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 .
Priority
The instant application is a Continuation of U.S. Application Nos. 17/826,081 (filed 05/26/2022) and 17/733,875 (filed 04/29/2022), and Application PCT/GB2020/053315 (filed 12/18/2020). Acknowledgement is made of Applicants’ claim for benefit of U.S. Provisional Application Nos. 63/047,431 (filed 07/02/2020), 62/982,470 (filed 02/27/2020), and 62/951,559 (filed 12/20/2019).
Claim Interpretation
The following comments are made to establish broadest reasonable interpretation for the record.
Regarding claim 8: This claim recites the limitation “…wherein the 1 to about 20 million TILs from the first population comprises a mixture of resident and emergent T cells.” The term emergent T cell is not known in the art, and there is no clear definition provided in the instant application. The specification teaches cells that grow out of disaggregated cells will be a mixture of resident and emergent T cells, wherein cells that are obtained via outgrowth of tumor chunks will be emergent T cells (par. 00301). Emergent properties of cell populations are known in the field of biology, i.e., a function or characteristic derived from interactions or combinations of individual parts or components. But lacking any clear guidance on which properties an emergent T cell has, or indeed whether emergent even refers to a biological property in this context, the term emergent T cell is interpreted as meaning any T cell capable of proliferation and/or migration from the culturing of a primary tumor.
Regarding claim 10: This claim recites the limitation, “…wherein the TILs comprise UTILs or wherein the TILs comprise MTILs.” The terms UTILs and MTILs as they pertain to 35 U.S.C. § 112(b) is discussed below; however, in the interest of compact prosecution, the term UTIL is interpreted as an unmodified TIL, and the term MTIL is interpreted as a modified TIL. Absent a clear definition, support for this interpretation can be found in par. 00265 of the instant specification.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 8: This claim recites the limitation, “…wherein the 1 to about 20 million TILs from the first population comprises a mixture of resident and emergent T cells.” The term emergent T cell is not known in the art, and there is no clear definition provided in the instant application. The specification teaches cells that grow out of disaggregated cells will be a mixture of resident and emergent T cells, wherein cells that are obtained via outgrowth of tumor chunks will be emergent T cells (par. 00301), but this is not a clear definition or teaching. Lacking any further guidance, it would not be immediately understood by a person having ordinary skill in the art what is meant by emergent T cell; thus, the metes and bounds are not clearly and precisely defined, rendering the instant claim indefinite.
Regarding claim 10: This claim recites the limitation, “…wherein the TILs comprise UTILs or wherein the TILs comprise MTILs.” The terms UTILs and MTILs are not defined by the claim or any clear definition in the specification of the instant application; a person having ordinary skill in the art would not immediately envisage the scope of claim 10 as it pertains to these terms. Thus, the metes and bounds are not clearly and precisely defined, rendering the instant claim indefinite.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-7 and 9-15 are rejected under 35 U.S.C. 103 as being unpatentable over Chartier-Courtaud, et al. (WO 2019/210131) in view of Guest, et al. (WO 2018/130845), as evidenced by ScienCell™ Research Team (“Technical Tip for Successful Primary Cell Culture”. 2018).
Chartier-Courtaud, et al. teaches expansion of tumor infiltrating lymphocytes in a closed system (Abstract).
Guest, et al. teaches a single use aseptic kit comprising a disaggregation module for receipt and processing of solid mammalian tissue (Abstract).
Regarding claim 1: Chartier-Courtaud, et al. teaches a method for expanding tumor infiltrating lymphocytes (TILs) and producing therapeutic populations thereof (par. 0004); this reads on the method for preparing a therapeutic population of tumor infiltrating lymphocytes (TILs) limitation recited in the preamble of claim 1.
Briefly, Chartier-Courtaud, et al. teaches a method for expanding tumor infiltrating lymphocytes (TILs) and producing therapeutic populations thereof , the method comprising: (a) obtaining a first population of TILs from a tumor resected from a patient by processing a tumor sample and (b) adding tumor fragments into a closed system; (c) performing a first expansion by culturing the first population of TILs in a medium comprising IL-2 to produce a second population of TILs, wherein the first expansion is performed for about 3-14 days to obtain a second population of TILs; (d) performing a second expansion by supplementing medium with additional IL-2, OKT-3, and APCs to produce a third, therapeutic population of TILs, wherein the expansion is performed for about 7-14 days; and (e) harvesting the therapeutic population of TILs (par. 0005). Chartier-Courtaud, et al. further teaches an embodiment wherein step (f) comprises cryopreserving the therapeutic TILs (par. 0006). All steps disclosed by Chartier-Courtaud, et al. are performed in a closed system (pars. 0005-0006).
Step (c) in the method taught by Chartier-Courtaud, et al. reads on the performing a first expansion by culturing the tumor product in a cell culture medium comprising IL-2 to produce a first population of TILs limitation recited in step (b) of claim 1; step (d) reads on the performing a second expansion by culturing the first population of TILs in a cell culture medium with additional IL-2, OKT-3, and antigen presenting cells (APCs), to produce a second population of TILs limitation recited in step (c) of claim 1; step (f) reads on the cryopreserving the second population of TILs to prepare a cryopreserved therapeutic population of TILs limitation recited in step (d) of claim 1; and the closed system reads on the wherein steps are performed in a closed system limitation recited in claim 1.
Chartier-Courtaud, et al. does not explicitly teach the first expansion of TILs as within 24 hours of processing of the tumor product, as required by the remaining limitation recited in part (b) of the instant claim; nor does the disclosure teach disaggregating the tumor within the closed system, as required by the remaining limitations recited in claim 1.
Regarding performing the first expansion within 24 hours:
It would have been prima facie obvious to a person having ordinary skill in the art to have performed the first expansion of TILs in the method of Chartier-Courtaud, et al. within 24 hours, if not sooner, of processing the tumor product. This conclusion is based on the ‘teaching, suggestion, or motivation rationale’. One would be motivated to do so because, as evidenced by ScienCell™ Research Team, it is well known in the art primary cells proliferate and adapt to the artificial cell culture environment, which can alter protein expression over time (pg. 5; lines 2-3); additionally, it is well known in the art to use primary cells as early as possible to prevent genetic drift (pg. 5; line 10). Thus, a person having ordinary skill in the art would be motivated to perform the first expansion of TILs within 24 hours in order to reduce the likelihood of introducing genetic drift or altered protein expression into the cells prior to expansion, which could potentially affect the protocol’s efficacy in production and expansion of TILs.
Regarding disaggregating the tumor within the closed system:
Guest, et al. teaches a single use aseptic kit comprising a disaggregation module for receipt and processing of material comprising solid mammalian tissue (pg. 2; par. 7), wherein the kit further comprises a programmable processor adapted to communicate with and control the disaggregation module to enable a physical and enzymatic breakdown of the solid tissue (pg. 5; pars. 2-3); the enzymatic breakdown is via media enzyme solution including collagenase and deoxyribonuclease (pg. 5; par. 4). Guest, et al. teaches the physical disaggregation, which is designed to compress the tissue using variable time and speed, may be from a few seconds to several hours, until the tissue is a liquid cell suspension (pg. 8; par. 2). This reads on the aseptically disaggregating a tumor resected from a subject thereby preparing a disaggregated tumor product, wherein the disaggregation comprises repeated physical pressure in the presence of a media enzyme solution, wherein the tumor is sufficiently disaggregated into a cell suspension so that the disaggregated tumor product can be subjected to a cell culture process limitation recited in step (a) of claim 1.
Guest, et al. does not explicitly teach the repeated physical pressure applied 120 to 360 times per minute at up to 6 N/cm² as required by the remaining limitation recited in step (a) of claim 1. However, the frequency and force of the physical pressure for the disaggregation step would have been routinely optimized by a person having ordinary skill in the art based on the cell culture conditions. Guest, et al. teaches the disaggregation is designed to compress the tissues using a variable speed and time depending upon the time taken to disaggregate as well as feedback via sensor within the disaggregation module (pg. 8; par. 2); thus, Guest, et al. teaches the conditions necessary to achieve sufficient disaggregation were result effective variables. Result effective variables would be optimized by routine experimentation by one having ordinary skill in the art. See MPEP 2144.05(II)(A). This renders obvious the remaining limitations recited in step (a) of claim 1.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Chartier-Courtaud, et al. by using the single use aseptic kit comprising a disaggregation module taught by Guest, et al. for the processing of the tumor sample of steps (a) and (b). This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’. One would be motivated to do so because, as disclosed by Guest, et al., an advantage of the single use aseptic kit comprising a disaggregation module is that solid tissue disaggregation can be performed in a closed system, i.e., an aseptic process with minimal risk of contaminations for subsequent cell culture processes (pg. 4; par. 8). Further, Guest, et al. teaches the final cellular material can be used for adoptive cell therapies, e.g., therapeutic TILs (pg. 6; par. 6); thus, a person having ordinary skill in the art would have more than a reasonable expectation of success.
Regarding claim 2: Following the above discussion, Guest, et al. teaches the physical disaggregation is designed to compress the tissue (pg. 8; par. 2); this reads on the wherein the resected tumor is not fragmented prior to disaggregation limitation recited in claim 2.
Regarding claim 3: Following the above discussion, the media enzyme solution comprising collagenase and deoxyribonuclease (pg. 5; par. 4) of Guest, et al. reads on the wherein the media enzyme solution comprises DNase and Collagenase limitation recited in the instant claim.
Regarding claim 4: Following the above discussion, Guest, et al. teaches removing the disaggregated tissues, associated material, and impurities by passing the disaggregated tissue and media through one or more filters (pg. 8; par. 3); further disclosed in Fig. 1 is an embodiment wherein after disaggregation, the disaggregated tissue is transferred via tubing (labeled 1h) into a filter unit (labeled 4a) via an attached filter (labeled 4b) (pg. 13; Fig. 1). This reads on the wherein the disaggregated tumor product is filtered by an in-line filter prior to the first expansion limitation recited in claim 4.
Regarding claims 5-6: Following the above discussion, Guest, et al. teaches an embodiment wherein the disaggregated tissue passes through a filter with 100 µm holes (pg. 8; par. 3); this reads on the wherein the filtered disaggregated tumor product constituents have an average size of less than 200 µm limitation recited in claim 5, as well as the wherein the filtered disaggregated tumor product constituents have an average size of less than 170 µm limitation recited in claim 6.
Regarding claim 7: Following the above discussion, Chartier-Courtaud, et al. teaches an embodiment wherein the second expansion is performed in T-175 flasks, wherein 1 x 106 TILs suspended in 150mL of media are added to each T-175 flask (par. 00421); this reads on the wherein the performing a second expansion by culturing the first population of TILs is performed on about 1 million TILs from the first population limitation recited in claim 7.
Regarding claim 9: Following the above discussion, Guest, et al. does not explicitly teach the disaggregation period as 90 minutes or less, as required by the limitations recited in the instant claim. However, Guest, et al. teaches the physical disaggregation may be from a few seconds to several hours until the tissue is a liquid cell suspension (pg. 8, par. 2), which encompasses the time period of the instant claim. Further, the duration of the disaggregation step would have been routinely optimized by a person having ordinary skill in the art based on the cell culture conditions. Guest, et al. teaches the disaggregation is designed to compress the tissues using a variable speed and time depending upon the time taken to disaggregate as well as feedback via sensor within the disaggregation module (pg. 8; par. 2); thus, Guest, et al. clearly teaches the conditions necessary to achieve sufficient disaggregation were result effective variables. Result effective variables would be optimized by routine experimentation by one having ordinary skill in the art. See MPEP 2144.05(II)(A). This renders obvious the remaining limitations recited in claim 9.
Regarding claim 10: Following the above discussion, Chartier-Courtaud, et al. teaches TIL cell population can include genetically modified TILs (par. 00225); this reads on the wherein the TILs comprise MTILs limitation recited in the instant claim.
Regarding claim 11: Following the above discussion, Chartier-Courtaud, et al. teaches an embodiment wherein the second expansion is shortened to 7 to 14 days, and includes processes referred to as rapid expansion (par. 00373); this reads on the wherein the second expansion comprises a rapid expansion limitation recited in claim 11.
Regarding claim 12: Following the above discussion, Chartier-Courtaud, et al. teaches an embodiment wherein the first TIL expansion can proceed for 14 days (par. 00399), and wherein the second TIL expansion can proceed for 14 days (par. 00410); this reads on the wherein the first expansion is performed over about two weeks; and the second expansion is performed over about two weeks limitation recited in claim 12.
Regarding claim 13: Following the above discussion, Chartier-Courtaud, et al. teaches an embodiment wherein the first TIL expansion can proceed for 14 days (par. 00399), and wherein the second TIL expansion can proceed for 7 days (par. 00410); this reads on the wherein the first expansion is performed over about two weeks; and the second expansion is performed over about 7 days limitation recited in claim 13.
Regarding claim 14: Following the above discussion, Chartier-Courtaud, et al. teaches an embodiment wherein the first expansion further employs a combination of IL-7, IL-15, and IL-21 (par. 00400), as well as an embodiment wherein the second expansion further employs a combination of IL-7, IL-15, and IL-21 (par. 00414); this reads on the wherein the media in the culturing in the first expansion and/or the second expansion further comprises IL-7, IL-15, and IL-21 limitation recited in claim 14.
Regarding claim 15: Following the above discussion, Chartier-Courtaud, et al. teaches the antigen-presenting cells may be artificial antigen-presenting cells (par. 00110); this reads on the wherein the APCs are artificial APCs limitation recited in claim 15.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Chartier-Courtaud, et al. (WO 2019/210131) in view of Guest, et al. (WO 2018/130845), further in view of Webb, et al. (Clin Cancer Res. 2014); as evidenced by ScienCell™ Research Team (“Technical Tip for Successful Primary Cell Culture”. 2018).
The teachings of Chartier-Courtaud, et al. and Guest, et al. are set forth above.
Webb, et al. teaches CD103+ tumor infiltrating lymphocytes in primary ovarian tumors (Abstract).
Regarding claim 8: Following the above discussion, the modified method of Chartier-Courtaud, et al. does not explicitly teach the limitations recited in the instant claim.
However, Webb, et al. teaches CD103 is a marker of tissue-resident memory CD8+ T cells (pg. 435; col. 1, par. 1); CD103+ TILs are detectable in high-grade serous ovarian cancer tumors of all stages and grades (pg. 438; col. 1, par. 1). Webb et al. further teaches CD103+CD8+ TILs are primarily responsible for improved prognosis in high-grade serous ovarian cancer, CD103+ TILs are found to have a highly activated, cytolytic phenotype, and that CD103+ TILs included CD8+ T cells in an analysis of primary tumor samples from patients (pg. 441, pars. 1-2).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Chartier-Courtaud, et al. by using tumor samples from high-grade serous ovarian cancer patients for TIL expansion. This modification would result in the TILs from the first population comprising tissue-resident memory CD103+CD8+ T cells, as taught by Webb, et al., which reads on the resident T cell limitation recited in the instant claim; additionally, the tumor sample would necessarily comprise T cells capable of proliferation and/or migration (i.e., outgrowth) from the primary tumor, which reads on the emergent T cell limitation recited in the instant claim. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’; one would be motivated to do so because Webb, et al. teaches TILs as effector cells for immunotherapy (pg. 443; col. 2, par. 1). Further, as Chartier-Courtaud, et al. teaches TIL expansion from a tumor resected from a patient (par. 0005), one skilled in the art would have more than a reasonable expectation of success.
Therefore, the limitations recited in claim 8 are rendered obvious.
Claims 16 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Chartier-Courtaud, et al. (WO 2019/210131) in view of Guest, et al. (WO 2018/130845), further in view of Imai, et al. (Eur J Immunol. 2009); as evidenced by ScienCell™ Research Team (“Technical Tip for Successful Primary Cell Culture”. 2018).
The teachings of Chartier-Courtaud, et al. and Guest, et al. are set forth above.
Imai, et al. teaches IFN-γ and TNF-α production and CD107a mobilization in adoptively transferred tumor-antigen-specific CD8+ T cells (Abstract).
Regarding claims 16, 20: Following the above discussion, Chartier-Courtaud, et al. teaches the cell culture medium may further comprise a 4-1BB agonist during the first expansion, second expansion, or both (par. 0045); the disclosure does not explicitly teach identifying in the second population of TILs the presence of T cells expressing 4-1BB (i.e., CD137). However, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Chartier-Courtaud, et al. by incorporating a step wherein T cells expressing 4-1BB are identified. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’; Chartier-Courtaud, et al. expressly teaches use of a 4-1BB agonist, thus one would be motivated to select cells appropriately reactive to said agonist, i.e., cells expressing 4-1BB/CD137. Additionally, Chartier-Courtaud, et al. teaches the method may further comprise a step wherein TILs are selected for superior tumor reactivity, wherein any selection method known in the art may be used (par. 00424); as selection methods such a flow cytometry are well-known in the art, one would have a reasonable expectation of success.
Thus, the modified method of Chartier-Courtaud, et al. teaches an embodiment wherein the presence of T-cells expressing marker CD137 is identified in the second population of TILs; it does not teach the remaining markers recited in the instant claims.
However, Imai, et al. teaches IFN-γ and TNF-α are important as effector cytokines in immunosurveillance and anti-tumor immune responses in T cells, and CD107a mobilization on these cells as a marker of cytolytic granule degranulation (pg. 242; col. 2, par. 2); therefore, the function of effector CD8+ T cell was monitored using these three biomarkers (pg. 242; col. 1, par. 2). Imai, et al. teaches T cells expressing all three biomarker exhibit superior cytokine secretion and cytolytic degranulation than T cells with only two of the three biomarkers, suggesting a better anti-tumor response in vivo (pg. 243; col. 2, par. 3).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Chartier-Courtaud, et al. by identifying the presence of T cells expressing markers CD107a, TNF-α, and IFN-γ, as taught by Imai, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’. One would be motivated to do so for the reasons disclosed by Imai, et al.; namely, cytokine secretion, cytolytic degranulation, and a better anti-tumor response in vivo. Further, as set forth above, Chartier-Courtaud, et al. teaches the method may further comprise a step wherein TILs are selected for superior tumor reactivity, wherein any selection method known in the art may be used (par. 00424); as selection methods such a flow cytometry are well-known in the art, one would have a reasonable expectation of success.
Thus, the limitations recited in claims 16 and 20 are rendered obvious.
Claims 21 and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Chartier-Courtaud, et al. (WO 2019/210131) in view of Guest, et al. (WO 2018/130845), further in view of Imai, et al. (Eur J Immunol. 2009) and Zhu, et al. (ACS Chem Biol. 2006); as evidenced by ScienCell™ Research Team (“Technical Tip for Successful Primary Cell Culture”. 2018).
The teachings of Chartier-Courtaud, et al., Guest, et al., and Imai, et al. are set forth above.
Zhu, et al. teaches mechanisms of cellular avidity regulation in CD2-CD58-mediated T cell adhesion (Title).
Regarding claims 21, 25-26: Following the above discussion, the modified method of Chartier-Courtaud, et al. does not teach the T cells expressing the combination of markers as CD2+ T cells.
However, Zhu, et al. teaches the CD2 receptor on T lymphocytes is essential for T cell adhesion and stimulation by antigen-presenting cells (APCs), and that blockade of CD2 function is immunosuppressive in vitro and in vivo (Abstract).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Chartier-Courtaud, et al. by including CD2 as a selection marker for the TILs, in addition to the markers of 4-1BB (i.e., CD137) as taught by Chartier-Courtaud, et al. and CD107a, TNF-α, and IFN-γ, as taught by Imai, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’. One would be motivated to do so for the strengthened T cell-APC adhesion and enhanced CD2 avidity disclosed by Zhu, et al. Further, as set forth above, Chartier-Courtaud, et al. teaches the method may further comprise a step wherein TILs are selected for superior tumor reactivity, wherein any selection method known in the art may be used (par. 00424); as selection methods such a flow cytometry are well-known in the art, one would have a reasonable expectation of success.
Thus, the limitations recited in claims 21 and 25-26 are rendered obvious.
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 1-16, 20-21, and 25-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 13-14 of U.S. Patent No. 11,767,510, in view of Chartier-Courtaud, et al. (WO 2019/210131) and Guest, et al. (WO 2018/130845).
The teachings of Chartier-Courtaud, et al. and Guest, et al. are set forth above.
Claims 1-4 of U.S. Patent No. 11,767,510 are drawn to a method of identifying potent T cells in a population of TILs, comprising identifying in an isolated and expanded ex vivo population of TILs from a subject’s cancer tissue the presence of T cells expressing markers CD107a, CD137, TNF-α, and IFN-γ; wherein the population of TILs has undergone disaggregation; wherein the identifying comprises intracellular staining and flow cytometry. Patented claims 5-8 further narrow the scope of the previous claims by specifying the T cells as CD2+ T cells. Patented claims 13-14 specify the population of TILs for treating cancer in a subject.
The two main differences between U.S. Patent No. 11,767,510 and the claims of the instant application is the instant claims require disaggregation of a tumor, and that all steps are performed in a closed system. However, disaggregation of the tumor and performing TIL expansion in a closed system would have been prima facie obvious to a person having ordinary skill in the art.
Regarding the specific expansion steps set forth in claim 1:
It would have been prima facie obvious to a person having ordinary skill in the art to have used the method taught by Chartier-Courtaud, et al. set forth above for the rapid expansion protocol in the method of U.S. Patent No. 11,767,510. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’; one would have been motivated to do so because the method for expanding TILs and producing therapeutic populations thereof taught by Chartier-Courtaud, et al. leads to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a short time period while allowing for reduced contamination risk, as disclosed by the same (Abstract). One skilled in the art would have a reasonable expectation of success in doing so, as well, as both disclosure teach similar expansion protocols in TIL populations isolated from primary tumor samples.
Regarding the disaggregation step within the closed system:
It would have been prima facie obvious to a person having ordinary skill in the art to have used the single use aseptic kit comprising a disaggregation module taught by Guest, et al. for the processing of the tumor sample because, as disclosed by Guest, et al., an advantage of the single use aseptic kit comprising a disaggregation module is that solid tissue disaggregation can be performed in a closed system, i.e., an aseptic process with minimal risk of contaminations for subsequent cell culture processes (pg. 4; par. 8). One skilled in the art would have a reasonable expectation of success in doing so, as well, as Guest, et al. teaches the final cellular material can be used for adoptive cell therapies, e.g., therapeutic TILs (pg. 6; par. 6).
Therefore, the modified method of claims 1-4 of U.S. Patent No. 11,767,510 as set forth above renders obvious the limitations recited in instant claims 1-16 and 20.
As set forth above, patented claims 5-8 specify the T cells as CD2+ T cells. Thus, following the same modifications as set forth above, the modified method of claims 5-8 of U.S. Patent No. 11,767,510 renders obvious the limitations recited in instant claims 21 and 25.
As set forth above, patented claims 13-14 specify the population of TILs for use in a method of treating cancer in a subject. One skilled in the art would have a reasonable expectation of success in doing so, as Chartier-Courtaud, et al. teaches administering a therapeutically effective dose of the TILs to a patient with cancer (par. 0065); thus, the modified method of claims 13-14 of U.S. Patent No. 11,767,510 renders obvious the limitations recited in instant claim 26.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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, CHRISTOPHER BABIC can be reached at (571)272-8507. 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.
/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633