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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant's arguments filed 6/9/2025, with respect to the rejections of claims 1-13 under 35 U.S.C. 103 as being unpatentable over Soon-Shiong and Gang and further in view of Le Tourneau, have been fully considered but they are not persuasive.
Applicant’s position is that 1) the teachings of Le Tourneau equate to only a general and conclusory assertion that one skilled in the art would have been motivated to make the currently claimed combination and 2) the combination of cited prior art does not teach or suggest a novel treatment regimen wherein there is a fixed or set number of induction cycles wherein the subject is administered an IL-15 protein/fusion protein, a PD-1 inhibitor, and a taxane in each cycle.
Regarding 1), Le Tourneau teaches dosage optimization of drugs or new combinations of drugs in phase I clinical trials for cancer. In other words, Le Tourneau teaches routine optimization of dosing and scheduling, which is dependent on a number of variables such as preclinical data, current disease-specific standard treatments, the expected control arm if a combination of drugs under evaluation may be benchmarked by future randomized trials, and/or empiricism. Thus, dosing and scheduling of drug combinations comprises a number of result-effective variables that require routine optimization by one skilled in the art. Therefore, the teachings of Le Tourneau render the claim limitations regarding a certain number of therapeutic cycles (amended claim 1), a certain order of administration of multiple therapeutics (claims 12 and 13), and a certain amount of days between cycles (claim 12) obvious. See MPEP 2144.05(II).
Regarding 2), although the prior claim set did not include the amended limitation regarding the induction phase cycles of treatment, the current claim set is still rendered obvious; see art rejections below.
Applicant’s arguments filed 6/9/2025, with respect to the rejections of claims 1-13 under 35 U.S.C. 103 as being unpatentable over NCT03228667 and Achour et al., as evidenced by Han, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the amended claims.
Applicant's arguments filed 6/9/2025, with respect to the double patenting rejections, have been fully considered but they are not persuasive.
Applicant’s position is that the instant claims are patentably distinct from those of US ‘201 and ‘679 and are not anticipated by or obvious in view of each other. This is not found persuasive as the instant claims can be rendered obvious by the claims of US ‘201 and ‘679 in view of the art cited in the art rejections below. Therefore, the double patenting rejections have been modified/maintained herein.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-13, in the reply filed on 2/11/2026 is acknowledged.
Claim Status
Claims 1-13 are pending. Claims 14-17 are cancelled. Claims 1, 12 and 13 are currently amended.
Priority
The application claims priority to the provisional applications 63/795,016, filed 4/25/2025, and 63/729,079, filed 12/6/2024. The priority date of 12/6/2024 is acknowledged.
Information Disclosure Statement
The IDS filed on 06/09/2026 is under consideration.
Claim Interpretation
Claim 1 recites that the method comprises administering a single round of two induction phase cycles of treatment, wherein each cycle comprises administering to the subject 1) an IL-15 protein or fusion protein, IL-15:IL-15α protein or fusion protein derivative thereof; 2) a PD-1 inhibitor antibody; and 3) a taxane, wherein the taxane is administered no more than once during each of the two induction phase cycles. This is being interpreted as two cycles of administration of 1-3 above, wherein 3) the taxane, is only administered once per cycle for a total of two times (two cycles, once per cycle).
Claim 9 recites that the IL-15 protein/fusion protein derivative or IL-15:IL-15Rα protein/fusion protein derivative “retains binding affinity and agonist activity to interleukin-15 receptor subunits beta gamma (IL-15Rβγ)”. This limitation describes a functional rather than a structural element of the instant invention. As such, the claim is being interpreted based upon the structural limitation (the IL-15 protein/fusion protein derivative or IL-15:IL-15Rα protein/fusion protein derivative), where the functional limitation is a property endowed by the structure.
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.
Rejection #1
Claim(s) 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Soon-Shiong (WO2018005973A1, published 1/4/2018) in view of Gang et al. (Immune checkpoint inhibitors rechallenge in non-small cell lung cancer: Current evidence and future directions. Cancer Lett. 2024 Nov 1;604:217241), as evidenced by Han et al. (IL-15:IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization. Cytokine. 2011 Dec;56(3):804-10.), and Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.).
Soon-Shiong teaches a method of treating cancer using coordinated treatment regimens that use various compounds and compositions that drive a tumor from the escape phase of cancer immunoediting to the elimination and equilibrium phase of cancer immunoediting (Abstract).
Soon-Shiong teaches a method of treating a tumor whereby the following treatment regimens are administered ([0019]): a) a first pharmaceutical composition comprises a drug such as Docetaxel (taxane; [0014, 0021]); a second pharmaceutical composition comprising an immune stimulatory cytokine such as IL-15 or IL-15 superagonist ([0016, 0023]) or an IL-15 superagonist/IL-15RaSushi-Fc fusion complex ([0097]); a third pharmaceutical composition comprising a checkpoint inhibitor (e.g., a PD-1 inhibitor) and an immune stimulatory cytokine (e.g., IL-15 or a superagonist thereof) ([0017, 0024]).
The tumor can be non-small cell lung cancer, which includes non-small cell lung carcinoma ([00367]).
Soon-Shiong also teaches that the treatment regimen will be followed until the desired therapeutic effect is achieved and/or for as long as the desired therapeutic effect is to be maintained, which can be determined by a clinician ([0262]). In other words, Soon-Shiong teaches optimization of the treatment regimen such that it is tailored to or suitable for the patient in need thereof.
Soon-Shiong does not teach treating an NSCLC patient in need thereof who has been previously treated with an immune checkpoint inhibitor and subsequently experienced disease progression nor administering a single round of two induction phase cycles of treatment comprising the IL-15 protein/fusion protein, PD-1 inhibitory antibody, and taxane, wherein the taxane is administered no more than once during each cycle.
Gang teaches that immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of NSCLC and have become the standard treatment for advanced NSCLC patients without driver mutations. The subsequent treatment of patients who discontinue ICIs for diverse reasons remains an unmet clinical need in NSCLC research. To address this gap, the concept of ICIs rechallenge has emerged, which involves reintroducing ICIs after their discontinuation due to serious immune-related adverse events or disease progression during/after previous ICIs treatment. The rationale for rechallenge is that previously responsive patients may retain ICI-susceptible tumor cells and the dynamic nature of the immune system and interaction within the tumor immune environment might offer renewed opportunities for ICIs when alternative options are limited or ineffective (Pg 1, “1. Background”, paragraphs one and two).
Gang further teaches that ICI rechallenge therapy can be combined with other therapies for improved outcomes, such as combination with other ICIs (i.e., anti-PD-1 antibodies) and/or targeted therapies (e.g., taxanes; Pg 5, “3.2.3.3. Combination with other ICIs”; Pg 6, “3.2.3.5. Combination with targeted therapies”).
Le Tourneau teaches dosage optimization of drugs or new combinations of drugs in phase I clinical trials for cancer (Title, Abstract). Le Tourneau explains that in rule-based phase I trials of drug combinations, the dose level of each drug may be based on several factors such as preclinical data, current disease-specific standard treatments, the expected control arm if a combination of drugs under evaluation may be benchmarked by future randomized trials, and/or empiricism (Pg 715, “Designs for trials of combinations of agents, second paragraph). Bayesian modeling as well as pharmacokinetic analyses may further provide information regarding toxicities and interactions between different anticancer drugs administered in combination (third and fourth paragraphs). All of these decisions impact the recommended schedules and dosages, which can determine the success or failure of a trial.
Thus, regarding claim 1, Soon-Shiong teaches a method of treating NSCLC comprising administering a combination of an IL-15 protein or fusion protein or an IL-15:IL-15Rα protein or fusion protein, a PD-1 inhibitory antibody, and a taxane. Gang teaches treating patients with NSCLC who previously received ICIs and experienced disease progression through rechallenging with ICIs, which can also be combined with other ICIs and other targeted therapies. Based on these teachings, it would be obvious to treat the patients of Gang using the method of treatment taught by Soon-Shiong in order to increase the chances of improved outcomes for patients with NSCLC. One would have a reasonable expectation of success as both Soon-Shiong and Gang teach that combination therapies can improve patient outcomes.
Soon-Shiong and Gang do not explicitly teach administering a single round of two induction phase cycles of treatment, wherein the taxane is administered no more than once during each cycle. However, Soon-Shiong does teach that a clinician can optimize the treatment regimen such that a desired therapeutic outcome is achieved and/or for as long as treatment is necessary. Additionally, Le Tourneau teaches dosage optimization in phase I cancer clinical trials. Thus, although Soon-Shiong and Gang do not explicitly teach administration of a single round of two induction phase cycles of treatment, wherein the taxane is administered no more than once per cycle, it would have been prima facie obvious to one of ordinary skill in the art because Le Tourneau recognized that scheduling combinations of anticancer therapeutics depended on a number of factors, as described above. Therefore, it would have been obvious to optimize the dosage schedule and dosages as claimed in order to effectively treat NSCLC. See MPEP 2144.05(II).
Regarding claim 2, Soon-Shiong teaches that 70% of newly diagnosed lung cancer patients present with advanced stage disease and most of these patients have metastatic disease ([00368]).
Regarding claim 3, Soon-Shiong teaches that prospective tumor molecular profiling will be conducted to inform HER2 expression and Ras mutational status ([00376]). The instant specification indicates a genomic alteration is considered actionable if it predicts therapy response (sensitivity or resistance), has demonstrated the ability to establish diagnosis or influence prognosis, affects the function of a cancer‐related gene and can be targeted directly or indirectly with approved or investigational therapies, is a specific eligibility criterion for enrollment onto genotype‐selected trials, is a germline alteration that predicts drug metabolism and/or adverse effects, is a germline alteration that predicts future risk of cancer or other diseases (instant [0053]).
Regarding claims 4 and 6, Soon-Shiong teaches administering the antibody nivolumab ([00368]; Figure 21), which is a IgG4 PD-1 inhibitor per the instant specification (instant [0006]).
Regarding claim 5, Soon-Shiong teaches administering ALT-803 ([00373]), which is another name for N-803 per the instant specification (instant [0049]).
Regarding claims 6 and 7, Gang teaches that some clinical trials on ICIs rechallenge for NSCLC involve tislelizumab (Table 1, number 13).
Regarding claim 8, as stated above, Soon-Shiong teaches administering docetaxel ([0014, 0021]).
Regarding claim 9, as stated above, Soon-Shiong teaches administering ALT-803 ([00373]). As evidenced by Han, N-803 (IL-15N72D:IL-15RαSu/Fc complex) has increased binding activity to IL-15Rβγc (Abstract).
Regarding claim 10, Soon-Shiong teaches administering ALT-803 subcutaneously ([00443]) and PD-1 inhibitors such as nivolumab intravenously ([00412]). Although not explicitly stated, it also would be obvious to administer a taxane, such as docetaxel taught by Soon-Shiong, intravenously as Soon-Shiong teaches that other taxanes such as paclitaxel can be administered in this way (see, for example, [00391, 00406, 00411] as part of the treatment regimen for NSCLC).
Regarding claim 11, as stated above, Soon-Shiong teaches that the IL-15 protein/fusion protein derivative or IL-15:IL-15Rα protein/fusion protein derivative, PD-1 inhibitor, and taxane are in pharmaceutical compositions [0014, 0016-0017, 0021, and 0023-0024]).
Regarding claims 12 and 13, as stated above, Le Tourneau teaches optimizing the scheduling combinations of anticancer therapeutics. Further, Soon-Shiong also teaches that the treatment regimen will be followed for as long as the desired therapeutic effect is to be maintained ([0262]), which renders obvious further administering a maintenance phase to a subject in need thereof undergoing treatment.
Rejection #2
Claim(s) 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03228667 (QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors; V25 updated 8/25/2023; hereafter referred to as “NCT”) and Achour et al. (WO 2023170008 A1, published 9/14/2023), as evidenced by Han et al. (IL-15:IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization. Cytokine. 2011 Dec;56(3):804-10.).
NCT is a phase IIb, multicohort, open-label multicenter study of combination immunotherapies in patients who have previously received treatment with PD-1/PD-L1 immune checkpoint inhibitors. All patients in Cohorts 1-4 will receive the combination treatment of PD-1/PD-L1 checkpoint inhibitor plus N-803 for up to 17 cycles; this reads on administering two phases cycles of treatment. Some patients who experience disease progression while on study in Cohorts 1-4 may roll over into Cohort 5 and receive combination therapy with a PD-1/PD-L1 checkpoint inhibitor, N-803, and PD-L1 t-haNK cellular therapy for up to an additional 17 cycles (Pg 8, Study Description, Brief Summary).
Cohorts 1-5 all comprise patients with NSCLC. Cohorts 2-5 comprise patients with NSCLC who have relapsed on a PD-1 checkpoint inhibitor after experience an initial complete response (CR) or partial response (PR) when they received checkpoint inhibitor as a single-agent for first-line treatment (cohort 2); had initial CR or PR subsequently relapsed on maintenance PD-1 checkpoint inhibitory therapy when they initially received checkpoint inhibitory therapy in combination with chemotherapy as first-line treatment (cohort 3); patients currently receiving PD-1/PD-L1 checkpoint inhibitory therapy and have disease progression after experience stable disease for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitory therapy (cohort 4); and patients that have experienced disease progression by investigator-assessment per irRECIST while receiving treatment in cohorts 1-4 (see Pg 31-34 for better images of Arms and Interventions section).
For each of the 5 cohorts, patients receive N-803 and a PD-1 inhibitor antibody such as pembrolizumab, nivolumab, atezolizumab, avelumab, or durvalumab; per the instant specification, these antibodies are PD-1 inhibitor antibodies (instant [0094]).
NCT does not teach also treating with an effective amount of a taxane.
Achour teaches methods of treating patients with cancer, for example, advanced non-small cell lung cancer (NSCLC), to obtain a greater overall survival based on an improved understanding of predictive and prognostic characteristics that are correlated with greater immunotherapy efficacy ([00048]). The method comprises evaluating biomarker levels prior to administering a standard of care anticancer therapeutic to the patient and/or one or more chemokines, cytokines, antibodies, antigen-presenting cells and/or synthetic scaffolds to the patient ([0008]). The standard of can anticancer therapeutic comprises one or more of a taxane ([0009]). The immunotherapy comprises a checkpoint inhibitor, such as an anti-PD-1 antibody ([00010]).
Thus, regarding claim 1, NCT teaches administering a combination of a N-803 and a PD-1 inhibitory antibody to treat patients with NSCLC. Achour teaches administering a combination of a chemotherapeutic agent, such as a taxane, and an anti-PD-1 antibody to treat NSCLC. Per MPEP 2144.06(I), combining equivalents known for the same purpose is one legal precedent recognized by the courts as directed to common practices that normally require only ordinary skill in the art and are considered routine expedients: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). By extension of this, it would be obvious to combine the method of treating NSCLC patients comprising administering N-803 and an anti-PD-1 antibody taught by NCT and the method of treating NSCLC patients comprising administering an anti-PD-1 antibody and a taxane as taught by Achour into one method because both method methods effectively target and treat NSCLC.
Regarding claim 2, NCT teaches treating patients included in the study can have metastatic NSCLC (PG 17-18, Eligibility, “Criteria”, Cohort 1, 1a). Achour also teaches that the NSCLC may be advanced ([0007]).
Regarding claim 3, NCT teaches patients with EGFR or ALK genomic tumor aberrations should have had disease progression on FDA-approved targeted therapy for these aberrations prior to receiving checkpoint inhibitor (Pg 17-18, Eligibility, “Criteria”, Cohort 1, 1a). The instant specification indicates a genomic alteration is considered actionable if it predicts therapy response (sensitivity or resistance), has demonstrated the ability to establish diagnosis or influence prognosis, affects the function of a cancer‐related gene and can be targeted directly or indirectly with approved or investigational therapies, is a specific eligibility criterion for enrollment onto genotype‐selected trials, is a germline alteration that predicts drug metabolism and/or adverse effects, is a germline alteration that predicts future risk of cancer or other diseases (instant [0053]).
Regarding claim 4, as stated above, NCT teaches treating patients with pembrolizumab or nivolumab; per the instant specification, these antibodies are PD-1 inhibitor antibodies (instant [0005, 0006]).
Regarding claim 5, as stated above, NCT teaches treating patients with N-803.
Regarding claims 6 and 7, as stated above, NCT teaches administering both pembrolizumab and nivolumab, which are anti-PD-1 antibodies (instant [0005, 0006]. Achour also teaches administering tislelizumab as the anti-PD-1 antibody ([0008]). Per the instant specification, tislelizumab is also known as BGB-A317 (instant [0096]).
Regarding claim 8, Achour teaches that the taxane can be docetaxel ([0008]).
Regarding claim 9, as stated above, NCT teaches administering N-803. As evidenced by Han, N-803 (IL-15N72D:IL-15RαSu/Fc complex) has increased binding activity to IL-15Rβγc (Abstract).
Regarding claim 10, NCT teaches that N-803 and the aforementioned anti-PD-1 antibodies are administered through subcutaneous injection and intravenously, respectively (PG 31-34, Arms and Interventions). Achour teaches that standard of care anticancer therapeutics can be administered intravenously ([00031, 00069]).
Regarding claim 11, Achour teaches compositions of the therapeutic agents ([00033]).
Regarding claim 12, Achour teaches that the time delays between successive treatment cycles (i.e., between the first and second treatment cycles, the second a third treatment cycles) can be as long as 1-3 weeks or 7-21 days. Achour further teaches a first therapeutic compound or agent may be administered before, concurrently with, or after administration of a second therapeutic compound or agent. The first therapeutic compound or agent and the second therapeutic compound or agent may be simultaneously or sequentially administered on the same day, or may be sequentially administered within 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, or 1 month of each other ([00032]). Therefore, it would be obvious to administer N-803, an anti-PD-1 antibody, and a taxane in that order as Achour teaches that the order in which therapeutic agents are administered can be optimized.
Claim(s) 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03228667 (QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors; V25 updated 8/25/2023; hereafter referred to as “NCT”) and Achour et al. (WO 2023170008 A1, published 9/14/2023), as evidenced by Han et al. (IL-15:IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization. Cytokine. 2011 Dec;56(3):804-10.), as applied to claims 1-12 above, and further in view of Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.).
The teachings of NCT and Achour have been set forth above; as stated above, NCT teaches some patients who experience disease progression while on study in Cohorts 1-4 may roll over into Cohort 5 and receive combination therapy with a PD-1/PD-L1 checkpoint inhibitor, N-803, and PD-L1 t-haNK cellular therapy for up to an additional 17 cycles, effectively reading on a maintenance phase cycle of treatment (Pg 8, Study Description, Brief Summary). NCT and Achour do not teach that the maintenance phase cycle of treatment is administered 40-44 days after the completion of the first cycle of treatment.
Le Tourneau teaches dosage optimization of drugs or new combinations of drugs in phase I clinical trials for cancer (Title, Abstract). Le Tourneau explains that in rule-based phase I trials of drug combinations, the dose level of each drug may be based on several factors such as preclinical data, current disease-specific standard treatments, the expected control arm if a combination of drugs under evaluation may be benchmarked by future randomized trials, and/or empiricism (Pg 715, “Designs for trials of combinations of agents, second paragraph). Bayesian modeling as well as pharmacokinetic analyses may further provide information regarding toxicities and interactions between different anticancer drugs administered in combination (third and fourth paragraphs). All of these decisions impact the recommended schedules and dosages, which can determine the success or failure of a trial.
Thus, regarding claim 13, although NCT and Achour do not explicitly teach that the maintenance phase of treatment is administered 40-44 days after the first cycle of treatment, it would have been prima facie obvious to one of ordinary skill in the art because Le Tourneau recognized that scheduling combinations of anticancer therapeutics depended on a number of factors, as described above. Therefore, it would have been obvious to optimize the dosage schedule as claimed in order to effectively treat NSCLC. See MPEP 2144.05(II).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 8, and 9 of U.S. Patent No. US 11,318,201 B2 (US ‘201) in view of NCT03228667 (QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors; V25 updated 8/25/2023; hereafter referred to as “NCT”), Achour et al. (WO 2023170008 A1, published 9/14/2023), and Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.).
In Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co., 95 USPQ2d 1797 (Fed. Cir. 2010), the Court determined that Claims of a later patent were held invalid for obviousness-type double patenting when the earlier patent claimed a compound and disclosed its utility in specification, and later patent claimed a method of using compound for use described in specification of earlier patent.
Claim 1 of US ‘201 recites an isolated soluble fusion protein complex comprising at least two soluble proteins, wherein a first soluble protein comprises an interleukin-15 (IL-15) polypeptide domain and a second soluble protein comprises a soluble IL-15 receptor alpha sushi-binding domain (IL-15RαSu) fused to an immunoglobulin Fc domain, wherein one of the first or second soluble protein further comprises a binding domain substantially identical to SEQ ID NO:2 or SEQ ID NO:6, and wherein the IL-15 domain of the first soluble protein binds to the IL-15RαSu domain of the second soluble protein to form a soluble fusion protein complex.
Dependent claims include the IL-15 polypeptide is a variant comprising an N72D mutation (claim 3; a mutation found in the instantly claimed N-803). Additional independent claims 8 and 9 recite additional isolated soluble fusion protein complexes.
US ‘201 does not teach using the soluble fusion protein complex in a method of treating NSCLC, wherein the patient was previously treated with an immune checkpoint inhibitor and subsequently experienced disease progression, comprising administering a single round of two induction phase cycles comprising administering said soluble fusion protein complex in addition to a PD-1 inhibitor and a taxane, wherein the taxane is only administered once in each cycle.
NCT teaches administering a combination of N-803 (an IL-15 fusion protein) and a PD-1 inhibitory antibody to treat patients with NSCLC who were previously treated with an immune checkpoint inhibitor and have experienced disease progression. Achour teaches administering a combination of a chemotherapeutic agent, such as a taxane, and an anti-PD-1 antibody to treat NSCLC. Le Tourneau teaches optimization of cancer therapeutic regiments, including dosing and scheduling.
Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of NCT, Achour, and Le Tourneau into US ‘201, thereby arriving at the instant invention. One skilled in the art would be motivated to do so and have a reasonable expectation of success as NCT, Achour, and Le Tourneau teach administering a combination of IL-15 fusion proteins, an PD-1 inhibitory antibody, and a taxane in an optimized treatment schedule (two induction phase cycles) to treat NSCLC. Thus, the claims are obvious in view of US ‘201.
Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-6, 9, and 12-16 of U.S. Patent No. US 11,369,679 B2 (US ‘679) in view of NCT03228667 (QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors; V25 updated 8/25/2023; hereafter referred to as “NCT”), Achour et al. (WO 2023170008 A1, published 9/14/2023), and Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.).
In Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co., 95 USPQ2d 1797 (Fed. Cir. 2010), the Court determined that Claims of a later patent were held invalid for obviousness-type double patenting when the earlier patent claimed a compound and disclosed its utility in specification, and later patent claimed a method of using compound for use described in specification of earlier patent.
Claim 1 of US ‘679 recites an isolated soluble fusion protein complex comprising at least two soluble proteins, wherein a first soluble protein comprises an interleukin-15 (IL-15) polypeptide domain and a second soluble protein comprises a soluble IL-15 receptor alpha sushi-binding domain (IL-15RαSu) fused to an immunoglobulin Fc domain, wherein one of the first or second soluble protein further comprises a binding domain substantially identical to SEQ ID NO:14 or SEQ ID NO:16, and wherein the IL-15 domain of the first soluble protein binds to the IL-15RαSu domain of the second soluble protein to form a soluble fusion protein complex.
Dependent claims include the IL-15 polypeptide is a variant comprising an N72D mutation (claim 3; a mutation found in the instantly claimed N-803), species of the first soluble protein (claims 4, 13, 14, and 16), a method for treating a neoplasia in a subject comprising administering an effective amount of the soluble fusion protein complex of claim 1 (claim 5) species of cancer to be treated, including NSCLC (claim 6), the mode of administration of the fusion protein complex (claim 9). Additional independent claims 12 and 15 recite additional isolated soluble fusion protein complexes.
US ‘679 does not teach using the soluble fusion protein complex in a method of treating NSCLC, wherein the patient was previously treated with an immune checkpoint inhibitor and subsequently experienced disease progression, comprising administering a single round of two induction phase cycles comprising administering said soluble fusion protein complex in addition to a PD-1 inhibitor and a taxane, wherein the taxane is only administered once in each cycle.
NCT teaches administering a combination of N-803 (an IL-15 fusion protein) and a PD-1 inhibitory antibody to treat patients with NSCLC who were previously treated with an immune checkpoint inhibitor and have experienced disease progression. Achour teaches administering a combination of a chemotherapeutic agent, such as a taxane, and an anti-PD-1 antibody to treat NSCLC. Le Tourneau teaches optimization of cancer therapeutic regiments, including dosing and scheduling.
Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of NCT, Achour, and Le Tourneau into US ‘201, thereby arriving at the instant invention. One skilled in the art would be motivated to do so and have a reasonable expectation of success as NCT, Achour, and Le Tourneau teach administering a combination of IL-15 fusion proteins, an PD-1 inhibitory antibody, and a taxane in an optimized treatment schedule (two induction phase cycles) to treat NSCLC. Thus, the claims are obvious in view of US ‘201.
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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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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