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
This application has PRO 63/352,491 dated 06/15/2022, PRO 63/317,654 dated 03/08/2022,
And PRO 63/282,017 dated 11/22/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/11/2025 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant's election without traverse of the species, pemigatinib as the FGFRl inhibitor and sotorasib (also referred to as "AMG-510") as the KRAS inhibitor, and lung cancer as the cancer in claims 1-3, 7, 14, 15, 17, 22, 28, 29, 33, 38-39, and 44-69 in the reply filed on 02/06/2025 is acknowledged.
Claims 4-6, 8-13, 16, 18-21, 23-27, 30-32, 34-37, 40-43, and 70-72 withdrawn from further consideration pursuant to 37 CPR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/06/2025.
Status of claims
Claims 45-66, 69, and 73-75 are pending in this application and are objected or rejected to for the reasons set forth below. Claims 44, 64 and 69 have been amended. Claims 1-43, 67-68, 70-72 have been cancelled without prejudice or disclaimer by applicant.
Applicant’s arguments, filed 11/11/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. They constitute the complete set presently being applied to the instant application.
The obviousness rejection below is repeated from the 05/12/2025 Office Action and modified in order to address the most recent amendments.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 44-66, 69, and 73-75 are rejected under 35 U.S.C. 103 as being unpatentable over Cee (WO 2020232130) in view of Liu (INCB054828 (pemigatinib ), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models) and further in view of Bhonde (WO 2021/079302).
The instant claims are directed to a method of treating non-small cell lung cancer in a
patient, comprising administering:
(i) an FGFRl inhibitor of pemigatinib; and
(ii) a KRAS inhibitor of sotorasib.
Cee et al. teaches administering compound A (AMG 510, sotorasib) to a patient with
KRASG12C nonsmall cell lung cancer (NSCLC) in a daily dose range of 180-960 mg [0152]. Cee also discloses the typical administration of compound A (sotorasib) is orally in the form of a tablet [0041]. Cee teaches that determination of optimal ranges of effective amounts of the
compound is within one of skill in the art and that compound dose ranges of about 1 mg/day to
about 960 mg/day [0057].
It is noted that a dose of 133 mg, 120 mg of sotorasib would be obvious over Cee. See
MPEP 2144.05 Obviousness of Similar and Overlapping Ranges, Amounts, and Proportions.
However, Cee et al. fail to disclose pemigatinib as an FGFRl inhibitor for treating cancer
in a patient.
Liu et al. teach the compound of INCB054828 (pemigatinib ), as a selective inhibitor of
fibroblast growth factor receptor (FGFR) 1, 2, and 3 (abstract). Liu also teaches pemigatinib has
antitumor effects as an oral dose (pg. 8/16, last paragraph). Liu also discloses a 0.1-10 mg/kg
oral dose of INCB054828 (pg. 8/16, 5th paragraph). Liu also teaches pemigatinib tumor growth
inhibition on H1581 non-small cell lung cancer cells with amplified FGFRl (table 1 pg. 9/16).
Liu further discloses "These findings suggest that, for example, in lung cancers characterized by
FGFRl gene amplification there is greater tumor complexity or heterogeneity within the
amplicon that may modulate the dependency on the FGFRl" (pg. 13/16, 1st paragraph).
However, Cee and Liu et al. fail to explicitly disclose the use of a KRAS inhibitor with a FGFR inhibitor.
Bhonde et al teach pharmaceutical combinations for treating and/or preventing cancer wherein the pharmaceutical combinations comprise a PRMT5 Inhibitor and a cellular activity modulator selected from a KRAS inhibitor, a KRAS-G l2C inhibitor, a FGFR inhibitor and an immune checkpoint inhibitor/modulator (Abstract). Bhonde teaches in some embodiments, the KRAS inhibitors and KRAS-G 12C inhibitors that can be used along with PRMT5 Inhibitors of Formula (I) can include Sotorasib (AMG510) (page 53, lines 14-16).
Bhonde also discloses an embodiment wherein a PRMT inhibitor is administered simultaneously, concurrently, sequentially, successively, alternately or separately with the at least one targeted agent/cellular activity modulator selected from a KRAS inhibitor, a KRASG12C inhibitor, and a FGFR inhibitor (Page 18, lines 20-28). Bhonde also discloses an embodiment wherein the immune checkpoint inhibitors/modulators (immuno-oncology agents) that can be used along with PRMT5 Inhibitors of Formula (I) and that the checkpoint inhibitors include PD-1 and pd-l1 (page 54, lines 4-18). Bhonde also discloses in some embodiments, a method of treating and/or preventing cancer in a human subject in need thereof, comprising administering to the human subject a pharmaceutical combination comprising a composition a PRMT5 Inhibitor of Formula (I), and at least one targeted agent/cellular activity modulator selected from KRAS inhibitor, a KRASG12C inhibitor, a FGFR inhibitor, wherein the cancer is non-small cell lung cancer (page 55, lines 9-23). Bhonde also teaches an embodiments, where the compound is administered orally, it is formulated as a pill, capsule, tablet, etc., with a pharmaceutically acceptable carrier and/or excipient and that Suitable doses and dosage regimens can be determined by range-finding techniques which are a function of the subjects mass, body volume, body surface area, regions and routes of administration, and the degree of cancer prognosis of the subject. (page 56, lines 21-page 57, line 1). Bhonde also teaches the dose of the pharmaceutically active agent(s) described herein for the described methods can be about 1 to about 1000 mg/kg body weight of the subject being treated per day (page 57 lines 14-18). Bhonde also discloses that the inventors have recognized that while a PRMT5 Inhibitor compound may be metabolized by a first set of metabolic enzymes, the at least one targeted agent/cellular activity modulator selected from an KRAS inhibitor, a KRASG12C inhibitor, a FGFR inhibitor or an immune checkpoint inhibitor/modulator may be metabolized by a second set of enzymes, such that the first set of enzymes and the second set of enzymes are not entirely the same. The result is that the toxicity of the combination will be less than those of the single components of the combination, or that the efficacy of the combination will be more than those of the single components of the combination (Synergistic/Enhanced Combination section, page 63, line 7-page 64, line 15).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art,
prior to the effective filing date of the claimed invention, to treat a patient with a non-small cell
lung cancer (NSCLC) by administering an oral pharmaceutical composition comprising the active compounds of pemigatinib and sotorasib as KRASG12C and FGFRl inhibitors because both Liu and Cee taught the compounds were effective at treating NSCLC and that combining pemigatinib and sotorasib in a therapy simultaneously or sequentially would have been obvious to try in light of the disclosures by Bhonde which tie Liu and Cee’s disclosure together to form a composition of pemigatinib and sotorasib to treat NSCLC. See MPEP 2144.06 Art Recognized Equivalence for the Same Purpose. The limitation of a daily oral dose of about 13.5 mg pemigatinib in instant claim 75, would have been prima facie obvious to try over Liu’s teaching of a 10 mg dose and Bhonde’s disclosure that Suitable doses and dosage regimens can be determined by range-finding techniques which are a function of the subjects mass, body volume, body surface area, regions and routes of administration, and the degree of cancer prognosis of the subject.
A person of ordinary skill in the art would have been motivated to use pemigatinib and
sotorasib to treat a patient with non-small cell lung cancer because Cee and Liu showed they
were each effective in a pharmaceutical composition to treat NSCLC disease and therefore
would have had an expectation of success in treating a patient with lung cancer due to the cumulative effects of combining two medications utilized for the same purpose. See MPEP 2144. A skilled artisan would have also used the disclosures of Bhonde of combining a KRASG12C and FGFRl inhibitors together in a composition for the treatment of NSCLC because of the beneficial synergistic effects disclosed by the combination of a KRASG12C and FGFRl inhibitors. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the
invention was made as evidenced by the references on the current record.
Response to Arguments
Applicant’s arguments with respect to claims 1-3, 7, 14, 15, 17, 22, 28, 29, 33, 38, 39, and 44-69 (Currently claims 44-66, 69, and 73-75) in the reply dated 11/11/2025 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant argues the Office has not provided any known examples of combinations of FGFR inhibitors and KRASGl2C inhibitors.
Bhonde (WO 2021/079302) is discussed above wherein the synergistic effects and combination of FGFR inhibitors and KRASGl2C inhibitors is disclosed. A skilled artisan would have found it prima facie obvious to follow the teachings of Liu and Cee in light of Bhonde to combing the compounds of pemigatinib and sotorasib to administer an oral pharmaceutical composition for the treatment of non-small cell lung cancer in a patient in need thereof.
Conclusion
All claims are rejected, no claims are allowed
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623