination to degrade proteins of interest, are useful for removing transmembrane proteins (para. 1899).
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644