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 1-124 have been cancelled; claim 148 has been amended; and, claims 149-151 have been newly added, as requested in the amendment filed on 01/30/2026. Following the amendment, claims 125-151 are pending in the instant application.
Claims 125-151 are under examination in the instant office action.
Priority - Updated
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claims 125-151 have an effective filing date of August 31, 2018 corresponding to PRO 62/725,976.
Claim Rejections - 35 USC § 112 - New as Necessitated by Amendment
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 149-151 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.
With regard to claim 149, the claim is drawn to the method of claim 125 further comprising steps (a)-(f) as recited. As currently presented, it is unclear as to how the additional steps recited in claim 149 are meant to modify the method of claim 125. As currently presented, it is unclear if steps (a)-(f) of claim 149 are to occur prior to or after the method of claim 125. In other words, it is unclear as to if the therapeutically effective population of TILs administered in the method of claim 125 are obtained via steps (a)-(f) of claim 149 or if after performing the method of claim 125 the steps of (a)-(f) of claim 149 are carried out for a second round of treatment with therapeutically effective TILs. Applicant should amend the claim such that it is clear how claim 149 is intended to modify the method of claim 125.
For the purposes of examination, claim 149 is being interpreted such that the therapeutically effective population of TILs administered in the method of claim 125 are obtained via steps (a)-(f) of claim 149.
Claim Rejections - 35 USC § 103 - Maintained
Claims 125, 132-142, and 147-148 stand as rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0052530 A1 (previously cited on PTO-892; herein after referred to as “Dudley”) in view of non-patent literature by Wang and Wu (International Immunopharmacology, 2017, 46, 210-219; previously cited on PTO-892; herein after referred to as “Wang”), non-patent literature by Ben-Avi et. al. (Cancer Immunology, Immunotherapy, May 2018, 67, 1221-1230; previously cited on PTO-892; herein after referred to as "Ben-Avi"), and non-patent literature by Schalper et. al. (JNCI J Natl Cancer Inst, 2015, 107(3), 1-9;previously cited on PTO-892; herein after referred to as “Schalper”).
Claims 143-146 stand as rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0052530 A1 (previously cited on PTO-892; herein after referred to as “Dudley”) in view of non-patent literature by Wang and Wu (International Immunopharmacology, 2017, 46, 210-219; previously cited on PTO-892; herein after referred to as “Wang”), non-patent literature by Ben-Avi et. al. (Cancer Immunology, Immunotherapy, May 2018, 67, 1221-1230; previously cited on PTO-892; herein after referred to as "Ben-Avi"), and non-patent literature by Schalper et. al. (JNCI J Natl Cancer Inst, 2015, 107(3), 1-9;previously cited on PTO-892; herein after referred to as “Schalper”) in further view of non-patent literature by Samejima et. al. (Japanese Journal of Clinical Oncology, 2015, 45(11), 1050-1054; previously cited on PTO-892; herein after referred to as "Samejima").
Claims 126-128 and 130 stand as rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0052530 A1 (previously cited on PTO-892; herein after referred to as “Dudley”) in view of non-patent literature by Wang and Wu (International Immunopharmacology, 2017, 46, 210-219; previously cited on PTO-892; herein after referred to as “Wang”), non-patent literature by Ben-Avi et. al. (Cancer Immunology, Immunotherapy, May 2018, 67, 1221-1230; previously cited on PTO-892; herein after referred to as "Ben-Avi"), and non-patent literature by Schalper et. al. (JNCI J Natl Cancer Inst, 2015, 107(3), 1-9;previously cited on PTO-892; herein after referred to as “Schalper”) in further view of non-patent literature by Gettinger et. al. (Cancer Discovery, 2017, 7(12), 1420-1435; previously cited on PTO-892; herein after referred to as "Gettinger").
Claims 129 and 131 stand as rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0052530 A1 (previously cited on PTO-892; herein after referred to as “Dudley”) in view of non-patent literature by Wang and Wu (International Immunopharmacology, 2017, 46, 210-219; previously cited on PTO-892; herein after referred to as “Wang”), non-patent literature by Ben-Avi et. al. (Cancer Immunology, Immunotherapy, May 2018, 67, 1221-1230; previously cited on PTO-892; herein after referred to as "Ben-Avi"), and non-patent literature by Schalper et. al. (JNCI J Natl Cancer Inst, 2015, 107(3), 1-9;previously cited on PTO-892; herein after referred to as “Schalper”) in further view of non-patent literature by Yoneda et. al. (J UOEH, June 2018, 40(2), 173-189; previously cited on PTO-892; herein after referred to as "Yoneda").
With regard to the above-listed claim rejections of record, Applicant argues the following on Pages 6-12 of Remarks (01/30/2026):
Dudley does not mention treating NSCLC at all, let alone treating NSCLC refractory to a PD-1 inhibitor or a PD-L1 inhibitor.
The deficiency of Dudley cannot be cured by Wang. Wang may be interpreted, at most, as TILs are needed for successful anti-PD-1/PD-L1 therapy, which may indicate a combination therapy using TILs and an anti-PD-1/PD-L1 agent to treat a standard NSCLC (i.e., those sensitive to anti-PD-1/PD-L1 therapies). The disclosure is not sufficient to show that administering TIL, even in combination with anti-PD-1/PD-L1 therapy, is sufficient to treat an NSCLC refractory to previous anti-PD-1/PD-L1 therapies. The combination of Dudley and Wang is at most an invitation to experiment which would require undue experimentation.
Wang focuses on a combination therapy of TILs and anti-PD-1/PD-L1 therapies, not a single TIL therapy without anti-PD-I/PD-LI treatments, as instantly claimed. Applicant points to the first paragraph under Figure 2 on Page 212 of Wang, and argues that skilled artisan would have understood that administering TILs, which generally express and secrete IFN-γ, may increase PD-L1 expression in tumor cells and help tumor cells to escape immune surveillance; such understanding may very likely support a combination therapy of TILs with anti-PD-I/PD-LI therapies, but teaches away from a single TIL therapy without anti-PD-1/PD-Ll agents.
The deficiencies of Dudley and Wang cannot be cured by Ben-Avi. Ben-Avi discloses a TIL treatment to cancer patients who failed standard treatments, but such "standard treatments" generally refer to surgery or systemic treatments such as platinum-based chemotherapy and other treatments, but not including anti-PD-1/PD-L1 therapies. Ben-Avi is silent on treating NSCLC refractory to anti-PD-1/PD-L1 therapies, and thus the single TIL treatment in Ben-Avi targets a different cancer patient subgroup from those in Wang. Even assuming, arguendo, a motivation to combine these two references, there would have been no reasonable expectation of success for treating refractory NSCLC with a single TIL therapy without undue experimentation.
The deficiencies of Dudley, Wang, and Ben-Avi cannot be remedied by Schalper. Schalper indicates that increased levels of CD8+ TILs in NSCLC patients is indicative of improved prognosis/survival; the Office Action does not explain how Schalper teaches or suggests treating refractory NSCLC with a TIL therapy without anti-PD-1/PD-L1 agents.
In view of the above, Applicant argues that no prima facie case of obviousness has been established.
With regard to the combination of Dudley, Wang, Ben-Avi, and Schalper:
- Dudley is relied upon for its disclosure of a method of promoting the regression of a cancer (e.g., lung cancer) in a mammal generally comprising administering a therapeutic population of expanded T cells, wherein said expanded T cells are enriched for CD8+ T cells and wherein CD8+ enriched, “young” T cells promote the regression of cancer (see Paragraph 0023, Pages 11-12, Pages 23-25). Dudley therefore indicates that treatment methods comprising the administration of expanded T cells (i.e., CD8+ enriched T cells) alone promotes the regression of cancer, and may be used in cases of lung cancer.
- Wang is relied upon for its disclosure that the clinical benefit of PD-1/PD-L1 therapies (e.g., for NSCLC, melanoma, RCC, prostate, and/or colorectal cancer patients) is hampered by a high rate of primary resistance and (ii) most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade (Abstract). Wang indicates that responders to PD-1/PD-L1 therapies have higher proliferation of intratumoral CD8+T cells, and larger numbers of CD8, PD-1 and PD-L1-expressing cells pre-treatment (Page 213, Column 1, First Partial Paragraph); Wang further indicates that primary/innate resistance to PD-1/PD-L1 therapy is due to a lack of PD-L1 expression and insufficient TILs (Page 213, Column 1, First Full Paragraph; Figure 2). In terms of acquired resistance, anti-PD-1-resistant tumors were infiltrated with PD-1high T cells, and the PD-1high T cells in resistant tumors failed to be rescued by anti-PD-1 therapy and remained dysfunctional (Page 213, Column 2, Paragraph 1); anti-PD-L1 treated exhausted CD8+T cells (TEX) never acquire a memory T cell phenotype despite of transcriptional rewiring and reengagement of effector circuitry in the TEX epigenetic landscape, and this epigenetic stability of TEX may lead to acquired resistance to checkpoint inhibitors (Page 218, Column 1, Paragraph 1). Thus, Wang indicates that a lack of CD8+ TILs and the presence of severely exhausted CD8+ TILs, which are dysfunctional, play crucial roles in PD-1/PD-L1 therapy resistance. Thus, the teachings of Wang suggest that TIL dysfunction and/or the absence of TILs in general are contributors to PD-1/PD-L1 resistance and addressing the absence/dysfunction could be a reasonable therapeutic responses in cases where a patient is resistant to PD-1/PD-L1 therapies.
- Ben-Avi is relied upon because the study provides the basis for the development of TIL ACT for patients with advanced NSCLC, which may offer an additional treatment option for those patients (Page 1229, Column 1, Paragraph 4); Ben-Avi suggests ACT of TILs (as a single agent) could be a potential treatment option for NSCLC patients.
- Schalper is relied upon for its demonstration that elevated CD3- and CD8-positive T cells is consistently associated with survival, but only CD8 provides independent prognostic information in NSCLC (Page 7); Schalper indicates the relationship between TIL phenotypes and survival wherein higher levels CD8+ TIL levels are the prominent phenotype associated with improved survival (regardless of tumor stage or other factors).
As such, Dudley, Ben-Avi, and Schalper all indicate that TILs are crucial to immune responses to cancer (including NSCLC as indicated by Ben-Avi and Schalper specifically) wherein the administration of TILs as single agents can be a therapeutic approach and can promote cancer regression (as indicated by Dudley and Ben-Avi). Wang is relied on purely to support that TILs and their presence/absence/phenotype are crucial to resistance to PD-1/PD-L1 therapies. It is therefore maintained that the administration of TILs, including CD8+ enriched TILs, as a single agent (suggested by Dudley and Ben-Avi, further supported by Schalper) to patients refractory to PD-1 and/or PD-L1 inhibitors (who would be expected to be deficient in TILs and/or would have an abundance of exhausted, dysfunctional TILs) would be expected to increase the functional CD8+ TIL population (as suggested by Dudley and Ben-Avi) which would reasonably be expected to stimulate immune responses to the cancer, improve survival, and improve prognosis because ACT of TILs is a feasible therapeutic option for NSCLC patients as cultured TILs demonstrate activity with autologous tumor cells and Schalper indicates that increased levels of CD8+ (i.e., CD8high) TILs in NSCLC patients is indicative of improved prognosis/survival.
Thus, the above-listed claim rejections under 35 U.S.C. 103 are deemed proper and are maintained.
Claim Rejections - 35 USC § 103 - New as Necessitated by Amendment
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
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 149-151 are rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0052530 A1 (previously cited on PTO-892; herein after referred to as “Dudley”) in view of non-patent literature by Wang and Wu (International Immunopharmacology, 2017, 46, 210-219; previously cited on PTO-892; herein after referred to as “Wang”), non-patent literature by Ben-Avi et. al. (Cancer Immunology, Immunotherapy, May 2018, 67, 1221-1230; previously cited on PTO-892; herein after referred to as "Ben-Avi"), and non-patent literature by Schalper et. al. (JNCI J Natl Cancer Inst, 2015, 107(3), 1-9;previously cited on PTO-892; herein after referred to as “Schalper”), as applied to claim 125 previously, and in further view of US 7,572,631 (herein after referred to as "Berenson") and US 2012/0244133 A1 (herein after referred to as "Rosenberg").
Dudley, Wang, Ben-Avi, and Schalper render claim 125 obvious for reasons of record.
It is further noted that Dudley teaches a method of promoting the regression of a cancer in a mammal that comprises (i) culturing autologous T cells; (ii) expanding the cultured T cells using OKT3 antibody, IL-2, and feeder lymphocytes, wherein the cultured T cells are enriched for CD8+ T cells prior to expansion of the T cells; (iii) administering to the mammal nonmyeloablative lymphodepleting chemotherapy; and (iv) after administering nonmyeloablative lymphodepleting chemotherapy, administering to the mammal the expanded T cells, wherein the T cells administered to the mammal are less than about 35 days old, e.g., about 19 to about 26 days old (Paragraph 0023). Example 1 teaches the following: generation of “young” TILs may be initiated by first obtaining a tumor sample from a patient and preparing single-cell suspensions; five days following initiation, IL-2 was added to the cells (first expansion); 10-18 days following initiation, rapid expansion (second expansion) was performed by culturing the cells in IL-2 with an anti-CD3 antibody and peripheral blood mononuclear cells (PBMCs); on day 14 of the rapid expansion, “young” TILs were produced with an average expansion of over 3000-fold (Paragraphs 0063-0066). As indicated above, Dudley teaches that TILs may be expanded using the anti-CD3 antibody, OKT-3. There are multiple options for the initial cell preparation for culturing TILs, including a fine needle aspirate from the tumor tissue; tumor fragments, cut with a scalpel or scissors to 1-1.5 min in each of 3 dimensions; a mechanically dispersed, single-cell suspension; and an enzymatically generated single-cell suspension (Paragraph 0076). Dudley further teaches that feeder cells may be allogenic peripheral blood mononuclear feeder cells (PMBCs) and they may be irradiated (Paragraph 0066). Expanded T cells may be administered to a patient having cancer (Abstract), and prior to infusing expanded T cells into patients, the cells are washed and harvested (Paragraph 0093). Dudley also teaches that with respect to the inventive methods disclosed, the cancer can be any cancer and can include lung cancer (Paragraph 0043). Thus, Dudley teaches or suggests a method of obtaining a tumor fragment comprising a first population of TILs; contacting the tumor fragment with a first cell culture medium; performing an initial expansion of the first population of TILs in the first cell culture medium to obtain a second population of TILs, and wherein the first cell culture medium comprises IL-2; performing a rapid expansion of the second population of TILs in a second cell culture medium to obtain a third population of TILs, wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), and irradiated allogeneic PBMCs (i.e., antigen presenting cells (APCs)), and wherein the rapid expansion is performed over a period of 14 days or less; harvesting the third population of TILs; and administering a therapeutically effective portion of the third population of TILs to the patient.
However, it is noted that none of the cited references disclose steps (a)-(f) of claim 149 for obtaining and administering a therapeutically effective portion of TILs (specifically wherein the first and second expansions are performed in containers providing gas-permeable surface areas for 3-11 and 7-11 days, respectively), nor closed containers or a closed system (claims 150 and 151, respectively). These deficiencies are remedied by Berenson and Rosenberg.
Berenson teaches methods for activating and expanding cells, and more particularly, to a novel method to activate and/or stimulate cells that maximizes the expansion of such cells to achieve dramatically high densities; cells are activated and expanded to very high densities in a short period of time (Abstract). Compositions of cells activated and expanded by the methods disclosed are also provided (Id.). One aspect of the present invention is directed to the surprising
finding that the combination of a force which induces the concentration of cells, ligation of cell surface moieties, and culturing cells in a rocking, closed system, results in a profound enhancement in activation and expansion of these cells; the present invention may function by providing optimal aeration for the expanding cells wherein cell surface moiety ligation combined with aeration through rocking and perfused media lead to unexpectedly robust cell activation and expansion of T cells to unexpectedly high densities and absolute numbers and, accordingly, within the context of T cells, the present invention provides a variety of unexpected advantages, first it eliminates the need for a separate monocyte-depletion step using "uncoated" particles, simplifies expansion of T cells by requiring fewer cell transfers and fewer reagents, increased level of T cell activation during activation process, significantly reduces the time to achieve cell numbers adequate for cell therapy, reduces time and labor involved in the processing of the cells, reduces the cost of manufacturing, and increases the flexibility of scheduling patient processing and infusions (Columns 10-11; emphasis added). In one particular embodiment, the cell stimulation methods of the invention are carried out in a closed system, such as a bioreactor, that allows for perfusion of medium at varying rates wherein the container of such a closed system comprises an outlet filter, an inlet filter, and a sampling port for sterile transfer to and from the closed system further wherein, in other embodiments, the container of such a closed system comprises a syringe pump and control for sterile transfer to and from the closed system (Column 30, Lines 41-60; emphasis added). One of ordinary skill in the art would recognize that the use of such containers could allow for multiple containers within the closed system, wherein transfer between contains could be accomplished without opening the system. In one embodiment the system comprises a gas manifold and, in another embodiment, the bioreactor of the present invention comprises a CO2 gas mix rack that supplies a mixture of ambient air and CO2 to the bioreactor container and maintains the container at positive pressure (Id.). Berenson further teaches that the methodologies of the present invention provide for the expansion of cells, such as T cells, to a concentration of about between 6xl06 cell/ml and about 90xl06 cells/ml in less than about two weeks; in particular the methodologies of the invention provide for the expansion of T cells wherein the cells reach a desired concentration by about day 5, 6, 7, 8, 9, 10, 11, or 12 of culture (Column 31, Lines 15-24). Berenson also teaches a method wherein positively selected cells are transferred to a 20 liter Wave bag on the rocker platform wherein the volume is increased to 2 liter by introducing complete medium into the bag via the outlet tube and the bag is then incubated on the Wave platform, without rocking, at 37 °C, 5% CO2; on day 3, gentle rocking (5-10 rocks/ minute) is initiated and the volume is increased to 6 liters; on day 4, the fluid delivery system is set to increase the volume of the bag by 2 liters per day; on day 6, perfusion is initiated at from about 0.5-3 mis/minute and the outlet pump is set to maintain the volume of the bag at 10 liters; on day 9 to day 12, cells are harvested wherein the fluid delivery system is disconnected and 5 liters of supernatant is removed through the outlet pump, the angular magnet is attached to the out-put line, the expanded cell product is allowed to flow out of the 20 liter bag into transfer packs after which the de-beaded expanded cell product is processed and cryopreserved (Column 69, Lines 31-47). It is noted that the use of pumps indicates the transfer to bags is performed without opening the system.
Rosenberg teaches a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining tumor infiltrating lymphocytes (TILs) from the tumor tissue sample; expanding the number of TILs in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and administering the expanded number of TILs to the mammal wherein methods of obtaining an expanded number of TILs from a mammal for adoptive cell immunotherapy are also provided (Abstract; emphasis added). Rosenberg further teaches that methods using gas-permeable containers advantageously reduce the final culture volume to lower than that obtained with non-gas permeable containers, which advantageously lowers the incubator capacity required to grow the cells, reduces the amount of reagents (e.g., cell culture medium and additives) necessary to grow the cells, and simplifies the equipment and/or procedures for concentrating and washing the cells; the development of a simpler, less expensive, and less labor-intensive method to generate clinically effective TILs is believed to advantageously aid in the more widespread use of adoptive cell therapy and permit the delivery of therapeutically effective TILs to more patients in a shorter time period (Paragraph 0011).
Thus, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of treatment rendered obvious by Dudley, Wang, Ben-Avi, and Schalper such that the method comprises: (a) obtaining and/or receiving a first population of TILs from a NSCLC tumor in the subject; (b) contacting the first population of TILs with a first cell culture medium; (c) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2 to produce a second population of TILs, wherein the first expansion is performed in a first container providing a first gas-permeable surface area, and wherein the first expansion is performed for 3-11 days to obtain the second population of TILs; (d) performing a second expansion by supplementing the culture medium of the second population of TILs with additional IL-2, OKT-3 (anti-CD3 antibody), and antigen presenting cells (APC) to produce a third population of TILs, wherein the second expansion is performed in a second container providing a second gas permeable surface area, and wherein the second expansion is performed for 7-11 days to obtain the third population of TILs; (e) harvesting the third population of TILs; and (f) administering a therapeutically effective portion of the third population of TILs to the subject. Such a modification would have been obvious, and would have had a reasonable expectation of success because:
Dudley discloses a method of expanding TILs comprising obtaining a tumor fragment comprising a first population of TILs; contacting the tumor fragment with a first cell culture medium; performing an initial expansion of the first population of TILs in the first cell culture medium to obtain a second population of TILs, and wherein the first cell culture medium comprises IL-2; performing a rapid expansion of the second population of TILs in a second cell culture medium to obtain a third population of TILs, wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), and irradiated allogeneic PBMCs (i.e., antigen presenting cells (APCs)), and wherein the rapid expansion is performed over a period of 14 days or less.
Berenson discloses that the combination of a force which induces the concentration of cells, ligation of cell surface moieties, and culturing cells in a rocking, closed system, results in a profound enhancement in activation and expansion of cells by providing optimal aeration for the expanding cells wherein cell surface moiety ligation combined with aeration through rocking and perfused media lead to unexpectedly robust cell activation and expansion of T cells to unexpectedly high densities and absolute numbers and, accordingly, within the context of T cells, provides a variety of advantages, including eliminating the need for a separate monocyte-depletion step using "uncoated" particles, simplifies expansion of T cells by requiring fewer cell transfers and fewer reagents, increased level of T cell activation during activation process, significantly reduces the time to achieve cell numbers adequate for cell therapy (e.g., expansion steps provide a desired concentration by about day 5, 6, 7, 8, 9, 10, 11, or 12 of culture), reduces time and labor involved in the processing of the cells, reduces the cost of manufacturing, and increases the flexibility of scheduling patient processing and infusions.
Rosenberg further teaches that methods using gas-permeable containers advantageously reduce the final culture volume to lower than that obtained with non-gas permeable containers, which advantageously lowers the incubator capacity required to grow the cells, reduces the amount of reagents (e.g., cell culture medium and additives) necessary to grow the cells, and simplifies the equipment and/or procedures for concentrating and washing the cells; the development of a simpler, less expensive, and less labor-intensive method to generate clinically effective TILs is believed to advantageously aid in the more widespread use of adoptive cell therapy and permit the delivery of therapeutically effective TILs to more patients in a shorter time period.
Thus, the modified method based on the above would reasonably be expected to provide a therapeutic population of TILs in a shorter period of time, providing patients with a more optimal therapeutic option.
Double Patenting - Maintained
It is noted that the tables of issued patents and copending applications have been updated to (i) reflect previously copending applications that have passed to issue/have been issued (see the end of the patents table) and (ii) to remove any since-abandoned copending applications.
Claims 125-148 stand as rejected under non-statutory double patenting over the pertinent claims identified for the reference patents listed in the following table in view of US 2011/0052530 A1 (previously cited on PTO-892; herein after referred to as “Dudley”), non-patent literature by Wang and Wu (International Immunopharmacology, 2017, 46, 210-219; previously cited on PTO-892; herein after referred to as “Wang”), non-patent literature by Ben-Avi et. al. (Cancer Immunology, Immunotherapy, May 2018, 67, 1221-1230; previously cited on PTO-892; herein after referred to as "Ban-Avi"), non-patent literature by Schalper et. al. (JNCI J Natl Cancer Inst, 2015, 107(3), 1-9; previously cited on PTO-892; herein after referred to as “Schalper”), non-patent literature by Samejima et. al. (Japanese Journal of Clinical Oncology, 2015, 45(11), 1050-1054; previously cited on PTO-892; herein after referred to as "Samejima"), non-patent literature by Gettinger et. al. (Cancer Discovery, 2017, 7(12), 1420-1435; previously cited on PTO-892; herein after referred to as "Gettinger"), and/or non-patent literature by Yoneda et. al. (J UOEH, June 2018, 40(2), 173-189; previously cited on PTO-892; herein after referred to as "Yoneda").
Patent Number
Brief Description of the Invention
Pertinent Claims
10130659
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 14-16, 18-21, 23-26, 28-29
10166257
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18-20
10272113
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18-20
10363273
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 14-16, 18-21, 22-26, 28-29
10463697
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18, 20-21
10517894
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-2, 5-7, 11-13, 16-18, 22
10646517
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18-20
10925900
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 14-15
11007225
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-13, 15-18, 20-21, 25, 27-29
11013770
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18, 20-21, 24
11058728
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-16, 18-20
11083752
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-16, 18-20
11202803
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-11, 13-16, 18-20
11202804
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 9-16, 18-19
11241456
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-10, 12-16, 18-20
11266694
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-15, 17-19
11273181
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 7-9, 11-15, 17-19
11311578
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 7-12, 16-18
11357841
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 4-5, 8-11, 13-14, 16
11364266
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 7-12, 16-20, 23
11369637
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 7-12, 16-23
11433097
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 2-3, 5-11, 13-16, 19-20, 22-23
11517592
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-13, 15-18, 20-24
11969444
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 6-11, 15-20,
11998568
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 6-11, 13-17, 19-23
12280140
Method for Expanding TILs into a Therapeutic Population
1, 3
12226522
Method of Administering TILs to a Subject with Cancer
1, 3, 8
12188048
A Population of Expanded TILs Obtainable by Expansion Method
1, 8-9, 22
12194061
A Cryopreserved Therapeutic Population of TILs Obtainable by Expansion Method
1, 10-14
12343380
Method for Preparing TILs for Adoptive T Cell Therapy/Method for Treating Cancer Comprising Administering Expanded TILs
1, 18
12226434
Method of Expanding TILs into a Therapeutic Population
1, 4-5
12121541
Methods for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-4, 8, 13, 15, 24-25, 29, 34
12104172
Method of Expanding TILs into a Therapeutic Population
1, 7
App. 17050552 (Passed to Issue)
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
65, 68-74, 76
12473532
Method of Expanding TILs into a Therapeutic Population
1-29
App. 17110179 (Passed to Issue)
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 17, 26-29, 31-34, 36-37
12453697
Method of Expanding TILs into a Therapeutic Population/Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-22
12558375
A Population of Expanded TILs Obtainable by Expansion Method
1-23
App. 17817239 (Passed to Issue)
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 6-11, 13-16, 18-22
App. 17823448 (Passed to Issue)
A Population of Expanded TILs Obtainable by Expansion Method
1, 12-26
12570959
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-30
12553029
Method for Treating a Subject with NSCLC Refractory to ICI Treatment by Administering Therapeutically Effective Amount of TILs
1-20
Claims 125-148 stand as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the copending Application Numbers listed in the following table in view of US 2011/0052530 A1 (previously cited on PTO-892; herein after referred to as “Dudley”), non-patent literature by Wang and Wu (International Immunopharmacology, 2017, 46, 210-219; previously cited on PTO-892; herein after referred to as “Wang”), non-patent literature by Ben-Avi et. al. (Cancer Immunology, Immunotherapy, May 2018, 67, 1221-1230; previously cited on PTO-892; herein after referred to as "Ban-Avi"), non-patent literature by Schalper et. al. (JNCI J Natl Cancer Inst, 2015, 107(3), 1-9; previously cited on PTO-892; herein after referred to as “Schalper”), non-patent literature by Samejima et. al. (Japanese Journal of Clinical Oncology, 2015, 45(11), 1050-1054; previously cited on PTO-892; herein after referred to as "Samejima"), non-patent literature by Gettinger et. al. (Cancer Discovery, 2017, 7(12), 1420-1435; previously cited on PTO-892; herein after referred to as "Gettinger"), and/or non-patent literature by Yoneda et. al. (J UOEH, June 2018, 40(2), 173-189; previously cited on PTO-892; herein after referred to as "Yoneda").
Application Number
Brief Description of the Invention
Pertinent Claims
16969362
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 16, 24, 32, 34, 36-38, 41-43, 52
17147080
Method of Expanding TILs into a Therapeutic Population
1, 10-14, 16-22, 24-27, 30-35
17147412
Method of Expanding TILs into a Therapeutic Population
1, 10-12, 14, 16-21, 23-25, 27, 29-33
17290705
Method of Expanding TILs into a Therapeutic Population/Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
2-3, 7, 44, 49, 52, 57, 60
17290710
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 14, 19, 26, 29, 31, 33, 35, 37, 39
17415175
Method of Expanding TILs into a Therapeutic Population/Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-2, 4-5, 19, 66, 70-71, 82-83, 88-89, 91, 97-98, 102-103
17610671
Method of Expanding TILs into a Therapeutic Population
367, 373-378, 392-394
17771723
A Population of Expanded TILs Obtainable by Expansion Method
159, 216-219
17817217
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-16, 18-19
17817247
A Population of Expanded TILs Obtainable by Expansion Method
1, 7-12, 14-20
17817273
A Population of Expanded TILs Obtainable by Expansion Method
1, 10-12, 14-18, 20-24
17817276
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-11, 13-16, 18-20
17823419
A Population of Expanded TILs Obtainable by Expansion Method
1, 14-28
17838127
Method of Expanding TILs into a Therapeutic Population/A Population of TILS for Treating a Subject with Cancer Obtainable by Expansion Method
35-36, 44, 46, 53-55, 57, 60, 64-67
17856793
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-18, 20-24
17856806
A Composition of Expanded TILs Obtainable by Expansion Method
1, 8-18, 20-24
17997648
Method of Expanding TILs into a Therapeutic Population/A Population of TILS for Treating a Subject with Cancer Obtainable by Expansion Method
2, 7, 160
17997731
Method of Expanding TILs into a Therapeutic Population
30, 65, 67-68, 70, 73-76, 81-82, 84, 91, 95-98, 107
18247877
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-2, 4, 7, 18-21, 23, 34-45, 56, 61
18247878
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-2, 4, 14, 19, 41, 43, 45, 56, 61, 71-72, 85-90
18256421
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
162-164, 167-172, 177-178
18262365
Method of Expanding TILs into a Therapeutic Population
10
18262843
Method of Expanding TILs into a Therapeutic Population/Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10, 33, 47-49, 58-61, 63-73, 75-76, 81, 105-107, 109, 122-129, 131-132, 136, 192
18291536
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method/Method of Expanding TILs into a Therapeutic Population/Compositions Thereof
1-8, 15-16, 46, 69, 113-116, 141
18429006
Method of Expanding TILs into a Therapeutic Population
68
18551138
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method/Method of Expanding TILs into a Therapeutic Population
136-137, 148-150
18560898
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method/Method of Expanding TILs into a Therapeutic Population
19
18609772
Method of Expanding TILs into a Therapeutic Population
12
18619119
Method of Expanding TILs into a Therapeutic Population
1-2, 5-8, 10-12, 15-17, 20-22, 24, 26-27
18661510
Method of Expanding TILs into a Therapeutic Population
1-4, 10, 15-25, 28, 30
18674562
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
107, 112, 114-116, 120-122
18693508
Method of Expanding TILs into a Therapeutic Population
121, 123
18707719
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method/Method of Expanding TILs into a Therapeutic Population/Compositions Thereof
1-15, 17-18, 26-43, 45-54, 62-65, 67-74, 76
18832493
Method of Generating Gene-Edited TILs/Compositions and Uses Thereof
226, 236, 242-246
18832901
Method of Expanding TILs into a Therapeutic Population
9, 85, 155
18849440
Methods of Making Cryopreserved TILs from NSCLC Patients and Methods of Treating Cancer Comprising Administering Said TILs
1-329
19050082
Methods of Treating Cancer Comprising Administering a Therapeutically Effective Amount of TILs
1, 3-5, 8, 10-16, 21, 25-26
It is noted that Applicant has requested that the above-listed claim rejections under nonstatutory double patenting be held in abeyance. As such, the above-listed claim rejections under nonstatutory double patenting are maintained.
Double Patenting - New as Necessitated by Amendment
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 149-151 are rejected under non-statutory double patenting over the pertinent claims identified for the reference patents listed in the following table in view of US 2011/0052530 A1 (previously cited on PTO-892; herein after referred to as “Dudley”), non-patent literature by Wang and Wu (International Immunopharmacology, 2017, 46, 210-219; previously cited on PTO-892; herein after referred to as “Wang”), non-patent literature by Ben-Avi et. al. (Cancer Immunology, Immunotherapy, May 2018, 67, 1221-1230; previously cited on PTO-892; herein after referred to as "Ban-Avi"), non-patent literature by Schalper et. al. (JNCI J Natl Cancer Inst, 2015, 107(3), 1-9; previously cited on PTO-892; herein after referred to as “Schalper”), non-patent literature by Samejima et. al. (Japanese Journal of Clinical Oncology, 2015, 45(11), 1050-1054; previously cited on PTO-892; herein after referred to as "Samejima"), non-patent literature by Gettinger et. al. (Cancer Discovery, 2017, 7(12), 1420-1435; previously cited on PTO-892; herein after referred to as "Gettinger"), non-patent literature by Yoneda et. al. (J UOEH, June 2018, 40(2), 173-189; previously cited on PTO-892; herein after referred to as "Yoneda"), US 7,572,631 (herein after referred to as "Berenson"), and/or US 2012/0244133 A1 (herein after referred to as "Rosenberg").
Patent Number
Brief Description of the Invention
Pertinent Claims
10130659
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 14-16, 18-21, 23-26, 28-29
10166257
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18-20
10272113
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18-20
10363273
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 14-16, 18-21, 22-26, 28-29
10463697
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18, 20-21
10517894
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-2, 5-7, 11-13, 16-18, 22
10646517
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18-20
10925900
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 14-15
11007225
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-13, 15-18, 20-21, 25, 27-29
11013770
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 18, 20-21, 24
11058728
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-16, 18-20
11083752
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-16, 18-20
11202803
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-11, 13-16, 18-20
11202804
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 9-16, 18-19
11241456
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-10, 12-16, 18-20
11266694
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-15, 17-19
11273181
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 7-9, 11-15, 17-19
11311578
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 7-12, 16-18
11357841
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 4-5, 8-11, 13-14, 16
11364266
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 7-12, 16-20, 23
11369637
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 7-12, 16-23
11433097
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 2-3, 5-11, 13-16, 19-20, 22-23
11517592
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-13, 15-18, 20-24
11969444
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 6-11, 15-20,
11998568
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 6-11, 13-17, 19-23
12280140
Method for Expanding TILs into a Therapeutic Population
1, 3
12226522
Method of Administering TILs to a Subject with Cancer
1, 3, 8
12188048
A Population of Expanded TILs Obtainable by Expansion Method
1, 8-9, 22
12194061
A Cryopreserved Therapeutic Population of TILs Obtainable by Expansion Method
1, 10-14
12343380
Method for Preparing TILs for Adoptive T Cell Therapy/Method for Treating Cancer Comprising Administering Expanded TILs
1, 18
12226434
Method of Expanding TILs into a Therapeutic Population
1, 4-5
12121541
Methods for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-4, 8, 13, 15, 24-25, 29, 34
12104172
Method of Expanding TILs into a Therapeutic Population
1, 7
App. 17050552 (Passed to Issue)
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
65, 68-74, 76
12473532
Method of Expanding TILs into a Therapeutic Population
1-29
App. 17110179 (Passed to Issue)
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 3-6, 8-11, 13-14, 17, 26-29, 31-34, 36-37
12453697
Method of Expanding TILs into a Therapeutic Population/Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-22
12558375
A Population of Expanded TILs Obtainable by Expansion Method
1-23
App. 17817239 (Passed to Issue)
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 6-11, 13-16, 18-22
App. 17823448 (Passed to Issue)
A Population of Expanded TILs Obtainable by Expansion Method
1, 12-26
12570959
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-30
12553029
Method for Treating a Subject with NSCLC Refractory to ICI Treatment by Administering Therapeutically Effective Amount of TILs
1-20
Claims 149-151 are rendered obvious by the combined teachings of the prior art as discussed in new grounds of rejection in the 103 section above, the 103s being incorporated here.
The addition of the patented claims above over related subject matter only further supports this obviousness. It is noted that all of the above-mentioned patented claims are generally drawn to expanded TILs (methods of making, methods of using, and subsequent populations and/or compositions). However, above-identified patented claims are not necessarily drawn to a method that comprises: (a) obtaining and/or receiving a first population of TILs from a NSCLC tumor in the subject; (b) contacting the first population of TILs with a first cell culture medium; (c) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2 to produce a second population of TILs, wherein the first expansion is performed in a first container providing a first gas-permeable surface area, and wherein the first expansion is performed for 3-11 days to obtain the second population of TILs; (d) performing a second expansion by supplementing the culture medium of the second population of TILs with additional IL-2, OKT-3 (anti-CD3 antibody), and antigen presenting cells (APC) to produce a third population of TILs, wherein the second expansion is performed in a second container providing a second gas permeable surface area, and wherein the second expansion is performed for 7-11 days to obtain the third population of TILs; (e) harvesting the third population of TILs; and (f) administering a therapeutically effective portion of the third population of TILs to the subject. These deficiencies are addressed by the cited references, as provided by the teachings/combinations of teachings specified in the new grounds of rejection in the 103 section.
Thus, it would have been obvious to one of ordinary skill in the art that the methods of the patented claims and/or compositions thereof could be modified/utilized such that the treatment method comprises: (a) obtaining and/or receiving a first population of TILs from a NSCLC tumor in the subject; (b) contacting the first population of TILs with a first cell culture medium; (c) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2 to produce a second population of TILs, wherein the first expansion is performed in a first container providing a first gas-permeable surface area, and wherein the first expansion is performed for 3-11 days to obtain the second population of TILs; (d) performing a second expansion by supplementing the culture medium of the second population of TILs with additional IL-2, OKT-3 (anti-CD3 antibody), and antigen presenting cells (APC) to produce a third population of TILs, wherein the second expansion is performed in a second container providing a second gas permeable surface area, and wherein the second expansion is performed for 7-11 days to obtain the third population of TILs; (e) harvesting the third population of TILs; and (f) administering a therapeutically effective portion of the third population of TILs to the subject.
Claims 149-151 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the copending Application Numbers listed in the following table in view of US 2011/0052530 A1 (previously cited on PTO-892; herein after referred to as “Dudley”), non-patent literature by Wang and Wu (International Immunopharmacology, 2017, 46, 210-219; previously cited on PTO-892; herein after referred to as “Wang”), non-patent literature by Ben-Avi et. al. (Cancer Immunology, Immunotherapy, May 2018, 67, 1221-1230; previously cited on PTO-892; herein after referred to as "Ban-Avi"), non-patent literature by Schalper et. al. (JNCI J Natl Cancer Inst, 2015, 107(3), 1-9; previously cited on PTO-892; herein after referred to as “Schalper”), non-patent literature by Samejima et. al. (Japanese Journal of Clinical Oncology, 2015, 45(11), 1050-1054; previously cited on PTO-892; herein after referred to as "Samejima"), non-patent literature by Gettinger et. al. (Cancer Discovery, 2017, 7(12), 1420-1435; previously cited on PTO-892; herein after referred to as "Gettinger"), non-patent literature by Yoneda et. al. (J UOEH, June 2018, 40(2), 173-189; previously cited on PTO-892; herein after referred to as "Yoneda"), US 7,572,631 (herein after referred to as "Berenson"), and/or US 2012/0244133 A1 (herein after referred to as "Rosenberg").
Application Number
Brief Description of the Invention
Pertinent Claims
16969362
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 16, 24, 32, 34, 36-38, 41-43, 52
17147080
Method of Expanding TILs into a Therapeutic Population
1, 10-14, 16-22, 24-27, 30-35
17147412
Method of Expanding TILs into a Therapeutic Population
1, 10-12, 14, 16-21, 23-25, 27, 29-33
17290705
Method of Expanding TILs into a Therapeutic Population/Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
2-3, 7, 44, 49, 52, 57, 60
17290710
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 14, 19, 26, 29, 31, 33, 35, 37, 39
17415175
Method of Expanding TILs into a Therapeutic Population/Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-2, 4-5, 19, 66, 70-71, 82-83, 88-89, 91, 97-98, 102-103
17610671
Method of Expanding TILs into a Therapeutic Population
367, 373-378, 392-394
17771723
A Population of Expanded TILs Obtainable by Expansion Method
159, 216-219
17817217
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10-16, 18-19
17817247
A Population of Expanded TILs Obtainable by Expansion Method
1, 7-12, 14-20
17817273
A Population of Expanded TILs Obtainable by Expansion Method
1, 10-12, 14-18, 20-24
17817276
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-11, 13-16, 18-20
17823419
A Population of Expanded TILs Obtainable by Expansion Method
1, 14-28
17838127
Method of Expanding TILs into a Therapeutic Population/A Population of TILS for Treating a Subject with Cancer Obtainable by Expansion Method
35-36, 44, 46, 53-55, 57, 60, 64-67
17856793
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 8-18, 20-24
17856806
A Composition of Expanded TILs Obtainable by Expansion Method
1, 8-18, 20-24
17997648
Method of Expanding TILs into a Therapeutic Population/A Population of TILS for Treating a Subject with Cancer Obtainable by Expansion Method
2, 7, 160
17997731
Method of Expanding TILs into a Therapeutic Population
30, 65, 67-68, 70, 73-76, 81-82, 84, 91, 95-98, 107
18247877
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-2, 4, 7, 18-21, 23, 34-45, 56, 61
18247878
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1-2, 4, 14, 19, 41, 43, 45, 56, 61, 71-72, 85-90
18256421
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
162-164, 167-172, 177-178
18262365
Method of Expanding TILs into a Therapeutic Population
10
18262843
Method of Expanding TILs into a Therapeutic Population/Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
1, 10, 33, 47-49, 58-61, 63-73, 75-76, 81, 105-107, 109, 122-129, 131-132, 136, 192
18291536
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method/Method of Expanding TILs into a Therapeutic Population/Compositions Thereof
1-8, 15-16, 46, 69, 113-116, 141
18429006
Method of Expanding TILs into a Therapeutic Population
68
18551138
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method/Method of Expanding TILs into a Therapeutic Population
136-137, 148-150
18560898
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method/Method of Expanding TILs into a Therapeutic Population
19
18609772
Method of Expanding TILs into a Therapeutic Population
12
18619119
Method of Expanding TILs into a Therapeutic Population
1-2, 5-8, 10-12, 15-17, 20-22, 24, 26-27
18661510
Method of Expanding TILs into a Therapeutic Population
1-4, 10, 15-25, 28, 30
18674562
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method
107, 112, 114-116, 120-122
18693508
Method of Expanding TILs into a Therapeutic Population
121, 123
18707719
Method for Treating a Subject with Cancer by Administering Expanded TILs Obtainable by Expansion Method/Method of Expanding TILs into a Therapeutic Population/Compositions Thereof
1-15, 17-18, 26-43, 45-54, 62-65, 67-74, 76
18832493
Method of Generating Gene-Edited TILs/Compositions and Uses Thereof
226, 236, 242-246
18832901
Method of Expanding TILs into a Therapeutic Population
9, 85, 155
18849440
Methods of Making Cryopreserved TILs from NSCLC Patients and Methods of Treating Cancer Comprising Administering Said TILs
1-329
19050082
Methods of Treating Cancer Comprising Administering a Therapeutically Effective Amount of TILs
1, 3-5, 8, 10-16, 21, 25-26
Claims 149-151 are rendered obvious by the combined teachings of the prior art as discussed in new grounds of rejection in the 103 section above, the 103s being incorporated here.
The addition of the copending claims above over related subject matter only further supports this obviousness. It is noted that all of the above-mentioned copending applications are generally drawn to expanded TILs (methods of making, methods of using, and subsequent populations and/or compositions). However, above-identified copending applications are not necessarily drawn to a method that comprises: (a) obtaining and/or receiving a first population of TILs from a NSCLC tumor in the subject; (b) contacting the first population of TILs with a first cell culture medium; (c) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2 to produce a second population of TILs, wherein the first expansion is performed in a first container providing a first gas-permeable surface area, and wherein the first expansion is performed for 3-11 days to obtain the second population of TILs; (d) performing a second expansion by supplementing the culture medium of the second population of TILs with additional IL-2, OKT-3 (anti-CD3 antibody), and antigen presenting cells (APC) to produce a third population of TILs, wherein the second expansion is performed in a second container providing a second gas permeable surface area, and wherein the second expansion is performed for 7-11 days to obtain the third population of TILs; (e) harvesting the third population of TILs; and (f) administering a therapeutically effective portion of the third population of TILs to the subject. These deficiencies are addressed by the cited references, as provided by the teachings/combinations of teachings specified in the new grounds of rejection in the 103 section.
Thus, it would have been obvious to one of ordinary skill in the art that the methods of the copending applications and/or compositions thereof could be modified/utilized such that the treatment method comprises: (a) obtaining and/or receiving a first population of TILs from a NSCLC tumor in the subject; (b) contacting the first population of TILs with a first cell culture medium; (c) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2 to produce a second population of TILs, wherein the first expansion is performed in a first container providing a first gas-permeable surface area, and wherein the first expansion is performed for 3-11 days to obtain the second population of TILs; (d) performing a second expansion by supplementing the culture medium of the second population of TILs with additional IL-2, OKT-3 (anti-CD3 antibody), and antigen presenting cells (APC) to produce a third population of TILs, wherein the second expansion is performed in a second container providing a second gas permeable surface area, and wherein the second expansion is performed for 7-11 days to obtain the third population of TILs; (e) harvesting the third population of TILs; and (f) administering a therapeutically effective portion of the third population of TILs to the subject.
These are provisional nonstatutory double patenting rejections.
Conclusion
Claims 125-151 are pending. Claims 125-151 are rejected. No claims are allowed.
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.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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