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 .
Priority
The instant application 17/312,144 filed on 05/04/2023 claims priority to the US Provisional application 63/338,788 filed on 05/05/2022. The instant application will be examined with an effective priority date of 05/05/2022.
Status of the Claims/Application
Claims 2-7 are cancelled. Claim 1 is currently amended. Claims 21-27 are new. Claims 1 and 8-27 are currently pending and are under examination herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/10/2023, 06/06/2024 and 10/23/2025 are acknowledged and are in compliance with the provisions of CFR 1.97. They have been considered by the examiner.
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.
Claims 1, 9-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2020/0181573 A1 herein further referred to as Rosen.
Regarding claim 1, Rosen teaches a method for modulating immune cells for adoptive therapies by contacting the immune cells population with an agent wherein the immune cells increase expansion, increased number or relative ratio of one or more desired cell subpopulations (Rosen para 0180-0181). Rosen further teaches a method where in T cells where activated on day 0 using anti-CD3/anti-CD28 beads, and then transduced on day 1 with CAR construct (Rosen Fig. 2) in the presence of vehicles, TWS119 or DCC-2036 (Bcr-Abl tyrosine kinase inhibitor) (Rosen Tab. 1) and then on day 4 the cells are transferred into 6-well plates and then on day 8 the cells were analyzed on a flow cytometry for surface expression of phenotypic markers and exhaustion markers (Rosen para 0217). Rosen further teaches the experimentation of effects of several immune cell modulation agents on the expansion of CD4+ and CD8+ cells (Rosen 0218). Rosen also teaches that the T cell can be transduced with a viral vector such as adeno virus, plasmid vector, retrovirus, lentivirus comprising the polynucleic acids of interest (Rosen 0148).
Regarding claim 9, and incorporating the analysis of claim 1 above, Rosen teaches that the tyrosine kinase inhibitors that can be sued for the manufacture of the modified T cell population can be selected from a group comprising dasatinib and bosutinib (Rosen para 0012).
Regarding claim 10, and incorporating the analysis of claim 1 above, Rosen teaches that the concentration of the TKi is between about 0.1 nM to about 5 nM , is between about 1 nM to about 100 nM , is between about 50 nM to about 250 nM , between about 100 nM to about 500 nM , between about 250 nM to about 1 uM , between about 500 nM to about 5 uM , between about 3 uM to about 10 uM , between about 5 uM to about 15 uM , between about 12 uM to about 20 uM , or between about 18 uM to about 25 UM , or any range in-between (Rosen para 0184).
Regarding claims 11- 13, and incorporating the analysis of claim 1 above, Rosen teaches that the T cells where activated from day 0 to day 1 (1day), transduced from day 1 to day 4 (4 days) and expanded from day 4 to day 8 (5 days) (Rosen para 0217).
Regarding claims 14- 15, and incorporating the analysis of claim 1 above, Rosen further teaches that the T cells were activated in the presence of IL-2 (Rosen para 0217).
Regarding claims 16- 17, and incorporating the analysis of claim 1 above, Rosen further teaches a composition comprising a population T cells obtained from the method above (Rosen para 0153).
Regarding claims 18, and incorporating the analysis of claim 1 above, Rosen further teaches that the composition comprising the modified population of T cells can further comprises a modulating agent such as GM-CSF, interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-12 (IL-12), interleukin-15 (IL-15), interleukin-18 (IL-18), interleukin-21 (IL-21) (Rosen para 0145) or an additive selected from a group comprising a chemotherapeutic agent such as cyclophosphamide, bevacizumab, interferon-alpha, interferon-beta or a combination thereof (Rosen para 0151).
Regarding claims 19-20, and incorporating the analysis of claim 1 above, Rosen teaches a method for treating and/or eliciting an immune response by administering a composition comprising the modulated T cell population (Rosen para 0195) to a patient having cancer cush as chronic or acute leukemia, myelogenous leukemia, cancer of the brain , prostate cancer, breast cancer, lung cancer, colon cancer, uterus cancer, liver cancer, pancreatic cancer, ovarian cancer and kidney cancer (Rosen para 0197).
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.
Claims 8 and 21-26 are rejected under 35 U.S.C. 103 as being obvious over Rosen as applied to claim 1 above, and further in view of Wu et al. Dasatinib promotes the potential of proliferation and antitumor responses of human γδT cells in a long-term induction ex vivo environment. Leukemia 28, 206–210 (2014), herein after referred to as Wu.
Regarding claims 8 and 21-25, Rosen teaches a method for modulating immune cells for adoptive therapies by contacting the immune cells population with an agent wherein the immune cells increase expansion, increased number or relative ratio of one or more desired cell subpopulations (Rosen para 0180-0181). Rosen further teaches a method where in T cells where activated on day o using anti-CD3/anti-CD28 beads, and then transduced on day 1 with CAR construct (Rosen Fig. 2) in the presence of vehicles, TWS119 or DCC-2036 (Bcr-Abl tyrosine kinase inhibitor) and then on day 4 the cells are transferred into 6-well plates and then on day 8 the cells were analyzed on a flow cytometry for surface expression of phenotypic markers and exhaustion markers (Rosen para 0217). Rosen further teaches the experimentation of effects of several immune cell modulation agents on the expansion of CD4+ and CD8+ cells (Rosen 0218). Rosen also teaches that the T cell can be transduced with a viral vector such as adeno virus, plasmid vector, retrovirus, lentivirus comprising the polynucleic acids of interest (Rosen 0148).
Rosen does not specifically teaches a method wherein the activating is performed in the presences of the TKI and the transducing and expanding are performed in the absence of the TKi, or the activating and the transducing are performed in the presence of the TKI and the expansion is performed in the absence of the TKi, or the activating and expanding are performed in the presence of the TKi and the transducing is performed in the absence of the TKi, or the transducing and expansion are performed in the presence of the TKi and the activating is performed in the absence of the TKi or the activating, transducing and expansion are performed in the presence of the TKi.
Wu teaches on the effects of the presence of TKis such as dasatinib on the yield and effector functions of ex vivo expanded human T cells (Wu Abstract). Wu also teaches that during T cell induction, PBMCs were treated with DMSO control, imatinib (5 and 0.6 uM), nilotinib (3.6 and 30 nM) and dasatinib (200 and 10 nM) separately corresponding to 50% inhibiting concentrations (IC50, related to inhibitory capacity towards the ABL kinase), and plasma peak levels reached in patients of either compound. DMSO and different concentrations of drugs/compounds were added from day 1 and supplemented every 3 days, the cells were cultured for 12 days and then used for functional analysis including proliferation, activation, apoptosis/necrosis induction, degranulation and phenotype. Wu teaches that dasatinib at IC50 was able to increase the absolute number of T cells while maintaining an ideal induced purity, as well as dasatinib enhanced the expression of activation-associated molecules CD69 and human leucocyte antigen-DR (Wu pg.207 col 1-2 and Fig. 1).
Therefore, it would have been obvious before the effective filing date for a skilled artisan to modify the method of Rosen in view of Wu with a reasonable high degree of predictable success to perform routine experimentation to obtain the desired population of modified T cells where T cells activation, transduction and/or expansion or a combination thereof is carried out in the presence or absence of the TKi. As indicated by Wu the activation of T cells and the number of expanded cells in the presence of dasatinib during activation and expansion depends on the dose of the TKi (optimal dose at 10 nmol/l in vitro for dasatinib) (Wu pg. 209 col 1) and the number of days in culture for the activation and expansion steps. Therefore, a skilled artisan would have been able to perform routine experimentation by modifying the teachings of Rosen in view of Wu to identify the effects of dasatinib of the activation, transduction and expansion steps in order to determine the optimal dosage and steps required for the use of dasatinib during activation, transduction and/or expansion of the modified T cells population.
Regarding claim 26, and incorporating the analysis of claims 1 and 9 above, Wu teaches that the tyrosine kinase inhibitors to be dasatinib (Rosen para 0012).
Claim 27 is are rejected under 35 U.S.C. 103 as being unpatentable over Rosen above, and further in view of Wang et al Histone Deacetylase Inhibitors and IL21 Cooperate to Reprogram Human Effector CD8+ T Cells to Memory T Cells. Cancer Immunol Res. 2020 Jun;8(6):794-805, herein further referred to as Wang.
Regarding claim 27, Rosen teaches a method for modulating immune cells for adoptive therapies by contacting the immune cells population with an agent wherein the immune cells increase expansion, increased number or relative ratio of one or more desired cell subpopulations (Rosen para 0180-0181). Rosen further teaches a method where in T cells where activated on day 0 using anti-CD3/anti-CD28 beads, and then transduced on day 1 with CAR construct (Rosen Fig. 2) in the presence of vehicles, TWS119 or DCC-2036 (Bcr-Abl tyrosine kinase inhibitor) (Rosen Tab. 1) and then on day 4 the cells are transferred into 6-well plates and then on day 8 the cells were analyzed on a flow cytometry for surface expression of phenotypic markers and exhaustion markers (Rosen para 0217). Rosen further teaches the experimentation of effects of several immune cell modulation agents on the expansion of CD4+ and CD8+ cells (Rosen 0218). Rosen also teaches that the T cell can be transduced with a viral vector such as adeno virus, plasmid vector, retrovirus, lentivirus comprising the polynucleic acids of interest (Rosen 0148).
Wang teaches that HDACi can be used in combination with IL-21 in vitro for the generation of highly persistent T cell populations that can augment the efficacy of adoptively transferred T cells (Wang Abstract).
Therefore, it would have been obvious before the effective filing date for a skilled artisan to modify the teachings of Rosen in view of Wang with a reasonable degree of predictable out come to use HDACi in place of the agents (including the TKi agents) thought by Rosen for the manufacturing of the modified T cell population. As indicated by Wang HDACi (Panobinostat) _ IL-21 expanded CD8+ T cells had enhanced proliferation in response to IL-2 and IL15 in vitro and will proliferate, persist and exert their tumor killing function well in vivo after transfusion to patients, leading to enhanced patient response (Wang pg. 804 col 1 para 3). Therefore, a skilled artisan would have been motivated to use an HDACi (Panobinostat) in place of the agents or TKis used by Rogen for the manufacture of the modified T cell population so as to improve in vivo proliferation, persistence and ability to kill tumor cells.
.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMMANUEL LED YOUTCHOM PENDIE whose telephone number is (571)272-6313. The examiner can normally be reached Mon - Fri: 8AM - 5PM CST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanna Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/EMMANUEL LED YOUTCHOM PENDIE/ Examiner, Art Unit 1647
/JOANNE HAMA/ Supervisory Patent Examiner, Art Unit 1647