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
This office action is in response to applicant’s reply filed on June 11, 2026.
Restrictions/Elections.
Applicant’s election without traverse of Group I (Claims 1-7) in the reply filed on June 11, 2026, is acknowledged.
Status of Claims
Claims 1-7 are currently pending and are the subject of this office action.
Claims 1-7 are presently under examination.
Priority
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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) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Soto et. al. (US 2021/0046059).
For claims 1-2 and 7, Soto teaches a method of treating gastrointestinal stromal tumors (GIST) comprising the administration of a composition comprising ripretinib (DCC-2618, instant Formula (I)) (see for example abstract). Wherein the amount of ripretinib is 150 mg once or twice a day (see [0020]).
Approximately 85% of all GIST share oncogenic mutations in 1 or 2 receptor tyrosine kinases (TK): KIT or PDGFRA. Constitutive activation of either of these TKs plays a central role in the oncogenic behavior of GIST (see [0003]).
Localized and resectable tumors are treated surgically which remains the mainstay of curative therapy for localized disease. Resected high-risk GIST is typically treated with adjuvant imatinib, whereas low-risk GIST is managed with surgery alone. Intermediate-risk GIST is managed on a per-case basis. In an advanced/metastatic setting, imatinib 400 mg daily is approved, with dose escalation to 800 mg at the time of progression and has been shown to yield dramatic results in disease control. Imatinib-refractory patients are treated with sunitinib as a second-line therapy and regorafenib as third-line therapy on resistance or intolerance to sunitinib (see [0004]).
At diagnosis, a mutation in the KIT gene occurs in 80% of GIST and is usually found in exon 11, and less commonly in exon 9. Exon 11 primary mutations are the most commonly seen in GISTs (around 70% of cases) and derive significant benefit from treatment with imatinib in both the adjuvant and metastatic settings (see [0005]).
Despite significant improvement in outcomes compared with those in the pre-mutation-driven/TKI therapy era, response to imatinib is not experienced by all patients, and most patients with GIST will ultimately develop resistance to imatinib, most commonly due to the development of secondary mutations in KIT. Secondary resistance mutations usually arise in the catalytic domain of the kinase:
1) at the switch pocket, which typically occur in KIT exons 13 and 14 or PDGFRA exons 14 and 15 and sterically disrupt drug binding or conformationally activate KIT, and
2) in the activation loop switch encoded by KIT exons 17 and 18 and PDGFRA 18.
Activation loop mutations act by shifting the kinase into an activated Type I or on-state conformation that is less amenable to drug binding by any of the approved Type II TKIs. Although uncommon in primary GIST (1%-2% of newly diagnosed cases), mutations in exons 13, 14 and 17 are often responsible for acquired imatinib resistance, with exon 17 mutations alone accounting for as many as 50% of the acquired resistance cases to imatinib, and later to sunitinib. A need exists for a TKI that can broadly inhibit clinically relevant KIT and PDGFRA mutations. (see [0006]).
Ripretinib proved to be effective in treating GIST patients with KIT exon 11 or KIT exon 17 (see [0053]-[0054] and [0131]). The data shows that ripretinib showed progression free survival (PFS) in all assessed groups compared to placebo (see [0053]). In some embodiments, a patient's tumor has an imatinib resistant mutation selected from the group consisting of a KIT exon 17 activation loop mutation or a KIT exon 18 activation loop mutation (see [0071]). PFS was determined by RESIST 1.1 (see [0092] and [0094]).
The method is effective in treating GIST in patients which are intolerant to a first line of administration of imatinib and a second line administration of sunitinib (see [0073] and [0081], see also claim 1).
In some embodiments, the patient tumor has an imatinib resistant, sunitinib resistant mutation selected from the group consisting of a KIT exon 17 activation loop mutation and exon 18 activation loop mutation among others (see [0096]).
In summary, Soto teaches a method of treating GIST comprising administering to a patient suffering from GIST that has: KIT exon 17 and/or KIT exon 18 and/or KIT exon 11 mutations, among others, comprising the administration of a composition comprising ripretinib, 150 mg once or twice daily, wherein the patient is intolerant to imatinib and sunitinib. Soto does not state that the patient has a) exon 17 and/or a KIT exon 18 mutation and b) a KIT exon 11 mutation. However, as stated above, Soto teaches that these are common mutations occurring in GIST patients and that each one of them was successfully treated with ripretinib. And since most GIST patients suffer from one or more mutations and since the administration of ripretinib was effective in the majority of the GIST population that is intolerant to imatinib and then sunitinib (because precisely the presence of these KIT mutations), before the effective filing date of the instant claims, it would have been prima facie obvious for the skilled in the art to treat GIST patients that are intolerant to imatinib sunitinib that show any combination of mutations, including a) KIT exon 17 and/or KIT exon 18 and b) KIT exon 11, since ripretinib has already been proven to be effective against each KIT mutation individually, and since ripretinib is effective in the majority of the population suffering from GIST which is intolerant to imatinib and sunitinib (i.e. have one or more KIT exon mutations), with a reasonable expectation of success.
The statement in claim 1: “wherein upon administration of the compound the patient achieves significantly more progression free survival time as determined by mRECIST1.1, and significantly more overall survival time, as compared to a patient with a KIT exon 17 and/or a KIT exon 18 mutation and a KIT exon 11 mutation suffering from an advanced gastrointestinal stromal tumor who has progressed on or was intolerant to imatinib and was then administered 50 mg sunitinib once daily” does not require additional steps to be performed and simply expresses the intended result of carrying the process made obvious by the prior art: “a method of treating GIST in a patient in need thereof, wherein the patient has a) a KIT exon 17 and/or a KIT exon 18 mutation and b) a KIT exon 11 mutation, comprising administering to the patient a composition comprising ripretinib, 150 mg once or twice daily".
MPEP 2111.04 states: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “ adapted to ” or “adapted for ” clauses;
(B) “ wherein ” clauses; and
(C) “ whereby ” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby’ clause states a condition that is material to patentability; it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” (Emphasis added).
In the instant case “the patient achieves significantly more progression free survival time as determined by mRECIST1.1, and significantly more overall survival time, as compared to a patient with a KIT exon 17 and/or a KIT exon 18 mutation and a KIT exon 11 mutation suffering from an advanced gastrointestinal stromal tumor who has progressed on or was intolerant to imatinib and was then administered 50 mg sunitinib once daily” appears to be the result of the process made obvious by the prior art: “a method of treating GIST in a patient in need thereof, wherein the patient has a) a KIT exon 17 and/or a KIT exon 18 mutation and b) a KIT exon 11 mutation, comprising administering to the patient a composition comprising ripretinib, 150 mg once or twice daily", e. g. the intended result of a process step positively recited. As such, this limitation in the instantly claimed method has not been given any weight.
Further, as stated in the above rejection, Soto teaches that GIST patients who were intolerant to imatinib and sunitinib achieve high PFS as determined by RECIST 1.1 when administered ripretinib.
All this will result in the practice of claims 1-2 with a reasonable expectation of success.
For claims 3 and 4, Soto teaches that:
at diagnosis, a mutation in the KIT gene occurs in 80% of GIST and is usually found in exon 11, and less commonly in exon 9. (see [0005]) and
although uncommon in primary GIST (1%-2% of newly diagnosed cases), mutations in exons 13, 14 and 17 are often responsible for acquired imatinib resistance, with exon 17 mutations alone accounting for as many as 50% of the acquired resistance cases to imatinib, and later to sunitinib (see [0006]).
The above clearly indicates that KIT exon 9, 13 and 14 are less common than KIT exon 11 and 17 mutations. In any case, as discussed above for claims 1-2, before the effective filing date of the instant claims, it would have been prima facie obvious for the skilled in the art to treat GIST patients with all type of combinations of mutations, thus resulting in the practice of claims 3 and 4 with a reasonable expectation of success.
The statement in claim 5: “wherein the patient being administered the compound has a progression free survival of at least about 14 months as compared to a progression free survival of about 1.5 months for the patient administered sunitinib” does not require additional steps to be performed and simply expresses the intended result of carrying the process made obvious by the prior art: “a method of treating GIST in a patient in need thereof, wherein the patient has a) a KIT exon 17 and/or a KIT exon 18 mutation and b) a KIT exon 11 mutation, comprising administering to the patient a composition comprising ripretinib, 150 mg once or twice daily".
MPEP 2111.04 states: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “ adapted to ” or “adapted for ” clauses;
(B) “ wherein ” clauses; and
(C) “ whereby ” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby’ clause states a condition that is material to patentability; it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” (Emphasis added).
In the instant case “the patient being administered the compound has a progression free survival of at least about 14 months as compared to a progression free survival of about 1.5 months for the patient administered sunitinib” appears to be the result of the process made obvious by the prior art: “a method of treating GIST in a patient in need thereof, wherein the patient has a) a KIT exon 17 and/or a KIT exon 18 mutation and b) a KIT exon 11 mutation, comprising administering to the patient a composition comprising ripretinib, 150 mg once or twice daily", e. g. the intended result of a process step positively recited. As such, this limitation in the instantly claimed method has not been given any weight.
All this will result in the practice of claim 5 with a reasonable expectation of success.
For claims 6, Soto teaches the administration of ripretinib for 42 days or more (see [0093]), thus resulting in the practice of claim 6 with a reasonable expectation of success.
Conclusion
No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCOS L SZNAIDMAN whose telephone number is (571)270-3498. The examiner can normally be reached Flexing M-F 7 AM-7 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached on 571 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARCOS L SZNAIDMAN/
Primary Examiner, Art Unit 1628
June 12, 2026.
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