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 .
Claim Status
Claims 1, 31, 34-38, 40-48 and 50-52 are pending. Claims 31, 34-38 and 51 are withdrawn. Claims 1, 40-48, 50 and 52 are rejected.
Response to Amendment/Arguments
Applicant’s amendments have overcome the previously presented rejections. Arguments pertaining to grounds of rejection other than those set forth below will not be addressed.
Applicant traverses the rejection of claim 43 and its dependent claims stating that the present invention “is based in part on the observation that high dose administration of glucocorticoids can produce, activate, and/or mobilize a novel subpopulation of natural killer T cells in a subject.” However, the mobilization of the NKT cells is an effect that would flow naturally from following the combined method of Deisher, Chaudary, and Pillai as set forth below wherein the claimed dose of dexamethasone base overlaps with claimed range. Applicant further argues that the Deisher disclosure relates to a different problem directed to enhancing ACT via lymphodepeletion and would only suggest that high dose glucocorticoids have beneficial benefits against cancer by enhancing co-administered adoptive cellular theory. Applicant references Examples 3, 15, 17, and 18 to support that the claim that in the instant method the population of NKT cells can directly treat the claimed cancers. Even if Applicant’s mobilized population of cells were a previously unrecognized benefit in the treatment, the instant claims are generic to methods of treatment which may include intermittent steps such as isolating the NKT cells from the subject, transforming the cells, and administering them back to the subject to ultimately treat the cancer. The disclosure of Deisher may not suggest that the claimed dose of GC directly treats the claimed cancers directly however the extended process is disclosed by Deisher, Pillai, and Chaudhary wherein Pillai and Chaudhary specifically disclose the treatment of solid cancers not excluded in amended claim 43. Claims 1, 40-48, 50 and 52 are rejected in view of Deisher, Pillai et al. and Chaudhary as set forth below.
Election/Restrictions
As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicant’s elected combination is not allowable under 35 USC 103. Therefore, examination has been limited to claims embracing the elected species which are claims 1, 40-48, 50, and 52. Claims 1, 40-48, 50, and 52 have been examined to the extent that they are readable on the elected embodiment. Subject matter not embraced by the elected embodiment is therefore withdrawn from further consideration. Any subject matter discussed beyond the scope of this has been presented in the interest of compact prosecution.
Claims 31, 34-38 and 51 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 40-48, 50 and 52 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018183927 A1 by Deisher cited in the IDS filed 10/23/2025. in view of WO 2015112793 A2 by Pillai et al. and WO 2020028444 A1 by Chaudhary.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
The prior art teaches “replacement of cytotoxic preconditioning before cellular immunotherapy” (title) and discloses a method of “enhancing adoptive cellular therapy (ACT) in a patient, by administering to the patient a non-toxic lymphodepleting agent (NTLA) at a dose that is effective to cause substantial lymphodepletion and/or cause ablation of secondary lymphatic germinal centers” (paragraph [0013]).
Regarding instant claims 1, 40, 43, and 46, the prior art discloses dexamethasone, prednisolone, methylprednisolone, dexamethasone sodium phosphate and betamethasone as suitable a NTLA (paragraph [0063]).
Regarding claims 1, 40, and 47, Deisher teaches that dexamethasone may be administered at a dose of at least about 6 mg/kg to at least about 26 mg/kg (paragraph [0017]).
Regarding instant claim 40, the prior art states “[t] he desired in vivo effects of exemplary NTLAs would include reductions in germinal center and marginal zones in secondary lymphatics, direct tumor killing of some cancers particularly; multiple myeloma, renal cell carcinoma, leukemia and lymphoma, non-small cell lung cancer (NSCLC), prostate and breast cancer” (paragraph [0066]). Accordingly, a person of ordinary skill would have been motivated to administer the glucocorticoid to subjects with solid tumor cancers such as NSCLC, prostate or breast cancer.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Deisher discloses a method of treating cancer comprising administering a glucocorticoid at a dose equivalent to at least 6 mg/kg (HED); however, the prior art does not teach that this method induces or mobilizes a population of natural killer T cells with particular cell markers or that the method is useful for treating solid cancers other than renal cell carcinoma, non-small cell lung cancer, prostate cancer or breast cancer. Furthermore, Deisher does not suggest isolating a population of NKT cells from the subject.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Deisher discloses an aspect of the invention which provides a method of performing adoptive cellular therapy (ACT) in a patient in need thereof, said method comprising performing a method of enhancing ACT by pretreating the patient with a nontoxic lymphodepleting agent such as dexamethasone and then performing the ACT by administering therapeutic cells to the patient (paragraph [0015]). Deisher provides a list of cell types that may be used for cellular immunotherapy including “T-cell Natural Killer cells” (paragraph [00217]).
Pillai et al. teach (title) “[m]ethods of expanding ex vivo natural killer t (NKT) cells and therapeutic uses thereof.” The prior art discloses that the NKT cells have therapeutic uses for treatment of cancers such as lymphomas, leukemias, pancreatic cancer, liver cancer, various sarcomas, etc. in accordance with instant claims 40 and 43 (pages 1 and 23). Regarding instant claims 1 and 42, Pillai et al. specify that the method for expanding NKT cells comprises steps of harvesting the cells from a subject, stimulating the harvested NKT cells, purifying the stimulated NKT cells and expanding the purified NKT cells (page 8). Additionally, Pillai states that the cells are introduced back into the same or different subject after expanding the cells.
Chaudhary teaches a method for “improving the efficacy and safety of adoptive cellular therapies” (title) and states that the method is for treatment of cancers including chronic myelogenous leukemia, pancreatic cancer, ovarian cancer, etc. (paragraphs [0037] and [00525]). The prior art teaches the following in paragraph [0007]:
The disclosure [is] related to improving the yield, expansion, activation, proliferation, expansion, diversity, tissue (e.g., tumor) penetrance, persistence and efficacy of immune cell therapies, such as engineered CAR-T, TCR-T, SIR-T, Ab-TCR-T cell therapies or NK cell therapies, by using mobilized immune cells for the manufacturing of cell therapy products. In various embodiments, the method involves mobilizing immune cells prior to collection of immune cells (e.g. leukopheresis) from the donor. In various embodiments, the immune cells are mobilized by administrating to the donor from whom the immune cells are harvested a CXCR antagonist ( e.g ., Mozibil or Plerixafor), a cytokine (e.g., G-CSF, GM-CSF or sargramostim, Neulasta or Pegfilgastrim), a beta2 adrenergic agonist (e.g., epinephrine), a tyrosine kinase inhibitor (e.g., dasatinib), chemotherapy drug(s) (e.g., cyclophosphamide, doxorubicin) or a combination of the above agents prior to the collection of immune cells.
Chaudhary et al. teach that the immune cells may include natural killer T cells (paragraph [0058]). However, in the method of Deisher, dexamethasone rather than a chemotherapy is administered as a lymphodepleting agent to mobilize the immune cells.
Regarding instant claims 1 and 41, Chaudhary discloses an aspect of the invention wherein a mobilizing agent is administered and the immune cells, such as NKT cells, are collected from the subject about 96 hours after administration of the agent (paragraph [00201]). Chaudhary further teaches that the immune cells can be obtained from the blood collected from the subject, washed to remove the plasma, and subjected to subsequent processing steps, for example the prior art discloses isolating T cells from peripheral blood lymphocytes (paragraphs [00242] and [00243]). Regarding instant claims 48 and 52, Chaudhary et al. teach an embodiment wherein the cells are activated and/or expanded in vitro under culture conditions that include cytokines such as IL-7, IL-15, etc. (paragraph [00218]).
Accordingly, a person of ordinary skill seeking to improve the method of adoptive cellular therapy disclosed by Deisher would have been motivated to expand and/or stimulate the NKT cells harvested from the subject and to test the treatment in subjects with other solid cancers, to include pancreatic cancers, sarcomas, etc. as taught by Pillai et al. Furthermore, a person of ordinary skill would be motivated to modify the method of Deisher and Pillai et al. to include a step of isolating the NKT cells harvested from the subject after administering the mobilizing or lymphodepleting agent as taught by Chaudhary in order to improve the efficacy of the adoptive cellular therapy.
Regarding the intended use of “producing a population of NKT cells” in claim 1 or the limitation from claim 43 which introduces the objective to produce or mobilize a population of NKT cells in a subject wherein the NKT cells treat the subject’s disease, these statements do not distinguish the instant claims from the prior art method which teaches the active step of administering a glucocorticoid at a dose equivalent to at least 6 mg/kg (HED). The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
The same rationale applies to instant claim 50 which requires that the population of NKT cells: treat the cancer via tumor infiltration; promote infiltration of other immune cells into the tumor; directly kill cancer cells via CD1d-directed apoptosis; and/or treat the cancer by causing tumor necrosis.
Instant claims 1, 40, and 44-45 include limitations regarding specific cell markers of the NKT population produced from administering the dose of glucocorticoid, however this aspect of the claims is another advantage which would flow naturally from following the suggestion of the prior art wherein the method of Deisher, Pillai et al. and Chaudhary teach the active step of administering the glucocorticoid dexamethasone in the appropriate dose that is required to achieve the claimed effect.
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.
Claims 1, 40-48, 50 and 52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11219628 in view of WO 2018183927 A1 by Deisher, WO 2015112793 A2 by Pillai et al. and WO 2020028444 A1 by Chaudhary.
Claims 1 and 8 of the patent disclose a method of enhancing adoptive cellular therapy in a human patient suffering from cancer comprising administering a dose of dexamethasone between 5-26 mg/kg which serves as the basis of a rejection under 35 USC 103. The teachings and rationale of
Deisher, Pillai et al. and Chaudhary relative to instant claims 1, 40-48, 50 and 52 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of the patent for the same reasons as under 35 USC 103.
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 ASHLI A CHICKS whose telephone number is (571)270-0582. The examiner can normally be reached M-Th 7 a.m.- 5 p.m..
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, James H Alstrum-Acevedo can be reached at (571)272-5548. 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.
/A.A.C./Examiner, Art Unit 1626
/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626
