Detailed Action
The present office action is in response to the remarks filed on 07 Aug 2026.
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
Claims 22-23 of the pending application have been examined on the merits. Claim 24 remains withdrawn. Acknowledgement is made of the cancellation of claims 1-21.
Priority
The instant application retains the priority date of 10 Dec 2019.
Response to Applicant Arguments
Acknowledgement is made of the remarks filed 07 Aug 2026.
Regarding the rejection of claims 22-23 under 35 U.S.C. § 103 over WO 2012/118492 (provided in IDS 09/14/22), hereinafter '492, further in view of Wenglowsky et al. (Bioorg Med Chem Lett, 2014, 24:1923-1927; provided in IDS 09/14/22), hereinafter Wenglowsky, and Liu et al. (Bioorg Med Chem, 2016, 24:2215-2234; provided in the office action mailed 09 Feb 2026), hereinafter Liu, applicant's arguments filed 07 Aug 2026 have been fully considered but they are not persuasive.
Applicant argues on pg. 2 of the remarks that the office has not properly established a prima facie case of obviousness. Applicant argues that the office action did not identify a lead compound or provide a reason why one of ordinary skill would have selected a specific compound as a starting point for further development. Applicant further argues that the office action does not explain why the artisan would find it obvious to retain the core structure of Example 29 and import a different sulfamide functionality. Applicant argues this is a hindsight-driven reconstruction.
Applicant argues on pgs. 2-3 of the remarks that the generic disclosure of Formula IV does not cure the deficiencies. Applicant further argues that although the claimed species falls into the genus of Formula IV, this does not establish obviousness.
Applicant finally argues on pg. 3 of the remarks that Liu does not cure the deficiencies of '492 and Wenglowsky because Liu investigates sulfonamides and sulfamides on a substantially different purinylpyridinylamino B-Raf inhibitor scaffold. Applicant argues that the comparison of sulfamide substituents does not show a uniform advantage when replacing a propyl sulfonamide with the claimed sulfamide. Applicant argues that Liu provides no reasonable expectation that transplanting the particular functionality onto the materially different scaffold of Example 29 would improve the desired properties.
This is not persuasive. Applicant identifies specific aspects of the cited references that individually do not render the instant claims obvious, but when considered together make a prima facie case of obviousness. Briefly, '429 is relied on for teaching a general formula for a B-Raf inhibitor and several examples which show it was within the scope of the reference to consider the same core structure and similar sulfamide substituents as the instant claims. Wenglowsky is relied on to teach that the compound of '429 with the same core structure as the instant claims inhibitors mutated B-Raf with a reported nanomolar IC50 and "desirable ADME characteristics." Liu teaches compounds with similar utility as both '429 and Wenglowsky and further explains in-depth how each sulfamide substituent changes binding to mutant B-Raf. Liu includes a teaching of the instantly claimed sulfamide structure and gives motivation for the artisan to select the instant sulfamide substituent. Taken together, '429, Wenglowsky, and Liu provide the teaching, suggestion, and motivation to modify the primary reference and arrive at the instant compounds with a reasonable expectation of success. Further, in response to applicant’s argument that the examiner’s conclusion of obviousness is based on improper hindsight reasoning, it must be recognized that any judgement 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 before the time of the claimed invention’s effective filing date, and does not include knowledge gleaned only from the applicant’s disclosure, such a reconstruction is proper. See MPEP § 2145(X).
In light of the discussion above, the rejection of claims 22-23 under 35 U.S.C. § 103, as obvious over ‘429, Wenglowsky, and Liu is maintained for the reasons of record and restated below.
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) 22-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2012/118492 (provided in IDS 09/14/22), hereinafter '492, further in view of Wenglowsky et al. (Bioorg Med Chem Lett, 2014, 24:1923-1927; provided in IDS 09/14/22), hereinafter Wenglowsky, and Liu et al. (Bioorg Med Chem, 2016, 24:2215-2234; provided in the office action mailed 09 Feb 2026), hereinafter Liu.
The instant claims are directed to the following compound (claim 22) and compositions of the compound with a therapeutically inert carrier (claim 23):
PNG
media_image1.png
87
205
media_image1.png
Greyscale
'492 teaches compounds of reference Formula IV (paragraph [0053]; Claim 6):
PNG
media_image2.png
153
281
media_image2.png
Greyscale
Formula IV is the genus of the species claims of the instant compound when R1 is hydrogen (paragraph [0099]); R2 is CN (paragraph [0099]); R3 is hydrogen (paragraph [0099]); R4 is NRaRb (paragraph [00119]); Ra and Rb are C1-C5 alkyl (paragraph [00119]); R5 is H (paragraph [00122]); R6 is methyl (paragraph [0058]); R11 is hydrogen (paragraph [0065]); L is NR14 (paragraph [0071]); and R14 is H (paragraph [0071]). '492 further teaches examples of Formula IV which include Example 29 and Example 30 (paragraphs [00332]-[00334]):
PNG
media_image3.png
174
557
media_image3.png
Greyscale
PNG
media_image4.png
159
449
media_image4.png
Greyscale
Example 29 contains the same core structure as the instant compound and Example 30 has an N-alkyl group as found in the instant compound. Examples 29 and 30 are further described as having utility as B-RafV600E inhibitors each with an IC50 of less than 900 nM (paragraphs [00204]-[00206]). '429 also teaches a pharmaceutical composition of the reference compounds and a pharmaceutically acceptable carrier or excipient (paragraph [0024]; claim 21). However, '429 does not teach the instant compound.
Wenglowsky teaches Compound 16 (the same compound as Example 29 of '429) which inhibits B-RafV600E with an IC50 of 2 nM and desirable ADME characteristics (pg. 1925, Table 2; pg. 1925, column 2; and pg. 1926, Table 5).
Liu teaches that the mutated protein B-RafV600E has a 500-fold higher kinase activity than the wild-type B-Raf protein with links to a number of cancers including melanoma, ovarian, colon, and thyroid cancers (pg. 2215, columns 1-2). Liu further teaches that inhibitors which target both the WT and mutated B-Raf protein, may result in a paradoxical activation of the MAPK pathway which B-Raf inhibitors are meant to reduce (pg. 2216, column 1). Liu teaches the MAPK pathway activation in cancer cells can be reduced by inhibitors which selectively target the mutated B-Raf protein over the WT protein (pg. 2216, column 2). Liu further teaches optimizing a B-Raf inhibitor using the same sulfonamide groups as '429 and the instant claims, specifically Liu varies an aryl sulfonamide (pg. 2220, Table 2, Compounds 4a-k), alkyl sulfonamide (pg. 2221, Table 3, Compounds 5a-p), or sulfonamide group (pg. 2222, Table 4, compounds 6a-i). Liu teaches that the alkyl sulfonamide group of Example 29 in '429 and Compound 16 in Wenglowsky has similar selectivity for both the WT and mutated B-Raf protein, whereas the sulfonamide group found in the instant claims has increased selectivity for the mutated B-Raf protein versus the WT B-Raf protein (see Compounds 5b and 6b for comparison).
Based on the teachings of '429, Wenglowsky, and Liu, a person of ordinary skill in the art would modify the B-Raf inhibitor taught by '429 and Wenglowsky by replacing the alkyl sulfonamide group with the sulfonamide group taught in Liu and so arrive at the instantly claimed compound. The artisan would be motivated to perform this replacement to increase the selectivity of Example 29 for B-RafV600E over the WT B-Raf protein to reduce the unwanted activation of the MAPK pathway in cancer. The artisan would have a reasonable expectation of success that making this swap would maintain the compounds activity versus the B-Raf protein based on the teachings of '429, Wenglowsky, and Liu.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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, Andrew Kosar can be reached at (571) 272-0913. 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.
/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
Prosecution Insights