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 .
Status of Claims
Claims 1, 3-14 and 16-22 are pending in the instant application. Claims 1, 5, 8, 14, 16 and 18 are amended and claims 2 and 15 are cancelled via the amendment filed February 27th, 2026.
Priority
This is a 35 U.S.C. 371 National Stage filing of l Application No. PCT/EP2021/081612 filed November 15th, 2021, and a continuation of 63/162,649, filed March 18th, 2021 and 63/114,144, filed November 16th, 2020.
Information Disclosure Statement
The Information Disclosure Statements (IDS) filed 09/16/2025, 11/05/2025 and 12/31/2025 were considered by the Examiner.
Withdrawn Rejections
Applicant’s arguments and amendments, filed February 27th, 2026, with respect to the 112(a) rejection of claims 8 and 18 have been fully considered and are persuasive. The 112(a) rejection of claims 8 and 18 has been withdrawn.
Applicant has overcome this rejection by amending the claims to remove the term “prophylaxis”.
Applicant’s arguments and amendments, filed February 27th, 2026, with respect to the 102(a)(1) rejection of claims 1 and 4-5 over Bladt, as evidenced by Scorsone have been fully considered and are persuasive. The 102(a)(1) rejection of claims 1 and 4-5 has been withdrawn.
Applicant has overcome this rejection by amending claims 1 and 5 to recite “wherein the MEK inhibitor is pimasertib”.
Response to Remarks
Applicants arguments with respect to the 112(a) and 102(a)(1) rejections are moot as the rejections have been overcome.
Applicant's arguments filed February 27th, 2026, with respect to the rejection of claims 1-22 under 35 U.S.C. 103 as being unpatentable over Huck have been fully considered but they are not persuasive.
Applicant traverse the rejection on the premise that the art does not suggest the particular claimed combinations of compounds.
In response, as stated in the previous rejection, as Huck teaches cancer therapeutic combinations including the compounds of the instant invention and each compound is known to treat cancer, it would have been obvious to combine the compounds for the same utility, the treatment of cancer. See MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
On p. 9 of the remarks, Applicant further traverses the rejection by stating the examples of record demonstrate unexpected results for the claimed combinations.
Examiner acknowledges the data in the instant specification, but respectfully disagrees.
Example 1 of the instant specification is concerned with administering M2698 and pimasertib to xenograft models of glioblastoma and orthotopic GSC xenograft models. Example 2 of the specification showcases the administration of M2698 and pimasertib to xenograft models of non-small cell lung cancer. Example 3 describes the administration of M2698 with pimasertib to xenograft models of breast cancer. Example 4 is M2698 and pimasertib with xenograft models of cholangiocarcinoma at dosages of 20 mg/kg. Example 5 describes the administration of the combination to xenograft models of colorectal cancer at dosages of 20-25 mg/kg. Example 6 showcases the administration of M2698 and cetuximab in xenograft models of SCCHN.
Applicant refers to these alleged unexpected, surprising results; however, even if the results were considered unexpected, the results would not be commensurate in scope with the scope of the claims. The results provided do not occur over the entire claimed range (an unclaimed amount). In the instant disclosure, dosages of 20-25 mg/kg of each compound were used, however, the present claims do not require a specific dosage amount. Further, the Figures is based on cell models and animal models. It is unclear how results in a cell model or animal model would correlate with treatment in a human patient.
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). See MPEP 716.02 (d) and MPEP 716.02 (e).
An affidavit or deceleration under 37 CFR 1.132 must compare the claimed subject matter with the closes prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
Regardless, Applicant has not compared the unexpected results provided to the prior art to effectively rebut the prima facie case of obviousness previously set forth.
In view of the above arguments, the 103 rejection is maintained.
Applicant's arguments filed February 27th, 2026, with respect to the double patenting rejection of claims 1-22 have been fully considered but they are not persuasive.
For the same reasons as above, the double patenting rejection is maintained.
Maintained 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, 3-14 and 16-22 stand rejected under 35 U.S.C. 103 as being unpatentable over Huck et al (WO 2015/149909 A1, as cited on the IDS).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Huck teaches combinations of cancer therapeutics. Huck teaches a combination of 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide (Compound A), a Her2 inhibitor and one or more cancer therapeutics (pages 8-9). Huck teaches that the cancer therapeutic added in the combination can be pimasertib (paragraph 9, page 9) and cetuximab (paragraph 11, page 9).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art does not explicitly teach a combination of 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide (Compound A), pimasertib and cetuximab.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
While the prior art does not explicitly teach a combination of 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide (Compound A), pimasertib and cetuximab, Huck teaches combinations of cancer therapeutics in which the aforementioned combination is included. A person having ordinary sill in the art would have been motivated to screen the example compounds in combinations of the prior art to determine which would provide optimum treatment outcome.
Further, Huck teaches that 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide (Compound A) is used for the treatment of cancer and has been shown to exhibit potent anti-tumor activity against a broad panel of cancer cell lines (page 1, paragraph 2). Also, Huck teaches that cetuximab and pimasertib are cancer therapeutics (pages 8-9). As such, it would have been obvious to combine the compounds for the same utility, the treatment of cancer.
See MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Regarding claims 1, 3 and 14, as such, it would have been prima facie obvious to have a compound mixture of 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide, pimasertib and cetuximab as one of ordinary skill in the art would have looked to optimize the teachings of Huck to choose the three compounds from the list of cancer therapeutics and would have had motivation to combine them as they are all known as being useful for the same purpose, the treatment of cancer.
Regarding claim 4, Huck teaches that the compound mixtures can be combined with excipients or adjuvants (page 11, paragraph 1).
Regarding claims 5-7 and 16-17, Huck teaches a set (kit) comprising separate packs of 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide (Compound A) and one or more cancer therapeutic agents (page 8, paragraph 4). As seen above, Huck teaches that the cancer therapeutic agents include pimasertib and cetuximab. As such, one of would have been motivated to screen the example compounds in combinations of the prior art to determine which would provide optimum treatment outcome to arrive at the instantly claimed invention.
Regarding claims 8-11, 18-19, and 22, Huck teaches that the compound mixture relates in particular to a method for the treatment of tumors such as breast cancer (page 6, paragraph 6). Furthermore, as 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide (Compound A), pimasertib and cetuximab are taught in Huck as being useful in the treatment of cancer, it would have been prima facie obvious to one of ordinary skill in the art to combine them and form a new composition. See MPEP 2144.06, above.
Regarding claims 12-13 and 20-21, Huck teaches that in the method of treating cancer, the compounds of the compound mixture can be administered simultaneously or sequentially (page 6, paragraph 4).
Maintained 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 1, 3, 8-14, 18-19 and 20-22 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 9,980,966 B2 in view of Huck et al (WO 2015/149909 A1, as cited on the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The patent claims a method for the treatment of cancer compressing administering to a subject an effective amount of 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide and a Her2 inhibitor (claim 1). The patent does not claim that an EGFR and MEK inhibitor were also administered. However, Huck teaches that 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide (Compound A) is used for the treatment of cancer and has been shown to exhibit potent anti-tumor activity against a broad panel of cancer cell lines (page 1, paragraph 2). Also, Huck teaches that cetuximab and pimasertib are cancer therapeutics (pages 8-9). As such, it would have been obvious to combine the compounds for the same utility, the treatment of cancer.
Regarding claims 1, 3, 8-11, 14, 18-19 and 22, As 4-[(S)-2-azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-quinazoline-8-carboxylic acid amide, pimasertib and cetuximab are known in the art to treat cancer, it would have been prima facie obvious to someone of ordinary skill in the art to combine them for the same utility.
See MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Regarding claims 12-13 and 20-21, the patent claims the pharmaceutical combination agents can be administered simultaneously (claim 6) or sequentially (claim 7).
Conclusion
No claim is 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 Anna Grace Kuckla whose telephone number is (703)756-5610. The examiner can normally be reached Monday-Friday 7:30-5.
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, Clinton A Brooks can be reached at (571)270-7682. 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.
/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
Prosecution Insights