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 .
Response to Amendment
The amendments received 12/15/2025 have been entered. Claims 90-96, 98-100, and 104-107 are pending. Any objection or rejection set forth in the Office Action mailed 08/05/2025 not maintained herein has been overcome and is withdrawn. The non-statutory double patenting rejection over co-pending application 18/912,278 has been withdrawn due to abandonment of the ‘278 application.
Priority
Examiner acknowledges that, according to the Filing receipt received 07/03/2025, that the instant application 19/237/500 filed 06/13/2025 claims domestic benefit of U.S. provisional applications 63/663,853 filed 06/25/2024 and 63/754,168 filed 02/05/2025.
However, the limitations of the instantly amended claims are not adequately supported or enabled in the manner provided by 35 U.S.C. 112(a) or pre-AIA U.S.C. 112, first paragraph by 63/663,853. More specifically, the limitation of restarting administration of the mirdametinib or pharmaceutically acceptable salt thereof at the same dose is not taught or suggested in its entirety by 63/663,853 which discloses restarting administration at a reduced dose. As such, all the instant claims have been awarded the effective filing date of 63/754,168 filed 02/05/2025.
Information Disclosure Statement
The Information Disclosure Statement filed on 12/15/2025 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of list of references cited from the IDS is included with this Office Action.
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.
Claim(s) 90-91, 94-96, 98-100, and 104-107 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weiss et al. (Journal of Clinical Oncology; 2021; IDS filed 06/13/2025).
Weiss et al. teaches a method of treating patients with neurofibromatosis type 1 (NF1) between the ages of 16 (pediatric, see specification paragraph [0101] to 39 (adult) (Abstract; p. 799 Table 1). Weiss et al. teaches administering mirdametinib orally, twice daily, at a dose of 2 mg/m2 to a maximum dose of 4 mg (p. 798, col. 1). Weiss et al. teaches that the patients received an ophthalmology assessment before and during treatment (p. 798, col. 2). Weiss et al. teaches that treatment was discontinued upon development of retinal vein occlusion or other development of unacceptable toxicity or plexiform neurofibroma progression (p. 798, col. 2). Weiss et al. teaches that the patients had plexiform neurofibromas (PN) that were either progressive or causing significant morbidity (Abstract, Methods section). Weiss et al. teaches that trial eligibility included patients with PN causing head and neck lesions compromising the airway or vessels, brachial or lumbar plexus lesions causing nerve compression and loss of function, lesions that cause major deformity or are significantly disfiguring, lesions that cause limb hypertrophy or loss of function, painful lesions, and paraspinal PN (Table A1).
While Weiss et al. does not teach the steady-state Cmax or AUC of claims 90 and 105-107, Weiss et al. teaches that most treatment responses were seen in patients when AUC was ≥ 600 ng h/mL.
It would have been prima facie obvious for one of ordinary skill in the art to determine the optimal plasma level of mirdametinib to achieve treatment response via routine optimization, with a reasonable expectation of success.
Claim(s) 92-93 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weiss et al. (Journal of Clinical Oncology; 2021; IDS filed 06/13/2025) as applied to claims 90-91, 94-107 above, and further in view of Koselugo (Drugs.com; IDS filed 07/24/2025) and as evidenced by Solares et al. (ESMO Open; IDS filed 07/24/2025).
Weiss et al. teaches or makes obvious as above.
Weiss et al. does not disclose guidance on missed doses or vomiting. However, these limitations are obvious over Koselugo as evidenced by Solares et al.
Koselugo (selumetinib, see page 1) discloses the following dosing guidance (page 5, Koselugo Dosage and Administration).
PNG
media_image1.png
124
907
media_image1.png
Greyscale
As evidenced by Solares et al., selumetinib and mirdametinib are both MEK inhibitors for treatment of neurofibromatosis type 1 (Abstract).
It would have been prima facie obvious for one of ordinary skill in the art to substitute mirdametinib for selumetinib in the dosage guidance of Koselugo, as one of ordinary skill in the art would be apprised that due to both mirdametinib and selumetinib having the same function, that following the same directions of missed doses and vomiting would yield predictable results.
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 90 and 105-107 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-9, 31, and 45 of U.S. Patent No. 12029711 B1. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention. Moreover, while the ‘711 patent does not teach the steady-state Cmax or AUC of claims 90 and 105-107, it would have been prima facie obvious for one of ordinary skill in the art to determine the optimal plasma level of mirametinib to achieve treatment response via routine optimization, with a reasonable expectation of success.
Claim 90 and 105-107 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 14 of U.S. Patent No. 11839595 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention. Moreover, while the ‘595 patent does not teach the steady-state Cmax or AUC of claims 90 and 105-107, it would have been prima facie obvious for one of ordinary skill in the art to determine the optimal plasma level of mirametinib to achieve treatment response via routine optimization, with a reasonable expectation of success.
Claim 90 and 105-107 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12324791 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention. Moreover, while the ‘791 patent does not teach the steady-state Cmax or AUC of claims 90 and 105-107, it would have been prima facie obvious for one of ordinary skill in the art to determine the optimal plasma level of mirametinib to achieve treatment response via routine optimization, with a reasonable expectation of success.
Claims 90-96, 98-100, and 104-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-12, 14-21 of copending Application No. 18/912,218 (allowed, not issued) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 90-96, 98-100, and 104-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46 and 49-56 of copending Application No. 18/912,328 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 90-96, 98-100, and 104-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 99-104, 111-117, 124-130, 137-143, and 150 of copending Application No. 18/912,367 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention. Moreover, while the dose of mirdametinib is not administered according to the patient’s body surface area, the instant specification (par. 0006) provides guidance regarding dosages determined by body surface area, such that one of ordinary skill in the art could arrive at the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 90-96, 98-100, and 104-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 19/237,400 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 90-96, 98-100, and 104-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-53 of copending Application No. 19/237,417 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 90-96, 98-100, and 104-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-53 of copending Application No. 19/237,465 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 90-96, 98-100, and 104-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-9, 31, and 45 of copending Application No. 18/608,748 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to or narrower than the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention. Moreover, while the ‘748 application does not teach the steady-state Cmax or AUC of claims 90 and 105-107, it would have been prima facie obvious for one of ordinary skill in the art to determine the optimal plasma level of mirametinib to achieve treatment response via routine optimization, with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 90 and 105-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-9, 31, and 45 of copending Application No. 18/765,632 (allowed, to issue 8/12/2025 as U.S. Patent No. 12383517) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are substantially similar to the scope of the instant invention, such that one of ordinary skill in the art could arrive at the instant invention. Moreover, while the ‘748 application does not teach the steady-state Cmax or AUC of claims 90 and 105-107, it would have been prima facie obvious for one of ordinary skill in the art to determine the optimal plasma level of mirametinib to achieve treatment response via routine optimization, with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 90-96, 98-100, and 104-107 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of U.S. Patent No. 11427534 B1 in view of Weiss et al. (Journal of Clinical Oncology; 2021; IDS filed 06/13/2025) and Koselugo (Drugs.com; IDS filed 07/24/2025) and as evidenced by Solares et al. (ESMO Open; IDS filed 07/24/2025).
Claim 6 of the ‘534 patent reads as follows.
PNG
media_image2.png
323
421
media_image2.png
Greyscale
Claim 6 does not teach the dosages based on body surface area, the steady-state Cmax or AUC, and directions for withholding treatments. These limitations are obvious over Weiss et al., Koselugo, and as evidenced by Solares et al.
Weiss et al., Koselugo, and Solares et al. teach as above.
It would have been prima facie obvious for one of ordinary skill in the art to combine the method of Weiss et al. with that of claim 6 in order to arrive at a dose of 2 mg/m2 and to further optimize the plasma level of mirametinib to achieve treatment response via routine optimization, with a reasonable expectation of success using the guidance of Weiss et al.
Moreover, for the same reasons as set forth in the above 103 rejections, it would have been prima facie obvious for one of ordinary skill in the art to arrive at the methods of instant claims 92 and 93.
Response to Arguments
Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive.
35 U.S.C. 103 and Non-statutory Double Patenting
In the Remarks filed 12/15/2025, Applicant argues that claim 90 has been amended to recite “upon the patient exhibiting a symptomatic retinal pigment epithelium detachment (RPED), withholding the mirdametinib until resolution to Grade 1 or less or baseline and then restarting administration of the mirdametinib at the same dose,” which is neither disclosed nor suggested by Weiss et al. (p. 8 of Remarks). This is not persuasive.
While this limitation is not explicitly taught by Weiss et al., Examiner notes that the limitation at issue is not required by the claimed method but is instead interpreted to be conditional. The phrase “wherein upon” suggests two patient groups: one group which does not exhibit symptomatic RPED, and another group that does exhibit symptomatic RPED. Thus, only if the patient exhibits symptomatic RPED would the limitations of step (iv)(B) be required. Weiss et al. does not disclose than any patient exhibited symptomatic RPED, and therefore step (iv)(B) need not be carried out. This interpretation also applies to claims 92 and 93.
Further regarding claims 92 and 93, Applicant argues that in addition to Weiss et al. not disclosing or suggesting the above limitation, Koselugo suggests resuming selumetinib at a reduced dose upon a patient exhibiting RPED (Remarks, p. 8-9). Applicant additionally argues that “Unlike Koselugo, mirdametinib does not require a dose reduction upon a patient exhibiting RPED. Mirdametinib surprisingly has a broader therapeutic window that permits resuming administration at the same dose as prior to the RPED symptoms” (Remarks, p. 9). This is not persuasive.
As above, the conditional nature of the claimed invention does not require that step (iv)(B) be carried out if a patient does not exhibit symptomatic RPED. Since Weiss et al. does not disclose than any patient exhibited symptomatic RPED, and step (iv)(B) need not be carried out. Moreover, regarding Applicant’s argument of surprising results, allegations of unexpected results must be supported by evidence. It is Applicant’s burden to establish that results are unexpected and significant. See MPEP 712.02(a) and (b). No such evidence has been set forth either by way of declaration or disclosure in the instant specification. In fact, the instant disclosure makes no reference to any “surprising” or “unexpected” results relevant to the claimed invention, nor is any mention made to the therapeutic window of mirdametinib. Examiner additionally notes that statements made by Applicant and Applicant’s attorney are not a substitute for factual evidence. See MPEP 2145(I). For these reasons, the rejection is maintained.
Similarly, the non-statutory double patenting rejections are maintained for the above reasons. Moreover, while page 10 of the Remarks states that a terminal disclaimer over U.S. applications 19/237,465; 19/237,400; and 19/237,417 has been submitted with Applicant’s response, no such terminal disclaimer has been received by the Examiner. The rejections are therefore maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/M.E.B./Examiner, Art Unit 1624 01/07/2026
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624