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 .
1. In view of the Appeal Brief filed on 06/20/2025, PROSECUTION IS HEREBY REOPENED. New grounds of rejections are set forth below.
To avoid abandonment of the application, Appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below.
Claims 1-67, 75, 76, 80, 82, 84, 85, and 89-96 have been cancelled. Claim 68 has been amended.
Claims 68-74, 77-79, 81, 83, 86-88, and 97 are pending and under examination.
2. All rejections set forth in the final Office action of 12/18/2024 are withdrawn in favor of new rejection using references providing a better motivation to arrive at the claimed invention.
Claim Objections
3. Claim 68 is objected to because of the recitation “into T-cells” in lines 5-6. Correction to “into the T-cell” is required.
Claim Rejections - 35 USC § 103
4. 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 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.
5. Claims 68-74, 77, 83, 86-88, and 97 are rejected under 35 U.S.C. 103 as being unpatentable over Pease (PGPUB 2012/0141537), in view of all Davenport et al. (PNAS, 2015, 115: E2068-E2076), Edes et al. (Mol. Ther., May 2016, 24: S201-S202), and Ebert et al. (Mol. Immunol., 2005, 42: 799-809), as evidenced by Tubo et al. (Cell, 2013, 153: 785-796).
Pease teaches in vivo activating the naïve self-reactive CD8+ T-cells in a subject having cancer, to focus the autoimmune cellular responses against cancer; the subject could be a human and activation occurs by administering an adenovirus encoding a modified MHC class I polypeptide having one or more amino acid changes from the wild-type (i.e., allogeneic), to generate primed self-reactive CD8+ T-cells capable of lysing the cancer cells expressing the self-antigen; administration could be subcutaneous (claims 68-70, 77, and 86) owever, activating (see Abstract; [0003]; [0005]-[0006]; [0009]; [0020]; [0038]-[0041]; [0043]; [0045]; [0048]; [0057]; [0072]). As evidenced by Tubo et al., each naïve T-cell comprises a different native TCR (see p. 785, column 1). Thus, by administering the allogeneic MHC class I polypeptide, Pease produces a polyclonal response of activated CD8+ T-cells, each comprising a different native TCR (claims 68 and 88).
Pease does not teach further administering a nucleic acid encoding a tumor-specific CAR (claims 68, 71, 72, and 87). Davenport et al. teach that dual-specific T-cells expressing a TCR recognizing an MHC class I antigen present on cancer cells and a CAR recognizing a different antigen present on the same cancer cells are capable of serially killing the targets tumor cells; Davenport et al. teach that the dual-specific T-cells could be tuned to the desired response depending on the disease status, resulting in a more rapid serial killing (via the CAR; when the initial disease burden is high) or a slower but more protracted killing (via the TCR; for tumor relapse) (see Abstract; paragraph bridging p. E2068 and E2069; p. E2069, column 1, first full paragraph; p. E2073, column 1, last paragraph and column 2; p. E2074, column 1, first paragraph and paragraph bridging columns 1 and 2). Furthermore, Edes et al. teach that the CD8+ T-cells could be transduced in vivo by intravenously administering a CD8-targeted retroviral vector encoding the desired heterologous antigen receptor (see Abstract 506). Based on these teachings, one of skill in the art would have found obvious to modify Pease by further administering a CD8-targeted retroviral vector encoding a CAR recognizing a different antigen present on the tumor cells expressing the self-antigen, with the reasonable expectation that doing so would generate CD8+ T-cells suitable to treat the cancer in the human subject, where the CD8+ T-cells are capable of eradicating large tumor burden as well as controlling residual cancer (claims 73 and 74).
Pease, Davenport et al., and Edes et al. teach administering the CAR-encoding retroviral vector intravenously, not into a lymph node (LN) (claim 68). However, the prior art teaches that the naïve T-cells circulate between the blood and LNs in search for antigen-presenting DCs (see Ebert et al., Abstract). One of skill in the art would have reasonably concluded that, similar to intravenous administration, direct administration to a LN would also result in the transduction of naïve CD8+ T-cells. Using direct administration to a LN would have been obvious to one of skill in the art to achieve the predictable result of activating the naïve self-reactive CD8+ T-cells.
It is noted that administering the adenoviral encoding the modified MHC class I polypeptide as taught by Pease would have produced a polyclonal response and would have activated more than 2.5% of the CD8+ T-cells in the LNs of the subject (including the LN used to further administer the CAR-encoding retroviral vector) because all that is required to achieve this is to administer the MHC class I-encoding adenovirus before administering the CAR-encoding retroviral vector (claim 68). The claims do not require more than this and the specification does not teach more than this.
Pease, Davenport et al., Edes et al., and Ebert et al. do not teach that the MHC class I polypeptide has the amino acid sequence set forth by SEQ ID NO: 3 (claim 97). However, as per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, there is no evidence of record that specifically using the polypeptide set forth by SEQ ID NO: 3 leads to unexpected results.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
6. Claims 68-74, 77, 78, 81, 86, 88, and 97 are rejected under 35 U.S.C. 103 as being unpatentable over Pease taken with all Davenport et al., Edes et al., and Ebert et al., as evidenced by Tubo et al., in further view of Yang et al. (Nat. Biotechnol., 2008, 26: 326-334).
The teachings of Pease, Davenport et al., Edes et al., and Ebert et al. are applied as above for claims 68-74, 77, 86, 88, and 97. Pease, Davenport et al., Edes et al., and Ebert et al. teach administering the adenovirus subcutaneously, not intradermally (claim 78). Yang et al. teach that subcutaneous administration of viral encoding tumor antigens results in dendritic cells (DCs) transduction and their migration to lymph nodes (LNs) to activate the resident naïve CD8+ T-cells to effect anti-tumor activity (see Abstract; p. 326, column 1, last paragraph; paragraph bridging p. 328 and 329; p. 332, column 2). Yang et al. teach that DCs are resident in the dermis (see p. 332, column 2, second paragraph). One of skill in the art would have found obvious to replace the subcutaneous injection of the modified MHC class I polypeptide-encoding adenovirus with intradermal injection, to achieve the predictable result of activating the naïve self-reactive tumor-specific CD8+ T-cells.
With respect to claim 81, Yang et al. teach that retroviruses and LVs are capable of transducing the same cell type (see p. 326, column 1, second paragraph) and thus, one of skill in the art would have reasonably concluded that an LV could be used instead of the retrovirus to transduce the CD8+ T-cells in vivo. Replacing the retrovirus with an LV would have been obvious to one of skill in the art to achieve the predictable result of obtaining genetically engineered CD8+ T-cells expressing the tumor-specific CAR.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
7. Claims 68-74, 77, 79, 86, 88, and 97 are rejected under 35 U.S.C. 103 as being unpatentable over Pease taken with all Davenport et al., Edes et al., Ebert et al., and Ebert et al., as evidenced by Tubo et al., in further view of Sixt et al. (Immunity, 2005, 22: 19-29)..
The teachings of Pease, Davenport et al., Edes et al., and Ebert et al. are applied as above for claims 68-74, 77, 86, 88, and 97. Pease, Davenport et al., Edes et al., and Ebert et al. do not teach administering the adenovirus to a LNs (claim 79). Sixt et al. teach that LNs comprise resident DCs (see Abstract). One of skill in the art would have found obvious to administer the MHC class I-encoding adenovirus to the same LN to transduce the resident DCs with the reasonable expectation that the transduced resident DCs would activate the LN resident naïve CD8+ T-cells.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
8. The arguments are answered below to the extent that they pertain to the new rejections.
The applicant argues that Pease does not teach a polyclonal response and activating more than 2.5% of T cells within a lymph node,
This argument is not found persuasive for the reasons set forth in the rejection. The only requirement in the claims for inducing a polyclonal response and activating more than 2.5% of T cells within a lymph node is to administer a modified MHC class I polypeptide, which is taught by Pease. The specification doers not teach more than is recited in the claims.
With respect to the argument that Pease does not teach further administering a nucleic acid encoding a heterologous antigen receptor into a LN, it is noted that Pease foes not have to teach every claim limitation.
9. No claim is allowed. No claim is free of prior art.
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/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633