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 .
Amendments & Claim Status
The amendment to the claims filed 09 April 2025 is acknowledged and entered.
Claims 15, 18-19, 21, and 23-25 are pending.
Claims 1-14, 16-17, 20, and 22 are cancelled.
Claims 15 and 18-19 are amended.
Claims 23-25 are newly added.
Benefit of Earlier Filing Date
The instant application, filed 19 May 2022, is a national stage application of PCT/US2020/063829, filed 08 December 2020, which claims the benefit of an earlier filing date to U.S. Provisional Patent Application Serial No. 63/085,483, filed 30 September 2020, and U.S Provisional Patent Application Serial No. 62/945,204, filed 08 December 2019. Acknowledgment is made of Applicant’s claim.
Response to Arguments
Applicant arguments, filed 09 April 2025, with respect the claim objections and the rejections under 112(b), 102, and 103 have been fully considered.
With respect to the objections of claims 7 and 20 due to informalities, Applicant’s arguments have been fully considered and are persuasive. Amendments moot the objections, as claims 7 and 20 have been cancelled by Applicant.
The objections of claims 7 and 20 of 10 January 2025 has been withdrawn.
With respect to the rejection of claim 3 under 112(b), Applicant’s arguments have been fully considered and are persuasive. Amendments moot the rejection, as claim 3 has been cancelled by Applicant.
The rejection of claim 3 of 10 January 2025 under 112(b) has been withdrawn.
With respect to the rejection of claims 1, 3-6, 9, 13-15, and 19-21 under 102(a)(1) as being anticipated by Diaz (Diaz et al., The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in in vitro and in vivo models of multiple myeloma by blockade of Ikaros and MYC signaling. Haemotologica. 2017 Oct; 102(10):1776-1784), Applicant’s arguments have been fully considered and are persuasive.
Amendments moot the rejections of claims 1, 3-6, 9, 13-14, and 20, as claims 1, 3-6, 9, 13-14, and 20 have been cancelled by Applicant.
Amendments moot the rejections of claims 15, 19, and 21, because, as Applicant correctly notes, Diaz does not explicitly teach the use of omacetaxine mepesuccinate
The rejections of claims 1, 3-6, 9, 13-15, and 19-21 under 102(a)(1) of 10 January 2025 as being anticipated by Diaz have been withdrawn.
With respect to the rejection of claims 15-16 and 18 under 102(a)(1) as being anticipated by Nemunaitis (Nemunaitis et al., Pharmacokinetic study of omacetaxine mepesuccinate administered subcutaneously to patients with advanced solid and hematologic tumors. Cancer Chemother. Pharmacol. 2013), Applicant’s arguments have been fully considered and are persuasive.
Amendments moot the rejection of claims 16, as claim 16 has been cancelled by Applicant.
Amendments moot the rejections of claims 15 and 18, because, as Applicant correctly notes, Nemunaitis does not explicitly teach the use of lenalidomide and/or pomalidomide.
The rejections of claims 15-16 and 18 of 10 January 2025 as being anticipated by Nemunaitis have been withdrawn.
With respect to the rejection of claims 15-17 under 102(a)(1) as being anticipated by Kajiguchi (Kajiguchi et al., Sustained activation of c-jun-N-terminal kinase plays a critical role in arsenic trioxide-induced cell apoptosis in multiple myeloma cell lines. Cancer Science, 97: 540-545. 2006), Applicant’s arguments have been fully considered and are persuasive.
Amendments moot the rejection of claims 16-17, as claims 16-17 have been cancelled by Applicant.
Amendments moot the rejection of claim 15, because, as Applicant correctly notes, Kajiguchi does not explicitly teach the use of omacetaxine mepesuccinate in combination with either lenalidomide and/or pomalidomide.
The rejection of claims 15-17 of 10 January 2025 as being anticipated by Kajiguchi have been withdrawn.
With respect to the rejection of claims 1 and 8 under 103 as being unpatentable over Diaz in view of Nemunaitis, the rejection of claims 1 and 7 under 103 as being unpatentable over Diaz in view of Nemunaitis and further in view of Young (US 10,071,129 B2), the rejection of claims 1 and 10 under 103 as being unpatentable over Diaz in view of Nemunaitis and further in view of Thakurta (US 10,034,872 B2), the rejection of claims 1 and 11 under 103 as being unpatentable over Diaz in view of Nemunaitis and further in view of Cavallo, and the rejection of claims 1 and 12 under 103 as being unpatentable over Diaz in view of Nemunaitis and further in view of Schafer (Schafer et al., Cereblon modulator iberdomide induces degradation of the transcription factors Ikaros and Aiolos: immunomodulation in healthy volunteers and relevance to systemic lupus erythematosus. Ann Rheum Dis. 2018 Oct;77(10):1516-15), Applicant’s arguments have been fully considered and are persuasive.
Amendments moot the rejections of claims 1, 7-8, and 10-12, as claims 1, 7-8, and 10-12 have been cancelled by Applicant.
The rejections of claims 1, 7-8, and 10-12 under 103 of 10 January 2025 have been withdrawn.
Accordingly, Applicant’s arguments in response to the Non-Final Office Action of 10 January 2024 have been fully considered and are persuasive. All objections and rejections of 10 January 2025 have been withdrawn. Note the claims have been amended and therefore require new grounds of rejection.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 15, 18, 19, 21, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Diaz (Diaz et al., The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in in vitro and in vivo models of multiple myeloma by blockade of Ikaros and MYC signaling. Haemotologica. 2017 Oct; 102(10):1776-1784) in view of Gandhi (Gandhi et al., Omacetaxine: a protein translation inhibitor for treatment of chronic myelogenous leukemia. Clin Cancer Res. 2014 April 1; 20(7): 1735-1740).
Regarding claims 15, 18, 21, and 24, Diaz teaches a method of treating multiple myeloma by co-administering an immunomodulatory drug and a protein translation inhibitor, which are lenalidomide and dexamethasone, respectively (p. 1776, Abstract; p. 1780, Fig. 3).
Diaz does not explicitly teach omacetaxine mepesuccinate or using 1.25 mg/m2 omacetaxine mepesuccinate.
Gandhi teaches omacetaxine mepesuccinate is a protein translation inhibitor, which is also called Synribo, is an FDA-approved chemotherapeutic (p. 1735, Abstract). Additionally, Gandhi describes a 1.25 mg/m2 omacetaxine mepesuccinate dose and dosing schedule (p. 1735, Col. 2). Furthermore, Gandhi describes an open-label single-arm trial involving patients who had developed resistance or intolerance to at least two previously-administered tyrosine kinase inhibitors (TKIs), such as imatinib or dasatinib (p. 1735, Abstract; p. 1735, Col. 2). Gandhi suggests omacetaxine mepesuccinate could be used on malignancies and/or cancer stem cells which rely on short-lived proteins and identifies cMet as a short-lived oncoprotein which supports myeloma cells (p. 1738, Col. 2, Single agent). Consequently, Gandhi indicates omacetaxine mepesuccinate may be useful in treating myeloma.
Gandhi does not explicitly teach lenalidomide or pomalidomide.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Diaz would have found it prima facie obvious to treat multiple myeloma by co-administering omacetaxine mepesuccinate and lenalidomide based on the teachings of Gandhi because Diaz describes treating multiple myeloma by co-administering lenalidomide and a protein translation inhibitor, which is dexamethasone, and Gandhi describes omacetaxine mepesuccinate, which is a protein translation inhibitor. Thus, a PHOSITA would have been motivated to substitute protein translation inhibitors and try treating multiple myeloma using omacetaxine mepesuccinate instead of dexamethasone (MPEP 2143(I)(B)). Furthermore, Gandhi and Diaz provide suggestions omacetaxine mepesuccinate and lenalidomide, respectively, are useful in treating myeloma. Therefore, a PHOSITA would have had a reasonable expectation of success in treating multiple myeloma by co-administering omacetaxine mepesuccinate and lenalidomide because, in view of Gandhi and Diaz, both components are being used according to an art-recognized purpose. Additionally, Gandhi indicates omacetaxine mepesuccinate has been effective in patients who have developed a resistance or intolerance to other TKIs, which a skilled artisan would recognize can have an immunomodulatory effect. Thus, a PHOSITA would have been motivated to try treating a subject resistant to at least one anti-multiple myeloma agent by co-administering omacetaxine mepesuccinate and lenalidomide.
Furthermore, as mentioned above in the response to Applicant arguments, Examiner has considered the objective evidence of nonobviousness presented in Example 3 in the Specification (¶ [0130]-[0133]). However, the claims, as written, are not commensurate in scope with the objective data since a synergistic effect is not observed for all omacetaxine and lenalidomide and/or pomalidomide concentration combinations. See MPEP 716.02(d).
Regarding claim 19, Diaz in view of Gandhi teaches all of the claimed elements as stated above. Furthermore, Diaz presents in vivo data indicating tumor growth may be attenuated by treating with both lenalidomide and dexamethasone alongside a BET bromodomain inhibitor, which is CPI203, and suggests dexamethasone in particular likely plays a crucial role (p. 1783, Col. 1, Middle Paragraph). Furthermore, Diaz states the combination of bortezomib, thalidomide, and dexamethasone has been shown to be an effective treatment for multiple myeloma patients (p. 1783, Col. 1, Middle Paragraph).
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Diaz would have found it prima facie obvious to treat multiple myeloma by co-administering omacetaxine mepesuccinate and lenalidomide as well as at least one additional agent like dexamethasone based on the teachings of Diaz because Diaz indicates treating multiple myeloma using multiple drugs can confer additional therapeutic benefit. Thus, a PHOSITA would have had a reasonable expectation of success in including additional therapeutic agents such as a proteasome inhibitor (i.e., bortezomib), an immunomodulatory drug (i.e., thalidomide), and/or a BET bromodomain inhibitor in the multiple myeloma treatment regimen.
Claims 23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Diaz (Diaz et al., The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in in vitro and in vivo models of multiple myeloma by blockade of Ikaros and MYC signaling. Haemotologica. 2017 Oct; 102(10):1776-1784) in view of Gandhi (Gandhi et al., Omacetaxine: a protein translation inhibitor for treatment of chronic myelogenous leukemia. Clin Cancer Res. 2014 April 1; 20(7): 1735-1740) and further in view of Thakurta (US 10,034,872 B2).
Regarding claims 23 and 25, Diaz in view of Gandhi teaches all of the claimed elements as stated above.
The combination of Diaz and Gandhi does not teach pomalidomide.
Thakurta teaches a method for treating multiple myeloma by administering an immunomodulatory compound, such as lenalidomide or pomalidomide (Abstract).
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Diaz would have found it prima facie obvious to treat multiple myeloma by co-administering omacetaxine mepesuccinate alongside pomalidomide and/or lenalidomide based on the teachings of Gandhi and Thakurta because Thakurta indicates immunomodulatory drugs, specifically pomalidomide and lenalidomide, “…significantly increased the response rates and prolonged progression free survival (PFS) and overall survival (OS) in multiple myeloma patients.” (Col. 2, Lines 44-49). Thus, a PHOSITA would have had a reasonable expectation of success in treating multiple myeloma using pomalidomide because Thakurta discloses pomalidomide’s utility in treating multiple myeloma.
Conclusion
Claims 15, 18-19, 21, and 23-25 are rejected.
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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/B.L.B./Examiner, Art Unit 1623
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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