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 22-41 are pending and under examination in the instant office action.
Information Disclosure Statement
Applicant’s duty to disclose information material to the patentability of the claimed invention is noted.
In the instant application, the examiner would like to note that Applicant has submitted information disclosure statement(s) with a total of over 2300 references. While the examiner has made every effort to thoroughly review these references, one could have very well missed a pertinent document.
As noted in MPEP §2004, “it is desirable to avoid the submission of long lists of documents if it can be avoided”. If a long list is submitted, Applicant has an obligation to call the most pertinent prior art to the attention of the Patent Office in a proper fashion and not “to disclose a pertinent prior art patent reference to the examiner in such a way as to ‘bury’ it or its disclosures in a series of disclosures of less relevant prior art references” (See Penn Yan Boats, Inc. v. Sea Lark Boats, Inc., 359 F. Supp. 948, 175 USPQ 260 (S.D. Fla. 1972), Golden Valley Microwave Food Inc. v. Weaver Popcorn Co., 837 F. Supp. 1444, 24 USPQ2d 1801 (N.D. Ind. 1992)).
Regarding the IDS filed 4/13/2026 (89 pages), Examiner has annotated the reference cited as JP-60-84288-B2 to JP-60-84288-A because JP-60-84288-A was the reference provided and JP-60-84288-B2 is a different, unrelated document.
Claim Rejections - 35 USC § 112(b)
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.
Claim 26 and 33 is 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.
Claim 26 recites “with an infusion time of up to 24 hours, 1 to 12 hours, 1 to 6 hours, and most preferably 1 hour”. First, it is unclear how these mutually exclusive ranges may be met if they are joined with an “and”. Second the term “most preferably” is an exemplary term which renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is suggested the applicant revise the claims to remove the term “most preferably” and the limitations following it and to recite the different limitations in the alternate.
Claim 33 recites “wherein the patient receives primary prophylaxis with G-CSF starting 24-72 hours after Day 1 of each cycle, and for five days”. However, the antecedent basis of “Day 1 of each cycle” is not clear because both claims 32 and claims 22 from which claim 33 ultimately depends recite “day 1 of a 21 day cycle”. Therefore, it is unclear whether the Day 1 referred to by claim 33 is the cycle of claim 22 or the cycle of claim 32. For the purposes of expedited prosecution, the claim will be interpreted as the patient receives primary prophylaxis with G-CSF starting 24-72 hours after the administration of lurbinectedin and atezolizumab of claim 22.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 33 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 33 reciteds "wherein the patient recieves primary prophylaxis with G-CSF starting 24-72 hours after Day 1 of each cycle". However, claim 32, from which claim 33 depends, recites "when G-CSF is administered on day 1 of a 21 day cycle". . Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 22-24, 26, 28, 30, 34, and 35-41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NCT04253145 "Study to Assess Safety, Tolerability, Efficacy of PM01183 and Atezolizumab in Patients w/ Advanced Small Cell Lung Cancer". Version V1 published 5 February 2020 (hereinafter NCT'145) (Related to NCT04253145 Cite No. 2 cited on IDS dated 12/13/2024, but version 1 only, no changes to 2023).
Regarding claim 22, NCT’145 teaches a method of treating extensive or limited small cell lung cancer (see Inclusion Criteria, third bullet) by administering a combination of PM01183 (equivalent to lurbinectedin) and atezolizumab wherein the dose of atezolizumab is 1200mg and a dose of i.v. PM01183 escalated from 2.5 to 3.2mg/m2, wherein the combination is administered on Day 1 every three weeks (equivalent to 21 day cycle) (Arms and Interventions section).
Regarding claim 23 and 24, NCT’145 teaches the atezolizumab is administered first followed by (reads on sequentially) PM01183.
Regarding claim 26, NCT’145 teaches the administration of PM01183 is with an infusion time of 1 hour (Arms and Interventions section).
Regarding claim 28, NCT’145 teaches intravenous atezolizumab (Arms and Interventions section).
Regarding claim 30, NCT’145 teaches the IV atezolizumab was administered with an infusion time of 1 hour and that the second and subsequent infusions may be 20 minutes.
Regarding claim 34, NCT’145 teaches one cycle (e.g. Primary Outcome Measure section “evaluable patients experience a DLT during Cycle 1”; also see Secondary Outcome Measures part 11).
Regarding claims 35-39, the claims recite intended results of the method rather than active method steps. Because NCT’145 teaches all of the active steps of claim 22, it must naturally result in the outcomes as claimed in claims 35-39 (See MPEP 2111.04 and 2112).
Regarding claim 40, as described above, NCT’145 teaches a method of treating cancer (reads on “inhibiting cancer cell growth”) comprising administering (reads on “contacting”) a combination of atezolizumab and lurbinectedin (Arms and Interventions) section a further teaches that the patients have extensive stage small cell lung cancer (Inclusion Criteria; reads on ES-SCLC cells).
Regarding claim 41, NCT’145 does not specifically use the language “kit” as recited in the claim. In the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the claimed ingredient lurbinectedin as it does not clearly invoke any additional ingredients or provide antecedent basis for terms in the body of the claim. Additionally, the phrase “for the combination use of lurbinectedin and atezolizumab in the treatment of …[ES-SCLC]” does not further limit the structure of the kit or the lurbinectedin. Regarding the instructions, MPEP §2112.01.III states that written instructions added to a known product, printed matter will not distinguish the invention from the prior art in terms of patentability. Therefore, NCT’145 teaches lurbinectedin (Arms and Interventions section), which reads on the instant kit and written instructions.
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.
Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over NCT04253145 "Study to Assess Safety, Tolerability, Efficacy of PM01183 and Atezolizumab in Patients w/ Advancde Small Cell Lung Cancer". Version V1 published 5 February 2020 (hereinafter NCT'145) as applied to claims 22 and 24 above, and further in view of Horn, Leora, et al. "First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer." New England Journal of Medicine 379.23 (2018): 2220-2229 (IDS dated 4/13/2026 REF #CEL).
The teachings of NCT’145 in regard to claim 22 and 24 are in the 102 rejection above.
NCT’145 does not teach the method wherein multiple administrations of either lurbinectedin, or atezolizumab, or both, are given.
This deficiency is resolved by Horn et. al.
Horn et. al. teaches a method of treating extensive-stage small-cell lung cancer comprising administering four 21-day cycles followed by maintenance phase of atezolizumab or placebo until they had unacceptable toxic effects, disease progression, or no additional clinical benefit (Abstract Methods section). Horn et. al. teaches that atezolizumab combined with chemotherapy resulted in improved overall and progression-free survival (Fig. 2).
It would have been obvious, at the time of filing, for a person of ordinary skill in the art to continue to treat the patients of NCT’145 with additional cycles of atezolizumab, or atezolizumab in combination with PM01183 in order to benefit from a treatment for cancer and to benefit from maintenance doses of atezolizumab after the DLT study as taught by NCT’145. This would have a reasonable expectation of success because a person of ordinary skill in the art would expect cancer treatment to require multiple cycles or maintenance therapy after an experimental dose-limiting toxicity and would continue to administer additional cycles of therapy unless a dose-limiting toxicity was reached; and even if it was, a person of ordinary skill in the art would choose to continue a maintenance therapy if possible as taught by Horn et. al.
Claim(s) 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over NCT04253145 "Study to Assess Safety, Tolerability, Efficacy of PM01183 and Atezolizumab in Patients w/ Advanced Small Cell Lung Cancer". Version V1 published 5 February 2020 (hereinafter NCT'145) as applied to claims 22 or 24 above, and further in view of Felip, Enriqueta, et al. "Results of a Dose‐Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non–Small Cell Lung Cancer." Clinical Pharmacology in Drug Development 10.10 (2021): 1142-1155 published 31 March 2021.
The teachings of NCT’145 in regard to claim 22 are in the 102 rejection above.
NCT’145 does not teach the method wherein the administration of atezolizumab is subcutaneous.
This deficiency is resolved by Felip et. al.
Felip et. al. teaches the results of a dose-finding study for subcutaneous atezolizumab in non-small cell lung cancer. Felip et. al. teaches that subcutaneous atezolizumab is being developed to “improve treatment options, reduce burden, and increase efficiency for patients and practitioners” (Abstract). Felip et. al. teaches that they studied one cohort of 1800mg once, 1200 mg every 2 weeks for 3 cycles, or 1800mg every 3 weeks for 3 cycles. Felip et. al. teaches that serum concentrations of SC atezolizumab showed a dose-dependent exposure. Felip et. al. teaches that atezolizumab SC was well tolerated and the safety profile was consistent with known risks of atezolizumab IV. Felip et. al. states “SC formulations can provide additional options for safe administration of monoclonal antibodies beyond the hospital setting, including the home.24, 27 Patient and practitioner preferences for SC administration compared with IV infusion are linked with spending less time in the clinic, easier administration, improved workflow, and scheduling flexibility”.
It would have been obvious, at the time of filing, for a person of ordinary skill in the art to provide a subcutaneous dose of atezolizumab to benefit from the spending less time in the clinic, easier administration, improved workflow, and scheduling flexibility as taught by Felip et. al. A person of ordinary skill in the art would have been able to optimize the dose and timing in the ranges as taught by Felip et. al. including 1200mg dose and administration schedules of 1 per 3 weeks in order to find the optimal dose in the context of a combination therapy as taught by NCT’145. This would have a reasonable expectation of success because Felip et. al. teaches that subcutaneous atezolizumab had a similar safety profile and methods of determining the pharmacokinetic profiles and similarity to IV administration of atezolizumab.
Claim(s) 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over NCT04253145 "Study to Assess Safety, Tolerability, Efficacy of PM01183 and Atezolizumab in Patients w/ Advancde Small Cell Lung Cancer". Version V1 published 5 February 2020 (hereinafter NCT'145) in view of Felip, Enriqueta, et al. "Results of a Dose‐Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non–Small Cell Lung Cancer." Clinical Pharmacology in Drug Development 10.10 (2021): 1142-1155 as applied to claim 27 above, and in further view of Chouksey, Akhilesh, et al. "Subcutaneous immunoglobulin-g replacement therapy with preparations currently available in the United States for intravenous or intramuscular use: reasons and regimens." Allergy, Asthma & Clinical Immunology 1.3 (2005): 120.
The teachings of NCT’145 in view of Felip et. al. in regard to claim 27 are in the 103 rejection above.
NCT’145 in view of Felip et. al. does not explicitly teach the method of subcutaneous administration wherein the atezolizumab is administered with an infusion time of 1 hour.
This deficiency is resolved by Chouksey et. al.
Chouksey et. al. teaches that preparations of antibodies typically used for intravenous or intramuscular use may be adapted for subcutaneous administration at patient preference such as difficulty with venous access (Abstract). Chouksey et. al. teaches that the infusion time varied between 1 and 3 hours for most patients. (“Dosage Regimens” section, ¶4).
It would have been obvious, at the time of filing, for a person of ordinary skill in the art to use an administration time range for subcutaneous administration of an antibody in the method of NCT’145 modified by Felip et. al. because the formulation of NCT’145 atezolizumab was designed for i.v. administration and therefore would be higher volume and to benefit from the patient preferences of administration as taught by Chouksey. Ths would have a reasonable expectation of success because a person of ordinary skill in the art would be able to optimize the infusion timing for the subcutaneous administration based on the formulation volume.
Claim(s) 31-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over NCT04253145 "Study to Assess Safety, Tolerability, Efficacy of PM01183 and Atezolizumab in Patients w/ Advanced Small Cell Lung Cancer". Version V1 published 5 February 2020 (hereinafter NCT'145) as applied to claim 22 above, and further in view of Cortinovis et. al. "Novel Cytotoxic Chemotherapies in Small Cell Lung Carcinoma." Cancers 13.5 (2021): 1152 (IDS dated 12/13/2024) and Lyman, Gary H., et al. "The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review." Supportive Care in Cancer 25.8 (2017): 2619-2629.
The teachings of NCT’145 in regard to claim 22 are in the 102 rejection above.
NCT’145 does not teach the method wherein the method further comprises the administration of G-CSF.
This deficiency is resolved by Cortinovis et. al. and Lyman et. al.
Cortinovis et. al. summarizes treatments for SCLC including one combination therapy comprising lurbinectedin and irinotecan. Cortinovis et. al. teaches that the maximum tolerated dose combination was 2.4mg/m2 lurbinectedin and 75mg/m2 irinotecan with prophylactic granulocyte-colony stimulating factor (G-CSF) (p. 7 ¶2).
Lyman et. al. teaches that prophylactic G-CSF is used in clinical practice to prevent febrile neutropenia from chemotherapy (Abstract Purpose section, Introduction ¶1-3). Lyman et. al. teaches that “The National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), and the European Organization for Research and Treatment of Cancer (EORTC) practice guidelines all recommend administration of filgrastim and pegfilgrastim 24 to 72 h after chemotherapy [16,17,18]”. Lyman et. al. states “Administration of pegfilgrastim at least 24 h after chemotherapy resulted in improved outcomes for patients across a variety of tumor types receiving myelosuppressive chemotherapy in most studies included in this review. These data support administration of pegfilgrastim to patients at least 1 day after the completion of a chemotherapy cycle”.
Regarding claim 31, it would have been obvious, at the time of filing, for a person of ordinary skill in the art to add G-CSF to the method of treating comprising lurbinectedin in combination with atezolizumab in order to benefit from prophylactic G-CSF in combination with high-dose lurbinectedin as taught by Cortinovis. This would have a reasonable expectation of success because Lyman et. al. teaches that it is routine in the art to administer G-CSF with chemotherapy.
Regarding claim 32, it would have been obvious, at the time of filing, for a person of ordinary skill in the art to administer the G-CSF at least 24 hours after lurbinectedin, resulting in a separate G-CSF 21-day cycle as taught by NCT’145 because Lyman et. al. teaches that administering G-CSF after chemotherapy is effective for treating febrile neutropenia. This would have a reasonable expectation of success because a person of ordinary skill in the art would follow the guidance to administer G-CSF after each cycle of chemotherapy, and NCT’145 teaches a 21-day cycle.
Claim(s) 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over NCT04253145 "Study to Assess Safety, Tolerability, Efficacy of PM01183 and Atezolizumab in Patients w/ Advanced Small Cell Lung Cancer". Version V1 published 5 February 2020 (hereinafter NCT'145) in view of Cortinovis et. al. "Novel Cytotoxic Chemotherapies in Small Cell Lung Carcinoma." Cancers 13.5 (2021): 1152 and Lyman, Gary H., et al. "The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review." Supportive Care in Cancer 25.8 (2017): 2619-2629 as applied to claim 31 and 32 above, and in further view of Clemons, M., et al. "A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer." Annals of Oncology 31.7 (2020): 951-957.
Claim interpretation: As described in the 112(b) above, it is unclear what Day 1 is referred to by claim 33 because there is more than one cycle recited; the claim will be interpreted as the patient receives primary prophylaxis with G-CSF starting 24-72 hours after the administration of lurbinectedin and atezolizumab of claim 22.
The teachings of NCT’145, Cortinovis, and Lyman in regard to claim 31 and 32 are in the 103 rejection above.
The Examiner notes that, as described for claim 32 above, modified NCT’145 in view of Lyman et. al. teaches that administration of G-CSF 24 hours after chemotherapy is effective for treating febrile neutropenia.
NCT’145 in view of Cortinovis and Lyman does not teach administration of G-CSF for five days.
This deficiency is resolved by Clemons et. al.
Clemons et. al. teaches a method of treating febrile neutropenia for breast cancer wherein the most commonly used duration of G-CSF prophylaxis are 5, 7, or 10 days with the choice based on physician preference (p. 951 left column-p. 952 left column ¶1). Clemons et. al. teaches “we have demonstrated that 5 days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days can be considered standard of care for breast cancer patients receiving commonly used adjuvant chemotherapy regimens” (p. 956 right column ¶2).
It would have been obvious, at the time of filing, for a person of ordinary skill in the art to treat the patients with prophylactic G-CSF as taught by modified NCT’145 in view of Cortinovis and Lyman with therapy for 5 days as taught by Clemons et. al. in order to benefit from a duration that is suitable for treatment of febrile neutropenia with prophylactic G-CSF and to benefit from the lower cost and toxicity of the 5 day regimen as taught by Clemons et. al. This would have a reasonable expectation of success because Clemons et. al. teaches that 5 days is among a limited number of choices physicians use and that the treating physician can determine a suitable length of the treatment.
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.
Claim 41 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 7763615. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate the instant claim.
The claims of ‘615 teach a compound of the formula:
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which as evidenced by the instant specification p.1 includes lurbinectedin. The claims also recite a pharmaceutical composition comprising the compound and an excipient (claim 31). Regarding claim 41, the claims of ’615 does not specifically use the language “kit” as recited in the claim. In the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the claimed ingredient lurbinectedin as it does not clearly invoke any additional ingredients or provide antecedent basis for terms in the body of the claim. Additionally, the phrase “for the combination use of lurbinectedin and atezolizumab in the treatment of …[ES-SCLC]” does not further limit the structure of the kit or the lurbinectedin. Regarding the instructions, MPEP §2112.01.III states that written instructions added to a known product, printed matter will not distinguish the invention from the prior art in terms of patentability. Therefore, the claims of ‘516 teach a composition comprising lurbinectedin (claim 1), which reads on the instant kit and written instructions.
Claim 41 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11590129. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate the instant claim.
The claims of ‘129 teach a method of treating cancer comprising administering to a patient in need of such treatment an amount of PM01183 or a pharmaceutically acceptable salt thereof with an amount of irinotecan that together are therapeutically effective and wherein the cancer is lung cancer. Regarding claim 41, the claims of ’129 does not specifically use the language “kit” as recited in the claim. In the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the claimed ingredient lurbinectedin as it does not clearly invoke any additional ingredients or provide antecedent basis for terms in the body of the claim. Additionally, the phrase “for the combination use of lurbinectedin and atezolizumab in the treatment of …[ES-SCLC]” does not further limit the structure of the kit or the lurbinectedin. Regarding the instructions, MPEP §2112.01.III states that written instructions added to a known product, printed matter will not distinguish the invention from the prior art in terms of patentability. Therefore, the claims of ‘129 teach a method of treating comprising a lurbinectedin composition (claim 1), which reads on the instant kit and written instructions.
Claim 41 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 12714706. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate the instant claim.
The claims of ‘706 teach a method of treating cancer including SCLC comprising administering to a patient in need of such treatment lurbinectedin 2.0mg/m2 on day 1 of a 21-day cycle with 75mg/m2 irinotecan that together are therapeutically effective and wherein the cancer is lung cancer. Regarding claim 41, the claims of ’706 does not specifically use the language “kit” as recited in the claim. In the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the claimed ingredient lurbinectedin as it does not clearly invoke any additional ingredients or provide antecedent basis for terms in the body of the claim. Additionally, the phrase “for the combination use of lurbinectedin and atezolizumab in the treatment of …[ES-SCLC]” does not further limit the structure of the kit or the lurbinectedin. Regarding the instructions, MPEP §2112.01.III states that written instructions added to a known product, printed matter will not distinguish the invention from the prior art in terms of patentability. Therefore, the claims of ‘706 teach a method of treating comprising a lurbinectedin composition (claim 1), which reads on the instant kit and written instructions.
Claim 41 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 12440490. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate the instant claim.
The claims of ‘490 teach a method of treating metastatic SCLC in a patient comprising administering a composition of lurbinectedin to patient with particular characteristics. Regarding claim 41, the claims of ’490 does not specifically use the language “kit” as recited in the claim. In the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the claimed ingredient lurbinectedin as it does not clearly invoke any additional ingredients or provide antecedent basis for terms in the body of the claim. Additionally, the phrase “for the combination use of lurbinectedin and atezolizumab in the treatment of …[ES-SCLC]” does not further limit the structure of the kit or the lurbinectedin. Regarding the instructions, MPEP §2112.01.III states that written instructions added to a known product, printed matter will not distinguish the invention from the prior art in terms of patentability. Therefore, the claims of ‘490 teach a method of treating comprising a lurbinectedin composition (claim 1), which reads on the instant kit and written instructions.
Claim 41 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12433890. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate the instant claim.
The claims of ‘890 teach a method of treating SCLC in a patient comprising administering a composition of lurbinectedin monotherapy to patient with particular characteristics. Regarding claim 41, the claims of ’890 does not specifically use the language “kit” as recited in the claim. In the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the claimed ingredient lurbinectedin as it does not clearly invoke any additional ingredients or provide antecedent basis for terms in the body of the claim. Additionally, the phrase “for the combination use of lurbinectedin and atezolizumab in the treatment of …[ES-SCLC]” does not further limit the structure of the kit or the lurbinectedin. Regarding the instructions, MPEP §2112.01.III states that written instructions added to a known product, printed matter will not distinguish the invention from the prior art in terms of patentability. Therefore, the claims of ‘890 teach a method of treating comprising a lurbinectedin composition (claim 1), which reads on the instant kit and written instructions.
Claim 41 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 12324806. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate the instant claim.
The claims of ‘806 teach a method of treating SCLC in a patient comprising administering a composition of lurbinectedin monotherapy to patient with particular characteristics. Regarding claim 41, the claims of ’806 does not specifically use the language “kit” as recited in the claim. In the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the claimed ingredient lurbinectedin as it does not clearly invoke any additional ingredients or provide antecedent basis for terms in the body of the claim. Additionally, the phrase “for the combination use of lurbinectedin and atezolizumab in the treatment of …[ES-SCLC]” does not further limit the structure of the kit or the lurbinectedin. Regarding the instructions, MPEP §2112.01.III states that written instructions added to a known product, printed matter will not distinguish the invention from the prior art in terms of patentability. Therefore, the claims of ‘806 teach a method of treating comprising a lurbinectedin composition (claim 1), which reads on the instant kit and written instructions.
Claim 41 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19190098 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of '098 anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of ‘098 teach a method of treatment of lung cancer, the method comprising administering lurbinectedin to a patient in need thereof, wherein lurbinectedin is administered in combination with atezolizumab and wherein lurbinectedin is administered every 21 days by intravenous infusion at a dose of 3.2 mg/m2 (claim 1).
Regarding claim 41, the claims of ‘098 does not specifically use the language “kit” as recited in the claim. In the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the claimed ingredient lurbinectedin as it does not clearly invoke any additional ingredients or provide antecedent basis for terms in the body of the claim. Additionally, the phrase “for the combination use of lurbinectedin and atezolizumab in the treatment of …[ES-SCLC]” does not further limit the structure of the kit or the lurbinectedin. Regarding the instructions, MPEP §2112.01.III states that written instructions added to a known product, printed matter will not distinguish the invention from the prior art in terms of patentability. Therefore, the claims of ‘098 teach lurbinectedin (claim 1), which reads on the instant kit and written instructions.
Claims 22-30 and 34-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-30 of copending Application No. 19190098 in view of NCT04253145 "Study to Assess Safety, Tolerability, Efficacy of PM01183 and Atezolizumab in Patients w/ Advancde Small Cell Lung Cancer". Version V1 published 5 February 2020 (hereinafter NCT'145) (Related to NCT04253145 Cite No. 2 cited on IDS dated 12/13/2024, but version 1 only, no changes to 2023).
This is a provisional nonstatutory double patenting rejection. The Examiner notes that the issue fee has been paid but the patent has not yet been issued.
The claims of ‘098 teach a method of treatment of lung cancer, the method comprising administering lurbinectedin to a patient in need thereof, wherein lurbinectedin is administered in combination with atezolizumab and wherein lurbinectedin is administered every 21 days by intravenous infusion at a dose of 3.2 mg/m2 (claim 1). Claim 2 teaches wherein the atezolizumab is administered every 21 days.
Regarding claim 23, claims 4, 14, and 23, teaches wherein the lurbinectedin and atezolizumab are administered concurrently, separately, or sequentially.
Regarding claim 25, claim 6 teaches wherein multiple administrations of either lurbinectedin, or atezolizumab, or both are given.
Regarding claim 26, claim 3 teaches wherein the lurbinectedin is administered as a 1 hour infusion.
Regarding claim 27, claim 8 teaches wherein the atezolizumab is administered subcutaneously.
Regarding claim 28, claim 7 teaches wherein the atezolizumab is administered intravenously.
Regarding claim 29, claim 27 teaches wherein the atezolizumab is administered subcutaneously as a 1-hour infusion.
Regarding claim 30, claim 24 teaches wherein the teaches wherein the atezolizumab is administered intravenous as a 1-hour infusion.
Regarding claim 34, although the claims do not explicitly disclose the number of cycles, at least cycle is inherent to the “administered every 21 days by intravenous infusion” of claim 1.
Regarding claim 35-39, these claims recite intended results of the method that do not import further active methods steps. Claim 12 recites the method wherein the method comprises prolonging survival, delaying disease progression, and/or reducing or delaying growth of a lung cancer tumor. Claim 18 recites the method wherein the treatment results in one or more of reduction in tumor size, delay in growth of tumor, prolongation of the life of the patient, delay in disease progression, remission.
Regarding claim 40, as described above, the claims of ‘098 teach a method of treating cancer (reads on “inhibiting cancer cell growth”) comprising administering (reads on “contacting”) a combination of atezolizumab and lurbinectedin.
Thus, the difference between the claims of ‘098 and the instant claims is that the claims of ‘098 do not recite extensive stage small cell lung cancer specifically and do not recite a 1200mg dose of atezolizumab.
This deficiency is resolved by NCT’145.
Regarding claim 22, NCT’145 teaches a method of treating extensive or limited small cell lung cancer (see Inclusion Criteria, third bullet) by administering a combination of PM01183 (equivalent to lurbinectedin) and atezolizumab wherein the dose of atezolizumab is 1200mg and a dose of i.v. PM01183 escalated from 2.5 to 3.2mg/m2, wherein the combination is administered on Day 1 every three weeks (equivalent to 21 day cycle) (Arms and Interventions section).
It would have been obvious, at the time of filing, for a person of ordinary skill in the art to use the doses and timing of atezolizumab and the ES-SCLC patient population of NCT’145 in a specific embodiment of the method of the claims of ‘098. This would have a reasonable expectation of success because a person of ordinary skill in the art would recognize the doses and patient population as species of the genus of the claims of ‘098.
Regarding claims 24 and 25, the claims of ‘098 do not teach the method wherein atezolizumab is administered initially, followed by lurbinectedin.
This deficiency is resolved by NCT’145.
NCT’145 teaches the atezolizumab is administered first followed by (reads on sequentially) PM01183 (Arms and Interventions section).
It would have been obvious, at the time of filing, for a person of ordinary skill in the art to administer atezolizumab first followed by lurbinectedin because there are only three variants: atezolizumab first, lurbinectedin first, or simultaneous administration and therefore a person of ordinary skill in the art would be able to choose the order as taught by NCT’145 as an embodiment of the method of the ‘098 claims with a reasonable expectation of success.
Claims 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-30 of copending Application No. 19190098 in view of NCT04253145 "Study to Assess Safety, Tolerability, Efficacy of PM01183 and Atezolizumab in Patients w/ Advancde Small Cell Lung Cancer". Version V1 published 5 February 2020 (hereinafter NCT'145) (Related to NCT04253145 Cite No. 2 cited on IDS dated 12/13/2024, but version 1 only, no changes to 2023) as applied to claim 22 above, and in further view of Cortinovis et. al. "Novel Cytotoxic Chemotherapies in Small Cell Lung Carcinoma." Cancers 13.5 (2021): 1152 and Lyman, Gary H., et al. "The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review." Supportive Care in Cancer 25.8 (2017): 2619-2629.
The teachings of the claims of ‘098 in view of NCT’145 are in the NSDP rejection above.
The claims of ‘098 in view of NCT’145 do not teach the method further comprising administration of G-CSF. This deficiency is resolved by Cortinovis et. al. and Lyman et. al.
Cortinovis et. al. summarizes treatments for SCLC including one combination therapy comprising lurbinectedin and irinotecan. Cortinovis et. al. teaches that the maximum tolerated dose combination was 2.4mg/m2 lurbinectedin and 75mg/m2 irinotecan with prophylactic granulocyte-colony stimulating factor (G-CSF) (p. 7 ¶2).
Lyman et. al. teaches that prophylactic G-CSF is used in clinical practice to prevent febrile neutropenia from chemotherapy (Abstract Purpose section, Introduction ¶1-3). Lyman et. al. teaches that “The National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), and the European Organization for Research and Treatment of Cancer (EORTC) practice guidelines all recommend administration of filgrastim and pegfilgrastim 24 to 72 h after chemotherapy [16,17,18]”. Lyman et. al. states “Administration of pegfilgrastim at least 24 h after chemotherapy resulted in improved outcomes for patients across a variety of tumor types receiving myelosuppressive chemotherapy in most studies included in this review. These data support administration of pegfilgrastim to patients at least 1 day after the completion of a chemotherapy cycle”.
Regarding claim 31, it would have been obvious, at the time of filing, for a person of ordinary skill in the art to add G-CSF to the method of treating comprising lurbinectedin in combination with atezolizumab of ‘098 in view of NCT’145 in order to benefit from prophylactic G-CSF in combination with high-dose lurbinectedin as taught by Cortinovis. This would have a reasonable expectation of success because Lyman et. al. teaches that it is routine in the art to administer G-CSF with chemotherapy.
Regarding claim 32, it would have been obvious, at the time of filing, for a person of ordinary skill in the art to administer the G-CSF at least 24 hours after lurbinectedin, resulting in a separate G-CSF 21-day cycle as taught by ‘098 claims in view of NCT’145 because Lyman et. al. teaches that administering G-CSF after chemotherapy is effective for treating febrile neutropenia. This would have a reasonable expectation of success because a person of ordinary skill in the art would follow the guidance to administer G-CSF after each cycle of chemotherapy, and both ‘098 claims and NCT’145 teaches a 21-day cycle.
Claim 33 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-30 of copending Application No. 19190098 in view of NCT04253145 "Study to Assess Safety, Tolerability, Efficacy of PM01183 and Atezolizumab in Patients w/ Advancde Small Cell Lung Cancer". Version V1 published 5 February 2020 (hereinafter NCT'145) (Related to NCT04253145 Cite No. 2 cited on IDS dated 12/13/2024, but version 1 only, no changes to 2023) in view of Cortinovis et. al. "Novel Cytotoxic Chemotherapies in Small Cell Lung Carcinoma." Cancers 13.5 (2021): 1152 and Lyman, Gary H., et al. "The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review." Supportive Care in Cancer 25.8 (2017): 2619-2629 as applied to claims 31-32 above, and in further view of Clemons, M., et al. "A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer." Annals of Oncology 31.7 (2020): 951-957.
Claim interpretation: As described in the 112(b) above, it is unclear what Day 1 is referred to by claim 33 because there is more than one cycle recited; the claim will be interpreted as the patient receives primary prophylaxis with G-CSF starting 24-72 hours after the administration of lurbinectedin and atezolizumab of claim 22.
The teachings of NCT’145, Cortinovis, and Lyman in regard to claim 31 and 32 are in the 103 rejection above.
The Examiner notes that, as described for claim 32 above, modified ‘098 claims in view of NCT’145, Cortinovis, and Lyman et. al. teaches that administration of G-CSF 24 hours after chemotherapy is effective for treating febrile neutropenia.
’098 claims NCT’145 in view of Cortinovis and Lyman does not teach administration of G-CSF for five days.
This deficiency is resolved by Clemons et. al.
Clemons et. al. teaches a method of treating febrile neutropenia for breast cancer wherein the most commonly used duration of G-CSF prophylaxis are 5, 7, or 10 days with the choice based on physician preference (p. 951 left column-p. 952 left column ¶1). Clemons et. al. teaches “we have demonstrated that 5 days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days can be considered standard of care for breast cancer patients receiving commonly used adjuvant chemotherapy regimens” (p. 956 right column ¶2).
It would have been obvious, at the time of filing, for a person of ordinary skill in the art to treat the patients with prophylactic G-CSF as taught by modified ‘098 in view of NCT’145, Cortinovis, and Lyman with therapy for 5 days as taught by Clemons et. al. in order to benefit from a duration that is suitable for treatment of febrile neutropenia with prophylactic G-CSF and to benefit from the lower cost and toxicity of the 5 day regimen as taught by Clemons et. al. This would have a reasonable expectation of success because Clemons et. al. teaches that 5 days is among a limited number of choices physicians use and that the treating physician can determine a suitable length of the treatment.
Additional Provisional NSDP Rejections:
Copending Application No.:
Claim(s) Rejected:
Rejected over Application Claims:
Limitations recited:
Application/Patent with similar (prov.) NSDP rejections:
19336350
41
1-30
A method of treating SCLC comprising a lurbinectedin composition
U.S. Patent No. 12324806
19336341
41
1-30
A method of treating SCLC comprising a lurbinectedin composition
U.S. Patent No. 12324806
19336364
41
1-30
A method of treating SCLC comprising a lurbinectedin composition
U.S. Patent No. 12324806
19778134
41
1-30
Pharmaceutical composition comprising lurbinectedin
U.S. Patent No. 7763615
19129420
41
1-30
Pharmaceutical composition comprising lurbinectedin
U.S. Patent No. 7763615
Conclusion
No claims are allowed.
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/KATHLEEN CUNNINGCHEN/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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