DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The application claims priority to provisional application 63/194026, filed on 27 May 2021 and is a 371 of PCT/US2022/031055, filed on 26 May 2022. The effective filing date is 27 May 2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 17 July 2024 was considered by the examiner.
Status of Application, Amendments, and/or Claims
Claims 1-48 are the original claims, filed on 21 November 2023. In the amendment of 17 July 2024, claim s7-10 and 30-48 were cancelled and claims 3-5, 11, 15, 16, 18, 21, 24, 25, and 28 were amended. Claims 1-6 and 11-29 are pending and the subject of this office action.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 1-5, and 11-29 are rejected under 35 U.S.C. 103 as being unpatentable over Dimopoulos MA, et al. (2018) Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. N Engl J Med. 2018 Nov 8;379(19):1811-1822 (herein Dimopoulos) in view of US20190008852 A1 (herein Alexander).
In regard to claim 1, Dimopoulos relates to a randomized trial in which the safety and efficacy were assessed, in regard to a method of treating relapsed or refractory multiple myeloma, comprising the administration of elotuzumab, pomalidomide, and dexamethasone (Introduction). An inclusion requirement for entry into the ELOQUENT-3 trial, which is discussed in the cited reference, was that the patients had previously received at least two previous treatments, including at least two cycles of lenalidomide and a proteosome inhibitors alone or in combination (shown to include bortezomib, carfilzomib, and ixazomib treatments) (Relevant to instant claims 11-17) (Section: Patients and Table 1). Patients, in the trial, were administered treatment in 28-day cycles, during which elotuzumab was intravenously administered on days 1, 8, 15, and 22 (cycles 1 and 2) using a dosage or 10 mg/kg or on day 1 (cycles 2+) using a dosage of 20 mg/kg (Section: Randomization and Treatment). Dexamethasone was administered weekly throughout the cycle either orally (28 mg for patients under 75 or 8 mg for patients over 75) or intravenously (8 mg) on days that the patients also received elotuzumab, days 1, 8, 15, and 22 of cycles 1 and 2 (Section: Randomization and Treatment). On days that the patients did not receive elotuzumab (days 1, 8, 15, and 22 of cycles 1 and 2, and day 1 of cycles 2+), the patients were orally administered 40 mg (patients under 75) or 20 mg (patients under 75). These treatment parameters align perfectly with the limitations regarding elotuzumab and dexamethasone in instant claims 2, 3, 4, 5, and 29. Additionally, it is taught that the immunomodulatory drug (pomalidomide) is administered daily (days 1-21), but not administered on days 22-28 (Relevant in part to instant claim 28) (Section: Randomization and Treatment). The authors concluded, that among patients with multiple myeloma that was refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor, the combination of elotuzumab plus pomalidomide and dexamethasone resulted in significantly longer progression-free survival and a higher overall response rate than pomalidomide and dexamethasone alone (Discussion).
Dimopoulos does not teach a method of treating multiple myeloma, comprising the administration of effective amounts of elotuzumab, dexamethasone, and a compound corresponding to Formula (I) of current application. Alexander teaches this deficiency.
Alexander teaches the use of 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof, for treating, preventing or managing multiple myeloma (Abstract). Alexander discloses 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile (Compound 1) and an enantiomer (Compound 2) that match the chemical structure of the compound described in Formula I of the instant application, shown below.
Compound 1:
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Compound 2:
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Alexander teaches that these compounds, or pharmaceutically acceptable salts thereof may be administered orally and provides exemplary embodiments in which the administered dosages range from 0.1 – 10 mg / day (Relevant to instant claims 21, 22, 24-27) ([0207] and [0201]). Additionally, it is taught that administration can be intermittent, so as to include periods of “rest” without the drug (Relevant to instant claim 28) ([0210]).
It would have been obvious to combine the teachings of Alexander (a potent isoindolinone derivative) with the efficacious method taught by Dimopoulos, which comprises the administration of elotuzumab (an immunotherapeutic), dexamethasone (a corticosteroid), and pomalidomide (an immunomodulatory isoindolinone derivative). Both pomalidomide and the compound described by Formula I perform the function (anti-proliferation), in the context of the method claimed in the current application, albeit the compound described by Formula I has a significantly higher potency, as shown in Table 3 of Alexander. The current application is essentially substituting one component (pomalidomide) with another (compound described by Formula I), both of which were known in the art at the time filing, as taught by Alexander, with predictable results. Furthermore, there is clear motivation to make this substitution, as Alexander teaches that Compound 2 (equivalent to the compound described in Formula of the current application) may possess a more desirable safety profile than pomalidomide ([0354]).
In regard to claim 18, Alexander teaches that the disclosed compounds may be used in methods to treat newly diagnosed multiple myeloma ([0007] and Claims 15 and 23).
In regard to claims 19 and 20, Alexander teaches that the disclosed compounds may be use in a method to treat multiple myeloma, in which the patient is transplant eligible, and defines that “transplant” encompasses autologous stem cell transplants ([0042] and [0188]).
In regard to claim 23, the choice of salt form is a matter of routine optimization, and the choice of hydrobromide as a counterion would have been obvious following routine optimization.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Attal M, et al. (2019) Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107 (herein Attal) in view of US20190008852 A1 (herein Alexander).
Attal relates to evaluation of a randomized, multicenter, open-label phase 3 clinical study for the treatment of relapsed or refractory multiple myeloma, comprising the administration of isatuximab, pomalidomide, and dexamethasone (Background and Methods). It was found that the addition of isatuximab to pomalidomide-dexamethason treatment significantly improved progression-free survival in patients with relapsed and refractory multiple myeloma (Interpretation).
Attal does not teach a method comprising the administration of a compound described by Formula I of the current application, isatuximab, and dexamethasone. Alexander teaches this deficiency.
As discussed for the 35 U.S.C. 103 rejections of claims 1-5, and 11-29, Alexander teaches a method for treating multiple myeloma, comprising the administration of isoindolinone derivatives possessing a structure identical that of the compound described in Formula I (Abstract and Compounds 1 and 2). Alexander also suggests that these compounds may be combined with one or more second active agents, and lists isatuximab, elotuzumab, dexamethasone as possible agents ([0229-0230]).
It would have been obvious to combine the teachings of Alexander (a potent isoindolinone derivative) with the efficacious method taught by Attal, which comprises the administration of isatuximab (an immunotherapeutic), dexamethasone (a corticosteroid), and pomalidomide (an immunomodulatory isoindolinone derivative). Both pomalidomide and the compound described by Formula I perform the function (anti-proliferation), in the context of the method claimed in the current application, albeit the compound described by Formula I has a significantly higher potency, as shown in Table 3 of Alexander. The current application is essentially substituting one component (pomalidomide) with another (compound described by Formula I), both of which were known in the art at the time filing, as taught by Alexander, with predictable results. Furthermore, there is clear motivation to make this substitution, as Alexander teaches that Compound 2 (equivalent to the compound described in Formula of the current application) may possess a more desirable safety profile than pomalidomide, due to its higher potency ([0354]).
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 1-5 and 11-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-17 and 19-25 of U.S. Patent No. 10357489 (herein ‘489) in view of Dimopoulos MA, et al. (2018) Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. N Engl J Med. 2018 Nov 8;379(19):1811-1822 (herein Dimopoulos), and US20190008852 A1 (herein Alexander). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed invention referenced in the cited claims encompass the claimed invention of the current application. The referenced claims do not teach a method of treating multiple myeloma, comprising the administration of effective amounts of elotuzumab, dexamethasone, and a compound corresponding to Formula (I) of current application, but the prior art cited in the 35 U.S.C. 103 rejections of claims 1-5 and 11-29, discussed above, would make this method obvious in view of the cited claims from ‘489.
The referenced patent teaches a method of treating refractory, resistant, or relapsed multiple myeloma comprising administering a therapeutically effective amount of a compound corresponding to the compound referenced in instant claim 1 (reference claims 11-15 and 19-23). ‘489 also teaches a method comprising the administration of the referenced compound with additional agents, such as dexamethasone (reference claims 16, 17, 24, and 25). Dimopoulos and Alexander teach that the combination of elotuzumab, dexamethasone, and a compound corresponding to Formula (I) (referenced in instant claim 1 and the claims of ‘489) would have been obvious to one skilled in the art, see 35 U.S.C. 103 rejections for instant claims 1-5, and 11-29. In short, Dimopoulos teaches a method for treating refractory/relapsed multiple myeloma, comprising the administration of elotuzumab, pomalidomide, and dexamethasone (Introduction), which when combined with Alexander’s teachings, showing that the compound (corresponding to Formula (I) of the current application and referenced in the claims of the ‘489) performs the same function as pomalidomide and has a significantly higher potency (Table 3), renders the methods of claims 1-5 and 11-29 obvious.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-17 and 19-25 of U.S. Patent No. 10357489 (herein ‘489) in view of Attal M, et al. (2019) Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107 (herein Attal) and US20190008852 A1 (herein Alexander). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed invention referenced in the cited claims encompass the claimed invention of the current application. The referenced claims do not teach a method of treating multiple myeloma, comprising the administration of effective amounts of isatuximab, dexamethasone, and a compound corresponding to Formula (I) of current application, but the prior art cited in the 35 U.S.C. 103 rejections, discussed above, would make this method obvious in view of the cited claims from ‘489.
The referenced patent teaches a method of treating refractory, resistant, or relapsed multiple myeloma comprising administering a therapeutically effective amount of a compound identical the compound referenced in instant claim 1 (reference claims 11-15 and 19-23). ‘489 also teaches a method comprising the administration of the referenced compound with additional agents, such as dexamethasone (reference claims 16, 17, 24, and 25). Attal and Alexander teach that the combination of isatuximab, dexamethasone, and a compound corresponding to Formula (I) (referenced in instant claim 1 and the claims of ‘489) would have been obvious to one skilled in the art, see 35 U.S.C. 103 rejections for instant claim 6. In short, Attal teaches a method for treating refractory/relapsed multiple myeloma, comprising the administration of isatuximab, pomalidomide, and dexamethasone (Background and Methods, and Intepretation), which when combined with Alexander’s teachings, showing that the compound (corresponding to Formula (I) of the current application and referenced in the claims of the ‘489) performs the same function as pomalidomide and has a significantly higher potency (Table 3), renders the method of claim 6 obvious.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW CURRAN METCALF whose telephone number is (571)272-5520. The examiner can normally be reached 7:30AM-5:00PM.
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/MATTHEW CURRAN METCALF/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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