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
Pending claims 1-3, 7-9, 11-12, 14-28 have been examined on the merits.
Withdrawn Rejections
The rejection of Claims 1-3, 7-9, 11-12, 14-20, and 24-28 under 35 U.S.C. 103 as being unpatentable over Wu et al. PLoS One. 2016 Sep 12;11(9):e0162491 (IDS 01/27/2026), Blanchard et al. WO-2007/058626, Kania (PG-PUB 2004/017634), and Patani et al., Chemical Reviews 96, no. 8 (January 1, 1996): 3147–76 is withdrawn in view of the claim amendments.
New Grounds of Rejection due to claim amendment
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 non-obviousness.
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.
Claims 1-3, 7-9, 11-12, 14-20, and 24-28 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et. al. WO 2010/129509 (“Chen”), Chen et. al., Endocrinology, 2005 Dec;146(12):5444-54 “Chen-2”, Blanchard et al. WO 2007/058626, and Dick et. al., Pharmaceuticals (Basel). 2020 Feb 28; 13(3):36.
Regarding claim 1-3, 7-9, 11-12, 14-20, and 24, 26-28, Chen (abstract, page 2, line 28-31 bridged page 3, line1-9) teaches vinyl indazoiyl compounds useful in the treatment of cancer, which may exist as the R or S enantiomer, or as a pharmaceutical salt thereof. Chen (page 1, line 29-31 bridged page 2, line 1-4) teaches the compounds are useful to treat breast cancer, non-small cell lung (NSCL) cancer, bladder cancer, gastric cancer, pancreatic cancer, prostate cancer, and colon cancer. Chen (abstract) discloses the following compound, wherein A1, A2 and A3 are CH; L is CH=CH; B2 is imidazole with a hydroxyethyl group; X1-X2 is -OCH(CH3)-; B1 is pyridine with chlorine substituted R4. Chen, does not explicitly disclose B1 is a benzene.
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However, Dick (page 2, section 3) teaches that -N= and -CH= groups are classical bioisosteres and provides benzene and pyridine as examples. See below.
Therefore, it would have been prima facie obvious to a POSITA that pyridine and benzene are predictable alternatives for B1 moiety in Chen’s structure.
Regarding X1-X2, Dick (page 2, section 3) teaches O, NH, and CH2 are classical bioisosteric equivalents, thus, providing a reason to the replace the oxygen in the -OCH(CH3)- linker with NH to arrive at the claimed -NHCH(CH3)- linker. Such substitution would have been expected to retain substantially similar biological properties due to the recognized bioisosteric relationship among these linker groups.
Furthermore, Kania (abstract) teaches the use of pharmaceutical compositions containing indazole compounds to treat cancer. Kania (p.4, [0034] and [0046]; page 133; page 90) teaches various options for linker at position X1-X2 including
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. Therefore, a POSITA would also have options to modify the teachings of Chen in view of Kania’s disclosure, to arrive at the following X1-X2 linker i.e., NH, CH2, -N(CH3)-, C=O, and SO2, as part of routine medicinal chemistry strategies aimed at expanding the therapeutic candidate library in the search for a lead compound, with a reasonable expectation of retaining or improving the compound therapeutic benefits.
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Regarding bioisosteric replacement on the B1 aryl group, Chen discloses chloro substituted benzene at the ortho position. But Chen-2 (abstract; page 5446-5447, Table 2 and Table 3) discloses that moving a chloro group or fluoro group from a meta-position to ortho-position, resulted in a 10-fold decrease in protein binding. Furthermore, Chen-2 (page 5447) discloses changing a fluoro group to a chloro group at the meta position significantly decreased compound binding affinity to the protein target. Therefore, it would have been obvious to a POSITA in need of improving a compound binding affinity to a target, to exchange chloro groups at ortho position to fluoro at a meta position and arrive at the claimed invention. Therefore, the combined teachings of Chen, Chen-2, Dick and Kania provide a reason
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to modify Chen’s compounds with a reasonable expectation of success, because such modification would retain or improve the compound pharmacological properties or activities. See MPEP 2144.09.
Regarding claim 25, and as applied to claims 1-3, 7-9, 11-12, and 14-20 above, Blanchard (abstract) teaches indazole compounds to treat proliferative disorders such as cancer, comparable to the instant claim. Blanchard (page 122-123) discloses a comparable genus of linker chemistry such as alkyl, heteroalkyl, alkylsulfonyl, alkylamino, as an example. Blanchard (page 142) discloses compounds with a sulfonamide and alkylamino groups at the X1-X2 linker position. Because the prior art recognizes indazole compounds as useful for treating cancer, and the teachings of Kania discloses sulfur containing linkers, therefore, a POSITA would have had reason to incorporate a sulfonamide linker into the compounds of Chen to arrive at the claimed invention. This is because such modification would have presented a predictable variation of the combined teachings in the prior art in the pursuit of lead compounds to treat proliferative diseases including cancer.
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Subject Matter Free of the Art of Record
Claims 21-23 are objected and free of the art of record. The closest prior art is Chen et. al. WO 2010/129509 in view of Kania et al., US 2004/0171634. Chen discloses indazolyl compounds which shared a core structure similar to that of the instant claim. Chen does not disclose or suggest such compounds bearing the claimed for R6, R7 substituents, as an example. Therefore, there is no motivation for an ordinary skill in the art to modify the teaching of Chen to arrive at the claimed compound. These claims are not allowable until the 103 rejection is overcome.
Response to Argument
Applicant argues that the claim amendment restricts B1 to a substituted benzene and that the X1-X2 linker, -OCH(CH3)-, does not read on the amended claim. Applicant’s argument is not persuasive. As discussed in the 103 rejection above, Dick teaches that -N= and -CH= groups are interchangeable, thus providing a reason to a POSITA to replace the -N= from the pyridine ring with -CH=, thereby arriving at the claimed substituted benzene. Furthermore, Dick also teaches O and NH as bioisosteric alternative, thus providing also a reason to the replace the oxygen in the -OCH(CH3)- linker with NH to arrive at the claimed -NHCH(CH3)- linker.
Applicant also argues Kania and Blanchard do not teach the claimed substituted B1 moiety and X1-X2 linker. Applicant’s argument is not persuasive. As previously noted for the substituted benzene, the same argument applies here as well. Regarding the linker, both Kania and Blanchard teach the same core concept of indazole compounds with distinct X1-X2 linkers. For example, as disclosed above in the 103 rejection, Kania teaches variations of the X1-X2 linker comprising
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, while Blanchard teaches linkers comprising sulfonamide and alkylamino. Given that both prior art references teach the same indazole core for use to treat cancer, thus, a POSITA would have been motivated to vary the linker in Chen’s in view of Kania and Blanchard disclosure to expand the chemical library and arrive at the claimed invention.
Applicant further argues that compounds containing a sulfonamide linker demonstrate stronger inhibitory activity compared with compounds having a non-sulfonamide linker. While Applicant’s argument is persuasive, however, and as discussed above, Kania teaches sulfur containing linkers, while Blanchard teaches a sulfonamide linker. Therefore, these disclosures would inform a POSITA that sulfur containing linkers may be important to the activity of indazole compounds. Therefore, a POSITA would have been motivated to employ the sulfonamide linker taught by Blanchard in view of Kania to Chens’s teachings with reasonable expectation of success of improving the compound binding or inhibitory properties against a target. See MPEP 2144.09.
Conclusion
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.
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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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