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 .
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Priority
This application is a continuation of U.S. Patent Application No. 19/316,575, filed September 2, 2025, which is a continuation of U.S. Patent Application No. 19/131,704, filed May 21, 2025, which is the U.S. National Stage of International Patent Application No. PCT/US2023/080859, filed November 22, 2023, which claims the benefit of priority to U.S. Provisional Patent Application No. 63/544,884, filed October 19, 2023; U.S. Provisional Patent Application No. 63/468,591, filed May 24, 2023; U.S. Provisional Patent Application No. 63/443,760, filed February 7, 2023; and U.S. Provisional Patent Application No. 63/427,317, filed November 22, 2022.
Claim Objections
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on July 15, 2026. Claims 1-9 are pending. Claims 1-9 are under examination.
Action Summary
Objection to Claims 2, 3, and 4 are withdrawn in light of Applicant’s armament
Claims 1-5 rejected under 35 U.S.C. 103 as being unpatentable over Jung et al (WO2007/099326 A1) cited in the IDS in view of Ha et al (Int J Mol Sci. 2022 Apr 30;23(9):5007), are maintained.
Claims 1-9 rejected under 35 U.S.C. 103 as being unpatentable over Jung et al (WO2007/099326 A1) cited in the IDS in view of Ha et al (Int J Mol Sci. 2022 Apr 30;23(9):5007). Jung is cited in the IDS filed on 02/13/2026 as applied to claims 1-5, in further view of Bonastre et al (Eur J Hosp Pharm 2021;28:353–355), are maintained.
Claims 1-9 provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-4, 8- 110 of copending Application No. 19/131,704 (reference application), are withdrawn in light of the terminal disclaimer filed on 07/15/2026.
Terminal Disclaimer
The terminal disclaimer filed on 07/15/2026 has been reviewed and is accepted. The terminal disclaimer has been recorded.
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 non-obviousness.
Claims 1-5 remain rejected under 35 U.S.C. 103 as being unpatentable over Jung et al (WO2007/099326 A1) cited in the IDS in view of Ha et al (Int J Mol Sci. 2022 Apr 30;23(9):5007). Jung is cited in the IDS filed on 02/13/2026.
Note: Applicant correctly notes that the structure reproduced in the previous Office Action corresponds to Compound 31 of Jung rather than Compound 30. The Office acknowledges this typographical error. The rejection is based on the structure depicted in the Office Action, i.e., Compound 31, and the rationale for the rejection remains unchanged. Accordingly, correction of the compound number does not alter the substance of the rejection or constitute a new ground of rejection.
Jung teaches a quinoline derivative of the Formula I
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as possessing potent inhibitory activity against the PDGF receptor family of tyrosine kinases including PDGFRα, PDGFRβ, wherein (R2)q can be (1-8C)alkyl, carboxy, and halogen and p is 0, 1, among a laundry list of substituents, and Ring A is a 6-membered monocyclic or a 10-membered bicyclic aryl ring or a 5- or 6-membered monocyclic or a 9- or 10-membered bicyclic heteroaryl ring with up to three ring heteroatoms selected from oxygen, nitrogen and sulphur; r is 0, 1, 2 or 3, and R6 can be a (1-8C)alkyl. (See claim 1; lines 54-47 of column 5 and lines 7-19 of page 7.) Moreover, Jung teaches the term “(1-8C) alkyl” includes tert-butyl, isopropyl and others. (See lines 9-12 of column 10.) Additionally, Jung teaches compounds 31 as preferred compound of the formula (I) as depicted below:
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. (See table 1 at column 74.) The structure of compound 31 is
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. (See Table V.) Furthermore, Jung teaches the compound can be administered a doe of 1-100 mg/kg and be used for treating inflammatory bowel disease. (See lines 14-16 in column 65 and lines 42-44 in column 66.) The method can be used for a human or an animal. (See lines 12-16 of line 1.) Lastly, Jung teaches the compound can be formulation in a pharmaceutical composition together with a pharmaceutically acceptable excipient. (See lines 44-48.)
Jung does not teach the claimed compound of formula
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. The difference between the compound of Jung and the claimed compound is as follow.
Prior art compound 31 Claimed compound
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Ha teaches adamdec1 mRNAs were found to be selectively expressed in colonic mucosal subepithelial PDGFRα+ cells. ADAMDEC1 protein was mainly released from PDGFRα+ cells and accumulated in the mucosal layer lamina propria space near the epithelial basement membrane. PDGFRα+ cells significantly overexpressed Adamdec1 mRNAs and protein in DSS-induced colitis mice. Adamdec1 was predominantly expressed in CD45− PDGFRα+ cells in DSS-induced colitis mice, with only minimal expression in CD45+ CD64+ macrophages. Additionally, overexpression of both ADAMDEC1 mRNA and protein was consistently observed in PDGFRα+ cells, but not in CD64+ macrophages found in human colonic mucosal tissue affected by Crohn’s disease. In summary, PDGFRα+ cells selectively express ADAMDEC1, which is localized to the colon mucosa layer. ADAMDEC1 expression significantly increases in DSS-induced colitis affected mice and Crohn’s disease affected human tissue, suggesting that this gene can serve as a diagnostic and/or therapeutic target for intestinal inflammation and Crohn’s disease. (See Abstract.) Moreover, Ha also teaches adamdec1 is predominantly expressed in colonic mucosal PDGFRα+ cells in mice and humans, with little or no expression within macrophages. In addition, we found that the ADAMDEC1 protein is mainly localized near the intestinal epithelium and is greatly induced in murine tissue affected by colitis as well as human colonic mucosa tissue from Crohn’s disease affected patients. These findings suggest an important role for colonic mucosal PDGFRα+ cells expressing ADAMDEC1 in the physiologic response to gut inflammation. (See second paragraph of page 2.)
With respect to claims 1 and 2, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to select compound 31 of Jung and modifying said compound by replacing one of the hydrogen atoms at the ortho-position on the phenyl ring with a methyl group and the methoxy group at the meta-position of the phenyl ring with a fluorine, along with replacing the isopropyl on the pyrazolyl ring with tert-butyl moiety to arrive at the claimed compound. The motivation to do so, is because Jung teaches these substituents are interchangeable at these positions. Since Jung teaches these substituents are interchangeable, a person of ordinary skill in the art would have a reasonable expectation that such modifications would maintain PDGFR inhibitory activity, leading them to expect success in achieving similar therapeutic activity.
With respect to claims 3-5, it would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was filed to combine the teachings of Jung, Khan, and Ha to arrive at the claimed method of treating ulcerative colitis. Jung teaches structurally similar PDGFRα inhibitors, and Ha demonstrates that PDGFRα+ pathways are implicated in colitis and inflammatory bowel disease. The motivation to combine these references arises from the known role of PDGFRα+ cells/model in colitis. Given Jung’s success with similar inhibitors and the established link between the pathway and colitis, there would have been reasonable expectation of success that adapting these compounds including the modified compound of Jung would yield an effective method of treatment of ulcerative colitis.
Claims 1-9 remain rejected under 35 U.S.C. 103 as being unpatentable over Jung et al (WO2007/099326 A1) cited in the IDS in view of Ha et al (Int J Mol Sci. 2022 Apr 30;23(9):5007). Jung is cited in the IDS filed on 02/13/2026 as applied to claims 1-5, in further view of Bonastre et al (Eur J Hosp Pharm 2021;28:353–355).
The teachings of Jung and Ha have been discussed supra.
Jung and Ha collectively do not teach vedolizumab and tofacitinib as recited in claims 6-9.
Bonastre teaches the use a combined therapy with tofacitinib and vedolizumab for treating ulcerative colitis. (See Abstract.)
It would have been prima facie obvious for a person of ordinary skill in the art at the time of the invention was made to combine the method taught by Jung and Ha collectively with the method set forth by Bonastre because each is taught by the prior art to be useful for the same purpose (i.e., treating ulcerative colitis). See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Following Bonastre, the prior art teaches each element as useful for treating ulcerative colitis. Under in re kerkhoven, one of ordinary skill would have expected success, since both therapeutic approaches independently serve the same purpose, and thus their combination would reasonably be expected to work similarly well.
With respect to the properties (anti-integrin agent for Vedolizumab and Janus inhibitor for tofacitinib) claimed, Bonastre may not teach the exact same terms (anti-integrin agent and Janus inhibitor), however, it teaches compounds performing the same functional roles. The prior art provides compounds (e.g. vedolizumab and tofacitinib) that are recognized to act as anti-integrin agents or Jak inhibitors. A person of ordinary skill would recognize these known therapeutic functions. Thus, substituting functional terminology with the known compounds does not render the claimed nonobvious, as the functional roles were already established in the art.
Acknowledgement is made of the receipt and entry of Applicant’s remarks/arguments filed on July 15, 2026. Applicant’s argument has been full considered but are not persuasive.
Applicant first argues that Office incorrectly identified the starting compound as compound 30 of Jung, whereas the structure reproduced in the Office Action corresponds to Compound 31. The Office acknowledges this typographical error. The structure relied upon in the rejection is Compound 31 of Jung. Correction of the compound number does not alter the substance of the rejection because has consistently relied upon the structure depicted in the Office Action and the modification of that structure. Accordingly, the correction does not constitute a new ground of rejection.
Applicant next argues that Jung discloses approximately 233 quinoline compounds, biological activity data are provided for only a small subset of those compounds, and Compound 31 is not among the compounds having biological data. Applicant therefore concludes that a person of ordinary skill in the art would not have selected Compound 31 as a starting point for further modification.
This argument is not persuasive. The determination of whether a compound would have been selected as a starting point does not require that the compound possess biological data or be identified as the single most active disclosed in the reference. Rather, the inquiry is whether the prior art, viewed as a whole, would have suggested the compound as a suitable starting point for further optimization. Jung specifically exemplifies Compound 31 as one of its synthesized PDGFR inhibitory quinoline derivatives within its disclosed structure-activity program. A person of ordinary skill in the art seeking additional PDGFR inhibitors would have reasonably considered specifically disclosed compounds, including 31, as appropriate candidates for routine medicinal chemistry optimization. The absence of biological data for Compound 31 does not teach away from its further modification nor discourage its selection.
Applicant further argues that Compound 31 is not among the compound highlighted elsewhere in Jung. However, the rejection is not predicated upon Compound 31 being identified as the most preferred compound. Nothing in Jung limits further optimization only to compounds specifically highlighted in particular sections of the reference. The fact that other compounds are discussed in greater detail does not remove Compound 31 from consideration as an expressly disclosed and synthesized embodiment suitable for routine structural modification.
Applicant further argues that a person of ordinary skill in the art would have been required to make these simultaneous structural modifications to arrive at the presently claimed compound.
This argument is unpersuasive. Obviousness does not require that the prior art disclose the claimed compound through a single expressed teaching or a single example containing all claimed substitutions simultaneously. The proper inquiry is whether the prior art would have suggested the claimed modifications with a reasonable expectation of success. Jung expressly teaches the relevant substituents are interchangeable at the disclosed positions. Accordingly, modifying the exemplified compound by selecting other expressly disclosed substituents represent nothing more than routine optimization of a known scaffold. The mere fact that multiple substitutions are selected from the teachings of the reference does not, by itself, render the claimed compound nonobvious.
Applicant also argues that none of the 233 specifically exemplified compounds contains the claimed methyl substituent, fluorine substituent, and tert-butyl substituent, or the claimed substitution pattern.
This argument is not persuasive because it improperly focusses solely upon the working examples while disregarding the broader teaching of Jung. A prior art reference must be considered for everything that it teaches to one of ordinary skill in the art, including both its generic disclosure and its specific examples. While Jung may not specifically exemplify every permissible combination of disclosed substituents withing a single compound, Jung expressly teaches that the relevant substituent positions may independently comprise halogen substituents, including fluoro, alkyl substituent, including tert-butyl. Accordingly, Jung expressly identifies the claimed substituents as suitable alternatives within the disclosed Formula I. The rejection therefore relies upon Jung’s express generic teachings rather than upon the limited number of specifically exemplified compound species. Thus, the fact that Jung does not specifically exemplify every permissible combination of expressly disclosed substituents does not negate the suggestion provided by the generic disclosure. A person of ordinary skill in the art would have recognized these disclosed substituent options as available alternatives for routine structural modification while maintaining the desired PDGFR inhibitory activity.
Applicant further contends that Ha cannot cure the alleged deficiencies of Jung because Ha doe not disclose quinoline compounds.
This argument is not persuasive because it mischaracterizes the basis of the rejection. Ha is not relied upon for teaching the claimed quinoline structure or the claimed structural modification. Rather, Ha is relied upon for its teaching that PDGFR-α-positive cells and PDGFR-α-associated signaling play an important role in inflammatory bowel disease and ulcerative colitis, thereby providing motivation to employ PDGFR inhibitors for treating such diseases. The structural teaching is provided by Jung, whereas Ha supplies additional motivation to employ PDGFR inhibition in the treatment of inflammatory bowel disease. A reference need not disclose every claimed feature to be properly combinable under 35 U.S.C 103.
Accordingly, Applicant has not persuasively shown reversible error in the rejection. The rejection under 35 U.S.C. 103 is therefore maintained.
Conclusion
Claims 1-9 are not 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 JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-5.30pm.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628
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