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
Claims 85-104 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
IDS
The references cited on the information disclosure statement(s) were considered and have been made of record.
Notably, one or more of the disclosure statements filed to date lists the following documents: Search Reports, PCT Written Opinion.
The listing of the document(s) noted above is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the document(s) noted above have not been considered.
Furthermore, the listing of references in the specification or claims is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the document(s) noted above are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Priority
The effective filing date of the claims is deemed the filing date of the provisional application (i.e., 63/227,264), namely July 29, 2021.
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.
Claims 85 and 87-104 are rejected under 35 U.S.C. 112(b) as failing to set forth the subject matter which the inventor or a joint inventor regards as the invention.
Claims 85 and 87-104 are indefinite in the recitation of "increasing an activity of a cell". Said phrase is unclear since a cell by itself has constant up- and downregulations of a multitude of possible activities. Said activity cannot be defined and no comparison with the art is
possible. Therefore, the scope of the claims cannot be established.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 85-87, 91-98 and 101-104 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zimmermann1.
Zimmermann teaches a NFATsyn.iGOI-GD2CAR construct transduced and expressed in CD3/CD28 beads-activated primary human T cells. NFATsyn is an inducible promoter comprising a 6xNFAT fused to a synthetic TATA box (NFATmlL2 is disclosed as alternative, in which a minimal IL2 promoter is fused to 6xNFAT) expressing a gene of interest (GOI) upon CAR activation. Exemplary genes of interest are EGFP, hlL-12 and hlL-18 (see, e.g., Fig. 2). The GD2CAR comprises a 14.G2a scFv, HCH2CH3 hinge domain, CD28 TM, and 4-1 BB/CD3s signaling domain (see, e.g., Fig. 1). Zimmermann further teaches: co-culturing said CART Cells inducibly expressing hIL-12 with GD2+ target cells resulted in increased cytotoxicity compared to non-transduced T cells (see, e.g., Figure 6A), increased activation markers CD3+CD69+, CD8+CD137+ and CD25+ (Figure 6B-D), upregulation of pro-inflammatory cytokines like tumor necrosis factor (TNF)a, Interferon (IFN)y, and IL2, as well as cytolytic effector cytokines like perforin and granzyme B (Figure 6F) and higher monocyte recruitment (Figure 7; reads on instant claims 85-94, 101-104). Zimmermann further teaches: wherein the polynucleotide is within a lentiviral vector (see. e.g., abstract, methods; reads on instant claims 95-96); further comprising stimulating the cell (see, e.g., methods; reads on instant claim 97-98); Said cells are foreseen for future therapeutic purposes (see, e.g., Discussion, p. 13-15).
Thus, Zimmermann anticipates the subject matter of instant claim(s) 85-98 and 101-104.
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 85-104 are rejected under 35 U.S.C. 103 as being unpatentable over Zimmermann (supra) in view of Wei2.
Regarding claims 85-98 and 101-104, the teachings of Zimmermann are discussed above and are incorporated herein.
The prior art of Zimmermann differs from the instantly claimed invention as follows: Zimmermann does not expressly disclose: the Syn Pro comprises transcription response element (TRE) combinations set forth in instant claims 88-90; contacting the cells with PMA or ionomycin and administering the cells into a subject, as required by instant claims 99-100.
Wei discloses CD8 T cells being co-transduced with a) SynPro-lL2mp-GFP and b) EF1a-CD19scFv-EGFRt (see, e.g., FIG. 27). The Syn Pro comprises transcription response element (TRE) combinations of E2F1, EGR1, FOS, HIF1 a, JUN, NFAT, LEF1, NFkB, SP1, PU.1, and STAT4. The CAR comprises EF1 a, CD19 scFv, lgG4 hinge TM, CD28, 4-1 BB, CD3z, T2A and EGFRt. The cells were first stimulated with CD3/CD28 beads prior to virus transfection (see, e.g., [0006], [0094]; reads on instant claims 88-90). Said cells showed GFP and EGFRt expression after coculture with CD19 positive LCL-cells.
Wei further discloses contacting the cells with ionomycin (see, e.g., [0008]; reads on instant claim 99).
Wei further discloses the injection of CD8/CD19CAR/S1-61-GFP: ffluc EGFRt cells into mice bearing Be2 tumour cells on each flank or Be2 cells on one flank and Be2/CD19 cells (CD19-positive Be2 cells) on the other flank or Be2/CD19 cells on both flanks. Expression of GFP could only be seen in mice bearing CD19 cells, as such showing GFP expression through the Syn Pro activated S1-61 promoter following CART cell activation (see, e.g., [0030-0032] and figs. 20-22; reads on instant claim 100).
Obviousness Analysis:
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the presently claimed invention in view of the prior art because it amounts to no more than: combining the prior art elements of the cited references according to known methods to yield predictable results e.g., the methods of Zimmermann and Wei, both of which teach inducible CAR cells. See MPEP 2143(I)(A),(G).
Additionally, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Thus, a skilled artisan could predictably and reasonably produce the methods of the instant invention, as the prior art references cited above provides support and motivation for doing so, as discussed above.
Accordingly, claims 85-104 are rejected.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Copending Application No.: 18/520,117 (US20240093178)
Claims 85-104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-66 of Copending Application No. 18/520,117 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other as described below.
MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an obviousness analysis.
Obviousness analysis: Regarding the instant claims, the reference application claims nucleotides, vectors, and cells encoding/comprising the transcription factor response element and CAR of the present invention (see reference claims 47-66). Although the reference application doesn’t expressly claim the methods set forth in the instant claims, these limitations are set forth in the reference specification (see, e.g., enhancement of cell activity such as cytokine activity and killing ability and methods of administering, set forth in Fig. 18, 22).
Accordingly, the present claims are directed to obvious variants3 of the claimed invention, and a skilled artisan would readily appreciate the limitations set forth in the reference application, as the they are obvious variations described in the specification of the reference application (see, e.g., MPEP § 804(II)(B)(1), regarding construing the claim using the reference disclosure).
Accordingly, the instant claims are not patentably distinct relative to the reference claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Patent No.: 11851649
Claims 85-104 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of Patent No. 11851649 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other as described below.
MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an obviousness analysis.
Obviousness analysis: Regarding the instant claims, the reference patent claims nucleotides, vectors, and cells encoding/comprising the transcription factor response element and CAR of the present invention (see reference claims 1-20). Although the reference application doesn’t expressly claim the methods set forth in the instant claims, these limitations are set forth in the reference specification (see, e.g., enhancement of cell activity such as cytokine activity and killing ability and methods of administering, set forth in Fig. 18, 22).
Accordingly, the present claims are directed to obvious variants4 of the claimed invention, and a skilled artisan would readily appreciate the limitations set forth in the reference patent, as the they are obvious variations described in the specification of the reference patent (see, e.g., MPEP § 804(II)(B)(1), regarding construing the claim using the reference patent disclosure).
Accordingly, the instant claims are not patentably distinct relative to the reference claims.
Conclusion
Claims 85-104 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEA S O'BRIEN whose telephone number is (703)756-4793. The examiner can normally be reached Monday - Thursday 9:00 AM to 6:00 PM PT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LEA S O'BRIEN/Examiner, Art Unit 1646
/MARK HALVORSON/Primary Examiner, Art Unit 1646
1 Katharina Zimmermann ET AL: "Design and Characterization of an "All-inOne" Lentiviral Vector System Combining Constitutive Anti-GD2 CAR Expression and Inducible Cytokines", Cancers, vol. 12, no. 2, 6 February 2020 (2020-02-06), page 375, XP055727985, DOI: 10.3390/cancers12020375; cited in the IDS.
2 US2020095573A1; cited on the IDS
3 Per MPEP § 804(II)(B)(1), it is permissible to rely on the Specification for obvious variants (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”).
4 Per MPEP § 804(II)(B)(1), it is permissible to rely on the Specification for obvious variants (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”).
Prosecution Insights