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 the Claims
Applicant’s submission filed 23 June 2026 has been entered. Claims 2-22 are pending. Claims 2-3 have been amended. Therefore, prosecution on the merits continues for claims 2-13 as being drawn to the elected invention, with claims 14-22 withdrawn for reading on the non-elected invention. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection of claim 2
Applicant’s amendments to instant claim 2 correct the minor informalities, thus obviating the objection of record.
Therefore, the objection is withdrawn.
RE: Rejection of claims 2-13 under 35 USC 103 over Siewart et al as evidenced by ATCC in view of Robinson et al
Applicant has amended independent claim 2 to require the engineered antigen-presenting cell to comprise a synthetic genomic receiver site which is a genetic construct designed for recombinase mediated cassette exchange or a synthetic construct designed for site directed homologous recombination. As this is a newly presented limitation, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s remarks are addressed in so far as they are applicable to the claims as currently written:
Applicant has traversed the rejection, asserting in Pages 7-8 of the Remarks filed 23 June 2026 that Siewart et al fail to disclose the stable expression of HLA-A2 and peptide-library constructs within the COS-7 cells. In response, the Examiner respectfully submits that although Siewart et al do disclose an embodiment wherein the HLA-A2 and peptide library construct are transiently expressed, Siewart et al do disclose an embodiment wherein at least HLA-A2 is stably expressed within the COS-7 cells. See, for example, Page 825 of Siewart et al.
With that, Applicant has further traversed the rejection, asserting in Pages 9-10 of the Remarks filed 23 June 2026 that the ordinary artisan would not have recognized that the integration of the HLA-A2 utilizes synthetic genomic receiver sites for RMCE or homologous recombination, as Siewart et al teach the transient and stable expression of HLA-A2 using plasmids. In response, the Examiner respectfully submits that while Siewart et al fail to teach recombination integration techniques, the disclosure of Robinson teaches the engineering of APCs to comprise a recombinant nucleic acid encoding an HLA class I molecule via standard recombination techniques, including site-directed homologous recombination. See, for example, Columns 13-17 of Robinson and Pages 119 and n282-n283 of the incorporated reference of Sambrook et al, Molecular Cloning: A Laboratory Manual, Second Ed., (1989). Therefore, the ordinary artisan would have recognized that the stable expression of HLA-A2 within the COS-7 cells could have been done via site-directed homologous recombination given the teachings of Robinson. It is of note that since both the plasmid integration in Siewart et al and the homologous recombination as taught by Robinson allows for the stable expression of HLA-A2, the principle of operation is not being altered.
Applicant has further traversed the rejection asserting in Page 10 of the Remarks filed 23 June 2026 that the ordinary artisan would have understood from the disclosure of Robinson that B7-family proteins are co-stimulatory molecules and not analyte antigen-presenting complexes or analyte antigenic molecules. In response, the Examiner respectfully submits that the ordinary artisan would have understood that the co-stimulatory molecules of Robinson aid in the presentation of antigens and activation of T cells, and as such qualify as a non-HLA analyte antigen presenting complex. See, for example, Columns 4 and 6-7 of Robinson.
New Grounds of Rejection
Interpretation of abbreviations in the claims
eAPCS (engineered antigen-presenting cell system),
ORFs (open reading frames),
aAPX (antigen-presenting complex),
aAM (analyte antigenic molecule),
CM (cargo molecule),
eAPC-p (“engineered cell containing a genomic receiver site and genetic donor vector for delivery of an ORF encoding an aAPX, wherein the eAPC-p expresses the aAPX on its surface”),
eAPC-a (“engineered cell containing a genomic receiver site and genetic donor vector for delivery of an ORF encoding an aAM or CM, wherein the eAPC-a expresses the aAM or CM on its surface”),
eAPC-pa (“engineered cell containing one or more genomic receiver sites and one or more genetic donor vector for delivery of one or more ORFs encoding (a) at least one aAPX; and (b) at least one aAM or CM, wherein the eAPC-pa expresses (a) the aAPX and aAM; (b) a complex comprising the aAPX and aAM (aAPX:aAM); (c) the aAPX and CM; and/or (d) a complex comprising the aAPX and CM (aAPX:CM) on its surface”),
eTPCS (engineered TCR-presenting cell system),
TCRsp (TCR surface protein; in complex with CD3), and
eTPC-t (“engineered cell containing one or more genomic receiver site and one or more genetic donor vector for delivery of one or more ORFs encoding at least two analyte TCR chains, wherein expression of the complementary analyte TCR chains results in expression of a TCR surface protein (TCRsp) on the surface of the eTPC-t”).
Claim Interpretation
The instant claims require component 1C to be “matched” to component 1B, as well as component 2C to be “matched” to component 2B. The Examiner is interpreting “matched” to indicate that the third component is homologous to the second component, such that the third component can deliver the one or two ORFs that integrate into a targeted region within the second component.
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.
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 2-13 are rejected under 35 U.S.C. 103 as being unpatentable over Siewert et al (Nature Medicine, 2012, of record on IDS filed 19 September 2025) as evidenced by ATCC (COS-7 Cell Technical Sheet, 2025), and in view of Robinson (US 5,962,320 A).
Siewert et al is considered prior art under 35 USC 102(a)(1). Robinson is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 2-6: Siewert et al disclose an unbiased method for the identification of disease-relevant T cell antigens via plasmid-encoded combinatorial peptide libraries and a single-cell detection system (Abstract).
As such, Siewert et al disclose that the single-cell detection system is comprised of recombinantly engineered APCs, wherein the APCs are COS-7 cells that are co-transfected with a plasmid-coded combinatorial nonamer peptide library and class I MHC cDNA, and reporter T hybridoma cells (Page 825, Column 1; Figure 1). In a particular embodiment, Siewert et al disclose that COS-7 APCs are stably transfected with at least HLA-A2 as well as transfected with a peptide representing amino acids 58-66 of the influenza matrix protein (flu (58-66)), and that the reporter T hybridoma cells are 58α-β- cells that endogenously lack expression of the TCR α and β chains – as well as the TCR δ and γ chains – but are engineered to express TCR α and β chains together with CD3, JM22, human CD8 α and β chains, and sGFP controlled by NFAT (Page 825, Column 1; Figure 1).
It is of note that the COS-7 cells are fibroblasts, as evidenced by Page 1 of the ATCC technical document.
Siewert et al do not disclose that the APCs are engineered to lack endogenous surface expression of at least one family of target HLA class I, target HLA class II, or non-HLA analyte antigen presenting complexes (aAPX) and/or at least one target analyte antigenic molecule (aAM), nor that the APCs comprise a genomic receiver site which is a genetic construct designed for recombinase mediated cassette exchange or a synthetic construct designed for site directed homologous recombination, as required by instant claim 2.
Robinson, however, discloses the generation of engineered APCs, wherein fibroblasts are engineered to lack endogenous expression of a costimulatory molecule necessary for T cell activation and antigen presentation (Abstract; Columns 6-7, 9, 18).
Robinson further discloses that the engineered APCs can comprise a recombinant nucleic acid encoding an HLA-A molecule via standard recombination techniques, including site-directed homologous recombination (Columns 6-8, 11, 13-17; Pages 119 and n282-n283 of the incorporated reference of Sambrook et al, 1989). It is of note that Robinson teaches that the standard recombination techniques involve synthetic genomic receiver sites for the integration of open reading frames encoding the recombinant nucleic acids (Columns 12-13).
Therefore, it would have been prima facie obvious to have modified the engineered COS-7 APCs of Siewert et al such that the cells are further engineered to lack endogenous expression of a costimulatory molecule, as detailed in Robinson. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to engineer the COS-7 fibroblasts such that they lack endogenous expression of a costimulatory molecule, as it allows for the induction of tolerance to the introduced selected antigens (Robinson: Column 6), and would have had a reasonable expectation of success given that the disclosures of Siewert et al and Robinson both utilize fibroblasts as antigen presenting cells. See MPEP § 2143(I)(G). Furthermore, it would have been prima facie obvious to have substituted the plasmid comprising the encoded HLA-A2 of Siewart et al with the vector comprising the recombinant nucleic acid encoding HLA-A2 of Robinson, as doing so would have been a simple substitution of one vector capable of stable expression for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two vectors are functionally comparable, as they both allow for the stable expression of an HLA-A molecule within fibroblasts, and thereby would have been able to substitute the vectors with predictable results.
Consequently, Siewert et al as modified by Robinson render obvious a two-part cellular device comprising an engineered antigen-presenting cell system and engineered T-cell receptor (TCR)-presenting cell system (claim 2). As such, the COS-7 eAPCs of Siewert et al in view of Robinson render obvious the engineered antigen presenting cell-pa (eAPC-pa) of the instant disclosure (claim 4), as the COS-7 eAPCs (instant component 1A) stably expresses an HLA-A2 (aAPX) (claim 5) and transiently expresses a flu(58-66) peptide (aAM), and are engineered to lack endogenous expression of a costimulatory molecule, which is a non-HLA analyte antigen presenting complex (aAPX). Furthermore, given that the disclosure of Robinson teaches the transfection of fibroblasts with a vector comprising a recombinant nucleic acid encoding an HLA-A molecule via standard recombination techniques, including site-directed homologous recombination, one of ordinary skill in the art would appreciate that the expressed molecules have been genomically integrated into the “receiver sites” (instant component 1B) of the COS-7 cell line via “donor vectors” (instant component 1C).
Likewise, the TCR-transfected T hybridoma cells of Siewert et al as modified by Robinson render obvious the engineered TCR-presenting cell t (eTPC-t) of the instant disclosure (claim 6), as the 58α-β- T hybridoma cells (instant component 2A) endogenously lack expression of the TCR α and β chains – as well as the TCR δ and γ chains – and JM22 antigenic molecule (aAM), but are engineered to express TCR α and β chains together with CD3, JM22, human CD8 α and β chains, and sGFP controlled by NFAT. Again, although Siewert et al are silent to the means of transduction regarding the TCR-transfected T hybridoma cells, one of ordinary skill in the art would appreciate that the expressed molecules have been genomically integrated into the “receiver sites” (instant component 2B) of the 58α-β- T hybridoma cells via “donor vectors” (instant component 2C) given that Robinson teaches the incorporation of antigenic molecules into cells via standard recombination techniques, including site-directed homologous recombination (claim 3). See, for example, Columns 11-16 of Robinson.
Regarding claim 7: As aforementioned in the discussion of claim 2, Siewert et al disclose the exogenous expression of TCR α and β in complex with CD3 (TCRsp) on the 58α-β- T hybridoma cells. This therefore reads on the two-part device of the instant claim.
Regarding claim 8: Following the discussion of claim 7 and as aforementioned in the discussion of claim 2, the 58α-β- T hybridoma eTPCs of Siewert et al comprise an sGFP reporter, which reads on the ORF encoding a synthetic TCR signal response element of claim 8.
Regarding claim 9: Following the discussion of claim 2, Siewert et al further disclose the combination of at least one COS-7 APC with at least one 58α-β- T hybridoma eTPC (Page 825; Figure 1). This therefore reads on the two-part device of the instant claim.
Regarding claims 10-12: Following the discussion of claim 9, Siewert et al further disclose the combination of the 58α-β- T hybridoma eTPCs with the COS-7 APCs (claim 10), wherein the 58α-β- T hybridoma eTPCs and COS-7 APCs form a complex between the TCR αβ-CD3-JM22-expressing 58α-β- T hybridoma eTPCs and flu(58-66) peptide presented by HLA-A2 on the COS-7 APCS (claim 11), resulting in the expression of sGFP within the 58α-β- T hybridoma eTPCs (claim 12) (Pages 825-827; Figures 1, 3). This therefore reads on the two-part device of the instant claims.
Regarding claim 13: Following the discussion of claim 9, Siewert et al further disclose the selection of the 58α-β- T hybridoma eTPC based on the expression of the synthetic TCR signal response element (sGFP) (Pages 825-827; Figures 1, 3). This therefore reads on two-part device of the instant claim.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, 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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633 /CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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