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 .
DETAILED ACTION
Request for Continued Examination Under 37 CFR 1.1143
A request for continued examination (RCE) under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission mailed on July 28, 2025 has been entered.
Claims 9, 10, 16 and 17 have been canceled. New claims 21-24 are acknowledged. Claims 1-8, 11-14, 18 and 20 have been amended.
Claims 1-8, 11-15 and 18-24 are pending in the instant application.
Accordingly, claims 1-8, 11-15 and 18-24 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Response to Arguments
Applicant's Amendment and Response filed July 28, 2025 has been considered. Communications, rejections and/or objections not reiterated from the previous Office Action mailed April 29, 2025 are hereby withdrawn. Any arguments addressing said rejections and/or objections are moot. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Claim Rejections - 35 USC § 103
In the previous Office Action mailed April 29, 2025, claims 1-20 were rejected under pre-AIA 35 U.S.C. 103(a) as being obvious over WO 2008/033403 A2 in view GenBank Accession No. U26710 and further in view of Curran et al. (J Gene Med., 2012 Vol. 14:405-415). This rejection is moot against claims 9, 10, 16 and 17 in view of Applicant’s Amendment filed July 28, 2025 to cancel these claims. This rejection is withdrawn against the remaining claims in view of Applicant’s Amendment to the claims filed July 28, 2025.
Double Patenting
In the previous Office Action mailed April 29, 2025, claims 1-13 and 20 were rejected on the grounds of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,597,934. This rejection is moot against claims 9 and 10 in view of Applicant’s Amendment filed July 28, 2025 to cancel these claims. This rejection is maintained against the remaining claims for the reasons of record set forth in the previous Office Action mailed April 29, 2025.
Response to Arguments
In response to this rejection, Applicants traverse and request that the Office hold any double patenting rejection over U.S. Patent No. 11,597,934 in abeyance until an allowable set of claims has been identified, upon which time Applicant will consider submitting a terminal disclaimer if so required.
Applicant’s request has been fully considered by the Examiner and the rejection with be held in abeyance until allowable subject matter has been identified.
Applicant’s Amendment to the claims filed July 28, 2025 and careful reconsideration of the application necessitated a new ground of rejection as presented below:
Specification
The Specification is objected to. 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, requires the specification to be written in “full, clear, concise, and exact terms.” The specification is replete with terms which are not clear, concise and exact. The specification should be revised carefully in order to comply with 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112. Examples of some unclear, inexact or verbose terms used in the specification are: Cb1b and Cblb. For example, the Specification throughout references the term, “Cb1b” however, at Tables 2, 2a, 3 and 6, “Cblb” is recited. Neither term is ever defined in the application. At Table 6, the function of Cblb is described as:
E3 ubiquitin ligase (degradation of TCR and signaling molecules; ko mice reject tumors)
The Examiner will assume that Applicants intend “Cb1b” to actually mean “Cblb”. Correction is required.
Claim Interpretation
Some claims recite “a nucleic acid sequence”. The claims in this application are given their broadest reasonable interpretation (BRI) using the plain meaning of the claim language in light of the Specification as it would be understood by one of ordinary skill in the art. See MPEP 2111. Interpreted broadly, “a nucleic acid sequence” is anticipated by any dinucleotide or larger oligonucleotide sequence. For examination and prior art purposes, the Examiner will therefore interpret the phrase, “a nucleic acid sequence” to be any dinucleotide or larger oligonucleotide sequence.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-8, 11-15 and 18-24 are rejected under pre-AIA 35 U.S.C. 103(a) as being obvious over WO 2008/033403 A2 (submitted and made of record on the IDS filed January 4, 2023) in view GenBank Accession No. U26710 (submitted and made of record on the IDS filed January 4, 2023) and further in view of Curran et al. (J Gene Med., 2012 Vol. 14:405-415) (submitted and made of record on the IDS filed January 4, 2023).
The claims are drawn to an immunoresponsive cell expressing a chimeric antigen receptor (CAR), wherein the cell comprises a nucleic acid that comprises a sequence encoding an shRNA, wherein the shRNA comprises 15 contiguous nucleotides complementary a nucleic acid sequence of SEQ ID NO: 612, and wherein the CAR comprises an antigen binding domain, a transmembrane domain, a stimulatory domain, and a co-stimulatory domain.
While the entire reference of WO 2008/033403 is relevant and relied upon in its entirety, WO 2008/033403 particularly describes an immunoresponsive cell - an isolated, purified CD8+ cytotoxic T lymphocyte for adoptive-transfer tumor immunotherapy - in which endogenous Cblb is knocked down by an siRNA that is complementary to the Cblb mRNA. The immunoresponsive cells of WO 2008/033403 are used as a powerful therapeutic approach against cancer immunotherapy. WO 2008/033403 teaches that reducing Cblb renders the T cell as a “super killer” in that it responds to antigen and mounts effector function independent of any costimulation. In WO 2008/033403, tumor specificity is conferred by a native or transgenic T cell receptor.
WO 2008/033403 teaches the siRNA is delivered and stably expressed via a retroviral vector. WO 2008/033403 also teach siRNA and shRNA are functional equivalents of each other. For example, WO 2008/033403 discloses:
In certain embodiments, Cbl-b CD8+ T cells include CD8+ T cells in which the activity of Cbl-b has been reduced by any suitable agent or method known in the art, including but not limited to knock-down by use siRNA, shRNA, transfection with a dominant negative form of Cbl-b, knock out of the genomic copy of Cbl-b, are sufficient to mediate the anti-tumor responses.
Applicant is reminded that it is obvious to substitute one functional equivalent for another, particularly when they are to be used for the same purpose. Furthermore, KSR forecloses that the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. See Board Decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d). Also, see M.P.E.P. §2144.07 which states, "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06.
WO 2008/033403 does not necessarily teach that the Cblb sequence is SEQ ID NO: 612 of the present invention, however, GenBank Accession No. U26710 teaches a nucleic acid sequence represented by SEQ ID NO: 612 of the present invention was known before the effective filing date of the claimed invention.
WO 2008/033403 also does not necessarily teach that the T cells are modified to express a tumor specific T cell receptor or chimeric antigen receptor (CAR). Curran et al. teach the genetic engineering of T cells by introduction of a chimeric antigen receptor to generate tumor-targeted T cells and describes the CAR architecture in full: an antigen biding domain, a transmembrane domain and a stimulatory and co-stimulatory domain that activates the T cell upon antigen binding.
Curran et al. teaches that targets for CAR modified T cells include prostate specific membrane antigen (PSMA) for the treatment of cancer. Curran et al. also teaches expression of an antibody derived single chain variable fragment (scFv) coupled to a T cell signaling domain will redirect T cell specificity and function.
Before the effective filing date of the claimed invention, an immunoresponsive cell expressing a Cblb interfering nucleic acid was known in the art of WO 2008/033403. It would have been prima facie obvious to one of ordinary skill in the art to modify the immunoresponsive cell of WO 2008/033403 so that its tumor specificity is conferred by a CAR as taught and suggested by Curran et al., thereby arriving at the immunoresponsive cell expressing both a CAR and a Cblb shRNA of the claimed invention.
A person of ordinary skill in the art seeking to direct WO 2008/033403 Cblb knockdown “super killer” T cell against a chosen tumor antigen would look to the CAR of Curran et al. as the art-recognized means of conferring tumor specificity. Combining WO 2008/033403 Cblb-knockdown T cell with Curran’s CAR is the combination of prior art elements according to known methods to yield no more than the predictable result of a tumor-antigen specific T cell with enhanced potency and co-stimulation independence. See MPEP 2143(A). Also, see KSR Int’l Co. v. Teleflex Inc. 550 U.S. 398, 416-417 (2007).
Both WO 2008/033403 and Curran et al. address the same field of adoptive T cell immunotherapy of tumors and the same cell type (e.g. T cells), so the skilled artisan would have had a reasonable expectation of success.
The combination of the prior art of WO 2008/033403 in view GenBank Accession No. U26710 and Curran et al. renders the present claims unpatentable. Therefore, a person of ordinary skill in the art would have found the instant invention prima facie obvious.
Response to Arguments
It should be noted that a similar 35 USC § 103 rejection was made in the Office Action filed April 29, 2025. In response to that rejection, Applicants traversed and argued that WO 2008/033403 aims to solve a different technical problem than the present application since the Cbl-b-/- mice of WO 2008/033403 become susceptible to autoimmune diseases. Applicants also argue that WO 2008/033403 teaches adoptive transfer of CD8+ T cells might cause a severe autoimmune disease. Applicants submit that the skilled person, knowing the risk of developing a severe autoimmune disease by adoptive transfer of Cbl-b-/- CD8+ T cells as described in WO 2008/033403, would not be motivated to knockdown Cblb in CAR-expressing cells.
Applicants also argue that the skilled person would not have a reasonable expectation of success that CAR-expressing cells with knockdown of Cblb would be suitable for therapeutic use for treating patients in clinics given that adoptive transfer of Cbl-b-/- CD8+ T cells could impose autoimmune consequences to the host. Applicants submit that the skilled artisan would be discouraged to combine the teachings of WO 2008/033403 and Curran et al. to arrive at the presently claimed cells.
The arguments have been fully considered by the Examiner and as they relate to the new 35 USC § 103 rejection supra, they are not found persuasive because in no way does WO 2008/033403 criticize, discredit or otherwise discourage the combination of their invention with CAR. In fact, the stated aim of WO 2008/033403 is to generate more potent tumor-specific T cells for adoptive transfer. This is precisely the goal of the CAR-modified T cells of Curran et al. WO 2008/033403 whole thrust is that Cblb knockdown in CD8+ T cells are therapeutically desirable “super killers” for adoptive transfer. The objectives are the same and one would be motivated to combine since WO 2008/033403 wants better tumor-killing T cells and Curran et al. supplies the redirecting receptor. The combination serves and flows from WO 2008/033403’s own expressed purpose.
In conclusion, WO 2008/033403 affirmatively seeks tumor-specific T cells, which invites the skilled artisan to apply any art-recognized purpose of conferring tumor specificity, including the CAR of Curran et al.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title.
Claims 1-7, 11-13 and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
The claimed invention is directed to non-statutory subject matter because Section 33(a) of the America Invents Act (AIA ) reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 1-7, 11-13 and 20 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). In the present case, the claims are drawn to an immunoresponsive cell expressing a chimeric antigen receptor (CAR), wherein the cell comprises a nucleic acid that comprises a sequence encoding an shRNA, wherein the shRNA comprises 15 contiguous nucleotides complementary a nucleic acid sequence of SEQ ID NO: 612, and wherein the CAR comprises an antigen binding domain, a transmembrane domain, a stimulatory domain, and a co-stimulatory domain. Since the claims are not limited to “an isolated immunoresponsive cell”, the claims are broadly interpreted to encompass stem cells which ultimately, include a human subject. Applicant is reminded that a claim directed to or including within its scope a human being will not be considered to be patentable subject matter. Section 33(a) of the AIA clearly indicates that no patent may issue on a claim encompassing a human organism, therefore, the claim is rejected under 35 U.S.C. 101.
It is noted that amending the claims such that they are limited to “an isolated immunoresponsive cell” would obviate this rejection.
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/ Primary Examiner, Art Unit 1635
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