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 .
DETAILED ACTION
Claim status
Claims 35-46 and 48-64 are pending. Claims 40, 45, 59 and 64 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Therefore, Claims 35-39, 41-44, 46, 48-58, and 60-63 are examined on the merits.
Election/Restrictions
Applicant’s election of (i) adult patients with neurofibromatosis type 1 (NF1) with symptomatic plexiform neurofibromas and a body surface area of at least 1.5 m2 as the patient population and (ii) initially administering 4 mg mirdametinib twice daily as the treatment regimen in the reply filed on 12/12/2025 has been recorded.
Priority
The present application claims the benefit of U.S. Provisional Application Nos. 63/663,853, filed June 25, 2024, and 63/754,168, filed February 5, 2025.
Information Disclosure Statement
No Information Disclosure Statement was filed with Applicant’s recent remarks.
Withdrawn Claim Rejections
Claims 35, 47, and 54 were 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. Applicant’s amendment and corresponding reply pertaining to the new amendments to Claims 35 and 54 have overcome the 35 U.S.C. 112(b) rejection made of record in the previous Office Action, specifically, the removal of the parentheses and its interior text. Additionally, Claim 47 was canceled by amendment. Therefore, the rejection is hereby withdrawn.
Claims 35-39, 41-44, 46, 48-58, and 60-63 were rejected under 35 U.S.C. 102a1 as being anticipated by Rosen, E. as evidenced by Drugbank.
Claims 35-39, 41-44, 46-58, and 60-63 were rejected under 35 U.S.C. 103 as being unpatentable over Iloeje et al. in view of Rosen, E. as evidenced by Drugbank.
Claims 35-39, 41-44, 46-58 and 60-63 were rejected on the ground of nonstatutory double patenting as being unpatentable over:
U.S. Patent No. 11,883,375 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 12,029,711 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 12,220,390 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 12,257,215 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 12,295,925 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 12,383,517 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 12,390,430 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 12,357,597 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 11,839,595 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 11,819,487 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 11,806,322 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 11,806,321 in view of Rosen, E. as evidenced by Drugbank,
U.S. Patent No. 11,571,402 in view of Rosen, E. as evidenced by Drugbank,
copending Application No. 19/237,500 (U.S. PG-PUB 2025/0387358) in view of Rosen, E. as evidenced by Drugbank,
copending Application No. 19/237,465 (U.S. PG-PUB 2025/0387357) in view of Rosen, E. as evidenced by Drugbank, and
copending Application No. 19/299,614 in view of Rosen, E. as evidenced by Drugbank.
Applicant’s argument at page 8 was found persuasive - particularly, Applicant’s statement that the Rosen reference cannot be relied upon as prior art because there is no evidence that the Rosen reference was made publicly accessible as of the August 29, 2022 approval date appearing on each page of the document. Applicant persuasively argued that the “approval date” does not necessarily mean that the reference was publicly accessible at that date. Therefore, the rejections that relied upon Rosen are hereby withdrawn.
Claim Rejections - 35 USC § 112
New rejection, not necessitated by amendment
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.
Claims 41, 42, 46, 48, 60, and 61 are 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.
Claims 41 and 60 recite the limitation “the first 21 days of each 28-day cycle”. There is insufficient antecedent basis for this limitation in the claims.
In Claims 42 and 61, the term “unacceptable toxicity” is a relative term which renders the claims indefinite. The term “unacceptable toxicity” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. No guidance is provided in order to determine what degree of toxicity is considered "unacceptable".
In Claim 46, the term “significant morbidity” is a relative term which renders the claim indefinite. The term “significant morbidity” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. No guidance is provided in order to determine what degree of morbidity is considered "significant".
In Claim 48, the term “major deformity” is a relative term which renders the claim indefinite. The term “major deformity” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. No guidance is provided in order to determine what degree of deformity is considered "major".
In Claim 48, the term “significant disfiguring” is a relative term which renders the claim indefinite. The term “significant disfiguring” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. No guidance is provided in order to determine what degree of disfiguring is considered "significant".
Claim Rejections - 35 USC § 112 – Scope of enablement
Rejection maintained; slight amended to address new changes to the claims
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 35-39, 41-44, 46, 48-58, and 60-63 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for slowing down or lessening plexiform neurofibromas associated with neurofibromatosis type 1 (NF1-PN), does not reasonably provide enablement for therapeutic treatment of NF1-PN. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The test of enablement requires a determination of whether the disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention. That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term “undue experimentation,” it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
Claim 1 broadly recites:
“a method of therapeutic treatment of plexiform neurofibromas associated with neurofibromatosis type 1 by administering mirdametinib (NF1-PN”
In defining the different iterations of “treating”, the definition of “therapeutic treatment” was also provided. At 0232 of US PG-Pub 2025/0387356 A1 (instant application’s publication), the terms “treat,” “treated,” and “treating” are defined to mean “both therapeutic treatment and prophylactic or preventative measures wherein the object is to prevent or slow down (lessen) an undesired physiological condition, disorder, or disease, or obtain beneficial or desired clinical results.” Thus, the claims are broadly drawn to therapeutic treatment – modified to encompass “measures wherein the object is prevention” – of NF1-PN by administering mirdametinib. This is claimed despite the lack of sufficient support for prevention of NF1-PN whether in vitro or in vivo.
The state of the art does not support the capability to prevent NF1-PN as contemplated by the specification and the claims.
The nature of the invention:
The invention relates to a method of therapeutic treatment (as defined broadly) of NF1-PN with mirdametinib administration. Therapeutic treatment broadly includes not only therapeutic intervention, but also prevention. The invention is not particularly based on a specifically identified mechanism of action that has been predictively demonstrated preventative intervention of NF1-PN as contemplated. Thus, the claims encompass embodiments that are not enabled by the as-filed specification.
Breadth of claim:
The breadth of the claims is broad insofar as encompassing embodiments purported to prevent NF1-PN from arising.
State and predictability of the art:
Neurofibromatosis 1-associated plexiform neurofibromas (NF1-PN) is caused by a genetic mutation that is either inherited or occurs spontaneously at conception. There is currently no known method to prevent this genetic change from happening. See Boston Children’s Hospital (Neurofibromatosis. © 2005-2026 Boston Children’s Hospital. All rights reserved. https://www.childrenshospital.org/conditions-treatments/neurofibromatosis#:~:text=Around%20half%20of%20all%20individuals,mutation%20of%20the%20NF1%20gene. Accessed 1/9/2026 – particularly p. 4 and p. 7.)
Relative skill level:
One of ordinary skill in the art is one with access to reagents, tools and equipment used for diagnosing disease, performing tests and/or administering treatment to individuals. The skilled artisan also has many years of training and experience in either the clinical or laboratory environment or both. Therefore, it is clear that the level of skill of one in the art is high. However, this high level of skill is overcome in view of the limited teachings provided by the specification and the unpredictable state of the art, it would require the skilled artisan undue experimentation to make and use the invention commensurate to the scope of the claims.
The amount of direction or guidance provided and the presence or absence of working examples:
The specification fails to provide substantive guidance to therapeutically treat (i.e., prevent) the claimed disease. While it provides a prophetic plan for a clinical trial to treat NF1-PN with mirdametinib, the specification does not demonstrate the prevention of NF1-PN as claimed.
The quantity of experimentation necessary:
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed agent could be predictably used for therapeutically treating the claimed disease as inferred by the claim and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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