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 .
Application Status
Claims 1 and 3-15 are pending and examined on the merits herein.
Grounds of Rejection Withdrawn
All previous objections and rejections of claim 2 are rendered moot by claim cancellation.
Previous objection of claim 9 is withdrawn in view of claim amendment.
Previous rejection of claim 9 under 35 U.S.C. 101 are withdrawn in view of claim amendment.
Previous rejection of claim 9 under 35 U.S.C. 112(b) are withdrawn in view of claim amendment.
Previous rejection of claims 1 and 3-12 under 35 U.S.C. 102 are withdrawn in view of claim amendments.
Claim Rejections - 35 USC § 102
New Rejection Necessitated by Amendment
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.
Claims 1 and 3-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Neiderman (Proc Natl Acad Sci U S A. 2002 May 14;99(10):7009-14; PTO-892).
Regarding claims 1, 3, and 10, Neiderman teaches an engineered CAR with the murine VEGF isoform 165 (VEGF-165) fused to the CD8α hinge region, and the transmembrane and signaling domain of the murine CD3-ζ chain (Fig 1A).
Regarding claims 4-5, Neiderman teaches construction of a retrovirus construct using VEGF-164, CD8 alpha, and murine TCR zeta cDNA (page 7009, col 2, para 4).
Regarding claims 6-7 and 15, Neiderman teaches retroviral transduction of CTLs (page 7010, col 1, para 4).
Regarding claims 8-9 and 13-14, Neiderman teaches that on the days of treatment, CTLs (4–7 days post transduction) were harvested, washed, resuspended in cold PBS, and injected in a volume of 300 ul into the retroorbital venous plexus (page 7010, col 2, para 3) and further that the VEGF construct reduced tumor volume in transplant models of adenocarcinoma, melanoma and fibrosarcoma (Fig 4 and 5).
Regarding claim 11, Neiderman teaches southern blot analysis confirming genomic DNA integration of retroviral constructs (page 7010, col 1, last para; Fig 1D).
Regarding claim 12, Neiderman teaches FACS analysis of VEGF construct expression (Fig 1B).
Response to Arguments
Applicant’s arguments with respect to claim(s) 1 and 3-12 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant submits: To the extent the Examiner may rely on any other reference (including, for example, any references submitted herewith in an Information Disclosure Statement), Applicant notes that the claimed invention is further distinguished by the specific, non-obvious selection of IL5, Plau, CCL11, CCL24, or VEGF as the antigen-binding domain.
As demonstrated in the original specification (see, e.g., Examples 1-20, FIGS. 1-16), ECARs built with ILS, Plau, CCL11, and CCL24 exhibit unexpected and highly effective selective killing of target cells expressing the corresponding receptors (IL5Ra, PlauR, CCR3, etc.). The functional data for these four molecules are fully set forth in the application as filed.
In Response: A submission of unexpected results would overcome an obvious type rejection but the new rejection detailed above is a 102/ anticipatory rejection and is not in view of the recited receptors that have unexpected results.
Applicant submits: With respect to the VEGF embodiment, Applicant has conducted additional experiments demonstrating that an ECAR comprising VEGF as the antigen-binding domain effectively and selectively kills cells expressing VEGF receptors (VEGFRs), thereby providing a basis for treating diseases such as cancer (e.g., by targeting VEGFR-expressing tumor vasculature or tumor cells). These results further confirm that VEGF, like ILS, Plau, CCL11, and CCL24, can function as an effective antigen-binding domain in an ECAR. The selection of VEGF, among numerous other growth factors, as an antigen-binding domain for an ECAR is itself non- obvious, and the demonstrated selective killing effects would not have been predictable from any prior art.
In Response: Please see the new 102 rejection detailed above wherein a VEGF ECAR is produced with demonstrated in vivo efficacy, which renders the selection of VEGF in a CAR as obvious and anticipatory.
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 AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMBER K FAUST/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
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