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 .
DETAILED ACTION
Status of the Claims
Claims 1-7, 9-15, 17-23, and 25-36 are pending. Claims 27-33 are withdrawn from further consideration as being directed towards a nonelected invention. Claims 1-7, 9-15, 17-23, 25-26, and 34-36 are examined on their merits.
Information Disclosure Statement
The Information Disclosure Statements filed on May 1st 2026 and March 18th 2026 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
Claim Objections
Claims 1, 10, and 37 are objected to for improper claim status. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
Claims 1, 10 are marked as amended, but no amendments are recited in the claims. Claim 27 (withdrawn) does not include the chemical structure previously recited in the claim. See 37 C.F.R. 1.121(c).
35 U.S.C. § 112(b) Rejections Maintained
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The rejection of Claim 4 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is maintained.
Applicant’s arguments in the response filed on May 1st 2026 are acknowledged. Applicant argues that claim 4, as amended, now recites a particular objective standard that can be measured and is thus definite. Applicant’s argument is found not persuasive.
Claim 4 is directed to the method of claim 1, wherein the compound has an IC50 value for human chymase of at least about 100-fold lower than the IC50 value for cathepsin G. While applicant is correct in that a measurable objective standard is recited, it is still unclear how the phrase further limits the compound as recited in claim 1. Specifically, claim 1 recites a method for treating hepatobiliary disease via administration of compound 1, which is defined in its entirety by its chemical structure,
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The objective measurement, as described by applicant, would constitute an inherent property of the molecule. Thus, one of ordinary skill in the art would not be able to distinguish “compound 1 wherein the compound has an IC50 value for human chymase of at least about 100-fold lower than the IC50 value for cathepsin G” from “compound 1 wherein the compound does not have an IC50 value for human chymase of at least about 100-fold lower than the IC50 value for cathepsin G.” As such, it is unclear how claim 4 further limits the method of claim 1, and claim 4 is thereby indefinite.
35 U.S.C. § 103 Rejections Overcome by Unexpected Results
Applicant’s arguments in the response filed on May 1st 2026 are acknowledged. Applicant argues that the unexpected over 1000-fold selectivity of compound 1 for chymase over cathepsin G constitutes evidence for unexpected results, and that compound 1 produced statistically significant reduction in various biomarkers related to hepatobiliary disease, far beyond what the prior art would have reasonably suggested. Applicant’s arguments are found persuasive and all 103 rejections are withdrawn.
35 U.S.C. § 102 Rejections Necessitated by Amendment
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 34-36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Muto (U.S. Patent No. 8,846,660 issued on September 30th 2014).
Claim 34 is directed towards a method for preventing hepatobiliary disease in a subject via administration of the compound,
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(compound 1).
It is noted that the prevention of the hepatobiliary disease necessarily requires that the patient population in question does not have hepatobiliary disease.
Muto teaches the treatment of atopic dermatitis via administration of the identical compound (Muto, claim 18). Muto thereby treats an identical patient population of “subjects without hepatobiliary disease,” and is anticipatory of claim 34.
Claim 35 is directed towards a method for preventing primary sclerosing cholangitis in a subject via administration of compound 1.
Muto teaches the treatment of atopic dermatitis via administration of the identical compound (Muto, claim 18). Muto thereby treats an identical patient population of “subjects without primary sclerosing cholangitis,” and is anticipatory of claim 35.
Claim 36 is directed towards a method for preventing primary biliary cholangitis in a subject via administration of the compound,
Muto teaches the treatment of atopic dermatitis via administration of the identical compound (Muto, claim 18). Muto thereby treats an identical patient population of “subjects without primary biliary cholangitis,” and is anticipatory of claim 36.
Allowable Subject Matter
Claims 1-7, 9-15, 17-23, 25-26 are free of the prior art.
Claims 1-3, 9-15, 17-23, and 25-26 are allowed.
Applicant has developed a method for treating hepatobiliary disease, primary sclerosing cholangitis, and primary biliary cholangitis via administration of the selective chymase inhibitor,
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The compound is previously found in the art as a treatment for atopic dermatitis in U.S. Patent No. 8,846,602. However, the patent does not teach the treatment of hepatobiliary disease with the compound.
There are cases in the art in which hepatobiliary disease or similar conditions have been treated with chymase inhibitors (Tashiro et al., Chymase inhibitor prevents the nonalcoholic steatohepatitis in hamsters fed a methionine- and choline-deficient diet. Hepatol Res. 2010 May;40(5):514-23), (Chapman RW, Lynch KD. Obeticholic acid-a new therapy in PBC and NASH. Br Med Bull. 2020 May 15;133(1):95-104), (Liu et al., Chymase inhibitor TY-51469 in therapy of inflammatory bowel disease. World J Gastroenterol. 2016 Feb 7;22(5):1826-33). However, the effectiveness of the treatments vary.
In particular, while the anti-inflammatory effects of this class of drugs is well-known, multiple drugs of this class have been found to have severe adverse side effects and/or oral toxicity, such as NK3201 and SUN13834 (Ahmad S, Ferrario CM. Chymase inhibitors for the treatment of cardiac diseases: a patent review (2010-2018). Expert Opin Ther Pat. 2018 Nov;28(11):755-764).
While chymase inhibitors, such as TY-51469 have been used for the treatment of hepatobiliary disease in the past, the significant increase in selectivity of compound 1 for chymase over cathepsin G is not found in other examples. This increase in selectivity would provide the benefit of decreasing off-target effects of the treatment. For example, as cathepsin G plays an important role in the human immune system, its inhibition may decrease immune activity and increase susceptibility to infection, the avoidance of which is a significant benefit. As this selectivity could not have been predicted from the art, applicant’s method is novel and nonobvious.
Claim 4 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Conclusion
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.
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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