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 .
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.
Current Status of 17/430,210
This Office Action is responsive to the amended claims received 20 April 2026.
Claims 1, 15-18, 48-50, 52-55, 58, 63, 71, 100-101, and 105 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications PCT/US2020/17941 (filed 12 February 2020), 62/804,523 (filed 12 February 2019), 62/863,904 (filed 20 June 2019), 62/908,431 (filed 30 September 2019), and 62/932,015 (filed 7 November 2019) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
For the purposes of the instant office action, the Examiner has determined the priority date of the instant claims to be 20 June 2019.
Information Disclosure Statement
The information disclosure statements (IDS) received on 2 December 2025, 15 January 2026, 20 April 2026, and 21 May 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, these information disclosure statements are being considered by the examiner.
Response to Amendments
The objections to the specification, present in the previous office action, are hereby maintained.
The 35 U.S.C. 112 rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are maintained herein.
The double patenting rejections to the claims, present in the previous rejection, are hereby withdrawn, due to Applicant’s arguments. New double patenting rejections are presented herein, as necessitated by Applicant’s recent filing of the reference application.
Response to Arguments
Applicant's arguments received 20 April 2026 have been fully considered.
Applicant argues that the Examiner has not appropriately practiced compact prosecution, as required by the MPEP. Applicant seems unhappy that the Examiner dropped certain rejections and then presented new rejections, and seems to be saying that the Examiner should have raised all possible 35 USC 102 and 103 rejections at the outset. Applicant argues that the Examiner previously used the GEDULIN and AGARWAL references, then dropped them from the rejections, and then brought them back.
The Examiner has appropriately followed the compact prosecution requirements of the MPEP. See MPEP 904.03, which states:
“The examiner is not called upon to cite all references that may be available, but only the "best." (See 37 CFR 1.104(c).) Multiplying references, any one of which is as good as, but no better than, the others, adds to the burden and cost of prosecution and should therefore be avoided.”
The Examiner did use GEDULIN in the first office action as a secondary reference, then dropped the rejection, and then brought GEDULIN back as a primary reference. Applicant does not mention is that GEDULIN was initially used only as a secondary reference to provide evidence. AGARWAL has always been used as a secondary reference within the prosecution of the instant application. It is the correct course of action for an Examiner to always present the best possible primary references within rejections, and the secondary references may drop in and out as necessary to support the primary reference. If Applicant is unsure about the meaning of MPEP sections in the future, they are invited to call the Examiner to discuss the matter.
Applicant argues that the examiner “accepted” a showing of long-felt need within the art and “accepted” that the results of a clinical trial were surprising.
The Examiner did write previously that he “accepted” the showing of long-felt need in the art and the surprising results of a clinical trial, and in those office actions, the Examiner was clear that those secondary considerations were not sufficient for the instant claims to overcome all rejections.
Applicant argues that the showings of long-felt need and unexpected clinical results, previously presented in the May 2025 declaration, should overcome the instant rejections.
As before, the Examiner accepts the secondary considerations presented by Applicant, meaning that the Examiner has no reason to doubt their validity. The only reason that independent claim 1 is not anticipated by the GEDULIN reference is that GEDULIN teaches a dosage range of 100 to 10,000 µg/kg once or twice daily, whereas instant claim 1 requires a dosage of about 1200 µg/kg/day. The range taught by GEDULIN entirely encompasses the instantly claimed range. Applicant does not appear to have submitted any arguments related to why one of ordinary skill in the art would not have immediately envisaged or found obvious a dosage of “about 1200 µg/kg/day” of maralixibat chloride when reading the dosage taught by GEDULIN, 100 to 10,000 µg/kg once or twice daily. The Examiner finds that one of ordinary skill in the art would have immediately envisaged the instantly claimed dosage when reading the disclosure of GEDULIN before the instant effective filing date. Alternatively, one of ordinary skill in the art could have acted through the “normal desire of scientists” to optimize the dosage within the range taught by GEDULIN. See MPEP 2144.05(I and II(A)). The secondary considerations presented by Applicant are not found to be sufficient to overcome these very strong arguments for obviousness.
Applicant argues that the double patenting rejections presented in the previous office action should be withdrawn because the ‘591 application is directed specifically to methods of treating biliary atresia.
The Examiner has withdrawn the double patenting rejections related to the ‘591 application.
Specification
The disclosure is objected to because of the following informalities: The instant specification refers to red and blue colors within the descriptions of Figs. 32A-32H, but these figures currently have no color. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
Claims 1, 15-18, 48-50, 52-53, 58, 63, 71, 100-101, and 105 are rejected under 35 U.S.C. 103 as being unpatentable over:
GEDULIN (Cited by Applicant in IDS of 11 August 2021; US 2013/0108573; Publication Date 2 May 2013).
Claims 24 and 25 of GEDULIN teach a method for treating a cholestatic liver disease through the administration of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) of Formula II. GEDULIN teaches maralixibat and maralixibat chloride as species of Formula II therein in paragraph [0247] and claim 6. GEDULIN teaches that the method of claim 24 therein can be used to treat progressive familial intrahepatic cholestasis (PFIC) type 2 and is also useful to treat pruritus (claim 41). GEDULIN teaches that the dosage of an ASBTI therein can be from 0.1 to 10 mg/kg (100 to 10,000 µg/kg) in a single dose (paragraph [0511]). Paragraph [0041] of GEDULIN teaches that the dosages therein may be given once per day or twice per day. Paragraph [0023] of GEDULIN teaches that the methods therein can be applied to children between 2 and 10 years of age.
Regarding the dosages within claims 1, 50, and 105: The term “about” does not have a closed definition within the instant specification. The dosage range taught by GEDULIN, being 100 to 10,000 µg/kg once or twice daily (see citations above), entirely encompasses the dosage ranges claimed by instant claims 1, 50, and 105. The Examiner does not find that the range taught by the reference is described with sufficient specificity to be anticipatory of the claimed ranges. See MPEP 2131.03(II). However, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). See MPEP 2144.05(I).
Regarding claim 17: GEDULIN teaches that PFIC2 is “associated with mutations in the ABCB11 gene” (paragraph [0094]). GEDULIN does not explicitly teach a patient or subject having a non-truncating mutation in a copy of the ABCB11 gene. It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to apply the treatment method of GEDULIN to a patient having a non-truncating mutation in a copy of the ABCB11 gene, because GEDULIN teaches the usefulness of the method for patients generally having mutations in that gene.
Regarding claims 52-53, 58, 63, 71, and 100-101: As shown above, all of the positive steps of the instantly claimed method, being those steps that can be performed by the artisan, are rendered obvious by GEDULIN. The effects of the instantly claimed method cannot be separated from the positive steps performed by the artisan. As long as the positive steps of the method are rendered obvious, the effects of the instantly claimed method must have occurred whether or not they were taught by the reference.
Claims 1, 15-18, 48-50, 52-55, 58, 63, 71, 100-101, and 105 are rejected under 35 U.S.C. 103 as being unpatentable over:
GEDULIN (Cited by Applicant in IDS of 11 August 2021; US 2013/0108573; Publication Date 2 May 2013)
in view of:
AGARWAL (Previously cited by the Examiner; Agarwal, S.; Lal, B.B.; Rawat, D.; et al. “Progressive Familial Intrahepatic Cholestasis (PFIC) in Indian Children: Clinical Spectrum and Outcome” Journal of Clinical and Experimental Hepatology | September 2016 | Vol. 6 | No. 3 | 203–208).
Teachings of GEDULIN are described within the rejections above.
Regarding claims 54-55: GEDULIN does not explicitly teach the measurement of height or weight Z-scores for patients therein.
AGARWAL provides teachings related to children suffering from PFIC (abstract). AGARWAL focuses on 24 children with PFIC in the results section. AGARWAL teaches that the “weight for height z score” showed wasting in 15 of these children suffering from PFIC, and 13 of the children were found to have a height for age z score indicating stunting (results section on Pg. 205).
The teachings of AGARWAL show that one of ordinary skill in the art would have known that determining height and weight z scores to monitor children with PFIC was a standard technique. It would have been obvious to one of ordinary skill in the art, before the effective instant filing date, to combine the standard technique of determining the height and weight z scores for children having PFIC with the method of treating PFIC taught by GEDULIN, for the purpose of determining the efficacy of the method of treatment taught by GEDULIN. The artisan would have expected success in this combination, because the methods of both AGARWAL and GEDULIN relate to pediatric patients having PFIC.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 15-18, 48-50, 52-55, 58, 63, 71, 100-101, and 105 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-3, 9, 12, 16-20, and 23-27 of copending Application No. 19/645,460 (referred to below as the ‘460 application).
Although the claims at issue are not identical, they are not patentably distinct from each other because: Claim 1 of the ‘460 application teaches a method of treating cholestatic liver disease in a subject through the administration of 10-1400 µg/kg/day of an ASBTI. This range reads on the instantly claimed ranges. See MPEP 2131.03(II). Claims 2-3 of the ‘460 application teaches that the ASBTI may be maralixibat chloride. Claims 9, 12, and 16 of the ‘460 application teach that the cholestatic liver disease therein may be PFIC type 2. Claim 17 of the ‘460 application teaches that the subject has a non-truncating mutation in the ABCB11 gene. Claim 18 of the ‘460 application teaches that the subject is a pediatric subject. Claims 19-20 of the ‘460 application teach once or twice daily administration. Claims 23, 24, 25, and 26-27 (together) respectively read on instant claims 52, 53, 54, and 55, and the claim language is nearly identical.
Regarding claims 58, 63, 71, and 100-101: As shown above, all of the positive steps of the instantly claimed method, being those steps that can be performed by the artisan, are rendered obvious by the ‘460 application. The effects of the instantly claimed method cannot be separated from the positive steps performed by the artisan. As long as the positive steps of the method are rendered obvious, the effects of the instantly claimed method must have occurred whether or not they were taught by the reference.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are currently allowable.
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 JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
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 D 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.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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