DETAILED ACTION
Status of Application
The Examiner acknowledges receipt of the arguments filed on 10/23/2025.
Claims 1-11, 14 and 16-22 are presented for examination on the merits. The following rejections are made.
Response to Applicants’ Arguments
Applicant’s arguments filed 10/23/2025 regarding the rejection of claims 1-4, 10, 11, 14, 21 and 22 made by the Examiner under 35 USC 102(a)(1) over Bjerkvig et al. (EP 3560516) have been fully considered but they are not found persuasive and is MAINTAINED for the reasons of record in the office action mailed on 7/25/2025.
In regards to the 102(a)(1) rejection, Applicant asserts the following:
Bjerkvig does not describe the exact combination of the compound of Formula 1 with trametinib but merely provides a list of BRAF and MEK inibitors. There are also over 20 BRAF inhibitors provided and over 15 MEK inhibitors which amounts to over 300 potential combinations.
In response to A, the Examiner is not persuaded because Bjerkvig discloses a composition comprising at least one BRAF inhibitor and at least one MEK inhibitor. The BRAF inhibitor is selected from “ARQ 736, ASN003, BGB-283, CEP-32496, CCT3833, Dabrafenib, Encorafenib, GDC-0879, HM95573, LXH254, LY3009120, PLX3603, PLX4720, PLX8394, RAF265, Regorafenib, RO5126766, Sorafenib, TAK-580, Vemurafenib, XL281” and the MEK inhibitor is selected from “ARRY-300, AS703988, AZD8330, BI 847325, Binimetinib, Capmatinib, Cobimetinib, Crizotinib, E6201, GDC-0623, PD0325901, Pimasertib, Refametinib, RO4987655, Selumetinib, Trametinib, TAK-733, WX-554, and/or the ERK inhibitor is BVD-523, CC-90003, GDC-0994, KO-947, Lapatinib, LTT462, LY 3214996 or ONC201” (emphasis Examiner’s own). This composition can be used in a method of treating embryonal sarcoma via administration of the combinatorial composition.
The instant claims are to a “method of treating sarcoma… comprising administering (a) a Raf inhibitor which is a Compound of formula (I)
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or a pharmaceutically acceptable salt thereof and (b) a MEK inhibitor, trametinib, or a pharmaceutically acceptable salt or solvate thereof.” LXH254 of Bjerkvig is the same as claimed formula I.
The Examiner maintains that Bjerkvig is sufficiently narrow to arrive at a method of treating sarcoma by administering a composition comprising a Raf inhibitor (LXH254) and a MEK inhibitor, trametinib. The present claims are open ended. Although myriad potential binary combination therapies are claimed, there is no requirement that the method employ only binary mixtures. In any regard, MPEP 2131.02(III) states that a reference can anticipate a claim even when the reference describes the limitations but “does not expressly spell out” the limitations as arranged in the claim so long as a person of skill in the art would ‘at once’ envisage the claimed arrangement from the reference. In the present case, one would be capable of selecting the RAF inhibitor and MEK inhibitor as claimed as the number of species within each group (20 and 15) are sufficiently limited.
Applicant’s arguments filed 10/23/2025 regarding the rejection of claims 1-11, 14 and 16-22 made by the Examiner under 35 USC 103 over Bjerkvig et al. (EP 3560516) have been fully considered but they are not found persuasive and is MAINTAINED for the reasons of record in the office action mailed on 7/25/2025.
In regards to the 103 rejection, Applicant asserts the following:
B) there is no motivation to select compound of Formula I and trametinib when Berkvig provides vemurafenib and dabrafenib as possible BRAF inhibitors. Given that the reference teaches over 20 BRAF inhibitors, there would be undue experimentation needed to achieve that claimed combination.
In response to B, the Examiner is not persuaded. Bjerkvig, as noted above, describes a method of administering a RAF inhibitor and MEK inhibitor. An exemplified RAF inhibitor if LXH254 (instant formula I) and an exemplified MEK inhibitor is trametinib.. Such a manipulation of Bjerkvig is nothing more than choosing from a finite number of identified and predictable solutions with a reasonable expectation is supportive of obviousness. See MPEP 2143(I)(E). Moreover, the selection of a known material (e.g. LXH254 as a RAF inhibitor, trametinib as a MEK inhibitor) based on its suitability for an intended benefit (method of treating sarcoma) is supportive of obviousness. See MPEP 2144.07. No undue experimentation would be needed have a reasonable expectation that a combination such as that claimed would be suitable for the treatment of a sarcoma in a patient in need of treatment. Applicant’s arguments are not considered persuasive.
Maintained Rejection, of Record
Claim Rejections - 35 USC § 102
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.
Claims 1-4, 10, 11, 14, 21 and 22 are rejected under 35 U.S.C. 102(a)(1) as being Bjerkvig et al. (EP 3560516).
Bjerkvig is directed to a combination therapy for the treatment of cancer using a combination therapy comprising a RAF inhibitor, such as LXH254 (i.e. compound 1), and a MEK inhibitor, such as trametinib (see [0012]) (see instant claims 1(a), 1(b) and 14). The inhibitors may be present as a salt (see [0035, 0036]). The cancer treated by the combination therapy includes sarcoma, specifically embryonal rhabdomyosarcoma (see claim 10) (see instant claims 1-3). Given that embryonal rhabdomyosarcoma affects small children, the method of treating the condition would necessarily encompass treating pediatric or young adult patients (see instant claim 4). Bjerkvig states that their composition may be provided as a kit that comprises the RAF and MEK inhibitors (see [0067]) wherein the pharmaceutical dosage forms are to be administered simultaneously, separately or sequentially (see [0001]) (see instant claims 10 and 11).
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.
Claims 1-11, 14 and 16-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bjerkvig et al. (EP 3560516) in view of Fabricius (WO 2019/038367).
Bjerkvig is relied upon for the rejection of claims 1-4, 10, 14, 21 and 22 under 102(a)(1) and are incorporated herein.
Bjerkvig fails to teach their method as providing 100-400 mg compound I (i.e. LXH254) as being administered twice daily and the trametinib being administered once daily.
Shah, like Bjerkvig, is directed to inhibiting cancers/tumors by administering combinations of RAF and MEK inhibitors (see [0002, 0004, 0084]) with trametinib being an exemplified MEK inhibitor (see [0089]). Shah teaches that the therapeutics may be administered once or twice daily and may be administered all at once or in multiple administrations and administered in an amount of between 20-500 mgs (see [0087]) (see instant claims 6, 7, 17 and 18). In an alternative embodiment, a suitable twice daily dose is between about 400 mg administered twice daily (see [0087]) (see instant claims 6 and 7). It would have been obvious to modify Bjerkvig’s method to utilize the dosage/schedule of Shah with a reasonable expectation for treating sarcoma given that Bjerkvig is largely silent with respect to such matters. See MPEP 2143(I)(A) which states that combining prior art elements according to known methods to yield predictable results is supportive of obviousness.
Shah’s teaching indicates that the composition may be presented as a kit comprising the dosage forms together with instructions for administering the dosage forms (see [0009]) (see instant claim 19).
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Potentially relevant prior art:
Fabricius (WO 2019/038367)
Conclusion
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 extension fee 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 KYLE A PURDY whose telephone number is (571)270-3504. The examiner can normally be reached from 9AM to 5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Bethany Barham, can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE A PURDY/Primary Examiner, Art Unit 1611