Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claim Status
The amendment filed January 7, 2026 has been received and entered.
Claims 1, 14, 16, and 28-30 have been amended.
Claim 5 has been canceled.
Claims 17-18 were previously canceled.
Claims 1-4, 6-16, and 19-30 are pending and under consideration.
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. However, Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
Claim 1 has been amended to recite the patient or subject is administered TILs in combination with one or more PD-1 inhibitors or PD-L1 inhibitors, wherein the one or more PD-1 inhibitors or PD-L1 inhibitors is administered every six weeks after the administration of the population of TILs.
None of the prior applications or the instant specification disclose the subject matter of the presently claimed invention. Specifically, the disclosures do not contemplate administering one or more PD-L1 inhibitors every six weeks after the administration of the population of TILs.
The specifications disclose dosing regimens for several anti-PD-1 and anti-CTLA-4 inhibitors, however, no dosing regimen for any PD-L1 inhibitor is disclosed. The PD-L1 inhibitor is merely recited as being administered in combination with TILs. Therefore, it cannot be determined when during the course of treatment the PD-L1 inhibitor is administered, how much is administered, or how long it is administered.
Should Applicant disagree with the examiner’s factual determination as to the disclosure of the various claim limitations, Applicant may point out the particular places within the instant application or prior applications which discloses the specific subject matter.
Accordingly, the September 16, 2024 filing date of the instant application will be used for the purpose of applying art for claims 1-4, 6-16, and 19-30.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 7, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 2 and 19 are objected to because of the following informalities:
Claims 2 and 19, line 6 - should read “a PIK3CA mutation, a CDKN2A mutation,”.
Appropriate correction is required.
Claim Rejections
In view of the Applicant’s claim amendments the previous grounds of rejection have been withdrawn. The following are new grounds of rejection necessitated by Applicant’s claim amendments, however, Applicant’s arguments relevant to the new grounds of rejection will be addressed below.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-4, 6-16, and 19-30 are rejected under 35 U.S.C. 112(a), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
Claims 1 and 14 are drawn to a method of treating a patient or subject with anti-PD-1/PD-L1 naïve NSCLC comprising administering a population of TILs in combination with one or more PD-1 inhibitors or PD-L1 inhibitors, wherein the one or more PD-1 inhibitors or PD-L1 inhibitors is administered every six weeks after the administration of the population of TILs.
None of the prior applications or the instant specification disclose the subject matter of the presently claimed invention. Specifically, there is no mention or contemplation for administering one or more PD-L1 inhibitors every six weeks after the administration of the population of TILs.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with
reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession
of the invention. The invention is, for purposes of the 'written description’ inquiry, whatever is now
claimed." (See Vas-Cath, p. 1117). The specification does not "clearly allow persons of ordinary skill in
the art to recognize that [he or she] invented what is claimed." (See Vas-Cath, p. 1116). Meeting the written description threshold requires showing that the applicant was in “possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning — i.e., what the written description and knowledge in the art would lead one to speculate as to modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997).
Claims 2-4, 6-13, 15-16, and 19-30 are included in the rejection because they depend from or otherwise require all the limitations of a rejected independent claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 4, 6, 8-10, and 12-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”).
The instant claims are drawn to a method of treating anti-PD-1/PD-L1 naive non-small cell lung carcinoma (NSCLC) by administering tumor infiltrating lymphocytes (TILs) in combination with one or more PD-1 or PD-L1 inhibitors to the subject or patient, wherein the NSCLC is PD-L1 negative as determined by a tumor proportion score (TPS) of <1%, and wherein the one or more PD-1 inhibitors or PD-L1 inhibitors is administered every six weeks after the administration of the population of TILs. The PD-1 inhibitor is pembrolizumab and is administered at a dosage of 400 mg every six weeks for up to 2 years. Further comprising the step of treating the patient or subject with an IL-2 regimen starting three to twenty-four hours after administration of a therapeutically effective amount of the population of TILs to the patient or subject; further comprising the step of treating the patient or subject with a non-myeloablative lymphodepletion regimen comprising cyclophosphamide and fludarabine.
Schoenfeld discloses data for TIL cell therapy plus pembrolizumab in patients with ICI-naïve metastatic NSCLC, wherein the majority of the patients (n=13/19) were PD-L1-negative as determined by PD-L1 tumor proportion score (TPS) <1% [Title, pg.1; Table 1, pg. 3]. Schoenfeld discloses after TIL transfer patients were administered pembrolizumab Q6W (400 mg) for ≤24 months [Fig. 1, pg. 2] (instant claims 1-4, 6, 8-9).
Schoenfeld further discloses that 6-7 days prior to TIL transfer patients underwent a non-myeloablative lymphodepletion regimen consisting of comprising cyclophosphamide at a dose of 60 mg/kg once a day for two days followed by administration of fludarabine at a dose of 25 mg/m2/day once a day for five days (instant claims 12-13). Beginning 3 to 24 hours after completion of TIL transfer, IL-2 (600,000 IU/kg) was administered every 8-12 hours for up to 6 doses of (instant claim 10) [Fig. 1 with footnotes, pg. 2]. In patients with ICI-naïve metastatic NSCLC, activity of TIL plus pembrolizumab was greater than either treatment as a monotherapy. Overall, the ORR was 80% in treatment naïve NSCLC patients [pg.7]. Therefore, absent a showing of any difference, the methods disclosed by the prior art are deemed to anticipate the claimed methods.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”) as applied to claims 1, 4, 6, 8-10, and 12-13 above, and in further view of Johnson (CGTLive; November 20, 2023) (“Johnson”).
The instant claims are drawn to a method of treating anti-PD-1/PD-L1 naïve non-small cell lung carcinoma (NSCLC) by administering tumor infiltrating lymphocytes (TILs) in combination with one or more PD-1 or PD-L1 inhibitors to the subject or patient, wherein the NSCLC is PD-L1 negative as determined by a tumor proportion score (TPS) of <1%, and wherein the one or more PD-1 inhibitors or PD-L1 inhibitors is administered every six weeks after the administration of the population of TILs. The PD-1 inhibitor is pembrolizumab and is administered at a dosage of 400 mg every six weeks for up to 2 years. Further comprising the step of treating the patient or subject with an IL-2 regimen starting three to twenty-four hours after administration of a therapeutically effective amount of the population of TILs to the patient or subject; further comprising the step of treating the patient or subject with a non-myeloablative lymphodepletion regimen comprising cyclophosphamide and fludarabine. Further, the patient or subject has a predetermined absence of an EGFR mutation or insertion.
The teachings of Schoenfeld are set forth above. In addition, Schoenfeld teaches that 8 of the PD-L1 negative patients were EFGR wild-type. Four of those patients observed significant durable responses with 60-80% change from baseline in target lesion [Fig. 3, pg. 5].
Johnson teaches these results have prompted FDA approval for a randomized confirmatory study to evaluate TIL therapy in combination with pembrolizumab as a frontline treatment in patients with advanced NSCLC who do not have mutations in EGFR [pg. 2, par. 3] (instant claims 2-3).
The teachings of Schoenfeld differ from the instantly claimed invention in that although TIL + pembrolizumab treatment for patients with anti-PD-1/PD-L1 naïve NSCLC is taught, the patients are not explicitly taught as having a predetermined absence of a driver mutation. However, one of ordinary skill in the art would screen for EGFR driver mutations, given that Johnson teaches TIL therapy in combination with pembrolizumab is a promising frontline treatment in patients with advanced NSCLC who do not have mutations in EGFR. Thus, the combination of prior art references provided a prima facie case of obviousness for the instantly claimed invention.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”) as applied to claims 1, 4, 6, 8-10, and 12-13 above, and in further view of Chesney et al. (ASCO 2019, Poster No. 290a) (“Chesney”).
The instant claims are drawn to a method of treating anti-PD-1/PD-L1 naïve non-small cell lung carcinoma (NSCLC) by administering tumor infiltrating lymphocytes (TILs) in combination with one or more PD-1 or PD-L1 inhibitors to the subject or patient, wherein the NSCLC is PD-L1 negative as determined by a tumor proportion score (TPS) of <1%, and wherein the one or more PD-1 inhibitors or PD-L1 inhibitors is administered every six weeks after the administration of the population of TILs. The PD-1 inhibitor is pembrolizumab and is administered via intravenous infusion at a dosage of 400 mg every six weeks for up to 2 years. Further comprising the step of treating the patient or subject with an IL-2 regimen starting three to twenty-four hours after administration of a therapeutically effective amount of the population of TILs to the patient or subject; further comprising the step of treating the patient or subject with a non-myeloablative lymphodepletion regimen comprising cyclophosphamide and fludarabine.
The teachings of Schoenfeld are set forth above.
Schoenfeld does not explicitly teach that pembrolizumab is administered intravenously.
Chesney teaches a study of autologous tumor infiltrating lymphocytes (TILs) + pembrolizumab in patients with solid tumors, including NSCLC patients that are checkpoint inhibitor naïve [Fig. 2A)]. Chesney teaches that pembrolizumab is administered intravenously following IL 2 completion for 24 months or until disease progression or unacceptable toxicity [Study Flowchart] (instant claim 7).
The teachings of Schoenfeld differ from the instant claims in that pembrolizumab is not specifically taught as being administered intravenously. However, it would have been obvious to one of ordinary skill in the art at the time of filing the instant invention that pembrolizumab is delivered by intravenous infusion as evidenced by Chesney. One would have more than a reasonable expectation of success in administering pembrolizumab intravenously in combination with TIL therapy as Chesney teaches this combination for the treatment of checkpoint inhibitor naïve NSCLC. Thus, the combination of prior art references provided a prima facie case of obviousness for the instantly claimed invention.
Claims 11, 14-16, 20, and 22-30 are rejected under 35 U.S.C. 103 as being unpatentable over Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”) as applied to claims 1, 4, 6, 8-10, and 12-13 above, and in further view of Fardis et al. (WO 2020/096989 A1; cited IDS - 9/16/2024) (“Fardis”).
The instant claims are drawn to a method of treating anti-PD-1/PD-L1 naïve non-small cell lung carcinoma (NSCLC) by administering tumor infiltrating lymphocytes (TILs) in combination with one or more PD-1 or PD-L1 inhibitors to the subject or patient, wherein the NSCLC is PD-L1 negative as determined by a tumor proportion score (TPS) of <1%, and wherein the one or more PD-1 inhibitors or PD-L1 inhibitors is administered every six weeks after the administration of the population of TILs. The PD-1 inhibitor is pembrolizumab and is administered at a dosage of 400 mg every six weeks for up to 2 years. Further comprising the step of treating the patient or subject with an IL-2 regimen starting three to twenty-four hours after administration of a therapeutically effective amount of the population of TILs to the patient or subject; further comprising the step of treating the patient or subject with a non-myeloablative lymphodepletion regimen comprising cyclophosphamide and fludarabine. Also claimed are methods for TIL production and harvesting as recited in claim 14, wherein the first expansion is performed over a period of about 11 days or about 12 days and the second expansion is performed over a period of about 11 days or about 12 days.
The teachings of Schoenfeld are set forth above.
Specifically, Schoenfeld teaches TIL cell therapy plus pembrolizumab in patients with ICI-naïve metastatic NSCLC, wherein the majority of the patients (n=13/19) were PD-L1-negative as determined by PD-L1 tumor proportion score (TPS) <1% [Title, pg.1; Table 1, pg. 3]. Schoenfeld discloses after TIL transfer patients were administered pembrolizumab Q6W (400 mg) for ≤24 months [Fig. 1, pg. 2] (instant claims 14 (partial), 15-16, 20, 22-26).
Schoenfeld further discloses that 6-7 days prior to TIL transfer patients underwent a non-myeloablative lymphodepletion regimen consisting of comprising cyclophosphamide at a dose of 60 mg/kg once a day for two days followed by administration of fludarabine at a dose of 25 mg/m2/day once a day for five days (instant claims 12-13). Beginning 3 to 24 hours after completion of TIL transfer, IL-2 (600,000 IU/kg) was administered every 8-12 hours for up to 6 doses of (instant claim 10) [Fig. 1 with footnotes, pg. 2].
Schoenfeld also teaches that the TIL procurement and manufacturing process takes 22 days, however, does not provide specific steps as recited in the instant claims. Additionally, although Schoenfeld teaches IL-2 administration, it does not specify that the IL-2 is administered as a 15-minute bolus intravenous infusion.
Fardis teaches a method of treating non-small cell lung carcinoma (NSCLC) with a population of tumor infiltrating lymphocytes (TILs) comprising the steps of obtaining and/or receiving a first population of TILs from surgical resection, contacting the tumor fragments with a first cell culture medium comprising IL-2, performing an initial expansion of the first population of TILs in the first cell culture medium to obtain a second population of TILs, performing a rapid expansion of the second population of TILs in a second cell culture medium comprising IL-2, OKT-3, and PBMCs wherein the third population of TILs is at least 50-fold greater in number than the second population of TILs after 7 days from the start of the rapid expansion, and wherein the rapid expansion is performed over a period of 14 days or less, and administering a therapeutically effective portion of the third population of TILs to a patient with NSCLC (claim 1), wherein the patient has not been previously treated with an anti-PD-1 and/or anti-PD-L1 antibody and has low expression of PD-L1 (claim 11). The initial expansion and rapid expansion is performed using a gas permeable container (claim 34).
Fardis teaches in Figure 8A, the 22-day process beginning with Step A) obtaining the patient tumor sample; B) cutting the tumor into fragments and first expansion 3-14 days in IL-2 rich media; C) first expansion to second expansion transition, no storage and closed system; D) second expansion, IL-2, OKT-3, and APCs in a closed system; E) harvest TILs in closed system; and F) final formulation and/or transfer to infusion bag with optional cryopreservation. The second expansion can proceed for 7-14 days [00538]. The first expansion can be shortened to 11 days, such as the combination of the first and second expansion totals 22 days [00492]. Fardis further teaches each container in the process can be a closed container [001395]. The closed system allows for TIL growth without microbial contamination [001192]. The closed cell culture system incorporates a gas exchanger that allows for partial pressure to be adjusted in real time [001193] (instant claim 14).
In addition, Fardis teaches the high-dose IL-2 regimen comprising 600,000 IU/kg of aldesleukin administered as a I5-minute bolus intravenous infusion every eight hours until tolerance (claim 40) (instant claims 11, 14, 27-30).
It would have been obvious at the time of filing the instant invention to combine the protocols of Schoenfeld with those of Fardis. Schoenfeld teaches administering TIL in combination with pembrolizumab for treating NSCLC in anti-PD-1/PD-L1 naïve patients, however, does not provide timing or duration of IL-2 administration or a detailed protocol for TIL production. Methods for treatment with autologous TIL that include IL-2 administration post transfer were known in the art at the time of filing, and a skilled artisan would easily be able to obtain detailed protocols for TIL production and transfer as evidenced by Fardis. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”) in view of Fardis et al. (WO 2020/096989 A1; cited IDS 9/16/2024) (“Fardis”) as applied to claims 1, 4, 6, 8-11, 12-16, 20, and 22-30 above, and in further view of Johnson (CGTLive; November 20, 2023) (“Johnson”).
The instant claims are drawn to a method of treating anti-PD-1/PD-L1 naïve non-small cell lung carcinoma (NSCLC) by administering tumor infiltrating lymphocytes (TILs) in combination with one or more PD-1 or PD-L1 inhibitors to the subject or patient, wherein the NSCLC is PD-L1 negative as determined by a tumor proportion score (TPS) of <1%, and wherein the one or more PD-1 inhibitors or PD-L1 inhibitors is administered every six weeks after the administration of the population of TILs. The PD-1 inhibitor is pembrolizumab and is administered at a dosage of 400 mg every six weeks for up to 2 years. Further comprising the step of treating the patient or subject with an IL-2 regimen starting three to twenty-four hours after administration of a therapeutically effective amount of the population of TILs to the patient or subject; further comprising the step of treating the patient or subject with a non-myeloablative lymphodepletion regimen comprising cyclophosphamide and fludarabine. Also claimed are methods for TIL production and harvesting as recited in claim 14, wherein the first expansion is performed over a period of about 11 days or about 12 days and the second expansion is performed over a period of about 11 days or about 12 days. Further, the patient or subject has a predetermined absence of an EGFR mutation or insertion.
The teachings of Schoenfeld and Fardis are set forth above.
Schoenfeld also teaches that 8 of the PD-L1 negative patients were EFGR wild-type. Four of those patients observed significant durable responses with 60-80% change from baseline in target lesion [Fig. 3, pg. 5].
Johnson teaches these results have prompted FDA approval for a randomized confirmatory study to evaluate TIL therapy in combination with pembrolizumab as a frontline treatment in patients with advanced NSCLC who do not have mutations in EGFR [pg. 2, par. 3] (instant claims 2-3).
The teachings of Schoenfeld and Fardis differ from the instantly claimed invention in that although TIL manufacturing and TIL + pembrolizumab treatment for patients with anti-PD-1/PD-L1 naïve NSCLC is taught, the patients are not explicitly taught as having a predetermined absence of a driver mutation. However, one of ordinary skill in the art would screen for EGFR driver mutations, given that Johnson teaches TIL therapy in combination with pembrolizumab is a promising frontline treatment in patients with advanced NSCLC who do not have mutations in EGFR. Thus, the combination of prior art references provided a prima facie case of obviousness for the instantly claimed invention.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”) in view of Fardis et al. (WO 2020/096989 A1; cited IDS 9/16/2024) (“Fardis”) as applied to claims 1, 4, 6, 8-11, 12-16, 20, and 22-30 above, and in further view of Chesney et al. (ASCO 2019, Poster No. 290a) (“Chesney”).
The instant claims are drawn to a method of treating anti-PD-1/PD-L1 naïve non-small cell lung carcinoma (NSCLC) by administering tumor infiltrating lymphocytes (TILs) in combination with one or more PD-1 or PD-L1 inhibitors to the subject or patient, wherein the NSCLC is PD-L1 negative as determined by a tumor proportion score (TPS) of <1%, and wherein the one or more PD-1 inhibitors or PD-L1 inhibitors is administered every six weeks after the administration of the population of TILs. The PD-1 inhibitor is pembrolizumab and is administered via intravenous infusion at a dosage of 400 mg every six weeks for up to 2 years. Further comprising the step of treating the patient or subject with an IL-2 regimen starting three to twenty-four hours after administration of a therapeutically effective amount of the population of TILs to the patient or subject; further comprising the step of treating the patient or subject with a non-myeloablative lymphodepletion regimen comprising cyclophosphamide and fludarabine. Also claimed are methods for TIL production and harvesting as recited in claim 14, wherein the first expansion is performed over a period of about 11 days or about 12 days and the second expansion is performed over a period of about 11 days or about 12 days.
The teachings of Schoenfeld and Fardis are set forth above.
Schoenfeld or Fardis do not teach pembrolizumab is administered via intravenous infusion.
Chesney teaches a study of autologous tumor infiltrating lymphocytes (TILs) + pembrolizumab in patients with solid tumors, including NSCLC patients that are checkpoint inhibitor naïve [Fig. 2A)]. Chesney teaches that pembrolizumab is administered intravenously following IL 2 completion for 24 months or until disease progression or unacceptable toxicity [Study Flowchart] (instant claim 7).
The teachings of Schoenfeld and Fardis differ from the instant claims in that pembrolizumab is not specifically taught as being administered intravenously. However, it would have been obvious to one of ordinary skill in the art before the effective filing date the instant invention that pembrolizumab is delivered by intravenous infusion as evidenced by Chesney. One would have more than a reasonable expectation of success in administering pembrolizumab intravenously in combination with TIL therapy as Chesney teaches this combination for the treatment of checkpoint inhibitor naïve NSCLC. Thus, the combination of prior art references provided a prima facie case of obviousness for the instantly claimed invention.
Response to Arguments
Applicant’s arguments with respect to the rejection of the instant claims under 35 U.S.C. 103 have been considered but are moot because the new grounds of rejection do not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
However, in the reply received January 7, 2026 Applicant relies on the Declaration of Dr. Jefferey Chou under 37 C.F.R. § 1.132(a) that was filed on November 22, 2024 to overcome the obviousness rejection regarding administering pembrolizumab every six weeks vs every three weeks. However, the Chou declaration was never filed in the present application. The Chou declaration was submitted in response to arguments regarding copending application 18/674,562.
In response to this Office Action, Applicant is advised to submit the Chou declaration that was filed in application 18/674,562. In addition, Applicant should also submit the Finckenstein declaration under 37 C.F.R. § 1.132(a) that was filed on March 2, 2026 in application 18/674,562 for further consideration regarding the particular facts of the present application.
Double Patenting - Withdrawn
The previous provisional nonstatutory double patenting rejections over copending Application No. 18/256,798 have been withdrawn because the copending application has since been abandoned making the rejections moot.
Double Patenting - Maintained/Updated
Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
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 1-4, 6, 8-10, 12-16, 19-20, 22-26, and 28-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 13, 15-16, 18, 40, and 91 of copending Application No. 18/247,877 in view of Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”). Although the claims at issue are not identical, they are not patentably distinct from each other because they teach methods for treating NSCLC by administering TILs to a subject that is PD-1/PD-L1 inhibitor naïve with negative PD-L1 expression and a TPS <1% with the absence of one or more driver mutations including an EFGR mutation.
The copending claims differ from the instant claims in that they do not teach the method is combined with pembrolizumab administration of 400 mg every 6 weeks, and that the method also includes a non-myeloablative lymphodepletion regimen and administration of a high-dose regimen of IL-2.
The teachings of Schoenfeld are set forth above specifically teaching the combination of pembrolizumab with TIL therapy for anti-PD-1/PD-L1 naïve NSCLC patients that includes a non-myeloablative lymphodepletion regimen and administration of IL-2 after TIL infusion. It would have been obvious to combine the protocols of the copending application with those of Schoenfeld because Schoenfeld teaches that TIL infusion combined with pembrolizumab administration is more effective than either treatment as a monotherapy. As such, the instant claimed invention is an obvious modification of the claims of the copending application in view of Schoenfeld.
This is a provisional nonstatutory double patenting rejection.
Claims 7 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 13, 15-16, 18, 40, and 91 of copending Application No. 18/247,877 in view of Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”), and in further view of Chesney et al. (ASCO 2019, Poster No. 290a) (“Chesney”). Although the claims at issue are not identical, they are not patentably distinct from each other because they teach methods for treating NSCLC by administering TILs to a subject that is PD-1/PD-L1 inhibitor naïve with negative PD-L1 expression and a TPS <1% with the absence of one or more driver mutations including an EFGR mutation.
The copending claims differ from the instant claims in that they do not teach pembrolizumab is administered intravenously.
The teachings of Schoenfeld and Chesney are set forth above. Specifically, Chesney teaches pembrolizumab administration via intravenous infusion. It would have been more than obvious that pembrolizumab is administered by intravenous injection as evidenced by Chesney. As such, the instant claimed invention is an obvious modification of the claims of the copending application in view of Schoenfeld and Chesney.
This is a provisional nonstatutory double patenting rejection.
Claims 11 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 13, 15-16, 18, 40, and 91 of copending Application No. 18/247,877 in view of Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”), and in further view of Fardis et al. (WO 2020/096989 A1; cited IDS 9/16/2024) (“Fardis”). Although the claims at issue are not identical, they are not patentably distinct from each other because they teach methods for treating NSCLC by administering TILs to a subject that is PD-1/PD-L1 inhibitor naïve with negative PD-L1 expression and a TPS <1% with the absence of one or more driver mutations including an EFGR mutation.
The copending claims differ from the instant claims in that they do not teach IL-2 is administered as a 15-minute bolus. Methods for IL-2 administration following TIL infusion were well known in the art at the time of filing. As such, the instant claimed invention is an obvious modification of the claims of the copending application in view of Schoenfeld and Fardis.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 6, 8-10, 12-16, 19-20, 22-26, and 28-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 14-18, 20-26, 35-36, 39-41, 72-75, 79-84, 87, 91,-92, 97, 105-117, 135, 190, 211-212, 220-233, 297-298, 301, 308-309, 312, 314, 316-318, 320-327, and 329 of copending Application No. 18/849,440, in view of Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”). Although the claims at issue are not identical, they are not patentably distinct from each other because they teach methods for treating NSCLC by administering TILs combined with a non-myeloablative lymphodepletion regimen and administration of a high-dose regimen of IL-2 to a subject that is PD-1/PD-L1 inhibitor naïve with negative PD-L1 expression and a TPS <1% with the absence of one or more driver mutations including an EFGR mutation.
The copending claims differ from the instant claims in that they do not teach the method is combined with pembrolizumab administration of 400 mg every 6 weeks.
The teachings of Schoenfeld are set forth above specifically teaching the combination of pembrolizumab with TIL therapy for anti-PD-1/PD-L1 naïve NSCLC patients that includes a non-myeloablative lymphodepletion regimen and administration of IL-2 after TIL infusion. It would have been obvious to combine the protocols of the copending application with those of Schoenfeld because Schoenfeld teaches that TIL infusion combined with pembrolizumab administration is more effective than either treatment as a monotherapy. As such, the instant claimed invention is an obvious modification of the claims of the copending application in view of Schoenfeld.
This is a provisional nonstatutory double patenting rejection.
Claims 7 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 14-18, 20-26, 35-36, 39-41, 72-75, 79-84, 87, 91,-92, 97, 105-117, 135, 190, 211-212, 220-233, 297-298, 301, 308-309, 312, 314, 316-318, 320-327, and 329 of copending Application No. 18/849,440 in view of Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”), and in further view of Chesney et al. (ASCO 2019, Poster No. 290a) (“Chesney”). Although the claims at issue are not identical, they are not patentably distinct from each other because they teach methods for treating NSCLC by administering TILs to a subject that is PD-1/PD-L1 inhibitor naïve with negative PD-L1 expression and a TPS <1% with the absence of one or more driver mutations including an EFGR mutation.
The copending claims differ from the instant claims in that they do not teach pembrolizumab is administered intravenously.
The teachings of Schoenfeld and Chesney are set forth above. Specifically, Chesney teaches pembrolizumab administration via intravenous infusion. It would have been more than obvious that pembrolizumab is administered by intravenous injection as evidenced by Chesney. As such, the instant claimed invention is an obvious modification of the claims of the copending application in view of Schoenfeld and Chesney.
This is a provisional nonstatutory double patenting rejection.
Claims 11 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 14-18, 20-26, 35-36, 39-41, 72-75, 79-84, 87, 91,-92, 97, 105-117, 135, 190, 211-212, 220-233, 297-298, 301, 308-309, 312, 314, 316-318, 320-327, and 329 of copending Application No. 18/849,440 in view of Schoenfeld et al. (IASLC 2023 World Conference on Lung Cancer, Singapore; September 9-12, 2023) (“Schoenfeld”), and in further view of Fardis et al. (WO 2020/096989 A1; cited IDS 9/16/2024) (“Fardis”). Although the claims at issue are not identical, they are not patentably distinct from each other because they teach methods for treating NSCLC by administering TILs to a subject that is PD-1/PD-L1 inhibitor naïve with negative PD-L1 expression and a TPS <1% with the absence of one or more driver mutations including an EFGR mutation.
The copending claims differ from the instant claims in that they do not teach IL-2 is administered as a 15-minute bolus. Methods for IL-2 administration following TIL infusion were well known in the art at the time of filing. As such, the instant claimed invention is an obvious modification of the claims of the copending application in view of Schoenfeld and Fardis.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is 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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/MAUREEN VARINA DRISCOLL/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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