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
Claims 1, 3, 8-14, 16-19 and 38 are presented for examination.
A request for continued examination under 37 C.F.R. §1.114, including the fee set forth in 37 C.F.R. §1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 C.F.R. §1.114, and the fee set forth in 37 C.F.R. §1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 C.F.R. §1.114. Applicant's submission filed on December 24, 2025 requesting entry of the December 8, 2025 after-final submission has been entered.
Claims 1, 3, 8-14, 16-19 and 38 are pending. Claims 1 and 19 are amended. Claims 4, 22-23 and 25 are cancelled.
Applicant’s arguments, filed December 24, 2025, have been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Requirement for Restriction/Election
Applicant is reminded of his election without traverse of (i) maralixibat as the single disclosed species of apical sodium-dependent bile acid transport inhibitor (ASBTI) compound to be administered to the subject, and (ii) Alagille syndrome (ALGS) as the single disclosed species of cholestatic liver disease, to which examination on the merits has been confined, as stated in the reply filed September 17, 2024, which is still in effect over the claims.
Claims 9-13 (claim 4 now being cancelled) remain withdrawn from consideration pursuant to 37 C.F.R. §1.142(b) as being directed to non-elected subject matter.
Accordingly, the claims that remain drawn to the elected species are claims 1, 3, 8, 14, 16-19 and 38, and such claims are herein acted on the merits infra.
Information Disclosure Statement
Applicant’s Information Disclosure Statements filed December 24, 2025 (five pages) and February 3, 2026 (four pages) have each been received and entered into the present application. As reflected by the attached, completed copies of form PTO/SB/08A (nine pages total), the Examiner has considered the cited references, except for the following Non-Patent Literature citations:
(i) on the December 24, 2025 statement, the Non-Patent Literature Citation Nos. 2, 13, 19 and 30; and (ii) on the February 3, 2026 statement, the Non-Patent Literature Citation Nos. 2-3, 5, 15-19, 21 and 25-26.
Regarding Non-Patent Literature Citation No. 19 on the December 24, 2025 statement, MPEP §609.04(a)(II)(C) states, “For each cited pending unpublished U.S. application, the application specification including the claims, and any drawings of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system. The requirement in 37 CFR 1.98(a)(2)(iii) for a legible copy of the specification, including the claims, and drawings of each cited pending U.S. patent application (or portion of the application which caused it to be listed) is sua sponte waived where the cited pending application is stored in the USPTO’s IFW system. See Waiver of the Copy Requirement in 37 CFR 1.98 for Cited Pending U.S. Patent Applications, 1287 OG 163 (October 19, 2004)”. However, as discussed further, “This waiver is limited to the specification, including the claims, and drawings in the U.S. application (or portion of the application). If material other than the specification, including the claims, and drawings in the file of a U.S. patent application is being cited in an IDS, the IDS must contain a legible copy of such material.” 37 C.F.R. §1.98 does not contain a provision to cite an entire application file history – as Applicant has done here - by providing only an application number, file history reference, or Image File Wrapper. Rather, 37 C.F.R. §1.98 requires that the IDS must specify which portions of the application are cited and – if other than the specification, claims, and drawings – provide those portions.
Regarding Non-Patent Literature Citation Nos. 13 and 30 on the December 24, 2025 statement and Non-Patent Literature Citation Nos. 18-19 and 25-26 on the February 3, 2026 statement, 37 C.F.R. §1.98(b) explicitly states that “[e]ach publication listed in an information disclosure statement must be identified by publisher, author (if any), title, relevant pages of the publication, date and place of the publication”. MPEP §609.04(a)(I) explains that “[t]he date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue.” Applicant’s non-patent literature citations indicated above have been lined out for failing to provide the relevant identifying information, including place of publication or date of publication, as required by 37 C.F.R. §1.98(b) and MPEP §609.04(a)(I) and such information cannot be readily ascertained from the documents as submitted. As such, the documents have been placed in the application file, but the information referred to therein has not been considered as to the merits1.
Regarding Non-Patent Literature Citation No. 2 on the December 24, 2025 statement and Non-Patent Literature Citation Nos. 2-3, 5, 15-17 and 21 on the February 3, 2026 statement, Applicant fails to provide clearly identifiable copies of the cited references. As a result, the information disclosure statements filed December 24, 2025 and February 3, 2026 each fail to fully comply with 37 C.F.R. §1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. The statements have been placed in the application file, but the information referred to therein as the above-identified non-patent literature sources has not been considered.
Applicant should note that several documents were provided with the February 3, 2026 Information Disclosure Statement, but did not contain sufficient identifying markings to clearly correlate such documents to each of the listed non-patent literature sources identified above.
Applicant is advised that the date of any re-submission of any item of information contained in these information disclosure statements or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 C.F.R. §1.97(e). MPEP §609.05(a).
Status of Rejections in the October 6, 2025 Final Action
In reply to the rejection of claims 1, 3, 8, 14, 16-19, 22-23, 25 and 38 under 35 U.S.C. §112(b) (pre-AIA second paragraph), as set forth at p.9-10 of the previous Office Action dated October 6, 2025, Applicant now amends claim 1 to remove the limitation “is maintained over a period of up to 20 weeks after the first administration of the ASBTI” and to now recite “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI”. Accordingly, the rejection is now hereby withdrawn.
In reply to the rejection of claims 22-23 and 25 under 35 U.S.C. §112(b) (pre-AIA second paragraph), as set forth at p.11-12 of the previous Office Action dated October 6, 2025, Applicant now cancels claims 22-23 and 25. Accordingly, the rejection is now hereby withdrawn.
In reply to the rejection of claim 19 under 35 U.S.C. §112(d) (pre-AIA fourth paragraph), as set forth at p.13-14 of the previous Office Action dated October 6, 2025, Applicant now amends claim 19 to recite that the ASBTI is administered in an amount of “about 200 mg/kg to about 400 mg/kg per dose” to comport with the twice daily administration defined by claims 1 and 18, from which claim 19 depends. Accordingly, the rejection is now hereby withdrawn.
In reply to the rejection of claim 23 under 35 U.S.C. §112(d) (pre-AIA fourth paragraph), as set forth at p.14-15 of the previous Office Action dated October 6, 2025, Applicant now cancels claim 23. Accordingly, the rejection is now hereby withdrawn.
As previously indicated at p.3-4 of the Advisory Action dated December 19, 2025, the following rejections were withdrawn in view of Applicant’s submission of a 37 C.F.R. §1.130(a) Declaration of inventor Thomas Jaecklin establishing the Gonzales publication relied on in the AIA 35 U.S.C. §102(a)(1) and AIA 35 U.S.C. §103 rejections as a prior art exception under AIA 35 U.S.C. §102(b)(1)(A):
(i) the rejection of claims 1, 8, 14, 16, 18-19, 22-23, 25 and 38 under 35 U.S.C. §102(a)(1) as being anticipated by Gonzales (“Durability of Treatment Effect with Long-Term Maralixibat in Children with Alagille Syndrome: 4-Year Safety and Efficacy”, Presentation Slides, Published Online November 2019; cited by Applicant in the 05/15/25 IDS), as set forth at p.15-18 of the previous Office Action dated October 6, 2025; and
(ii) the rejection of claims 3 and 17 under 35 U.S.C. §103 as being unpatentable over Gonzales (“Durability of Treatment Effect with Long-Term Maralixibat in Children with Alagille Syndrome: 4-Year Safety and Efficacy”, Presentation Slides, Published Online November 2019; cited by Applicant in the 05/15/25 IDS) in view of Gedulin et al. (U.S. Patent Application Publication No. 2014/0275090 A1; 2014, cited by Applicant on the 08/11/21 IDS), citing to PubChem (“Maralixibat Chloride”, CID 9831642, cited by Applicant in the 08/11/21 IDS) as factual evidence, as set forth at p.18-21 of the previous Office Action dated October 6, 2025.
Upon further reconsideration of the claimed subject matter, however, new grounds for rejection are necessitated and set forth infra.
Claim Rejections - 35 USC § 112(b) (Pre-AIA Second Paragraph)
(New Grounds of Rejection)
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.
(1) Claims 1, 3, 8, 14, 16-19 and 38 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.
Applicant recites a first active step of “administering to the subject an effective amount” of the recited ASBTI in claim 1.
The limitation “the subject” lacks clear antecedent basis because the preceding text of the claim references only “a pediatric subject”, not “a subject” per se. As a result, it is unclear if this first active step is practiced in “the pediatric subject” referenced in the preamble objective of the claim, or any subject.
Clarification is required.
As claims 3, 8, 14, 16-19 and 38 do not remedy this point of ambiguity in claim 1, they must also be rejected on the same grounds applied thereto.
For these reasons, the claims fail to meet the tenor and express requirements of 35 U.S.C. §112(b) (pre-AIA second paragraph) and are, thus, properly rejected.
Claim Rejections - 35 USC § 102 (New Grounds of Rejection)
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.
(2) Claims 1, 8, 14, 16-19 and 38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Healio (“Maralixibat Reduces Pruritus, Xanthoma in Children with Alagille Syndrome”, Published November 12, 2019, cited by Applicant on the 12/24/25 IDS), citing to Gonzales et al. (“Efficacy and Safety of Maralixibat Treatment in Patients with Alagille Syndrome and Cholestatic Pruritus (ICONIC): A Randomised Phase 2 Study”, Lancet, 2021; 398:1581-1592, cited by Applicant on the 03/24/22 IDS) as factual evidence.
Healio teaches maralixibat as an orally administered, minimally absorbed ASBTI used in the core ICONIC study and its long-term open extension in children with ALGS (p.1, para.3-4). Healio teaches that 29 patients reached week 48 of the ICONIC study and were eligible to continue treatment with maralixibat at a dose of 400 mg/kg, increasing from once per day to twice per day (thus, an increase from 400 mg/kg/day given as a 400 mg/kg once daily dose to 800 mg/kg/day given as two 400 mg/kg doses per day; p.1, para.4). Healio teaches that 15 patients remained on maralixibat treatment for a median duration of 44.5 months, with a range from 42.1 to 51.7 months (p.1, para.5). Healio teaches that maralixibat was safe and well-tolerated during long-term therapy with no increase in severity or frequency of adverse events from the core study (p.1, para.7). Healio teaches that height z-score increased (-1.82 vs. -1.37, p < 0.01) as compared to baseline (p.1, para.6). Healio teaches that maralixibat therapy with 400 mg/kg twice daily exhibited similar efficacy and safety to once per day dosing (p.1, para.8).
The teachings of Healio provide for a method of administering to the pediatric ALGS subject the ASBTI maralixibat in an amount of 400 mg/kg once daily (thus, 400 mg/kg/day) or 400 mg/kg twice daily (thus, 800 mg/kg/day), then measuring the pediatric ALGS subject’s increase in height z-score to quantify this increase in growth as measured by height, thereby meeting the limitations of Applicant’s claims 1, 8, 14, 16—19 and 38.
As the increase in height z-score is reported in Healio as an increase from -1.82 versus -1.37 compared to baseline, such teachings meet Applicant’s limitations directed to “an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” (i.e., baseline).
The teachings to Gonzales et al. are cited as factual evidence to explicitly document that this increase of “at least 0.1” in height z-score was “observed less than 1 year after the first administration of the ASBTI”. See, specifically, Fig.6, p.1589 of Gonzales et al., which documents that this change in height z-score observed in the ICONIC study was > 0.1 relative to baseline at week 48, which is less than 1 year following first administration of the ASBTI maralixibat.
MPEP §2131.01 states that “[n]ormally, only one reference should be used in making a rejection under 35 U.S.C. 102”, but that it is proper to apply a second reference when the extra reference is cited for the purpose of “show[ing] that a characteristic not disclosed in the reference is inherent”.
Therefore, instant claims 1, 8, 14, 16-19 and 38 are properly anticipated under AIA 35 U.S.C. §102(a)(1).
Claim Rejections - 35 USC § 103 (New Grounds of Rejection)
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.
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.
(3) Claims 1, 3, 8, 14, 16-19 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Study NCT02160782 (“Safety and Efficacy Study of LUM001 with a Drug Withdrawal Period in Participants with Alagille Syndrome (ALGS) (ICONIC)”, U.S. National Library of Medicine, ClinicalTrials.Gov Archive, Published Online September 19, 2018, cited by Applicant on the 08/11/21 IDS, hereinafter “US NLM”) in view of Quiros-Tejeira et al. (“Does Liver Transplantation Affect Growth Pattern in Alagille Syndrome?”, Liver Transpl, 2000; 6:582-587, cited by Applicant on the 08/11/21 IDS),
citing to PubChem (“Maralixibat Chloride”, CID 9831642, cited by Applicant on the 08/11/21 IDS) as factual evidence.
US NLM teaches a long-term, open-label study with a double-blind, placebo-controlled, randomized drug withdrawal period in children with ALGS designed to evaluate the safety and efficacy of LUM-001 ("Study Description", p.4). US NLM teaches that the study is divided into 6 parts: a 6-week open- label, dose escalation period, a 12-week open-label dosing period, a 4-week randomized, double-blind, placebo-controlled drug withdrawal period, a 26- week long-term stable dosing period, and a long-term optional follow-up treatment period for eligible participants that choose to stay on treatment with LUM-001 ("Study Description", p.4). US NLM teaches that LUM-001 is administered orally once per day up to 400 µg/kg/day up to Week 52, followed by an increase in dose orally twice a day (i.e., 400 µg/kg twice daily, or 800 µg/kg/day) during long-term follow-up based on efficacy (serum bile acid level and ItchRO™ score) and safety assessment, and placebo is administered orally once per day during the randomized withdrawal period (Weeks 19-22) ("Arms and Interventions", p.5). US NLM teaches that eligible patients are between the ages of 12 months (1 year) to 18 years of age, have a clinical diagnosis of ALGS, and exhibit an average daily score of > 2 on the ItchRO™ questionnaire for two consecutive weeks in the screening period prior to dosing ("Eligibility", p.10-11).
PubChem documents that LUM-001 referenced in US NLM as the form of maralixibat administered is synonymous with maralixibat chloride (p.1).
US NLM differs from the instant claims only insofar as it does not explicitly teach the additional step of “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score” (claim 1), or the resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” (claim 1) and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI” (claim 1).
Quiros-Tejeira et al. teaches that pediatric subjects with ALGS frequently exhibit growth failure as a common manifestation of the disease, reported in 50-90% of ALGS subjects (col.2, para.3, p.582). Quiros-Tejeira et al. teaches subjects with ALGS diagnosed with failure to thrive as evidenced by below normal gains in height and weight for their age group (col.1, para.5, p.582; col.2, para.2, p.583). Quiros-Tejeira et al. teaches the use of height and weight as reported in growth charts for pediatric ALGS subjects to provide height and weight z-scores for the assessment of growth in these pediatric ALGS subjects (col.2, para.3, p.582-col.1, para.2, p.583). Quiros-Tejeira et al. teaches the analysis of height and weight z-scores in patients receiving liver transplantation for treatment of ALGS as compared to control patients, noting that an improvement in growth was observed following liver transplantation (col.1, para.2, p.586; col.2, para.3, p.586).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in measuring the pediatric ALGS subject’s height or weight z-score following LUM-001 (maralixibat chloride) therapy described by US NLM because Quiros-Tejeira et al. teaches the routine assessment of height and weight growth in pediatric ALGS subjects by determining the subject’s height and/or weight z-score for comparison to normal pediatric subjects, particularly following therapeutic interventions. It would have been prima facie obvious to the ordinarily skilled artisan before the effective filing date of the claimed invention to first administer the LUM-001 (maralixibat chloride) therapy of US NLM to the pediatric ALGS subject and to then measure the subject’s height and/or weight z-score to determine any changes related thereto, as well as the effect of such therapy on the subject’s overall growth as compared to normal subjects.
Claim 1 recites the intended effect of “increasing growth” in the pediatric ALGS subject by administering the ASBTI maralixibat (or its chloride salt form, as further defined in claim 3) and “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score”, with the additional resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI”.
Here, the combined teachings of US NLM and Quiros-Tejeira et al. provide for execution of an identical series of active steps to those instantly claimed. The intended results, then, of “increasing growth” – or, more specifically, “an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ABSTI” and that the increase “is observed less than 1 year after the first administration of the ASBTI” - must necessarily yield from the practice of the method of these teachings as combined above. The performance of the same series of active steps must necessarily yield the same resultant effects or properties.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting (New Grounds of Rejection)
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.
(4) Claims 1, 8, 14, 16-19 and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 103 and 105-123 of U.S. Patent Application No. 18/423,029 in view of Quiros-Tejeira et al. (“Does Liver Transplantation Affect Growth Pattern in Alagille Syndrome?”, Liver Transpl, 2000; 6:582-587, cited by Applicant on the 08/11/21 IDS).
Claims 103, 105-112, 115-117, 119 and 122-123 of the ‘029 application recite a method for treating ALGS in a subject in need of such treatment comprising administering to the subject a liquid pharmaceutical composition of maralixibat in an amount from about 400 mg/kg/day to about 800 mg/kg/day, a sweetener, a flavoring agent, and a liquid carrier. Claims 113-114 of the ‘029 application recites that the composition is administered once daily2 (claim 113) or twice daily3 (claim 114). Claim 118 of the ‘029 application recites that the subject exhibits below normal height or weight prior to administration of the composition. Claims 120-121 of the ‘029 application defines the subject as a pediatric subject (claim 120) or at least one year of age (claim 121).
In the ‘029 disclosure, the applicant defines the cholestatic liver disease as ALGS, and the subject as “a pediatric subject” (p.5, para.[0016]), thereby establishing that the broadly recited method of the ‘029 claims embraces the treatment of a pediatric ALGS subject.
‘029 differs from the instant claims only insofar as it does not explicitly teach the additional step of “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score” (claim 1), or the resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” (claim 1) and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI” (claim 1).
Quiros-Tejeira et al. teaches that pediatric subjects with ALGS frequently exhibit growth failure as a common manifestation of the disease, reported in 50-90% of ALGS subjects (col.2, para.3, p.582). Quiros-Tejeira et al. teaches subjects with ALGS diagnosed with failure to thrive as evidenced by below normal gains in height and weight for their age group (col.1, para.5, p.582; col.2, para.2, p.583). Quiros-Tejeira et al. teaches the use of height and weight as reported in growth charts for pediatric ALGS subjects to provide height and weight z-scores for the assessment of growth in these pediatric ALGS subjects (col.2, para.3, p.582-col.1, para.2, p.583). Quiros-Tejeira et al. teaches the analysis of height and weight z-scores in patients receiving liver transplantation for treatment of ALGS as compared to control patients, noting that an improvement in growth was observed following liver transplantation (col.1, para.2, p.586; col.2, para.3, p.586).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in measuring the pediatric ALGS subject’s height or weight z-score following maralixibat therapy of the ‘029 claims because Quiros-Tejeira et al. teaches the routine assessment of height and weight growth in pediatric ALGS subjects by determining the subject’s height and/or weight z-score for comparison to normal pediatric subjects, particularly following therapeutic interventions. It would have been prima facie obvious to the ordinarily skilled artisan before the effective filing date of the claimed invention to first administer maralixibat therapy of the ‘029 claims to the pediatric ALGS subject and to then measure the subject’s height and/or weight z-score to determine any changes related thereto, as well as the effect of such therapy on the subject’s overall growth as compared to normal subjects.
Claim 1 recites the intended effect of “increasing growth” in the pediatric ALGS subject by administering the ASBTI maralixibat and “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score”, with the additional resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI”.
Here, the ‘029 claims taken in view of Quiros-Tejeira et al. provide for execution of an identical series of active steps to those instantly claimed. The intended results, then, of “increasing growth” – or, more specifically, “an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ABSTI” and that the increase “is observed less than 1 year after the first administration of the ASBTI” - must necessarily yield from the practice of the method of these teachings as combined above. The performance of the same series of active steps must necessarily yield the same resultant effects or properties.
This is a provisional nonstatutory double patenting rejection.
(5) Claim 3 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 103 and 105-123 of U.S. Patent Application No. 18/423,029 in view of Quiros-Tejeira et al. (“Does Liver Transplantation Affect Growth Pattern in Alagille Syndrome?”, Liver Transpl, 2000; 6:582-587, cited by Applicant on the 08/11/21 IDS),
as applied above to claims 1, 8, 14, 16-19 and 38,
further in view of Gedulin et al. (U.S. Patent Application Publication No. 2016/0310518 A1; 2016, cited by Applicant on the 10/25/23 IDS),
citing to PubChem (“Maralixibat Chloride”, CID 9831642, cited by Applicant on the 08/11/21 IDS) as factual evidence.
‘029 in view of Quiros-Tejeira as applied above to claims 1, 8, 14, 16-19 and 38.
‘029 in view of Quiros-Tejeira differs from the instant claim only insofar as it does not explicitly teach that the maralixibat is in the form of its chloride salt (claim 3).
Gedulin et al. teaches a method for treating or ameliorating pruritus comprising non-systemically administering to a pediatric patient suffering from a pediatric cholestatic liver disease a therapeutically effective amount of a composition comprising an ASBTI or a pharmaceutically acceptable salt thereof (p.1, para.[0006]). Gedulin et al. teaches that the pediatric cholestatic liver disease is, e.g., ALGS (p.3, para.[0022]; p.14, para. [0103]-[0104]). Gedulin et al. teaches that the dosage of the ASBTI is between about 1 mg/kg/day and about 10 mg/kg/day, or about 5 mg/kg/day and about 1 mg/kg/day (equivalent to 1000 mg/kg/day), wherein the dosage of the ASBTI is given once per day, or twice per day (p.6-7, para.[0038]; p.7, para. [0042]). Gedulin et al. teaches that the ASBTI includes, e.g., maralixibat (p.25-26, para.[0238]). Gedulin et al. exemplifies an experimental study in which LUM001 was administered to pediatric patients with ALGS and was shown to be well-tolerated (Ex.25, p.77, para.[0737]-[0748]).
PubChem documents that LUM001 as referenced in Gedulin et al. is synonymous with maralixibat chloride (p.1).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in employing maralixibat chloride as the form of maralixibat to be administered in the ‘029 method as modified by Quiros-Tejeira et al. because Gedulin et al. teaches both maralixibat or LUM001 (the chloride salt of maralixibat) as suitable forms of maralixibat for administration to pediatric subjects with cholestatic liver disease, including ALGS. The use, therefore, of maralixibat or its chloride salt would have been prima facie obvious to the ordinarily skilled artisan before the effective filing date of the claimed invention in light of this recognized interchangeability of maralixibat or its chloride salt for the treatment of pediatric cholestatic liver disease, including ALGS. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-96, quoting Sakraida v. AG Pro., Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious”).
This is a provisional nonstatutory double patenting rejection.
(6) Claims 1, 3, 8, 14, 16-19 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,229,647 B2 (already of record) in view of Quiros-Tejeira et al. (“Does Liver Transplantation Affect Growth Pattern in Alagille Syndrome?”, Liver Transpl, 2000; 6:582-587, cited by Applicant on the 08/11/21 IDS).
Claims 1, 4-6 and 8-11 of the ‘647 patent recite a method for treating ALGS in a pediatric subject in need of such treatment comprising administering to the subject maralixibat chloride in an amount of about 400 mg/kg/day to about 800 mg/kg/day. Claim 2 of the ‘647 patent specifies that the maralixibat chloride is administered once daily. Claim 3 of the ‘647 patent specifies that the maralixibat chloride is administered twice daily (thus, suggesting that each of the two daily doses is about 200 to about 400 mg/kg for a total daily amount of about 400 mg/kg/day to about 800 mg/kg/day). Claim 7 of the ‘647 patent recites that the subject exhibits below normal height or weight prior to the administration of maralixibat chloride.
Claim 12 of the ‘647 patent recites a method for treating ALGS in a pediatric subject in need of such treatment comprising administering to the subject maralixibat chloride in an amount of about 400 mg/kg/day.
Claim 13 of the ‘647 patent recites a method for treating ALGS in a pediatric subject in need of such treatment comprising administering to the subject maralixibat chloride in an amount of about 800 mg/kg/day.
‘647 differs from the instant claims only insofar as it does not explicitly teach the additional step of “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score” (claim 1), or the resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” (claim 1) and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI” (claim 1).
Quiros-Tejeira et al. teaches that pediatric subjects with ALGS frequently exhibit growth failure as a common manifestation of the disease, reported in 50-90% of ALGS subjects (col.2, para.3, p.582). Quiros-Tejeira et al. teaches subjects with ALGS diagnosed with failure to thrive as evidenced by below normal gains in height and weight for their age group (col.1, para.5, p.582; col.2, para.2, p.583). Quiros-Tejeira et al. teaches the use of height and weight as reported in growth charts for pediatric ALGS subjects to provide height and weight z-scores for the assessment of growth in these pediatric ALGS subjects (col.2, para.3, p.582-col.1, para.2, p.583). Quiros-Tejeira et al. teaches the analysis of height and weight z-scores in patients receiving liver transplantation for treatment of ALGS as compared to control patients, noting that an improvement in growth was observed following liver transplantation (col.1, para.2, p.586; col.2, para.3, p.586).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in measuring the pediatric ALGS subject’s height or weight z-score following maralixibat therapy of the ‘647 claims because Quiros-Tejeira et al. teaches the routine assessment of height and weight growth in pediatric ALGS subjects by determining the subject’s height and/or weight z-score for comparison to normal pediatric subjects, particularly following therapeutic interventions. It would have been prima facie obvious to the ordinarily skilled artisan before the effective filing date of the claimed invention to first administer maralixibat therapy of the ‘647 claims to the pediatric ALGS subject and to then measure the subject’s height and/or weight z-score to determine any changes related thereto, as well as the effect of such therapy on the subject’s overall growth as compared to normal subjects.
Claim 1 recites the intended effect of “increasing growth” in the pediatric ALGS subject by administering the ASBTI maralixibat (or its chloride salt form, as further defined in claim 3) and “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score”, with the additional resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI”.
Here, the ‘647 claims as taken in view of Quiros-Tejeira et al. provide for execution of an identical series of active steps to those instantly claimed. The intended results, then, of “increasing growth” – or, more specifically, “an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ABSTI” and that the increase “is observed less than 1 year after the first administration of the ASBTI” - must necessarily yield from the practice of the method of these teachings as combined above. The performance of the same series of active steps must necessarily yield the same resultant effects or properties.
This is a nonprovisional nonstatutory double patenting rejection.
(7) Claims 1, 8, 14, 16-19 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,497,745 B2 (already of record) in view of Quiros-Tejeira et al. (“Does Liver Transplantation Affect Growth Pattern in Alagille Syndrome?”, Liver Transpl, 2000; 6:582-587, cited by Applicant on the 08/11/21 IDS).
Claims 1, 5-7, 9 and 12-13 of the ‘745 patent recites a method for treating ALGS in a subject in need of such treatment comprising administering to the subject maralixibat in an amount of from 360 mg/kg/day to 880 mg/kg/day. Claim 2 of the ‘745 patent further limits the dose to 360 mg/kg/day to 440 mg/kg/day. Claim 3 of the ‘745 patent specifies once daily administration4. Claim 4 of the ‘745 patent specifies twice daily administration5. Claims 10-11 of the ‘745 patent specifies that the subject is a pediatric subject (claim 10) or at least one year of age (claim 11).
In the ‘745 disclosure, the patentee defines the cholestatic liver disease as ALGS, and the subject as “a pediatric subject” (col.4, l.56-58), thereby establishing that the broadly recited method of the ‘745 claims embraces the treatment of a pediatric ALGS subject.
‘745 differs from the instant claims only insofar as it does not explicitly teach the additional step of “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score” (claim 1), or the resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” (claim 1) and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI” (claim 1).
Quiros-Tejeira et al. teaches that pediatric subjects with ALGS frequently exhibit growth failure as a common manifestation of the disease, reported in 50-90% of ALGS subjects (col.2, para.3, p.582). Quiros-Tejeira et al. teaches subjects with ALGS diagnosed with failure to thrive as evidenced by below normal gains in height and weight for their age group (col.1, para.5, p.582; col.2, para.2, p.583). Quiros-Tejeira et al. teaches the use of height and weight as reported in growth charts for pediatric ALGS subjects to provide height and weight z-scores for the assessment of growth in these pediatric ALGS subjects (col.2, para.3, p.582-col.1, para.2, p.583). Quiros-Tejeira et al. teaches the analysis of height and weight z-scores in patients receiving liver transplantation for treatment of ALGS as compared to control patients, noting that an improvement in growth was observed following liver transplantation (col.1, para.2, p.586; col.2, para.3, p.586).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in measuring the pediatric ALGS subject’s height or weight z-score following maralixibat therapy of the ‘745 claims because Quiros-Tejeira et al. teaches the routine assessment of height and weight growth in pediatric ALGS subjects by determining the subject’s height and/or weight z-score for comparison to normal pediatric subjects, particularly following therapeutic interventions. It would have been prima facie obvious to the ordinarily skilled artisan before the effective filing date of the claimed invention to first administer maralixibat therapy of the ‘745 claims to the pediatric ALGS subject and to then measure the subject’s height and/or weight z-score to determine any changed related thereto, as well as the effect of such therapy on the subject’s overall growth as compared to normal subjects.
Claim 1 recites the intended effect of “increasing growth” in the pediatric ALGS subject by administering the ASBTI maralixibat and “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score”, with the additional resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI”.
Here, the ‘745 claims as taken in view of Quiros-Tejeira et al. provide for execution of an identical series of active steps to those instantly claimed. The intended results, then, of “increasing growth” – or, more specifically, “an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ABSTI” and that the increase “is observed less than 1 year after the first administration of the ASBTI” - must necessarily yield from the practice of the method of these teachings as combined above. The performance of the same series of active steps must necessarily yield the same resultant effects or properties.
This is a nonprovisional nonstatutory double patenting rejection.
(8) Claim 3 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,497,745 B2 (already of record) in view of Quiros-Tejeira et al. (“Does Liver Transplantation Affect Growth Pattern in Alagille Syndrome?”, Liver Transpl, 2000; 6:582-587, cited by Applicant on the 08/11/21 IDS),
as applied above to claims 1, 8, 14, 16-19 and 38,
further in view of Gedulin et al. (U.S. Patent Application Publication No. 2016/0310518 A1; 2016, cited by Applicant on the 10/25/23 IDS),
citing to PubChem (“Maralixibat Chloride”, CID 9831642, cited by Applicant on the 08/11/21 IDS) as factual evidence.
‘745 in view of Quiros-Tejeira as applied above to claims 1, 8, 14, 16-19 and 38.
‘745 in view of Quiros-Tejeira differ from the instant claim only insofar as they do not explicitly teach that the maralixibat is in the form of the chloride salt (claim 3).
Gedulin et al. teaches a method for treating or ameliorating pruritus comprising non-systemically administering to a pediatric patient suffering from a pediatric cholestatic liver disease a therapeutically effective amount of a composition comprising an ASBTI or a pharmaceutically acceptable salt thereof (p.1, para.[0006]). Gedulin et al. teaches that the pediatric cholestatic liver disease is, e.g., ALGS (p.3, para.[0022]; p.14, para. [0103]-[0104]). Gedulin et al. teaches that the dosage of the ASBTI is between about 1 mg/kg/day and about 10 mg/kg/day, or about 5 mg/kg/day and about 1 mg/kg/day (equivalent to 1000 mg/kg/day), wherein the dosage of the ASBTI is given once per day, or twice per day (p.6-7, para.[0038]; p.7, para. [0042]). Gedulin et al. teaches that the ASBTI includes, e.g., maralixibat (p.25-26, para.[0238]). Gedulin et al. exemplifies an experimental study in which LUM001 was administered to pediatric patients with ALGS and was shown to be well-tolerated (Ex.25, p.77, para.[0737]-[0748]).
PubChem documents that LUM001 as referenced in Gedulin et al. is synonymous with maralixibat chloride (p.1).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in employing maralixibat chloride as the form of maralixibat to be administered in the ‘029 method as modified by Quiros-Tejeira et al. because Gedulin et al. teaches both maralixibat or LUM001 (the chloride salt of maralixibat) as suitable forms of maralixibat for administration to pediatric subjects with cholestatic liver disease, including ALGS. The use, therefore, of maralixibat or its chloride salt would have been prima facie obvious to the ordinarily skilled artisan before the effective filing date of the claimed invention in light of this recognized interchangeability of maralixibat or its chloride salt for the treatment of pediatric cholestatic liver disease, including ALGS. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-96, quoting Sakraida v. AG Pro., Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious”).
This is a nonprovisional nonstatutory double patenting rejection.
(9) Claims 1, 8, 14, 16-17 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,918,578 B2 (already of record) in view of Quiros-Tejeira et al. (“Does Liver Transplantation Affect Growth Pattern in Alagille Syndrome?”, Liver Transpl, 2000; 6:582-587, cited by Applicant on the 08/11/21 IDS).
Claims 1, 7-9 and 12-17 of the ‘578 patent recite a method for treating cholestatic pruritus in a subject having ALGS comprising administering to the subject maralixibat in an amount of from about 400 mg/kg/day to about 800 mg/kg/day, wherein the maralixibat is administered as a liquid pharmaceutical composition comprising about 0.001 mg/mL to about 16 mg/mL maralixibat. Claim 2 of the ‘578 patent further limits the dose to about 400 mg/kg/day. Claim 3 of the ‘578 patent further limits the dose to 360 mg/kg/day to 400 mg/kg/day. Claim 4 of the ‘578 patent specifies once daily administration6. Claims 5-6 specify that the maralixibat is administered once daily in an amount of about 400 mg/kg/day (claim 5) or 360 mg/kg/day to 400 mg/kg/day (claim 6). Claims 10-11 of the ‘578 patent specifies that the subject is a pediatric subject (claim 10) or at least one year of age (claim 11).
In the ‘578 disclosure, the patentee defines the cholestatic liver disease as ALGS, and the subject as “a pediatric subject” (col.4, l.56-58), thereby establishing that the broadly recited method of the ‘578 claims embraces the treatment of a pediatric ALGS subject.
‘578 differs from the instant claims only insofar as it does not explicitly teach the additional step of “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score” (claim 1), or the resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” (claim 1) and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI” (claim 1).
Quiros-Tejeira et al. teaches that pediatric subjects with ALGS frequently exhibit growth failure as a common manifestation of the disease, reported in 50-90% of ALGS subjects (col.2, para.3, p.582). Quiros-Tejeira et al. teaches subjects with ALGS diagnosed with failure to thrive as evidenced by below normal gains in height and weight for their age group (col.1, para.5, p.582; col.2, para.2, p.583). Quiros-Tejeira et al. teaches the use of height and weight as reported in growth charts for pediatric ALGS subjects to provide height and weight z-scores for the assessment of growth in these pediatric ALGS subjects (col.2, para.3, p.582-col.1, para.2, p.583). Quiros-Tejeira et al. teaches the analysis of height and weight z-scores in patients receiving liver transplantation for treatment of ALGS as compared to control patients, noting that an improvement in growth was observed following liver transplantation (col.1, para.2, p.586; col.2, para.3, p.586).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in measuring the pediatric ALGS subject’s height or weight z-score following maralixibat therapy of the ‘578 claims because Quiros-Tejeira et al. teaches the routine assessment of height and weight growth in pediatric ALGS subjects by determining the subject’s height and/or weight z-score for comparison to normal pediatric subjects, particularly following therapeutic interventions. It would have been prima facie obvious to the ordinarily skilled artisan before the effective filing date of the claimed invention to first administer maralixibat therapy of the ‘578 claims to the pediatric ALGS subject and to then measure the subject’s height and/or weight z-score to determine any changes related thereto, as well as the effect of such therapy on the subject’s overall growth as compared to normal subjects.
Claim 1 recites the intended effect of “increasing growth” in the pediatric ALGS subject by administering the ASBTI maralixibat and “measuring the pediatric subject’s increase in growth as an increase in height or weight Z-score”, with the additional resultant effects of “wherein the pediatric subject exhibits an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ASBTI” and that “the increase in the height or weight Z-score is observed less than 1 year after the first administration of the ASBTI”.
Here, the ‘578 claims as taken in view of Quiros-Tejeira et al. provide for execution of an identical series of active steps to those instantly claimed. The intended results, then, of “increasing growth” – or, more specifically, “an increase in height or weight Z-score of at least 0.1 relative to prior to the first administration of the ABSTI” and that the increase “is observed less than 1 year after the first administration of the ASBTI” - must necessarily yield from the practice of the method of these teachings as combined above. The performance of the same series of active steps must necessarily yield the same resultant effects or properties.
This is a nonprovisional nonstatutory double patenting rejection.
(10) Claims 3 and 18-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,918,578 B2 (already of record) in view of Quiros-Tejeira et al. (“Does Liver Transplantation Affect Growth Pattern in Alagille Syndrome?”, Liver Transpl, 2000; 6:582-587, cited by Applicant on the 08/11/21 IDS),
as applied above to claims 1, 8, 14, 16-17 and 38,
further in view of Gedulin et al. (U.S. Patent Application Publication No. 2016/0310518 A1; 2016, cited by Applicant on the 10/25/23 IDS),
citing to PubChem (“Maralixibat Chloride”, CID 9831642, cited by Applicant on the 08/11/21 IDS) as factual evidence.
‘578 in view of Quiros-Tejeira as applied above to claims 1, 8, 14, 16-17 and 38.
‘578 in view of Quiros-Tejeira differ from the instant claims only insofar as they do not explicitly teach that the maralixibat is in the form of the chloride salt (claim 3), or that the recited daily dose is administered as a twice daily administration (claims 16-19).
Gedulin et al. teaches a method for treating or ameliorating pruritus comprising non-systemically administering to a pediatric patient suffering from a pediatric cholestatic liver disease a therapeutically effective amount of a composition comprising an ASBTI or a pharmaceutically acceptable salt thereof (p.1, para.[0006]). Gedulin et al. teaches that the pediatric cholestatic liver disease is, e.g., ALGS (p.3, para.[0022]; p.14, para. [0103]-[0104]). Gedulin et al. teaches that the dosage of the ASBTI is between about 1 mg/kg/day and about 10 mg/kg/day, or about 5 mg/kg/day and about 1 mg/kg/day (equivalent to 1000 mg/kg/day), wherein the dosage of the ASBTI is given once per day, or twice per day (p.6-7, para.[0038]; p.7, para. [0042]). Gedulin et al. teaches that the ASBTI includes, e.g., maralixibat (p.25-26, para.[0238]). Gedulin et al. exemplifies an experimental study in which LUM001 was administered to pediatric patients with ALGS and was shown to be well-tolerated (Ex.25, p.77, para.[0737]-[0748]).
PubChem documents that LUM001 as referenced in Gedulin et al. is synonymous with maralixibat chloride (p.1).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in employing maralixibat chloride as the form of maralixibat to be administered in the ‘578 method as modified by Quiros-Tejeira et al. because Gedulin et al. teaches both maralixibat or LUM001 (the chloride salt of maralixibat) as suitable forms of maralixibat therapy for administration to pediatric subjects with cholestatic liver disease, including ALGS. The use, therefore, of maralixibat or its chloride salt would have been prima facie obvious to the ordinarily skilled artisan before the effective filing date of the claimed invention in light of this recognized interchangeability of maralixibat or its chloride salt for the treatment of pediatric cholestatic liver disease, including ALGS. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-96, quoting Sakraida v. AG Pro., Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious”).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have found it prima facie obvious to administer the maralixibat dose of the ‘578 claims as modified by Quiros-Tejeira et al. to the pediatric ALGS subject as a twice daily dose because Gedulin et al. teaches the use of once or twice daily dosing of ASBTI therapy, such as maralixibat, for the treatment of pediatric ALGS subjects.
As the skilled artisan would have utilized twice daily dosing as suggested by Gedulin et al. as applied to the range of from about 400 mg/kg/day to 800 mg/kg/day recited in the ‘578 patent claim, such dosage range would be comparable to a dose of 200 mg/kg to 400 mg/kg twice daily in equal doses, which meets Applicant’s limitations of claims 18-19.
This is a nonprovisional nonstatutory double patenting rejection.
Response to Applicant’s Arguments
In reply, Applicant traverses the previously applied rejections in view of the submitted amendments and arguments (Remarks, p.5-8).
Applicant’s traversal and amendments have been fully and carefully considered, and the previously applied rejections have been withdrawn as indicated above.
Upon further reconsideration of the claimed subject matter as amended, however, new grounds for rejection are necessitated and are set forth infra.
For these reasons supra, rejection of claims 1, 3, 8, 14, 16-19 and 38 is proper.
Conclusion
Rejection of claims 1, 3, 8, 14, 16-19 and 38 is proper.
Claims 9-13 are withdrawn from consideration pursuant to 37 C.F.R. 1.142(b).
No claims of the present application are allowed.
Applicant is requested to specifically point out the support for any amendments made to the disclosure in response to this Office action, including the claims (M.P.E.P. §§ 714.02 and 2163.06). In doing so, applicant is requested to refer to pages and line (or paragraph) numbers (if available) in the as-filed specification, not the published application. Due to the procedure outlined in M.P.E.P. § 2163.06 for interpreting claims, other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
Applicant is reminded that MPEP §2001.06(b) clearly states that “[t]he individuals covered by 37 C.F.R. 1.56 have a duty to bring to the attention of the examiner, or other Office official involved with the examination of a particular application, information within their knowledge as to other copending United States applications which are "material to patentability" of the application in question." See Armour & Co. v. Swift & Co., 466 F.2d 767, 779, 175 USPQ 70, 79 (7th Cir. 1972). MPEP §2001.06(b) clearly indicates that “if a particular inventor has different applications pending in which similar subject matter but patentably indistinct claims are present that fact must be disclosed to the examiner of each of the involved applications.” See Dayco Prod. Inc. v. Total Containment, Inc., 329 F.3d 1358, 1365-69, 66 USPQ2d 1801, 1806-08 (Fed. Cir. 2003).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Leslie A. Royds Draper whose telephone number is (571)272-6096. The examiner can normally be reached Tuesday to Thursday (08:30 AM to 05:00 PM).
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/Leslie A. Royds Draper/Primary Examiner, Art Unit 1629
February 26, 2026
1 Regarding Non-Patent Literature Citation No. 30 on the December 24, 2025 statement, Applicant provides a narrative citation that appears to exceed the allowable space. This is improper. There is no provision in 37 C.F.R. §1.98(b) to provide a lengthy narrative explanation when citing non-patent literature sources.
2 A once daily administration provides for a single dose of 400 mg/kg to 800 mg/kg administered per day, which meets Applicant’s limitations of claims 16-17 and 38.
3 A twice daily administration provides for two doses of 200 mg/kg (a total of 400 mg/kg/day) to 400 mg/kg (a total of 800 mg/kg/day), which meets Applicant’s limitations of claims 18-19.
4 A once daily administration provides for a single dose of 360 mg/kg to 880 mg/kg administered per day, which meets Applicant’s limitations of claims 16-17 and 38.
5 A twice daily administration provides for two doses of 180 mg/kg (a total of 360 mg/kg/day) to 440 mg/kg (a total of 880 mg/kg/day), which meets Applicant’s limitations of claims 18-19.
6 A once daily administration provides for a single dose of about 400 mg/kg to about 800 mg/kg administered per day, which meets Applicant’s limitations of claims 16-17 and 38.