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 .
Interview Summary
Examiner Anthony Seitz interviewed with Attorney of Record Jonathan Harris on October 15th 2025. Examiner and Attorney discussed a restriction requirement between claims 1-26 and claims 27-33 due to the search burden between the two sets of claims. Attorney authorized the election of Group I, comprising claims 1-26. Attorney also noted relevant art, U.S. Patent No. 8,846,660 in order to ensure a complete search by Examiner.
DETAILED ACTION
Restriction and Status of the Claims
Applicant’s election of claims 1-26 in the telephone call on October 15th 2025 is acknowledged. Claims 1-33 are pending. Claims 27-33 have been withdrawn from further consideration as being directed towards nonelected species. Claims 1-26 are examined on their merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 120 is acknowledged. Applicant has complied with all conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 based on the date of the provisional applications 63/350,961 filed on June 10th 2022 and 63/429,004 file don November 30th 2022.
Claim Rejections - 35 USC § 112(b)
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.
Claim 4, 8, 16, and 24 are rejected 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.
Claim 4 is indefinite for the functional descriptive limitation, “wherein the compound 1 or a pharmaceutically acceptable salt or solvate thereof is a selective for chymase over cathepsin G,” because one of ordinary skill in the art could not reasonably determine how the phrase further limits the compound of claim 1. The specification repeats this language (specification, pg. 16, paragraph [057]), but does not provide guidance as to how the structure of compound 1 must be further limited in order to achieve the activity described by claim 4.
Claim 8 is indefinite for failing to further limit the method of claim 1. Claim 8 is directed towards “the method of claim 1, wherein said method for treating comprises preventing hepatobiliary disease in said subject.” Claim 1 is directed towards “a method for treating hepatobiliary disease in a subject in need thereof,” via administration of compound 1. As the treatment of a disease (i.e. administration to a patient who has the disease) and the prevention of a disease (i.e. administration to a patient who does not have the disease) necessarily have contradicting patient populations, claim 8 is not further limiting to claim 1.
Claims 16 and 24 are similarly indefinite for failing to further limit claims 10 and 18, respectively, as claim 16 is directed towards a method of preventing primary sclerosing cholangitis and thus is not further limiting to the method of treating primary sclerosing cholangitis of claim 10, and claim 24 is directed towards a method of preventing primary biliary cholangitis, and thus is not further limiting to the method of treating primary biliary cholangitis of claim 18.
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.
Claims 1-2 and 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over Muto (U.S. Patent No. 8,846,660 issued on September 30th 2014) in view of Tashiro (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).
Claim 1 is directed towards a method for treating hepatobiliary disease in a subject via administration of the compound,
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Muto teaches the identical compound and its activity as a chymase inhibitor (Muto, col. 154, claim 17). Muto does not explicitly teach the treatment of hepatobiliary disease with the compound, but one of ordinary skill in the art would have a reasonable expectation of success in treating hepatobiliary disease with the compound, because chymase inhibitors are known in the art to be used in the treatment of hepatobiliary diseases, such as nonalcoholic steatohepatitis. See Tashiro, who treats nanalcoholic steatohepatitis with the chymase inhibitor, TY-51469 (Tashiro, Results). One of ordinary skill in the art would have a reasonable expectation of success in substituting Muto’s chymase inhibitor for Tashiro’s, and claim 1 is therefore prima facie obvious.
Claim 2 requires that the method of claim 1 ameliorates the infiltration of mast cells. Tashiro teaches a decrease in mast cells after the administration of a chymase inhibitor (Tashiro, results), and claim 2 is therefore prima facie obvious.
As it is unclear how claim 4 further limits the method of claim 1 (see the above 112(b) rejection for claim 4), it too is prima facie obvious.
Claim 5 limits the hepatobiliary disease of claim 1 to nonalchoholic steatohepatitis. Claim 5 is therefore prima facie obvious for the same reasons as claim 1.
Claim 6 requires that, in the method of claim 1, the amount administered is between 20 and 400 mg. Muto teaches dosages of the compound at 1 mg/kg and 0.5 mg/kg (Muto, col. 140). For an ordinary 80 kg human, this amounts to dosages of 80 mg and 40 mg, within the range of claim 6. Claim 6 is therefore prima facie obvious.
Claim 7 requires that the compound administered in claim 1 is the monoacetic acid solvate. Muto teaches the monoacetic acid solvate of the compound (Muto, col. 154, claim 17), and claim 7 is therefore prima facie obvious.
As it is unclear how claim 8 further limits the method of claim 1 (see the above 112(b) rejection for claim 8), it too is prima facie obvious.
Claim 9 requires that, in the method of claim 1, administration is daily. Muto teaches daily administration (Muto, col. 36), and claim 9 is therefore prima facie obvious.
Claims 1-4 and 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Muto (U.S. Patent No. 8,846,660 issued on September 30th 2014) in view of Liu (Liu et al., Chymase inhibitor TY-51469 in therapy of inflammatory bowel disease. World J Gastroenterol. 2016 Feb 7;22(5):1826-33).
Claim 1 is directed towards a method for treating hepatobiliary disease in a subject via administration of the compound,
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Muto teaches the identical compound and its activity as a chymase inhibitor (Muto, col. 154, claim 17). Muto does not explicitly teach the treatment of hepatobiliary disease with the compound, but one of ordinary skill in the art would have a reasonable expectation of success in treating hepatobiliary disease with the compound, because chymase inhibitors are known in the art to be used in the treatment of hepatobiliary diseases, such as inflammatory bowel disease. See Liu, who treats inflammatory bowel disease with the chymase inhibitor, TY-51469 (Liu, pg. 1832). One of ordinary skill in the art would have a reasonable expectation of success in substituting Muto’s chymase inhibitor for Liu’s, and claim 1 is therefore prima facie obvious.
Claim 2 requires that the method of claim 1 ameliorates fibrosis. Liu suggests the administration of chymase inhibitors to treat fibrosis (Liu, pg. 1827), and claim 2 is therefore prima facie obvious.
Claim 3 limits the hepatobiliary disease of claim 1 to inflammatory bowel disease. Claim 3 is therefore prima facie obvious for the same reasons as claim 1.
As it is unclear how claim 4 further limits the method of claim 1 (see the above 112(b) rejection for claim 4), it too is prima facie obvious.
Claim 6 requires that, in the method of claim 1, the amount administered is between 20 and 400 mg. Muto teaches dosages of the compound at 1 mg/kg and 0.5 mg/kg (Muto, col. 140). For an ordinary 80 kg human, this amounts to dosages of 80 mg and 40 mg, within the range of claim 6. Claim 6 is therefore prima facie obvious.
Claim 7 requires that the compound administered in claim 1 is the monoacetic acid solvate. Muto teaches the monoacetic acid solvate of the compound (Muto, col. 154, claim 17), and claim 7 is therefore prima facie obvious.
As it is unclear how claim 8 further limits the method of claim 1 (see the above 112(b) rejection for claim 8), it too is prima facie obvious.
Claim 9 requires that, in the method of claim 1, administration is daily. Muto teaches daily administration (Muto, col. 36), and claim 9 is therefore prima facie obvious.
Claims 10-11, 14-19, and 22-26 are rejected under 35 U.S.C. 103 as being unpatentable over Muto (U.S. Patent No. 8,846,660 issued on September 30th 2014) in view of Tashiro (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) and Chapman (Chapman RW, Lynch KD. Obeticholic acid-a new therapy in PBC and NASH. Br Med Bull. 2020 May 15;133(1):95-104).
Claim 10 is directed towards the treatment of primary sclerosing cholangitis, a form of primary biliary cholangitis characterized by cirrhosis, via administration of the compound,
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For the teachings of Muto and Tashiro as they relate to the treatment of nonalcoholic stateohepatitis via the administration of the compound, see the above 103 rejection for claim 1.
While the combination of Muto and Tashiro does not explicitly teach the treatment of primary sclerosing cholangitis, one of ordinary skill in the art would have a reasonable expectation of success in treating primary sclerosing cholangitis with the compound, because NASH and sclerosing cholangitis are known in the art to have similar pathologies (i.e. fibrosis, cirrhosis, and high levels of inflammation), albeit from different primary causes (genetic predisposition for biliary cholangitis vs. hepatitis/diabetes for NASH). Consequently, treatments directed towards one are used in the art to treat the other. For example, see Chapman, who describes such pathologies (Chapman, pg. 97, 101) and proposes identical treatments for each (Chapman, pg. 97-98, 101-102). As one of ordinary skill in the art would have a reasonable expectation of success in treating primary sclerosing cholangitis, known to have a similar pathology to NASH, with chymase inhibitors such as Muto’s, claim 10 is prima facie obvious.
Claim 11 requires that the method of claim 10 ameliorates the infiltration of mast cells. Tashiro teaches a decrease in mast cells after the administration of a chymase inhibitor (Tashiro, results), and claim 11 is therefore prima facie obvious.
Claim 14 requires that, in the method of claim 10, the amount administered is between 20 and 400 mg. Muto teaches dosages of the compound at 1 mg/kg and 0.5 mg/kg (Muto, col. 140). For an ordinary 80 kg human, this amounts to dosages of 80 mg and 40 mg, within the range of claim 14. Claim 14 is therefore prima facie obvious.
Claim 15 requires that the compound administered in claim 10 is the monoacetic acid solvate. Muto teaches the monoacetic acid solvate of the compound (Muto, col. 154, claim 17), and claim 15 is therefore prima facie obvious.
As it is unclear how claim 16 further limits the method of claim 10 (see the above 112(b) rejection for claim 16), it too is prima facie obvious.
Claim 17 requires that, in the method of claim 10, administration is daily. Muto teaches daily administration (Muto, col. 36), and claim 17 is therefore prima facie obvious.
Claim 18 is directed towards the treatment of primary biliary cholangitis via administration of the above compound. Claim 18 is prima facie obvious for the same reasons as claim 10.
Claim 19 requires that the method of claim 18 ameliorates the infiltration of mast cells. Claim 19 is prima facie obvious for the same reasons as claim 11.
Claim 22 requires that, in the method of claim 18, the amount administered is between 20 and 400 mg. Claim 22 is prima facie obvious for the same reasons as claim 14.
Claim 23 requires that the compound administered in claim 18 is the monoacetic acid solvate. Claim 23 is prima facie obvious for the same reasons as claim 15.
As it is unclear how claim 24 further limits the method of claim 18 (see the above 112(b) rejection for claim 24), it too is prima facie obvious.
Claim 25 requires that, in the method of claim 18, administration is daily. Claim 25 is prima facie obvious for the same reasons as claim 17.
Claim 26 further limits the method of claim 25 to wherein the dosage is in tablet form. As Muto teaches tablets (Muto, col. 35), claim 26 is prima facie obvious.
Claims 12-13 and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Muto (U.S. Patent No. 8,846,660 issued on September 30th 2014) in view of Tashiro (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 (Chapman RW, Lynch KD. Obeticholic acid-a new therapy in PBC and NASH. Br Med Bull. 2020 May 15;133(1):95-104), and Liu (Liu et al., Chymase inhibitor TY-51469 in therapy of inflammatory bowel disease. World J Gastroenterol. 2016 Feb 7;22(5):1826-33).
Claims 12-13 are directed towards the method of claim 10 wherein the method ameliorates irritable bowel disease. For the teachings of Muto, Tashiro, and Chapman as they relate to claim 10, see the above 103 rejection for claim 10. Regarding the treatment of irritable bowel disease, Liu, treats inflammatory bowel disease with the chymase inhibitor, TY-51469 (Liu, pg. 1832). One of ordinary skill in the art would reasonably expect a subject receiving administration of Muto’s chymase inhibitor to have similar results (i.e. the treatment of irritable bowel disease), and claims 12-13 are therefore prima facie obvious.
Claims 20-21 are directed towards the method of claim 18 wherein the method ameliorates irritable bowel disease. For the teachings of Muto, Tashiro, and Chapman as they relate to claim 18, see the above 103 rejection for claim 18. Regarding the treatment of irritable bowel disease, Liu, treats inflammatory bowel disease with the chymase inhibitor, TY-51469 (Liu, pg. 1832). One of ordinary skill in the art would reasonably expect a subject receiving administration of Muto’s chymase inhibitor to have similar results (i.e. the treatment of irritable bowel disease), and claims 20-21 are therefore prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 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, Jeffrey Lundgren can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629