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 is a national stage entry of PCT/IB2019/057711 filed on 09/12/2019 which claims benefit of U.S. Provisional No. 62/730,046 filed on 09/12/2018.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 25, 2026 has been entered.
Response to Amendment
No amendments to claim 40 were identified by Applicant’s reply filed on February 25, 2026 even though it is indicated that claim 40 is currently amended. Claims 1-39 and 41-46 were previously canceled. Claim 40 is currently pending.
Claim 40 is currently being examined as it reads on the elected species of HSN748 as a compound of formula I.
Response to Arguments
Applicant's arguments filed February 25, 2026 have been fully considered but they are not persuasive.
Applicant argues that minor modifications of a ring structure can result in differences in kinase selectivity or killing of specific cancers. Applicant argues that the claimed compound HSN748 inhibits AML cell lines better than ponatinib. Applicant further argues that the claimed compound HSN748 inhibits cancer cell lines better than another compound with a similar structure. Thus Applicant argues that even with minor structural changes significant difference in the activity occurs.
Applicant argues that their prior response provided evidentiary references and data showing that minor modification of a ring structure achieved significant difference in kinase selectivity or killing of specific cancers. Applicant argues that the Office Action did not rebut that data and cites erroneous case law that is not applicable to the present claims and situation. Applicant argues that given that the art recognizes that minor modification of a ring structure achieved significant difference in kinase selectivity or killing of specific cancers, the Office Action has not provided any rationale as to why the skilled artisan, without knowing the present structure of HSN748 would modify the unrelated chemistry in either Gozgit or Wan to arrive at the presently claimed compounds.
Applicant further argues that Gozgit provides many alternatives for alkyl and there is no reason to select CF3. Applicant further argues that of all the compounds made in Wan, all but one includes a methyl or methyl substituted moiety at this position on the pyridine.
These arguments are found not persuasive for reasons of record. It is maintained that the structures identified by Applicant (ponantinib and HSL382) in an attempt to provide evidence that minor modifications lead to vastly different responses are found not persuasive since the references cited in the rejections of record disclose compounds that are closer in structure to the claimed compound. The compounds of Gozgit et al. and Wan et al. do not involve any nonobvious changes to ring atoms as does ponantinib and HSL382. Rather the references cited disclose compounds having the same core structure as compound HSN748 and only differ in the substituents attached to the core structure. Claim 40 claims HSN748 having the following structure:
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and as detailed in the previous office action Gozgit et al. discloses the following compound of Formula I:
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(claim 17 page 80) and Wan et al. Wan et al. specifically teaches the following compound
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. Thus the compounds of Gozgit et al. and Wan et al. are closer in structure than ponatinib or HSL382.
It is maintained that a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and/or similar utilities. “An obviousness rejection based on similarity in chemical structure and/or function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991). In the instant case, a person of ordinary skill in the art would have been motivated to make the claimed compounds from the disclosure of Wan et al. and Gozgit et al. since both teach alternatives for the substituents attached to the core structure in the same positions that will result in the claimed compound.
For example, the teachings of Gozgit et al. render obvious Applicant’s elected species HSN748 since Gozgit et al. teaches the following compound:
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wherein the only difference is the substituent on the phenyl ring. However, claim 1 of Gozgit et al. teaches that the substituent on the B ring can be chosen as halo or R4 wherein R4 is alkyl (page 72). Gozgit et al. further teaches that alkyl includes trifluoromethyl [0057]. With respect to Applicant’s argument that Gozgit provides many alternatives for alkyl and there is no reason to select CF3, Gozgit et al. specifically teaches that in addition to Cl a preferred substituent on Ring B is CF3 [0113]. Thus Gozgit et al. specifically exemplifies CF3 as a suitable alternative for Cl and thus motivating an ordinary skilled artisan to make said substitution with a reasonable expectation of similar success.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to substitute one preferred substituent with another according to the teachings of the prior art with a reasonable expectation of predictable results. Thus a person of ordinary skill in the art would have been motivated to substitute CF3 for Cl in the above compound to arrive at a compound claimed in the instant claims.
Likewise, the teachings of Wan et al. render obvious Applicant’s elected species HSN748 since Wan et al. specifically teaches the following compound
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wherein the only difference between the claimed compound HSN748 and said compound is a methyl substituent on the pyridine ring (page 14). However, Wan et al. teaches that m on ring A is preferably 0 or 1.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to prepare the above compound excluding the methyl substituent on the pyridine ring according to the teachings of Wan et al. to arrive at a compound as claimed. One would have been motivated to prepare a compound excluding the methyl substituent on the pyridine ring with a reasonable expectation of predictable results.
With respect to Applicant’s argument that of all the compounds made in Wan, all but one includes a methyl or methyl substituted moiety at this position on the pyridine, it has been well established that consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches, when viewed in light of the admitted knowledge in the art, to a person of ordinary skill in the art. In re Boe, 355 F.2d 961,148 USPQ 507, 510 (CCPA 1966); In re Lambedi, 545 F.2d 747, 750, 192 USPQ 279,280 (CCPA 1976): In re FracalossL 681 F.2d 792,794, 215 USPQ 569, 570 (CCPA 1982)4 In re Kaslow, 707 F.2d 1366, 13:4,217 USPQ 1089, 1095 (Fed. Cir. 1983). Furthermore, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ423 (CCPA 1971). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Thus, as previously argued Applicant’s arguments are not sufficient to overcome the rejections of record since Applicant’s comparisons are not against the closest prior art identified in the rejections of record. Applicant has not presented any evidence that minor modifications of the substituents as taught in the prior art, while preserving the same core structure would result in vastly different activities. Evidence of secondary considerations must compare the claimed subject matter with the closest 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).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Accordingly, the previous rejections under 35 USC 103 over Gozgit et al. and over Wan et al. are hereby maintained and reproduced below. This action is FINAL.
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.
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Gozgit et al. U.S. Publication No. 2015/0105377 A1 (Provided on IDS dated 03/10/2021).
Claim 40 of the instant application claim a pharmaceutical composition comprising a compound such as
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(HSN748) wherein the compound is present in the composition in a therapeutically effective amount for treating a cancer selected from the group consisting of acute myeloid leukemia, chronic myeloid leukemia, ovarian cancer, cervical cancer, pancreatic cancer, breast cancer, brain cancer, skin cancer, lung cancer, prostate cancer, Lymphoma, Leukemia, colon cancer, head cancer, neck cancer, thyroid cancer, kidney cancer, liver cancer, and stomach cancer.
Gozgit et al. teaches methods and compositions for treating or preventing RAF kinase mediated diseases or conditions by administering a compound of Formula I (abstract). Gozgit et al. provides pharmaceutical compositions for treating or preventing a RAF kinase mediated disease or condition in a subject in need thereof comprising an effective amount of a RAF inhibitor, wherein the RAF inhibitor is a compound of Formula I [0013]. Gozgit et al. discloses the following compound of Formula I:
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(claim 17 page 80).
Gozgit et al. specifically teaches pharmaceutical compositions for treating or preventing a RAF kinase mediated disease or condition in a subject in need thereof comprising an effective amount of a RAF inhibitor, wherein the RAF inhibitor is a compound of Formula I ([0013], [0093], and claim 25). Gozgit et al. specifically teaches that exemplary diseases or conditions that are mediated by RAF include, but are not limited to, certain hematological cancers including acute myeloid leukemia and solid tumors such as melanoma, colorectal cancer, medullary thyroid cancer, carcinoid, small cell lung cancer and pheochromocytoma [0054].
Gozgit et al. specifically teaches in certain embodiments, the RAF kinase mediated disease or condition treated or prevented with a compound of Formula I is a hematological cancer that is known to be implicated by the inhibition of a RAF tyrosine kinase such as acute myeloid leukemia (AML), and in alternative embodiments, the RAF kinase mediated disease or condition treated or prevented with a compound of Formula I is a solid tumor that is known to be implicated by the inhibition of a RAF tyrosine kinase such as melanoma, colorectal cancer, medullary thyroid cancer, carcinoid, small cell lung cancer and pheochromocytoma [0084].
Thus Gozgit et al. teaches a pharmaceutical composition for the treatment of a RAF kinase mediated disease or condition wherein the RAF kinase mediated disease or condition are the same cancers as claimed, comprising an effective amount of the RAF inhibitor.
Gozgit et al. does not specifically exemplify compound HSN748.
However, as detailed above, Gozgit et al. teaches the following compound:
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wherein the only difference is the substituent on the phenyl ring. However, claim 1 of Gozgit et al. teaches that the substituent on the B ring can be chosen as halo or R4 wherein R4 is alkyl (page 72). Gozgit et al. further teaches that alkyl includes trifluoromethyl [0057]. Gozgit et al. specifically teaches that in addition to Cl a preferred substituent on Ring B is CF3 [0113].
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to substitute one preferred substituent with another according to the teachings of the prior art with a reasonable expectation of predictable results. Thus a person of ordinary skill in the art would have been motivated to substitute CF3 for Cl in the above compound to arrive at a compound claimed in the instant claims. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and/or similar utilities. “An obviousness rejection based on similarity in chemical structure and/or function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991).
Thus claims 40 of the instant application is rendered obvious in view of the cited prior art teachings.
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Wan et al. WO 2013/170770-English Translation provided (Provided on IDS dated 03/10/2021).
Claim 40 of the instant application claims a pharmaceutical composition comprising a compound such as
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(HSN748) wherein the compound is present in the composition in a therapeutically effective amount for treating a cancer selected from the group consisting of acute myeloid leukemia, chronic myeloid leukemia, ovarian cancer, cervical cancer, pancreatic cancer, breast cancer, brain cancer, skin cancer, lung cancer, prostate cancer, Lymphoma, Leukemia, colon cancer, head cancer, neck cancer, thyroid cancer, kidney cancer, liver cancer, and stomach cancer.
Wan et al. teaches compounds of formula I:
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wherein Ring A is heteroaryl; m and p are preferably 0 or 1; Ring B is preferably a phenyl group; L is a linking group -CONR1 and R1 is H (page 4). Wan et al. teaches that T is preferably
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(page 13).
Another aspect of Wan et al. relates to a pharmaceutical composition comprising a compound of the invention, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a solvate, a polymorph, a tautomer, a metabolite or a prodrug thereof, and a pharmaceutically acceptable carrier (claim 11).
Moreover, Wan et al. specifically teaches to a pharmaceutical composition comprising a compound of the invention, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a solvate, a polymorph, a tautomer, a metabolite or a prodrug thereof, and a pharmaceutically acceptable carrier (page 18 of translation). Wan et al. further teaches a composition for preventing and/or treating a tumor and effectively inhibiting the growth of various tumor cells (page 18 of translation). Wan et al. teaches the term "tumor" includes but is not limited to: leukemia, gastrointestinal stromal tumor, histiocytic lymphoma, non-small cell lung cancer, small cell lung cancer, pancreatic cancer, lung squamous cell carcinoma, lung adenocarcinoma, breast cancer, prostate cancer, liver cancer, skin cancer, epithelial cell carcinoma, cervical cancer, ovarian cancer, intestinal cancer, nasopharyngeal cancer, brain cancer, bone cancer, esophageal cancer, melanoma, kidney cancer, oral cancer and other diseases (page 19 of translation). Wan et al. further teaches effective dosages of the compounds disclosed therein for treating cancer (page 19 of translation). Wan et al. further specifically demonstrates the anti-tumor effect of the compounds in chronic myeloid leukemia utilizing in vitro and in vivo models (pages 37-39 of translation).
Thus Wan et al. teaches a pharmaceutical composition comprising an effective amount of the compounds disclosed therein for the treatment of a tumor wherein the tumor is the same as claimed in instant claim 40.
Wan et al. specifically teaches the following compound:
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wherein the only difference between the claimed compound of claim 29 and said compound is a methyl substituent on the pyridine ring (page 14). However, Wan et al. teaches that m on ring A is preferably 0 or 1.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to prepare the above compound excluding the methyl substituent on the pyridine ring according to the teachings of Wan et al. to arrive at a compound as claimed. One would have been motivated to prepare a compound excluding the methyl substituent on the pyridine ring with a reasonable expectation of predictable results. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and/or similar utilities. “An obviousness rejection based on similarity in chemical structure and/or function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991).
Thus claim 40 is rendered obvious in view of the cited prior art teachings.
Conclusion
Claim 40 is rejected. Claims 1-39 and 41-46 are canceled. No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached on (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM