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 .
Priority
Instant application 18/382,636 filed on 10/23/2023 claims benefit as follow:
CONTINUING DATA:
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Status of the Application
Claims 1-3, 7, 9, 18, 19, 21, 24, 25, 27, 29, 30, 37, 47, 54, 67, 68, 69, 75, 81 and 85 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/12/2024 was in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 21, 29, 37, 47, 54 and 69 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Study NCT04185363 (“An Extension Study of Maralixibat in Patients with Progressive Familial Intrahepatic Cholestasis (PFIC)”, U.S. National Library of Medicine, ClinicalTrials.gov Archive, Published Online December 4, 2019).
NCT04185363 teaches a phase 3, open-label extension study to evaluate the long-term safety and efficacy of maralixibat in the treatment of subjects with PFIC (“Study Details”, p.3-4; “Study Design”, p.7).
NCT04185363 teaches that all subjects will receive administration of maralixibat oral solution at a dose of up to 600 μg/kg twice daily for up to 104 weeks (“Arms and Interventions”, p.8).
It should be noted that 600 μg/kg twice daily is equivalent of 1200 μg/kg/day.
NCT04185363 describes outcome measures of the study, including a secondary outcome measure of a change in ItchRO (Itch Reported Outcome) severity and frequency score from maralixibat baseline over the course of the study (“Outcome Measures”, p.8-9).
Regarding instant claim 21, 29 and 69, NCT04185363 teaches administration of an oral solution of maralixibat in an amount of up to 600 μg/kg twice daily (equivalent to up to 1200 μg/kg/day) to pediatric PFIC subjects of 1-18 years of age.
Regarding instant claims 37, 47 and 54, it should be noted that those claims recite results to be achieved. MPEP 2111.04 states that ‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 9, 37, 47 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Thompson (Thompson et al. “Genotype and Dose-Dependent Response to Maralixibat in Patients with Bile Salt Export Pump Deficiency” (Abstract No. 82), Hepatology, 2019 October; 70(Suppl.1), p.56A).
Thompson teaches the INDIGO clinical study of the apical sodium-dependent bile acid transport (ASBT) inhibitor maralixibat (which functions to interrupt the enterohepatic circulation of bile acids) for the treatment of patients with PFIC due to FIC1 deficiency or bile salt export pump (BSEP) deficiency (see “Background”, abstract).
Thompson teaches that 25 patients with BSEP deficiency were enrolled and treated with doses of 280 μg/kg/day with allowable increases to 560 μg/kg/day in an extension study (see “Methods”, abstract).
Thompson teaches that six patients were found to have no BSEP and did not respond to drug therapy, with the remaining 19 classified as “mild” (seven patients with E297G or D482G mutations) or “moderate” (12 missense patients) (see “Results”, abstract).
Thompson teaches that two of the “mild” patients were exposed to doses of 560 μg/kg/day of maralixibat, with one responding to therapy, and six of the “moderate” patients responded to doses of 280 μg/kg/day maralixibat (see “Results”, abstract).
Thompson teaches that maralixibat reduces serum bile acids (sBA) and pruritus in a proportion of BSEP deficient patients, noting that higher doses may be required to block absorption of bile acids in those with greater retained canalicular transport (see “Results”, abstract).
In instant claim 9, Applicant defines the PFIC as PFIC1, PFIC2, PFIC3, PFIC4, PFIC5 or PFIC6.
Regarding instant claim 9, it should be noted that instant specification paragraph [00119] defines “PFIC2” as synonymous with “BSEP deficiency”, thereby establishing that the PFIC patients with BSEP deficiency of Thompson have PFIC2:
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Thompson describes the administration of maralixibat in an amount of 560 μg/kg/day to PFIC2 subjects, which was therapeutically effective to reduce sBA and pruritus.
However, Thompson teaches that “Patients with biochemical effect (7αC4/BA ratio) but not clinical response may be rescued with higher maralixibat doses” (see “Conclusion”).
Therefore, based on the suggestion from Thompson one of ordinary skill in the art would have been motivated to use higher dose of maralixibat. Further, optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.”
Regarding instant claims 37, 47 and 54, it should be noted that those claims recite results to be achieved. MPEP 2111.04 states that ‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003).
Claims 1, 2, 3, 7, 9, 18, 19, 21, 29, 30, 37, 47, 54, 67, 68, 69, 75, 81, and 85 are rejected under 35 U.S.C. 103 as being unpatentable over Gedulin (U.S. Patent Application Publication No. 2016/0310518 A1; 2016) evidenced by PubChem (“Maralixibat Chloride”, CID 9831642, printed 07/29/2026).
Gedulin 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 apical sodium-dependent bile acid transporter inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof (see p.1, para. [0006]).
Gedulin teaches that the pediatric cholestatic liver disease is, e.g., PFIC, including PFIC type 1 (PFIC1), PFIC type 2 (PFIC2) and PFIC type 3 (PFIC3), in which the PFIC subjects may exhibit signs of malnutrition and shortened stature (see p.3, para. [0022]; p.12, para. [0086]-p.13, para. [0104]).
Gedulin teaches that the dosage of the ASBTI is between about 1 μg/kg/day and about 10 mg/kg/day, or about 5 μg/kg/day and about 1 mg/kg/day (equivalent to 1000 μg /kg/day), which may be administered twice per day (see p.6-7, para. [0038]; p.7, para. [0042]).
Gedulin further teaches that the ASBTI is administered in a pediatric dosage form before the ingestion of food (see p.8, para. [0047]).
Gedulin teaches that the ASBTI is, e.g., maralixibat chloride (see p.25-26, para. [0238]).
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Gedulin teaches patients genetically diagnosed with anomalies in ATP8B1, ABCB11, or ABCB4 gene and who present with PFIC-1 are eligible for enrollment (see p.76, para. [0724]).
Regarding instant claim 19, Gedulin teaches biliary diversion surgery (Kasai procedure) (see para. [0106]).
Gedulin teaches that the ASBTI is administered as part of a pharmaceutical composition, including liquids, e.g., a solution (see p.58, para. [0543]-[0544]; p.59-60, para.[0554]).
Gedulin teaches that the ASBTI is dissolved in the liquid to form the solution (p.62, para. [0580]-[0581]).
Regarding instant claim 81, Gedulin teaches the composition may contain EDTA (see p. 57, para. [0537).
Further, Gedulin exemplifies aqueous oral solutions of LUM001 with propylene glycol or PEG 200 (or 300, 400 or 600), and water, to which may be further added 0.5-2% of sweetener (e.g., sucralose, mannitol, sucrose) and/or 0.5-2% of a flavoring agent (e.g., grape, cherry, bubble gum, orange, lemon, strawberry) (see Ex.15, p.72, para.[0675]-[0676]).
Gedulin additionally exemplifies a clinical study of LUM001 in the treatment or alleviation of symptoms associated with FIC1 disease (PFIC1) or Alagille syndrome (Ex.25, p.77, para.[0737]-[0749]).
PubChem documents that LUM001 as referenced in Gedulin is synonymous with maralixibat chloride (see p.1).
Gedulin does not explicitly teach administration of maralixibat chloride in an amount of “about 1200 μg/kg/day” (as required by instant claim 7). Regarding claim 18, Gedulin does not teach the PFIC is heterozygous. Regarding claim 67, Gedulin does not explicitly teach administration 30 min before the morning and evening meal. Regarding instant claim 85, Gedulin does not teach the recited concentrations.
However, 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 ASBTI therapy in an amount of “1200 μg/kg/day” to all patients suffering from PFIC because Gedulin teaches the administration of ASBTI therapy (including maralixibat chloride) for the treatment of cholestatic liver disease, including PFIC, in an amount of about 1 μg/kg/day and about 10 mg/kg/day (equivalent to 10,000 μg/kg/day) or about 5 μg/kg/day and about 1 mg/kg/day (equivalent to 1000 μg/kg/day), which are ranges that clearly overlap the ranges recited in instant claims. MPEP §2144.05 states, “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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) … “[A] prior art reference that discloses a range encompassing a somewhat narrower range is sufficient to establish a prima facie case of obviousness.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005).”
Further, regarding the pharmaceutical composition, a person of ordinary skill before the effective filing date of the instant application would have been capable to adjust concentrations of maralixibat, propyl glycol and EDTA by routine experimentation.
Further, since Gedulin further teaches that the ASBTI is administered in a pediatric dosage form before the ingestion of food (see p.8, para. [0047]), a person of ordinary skill before the effective filing date of the instant application would have been capable to adjust administration time to about 30 minutes before morning and evening meal.
Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Furthermore, regarding instant claims 37, 47, and 54, it should be noted that those claims recite results to be achieved. MPEP 2111.04 states that ‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003).
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.
Claims 1, 2, 3, 7, 9, 21, 24, 25, 27, 29, 37, 47, 54 ,67-69, 75, 81 and 85 are rejected under are rejected under 35 U.S.C. 103 as being unpatentable over Dorenbaum (U.S. 2022/0105092-A1 Pub. Date Apr.07, 2022).
Dorenbaum teaches a method for treating cholestatic liver disease in a subject comprising administering to the subject an Apical Sodium dependent Bile Acid Transporter Inhibitor (ASBTI). The ASBTI is administered in an amount of from about 10 μg/kg/day to about 1400 μg/kg/day (see para [0006]).
Dorenbaum teaches maralixibat chloride:
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Regarding claim 21, Dorenbaum teaches pediatric subjects (see p.2, para. [0008]).
Regarding instant claims 24 and 27, Dorenbaum teaches the cholestatic liver diseases is PFCI (including type 1, 2 and 3). Dorenbaum also teaches the subject has a non-truncating mutation in ABC11 gene (see para. [0009]):
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Further, regarding claim 27, Dorenbaum teaches truncated BSEP (see Table 5):
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Further, Dorenbaum teaches maralixibat is administered once or twice daily (see p. 66, para. [0754], p. 67, Table 10 and claim 107).
Furthermore, Dorenbaum teaches and claims maralixibat is administered prior to ingestion of food (see claim 115).
Regarding claim 68, Dorenbaum teaches pharmaceutical compositions comprising one or more pharmaceutically acceptable additives such as a compatible carrier, binder, filling agent, suspending agent, flavoring agent, sweetening agent, disintegrating agent, dispersing agent, surfactant, lubricant, colorant, diluent, solubilizer, moistening agent, plasticizer, stabilizer, penetration enhancer, wetting agent, anti-foaming agent, antioxidant, preservative, or one or more combination thereof (see p. 54, para. [0656]).
Regarding claim 69, Dorenbaum teaches aqueous or non-aqueous oral dispersions, liquids, gels, syrups (see p. 54, para [0659]).
Regarding claim 75, Dorenbaum teaches preservatives, for example, sorbic acid, phenylmercuric nitrate and thimerosal (see p. 52, para. [0644]).
Regarding claim 81, Dorenbaum teaches EDTA (see p. 52, para [0642]).
Further, Dorenbaum teaches:
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Dorenbaum also teaches pharmaceutical composition wherein at least one excipient is a flavoring agent or a sweetener (p.54, para [0660]).
Dorenbaum does not explicitly teach administration of maralixibat chloride in an amount of “about 1200 μg/kg/day” in one single embodiment. Regarding claim 67, Dorenbaum does not explicitly teach administration 30 min before the morning and evening meal. Regarding instant claim 85, Dorenbaum does not teach the recited concentrations.
However, Dorenbaum teaches ASBTI is administered in an amount of from about 10 μg/kg/day to about 1400 μg/kg/day, therefore, it would been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select a dose inside the range disclosed by Dorenbaum. One of ordinary skill in the art would have been motivated to select a dose within the range disclosed by Dorenbaum because Dorenbaum teaches that the said range is both safe and effective for treating cholestatic liver diseases.
Further, regarding the pharmaceutical composition, a person of ordinary skill before the effective filing date of the instant application would have been capable to select propyl glycol and EDTA from the list of preservatives and antioxidants disclosed by Dorenbaum and adjust concentrations of maralixibat, propyl glycol and EDTA by routine experimentation.
Regarding administrations 30 min before the morning and evening meal, a person of ordinary skill before the effective filing date of the instant application would have been capable to adjust administration time to about 30 minutes before morning and evening meal because Dorenbaum teaches and claim maralixibat administered prior to ingestion of food (see claim 115).
Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Regarding instant claims 37, 47 and 54, it should be noted that those claims recite results to be achieved. MPEP 2111.04 states that ‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003).
In addition, regarding instant claim 54, Dorenbaum teaches reduction of total bilirubin by at least 0.2 mg/dl (from 2.9 into 0.8 mg/dL) (see Table 7):
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Regarding instant claim 37, Dorenbaum teaches reduction in severity of pruritis measured as a reduction of at least 1.0 in an observer-reported itch reported outcome (ITCHRO(OBS)) score:
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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 1-3, 7, 9, 18, 19, 21, 24, 25, 27, 29, 30, 37, 47, 54, 67, 68, 69, 75, 81 and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 103, 109, 110-119 and 121-126 of U.S. Patent Application No. 18/417,725.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of U.S. Patent Application No. 18/417,725 recite a method for treating progressive familial intrahepatic cholestasis (PFIC) in a pediatric subject in need of such treatment comprising administering to the pediatric subject maralixibat, or a pharmaceutically acceptable salt thereof, in an amount of from 560 μg/kg/day to 1200 μg/kg/day.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 7, 9, 18, 19, 21, 24, 25, 27, 29, 30, 37, 47, 54, 67, 68, 69, 75, 81 and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10, 12, 14-18, 24 and 27-34 of U.S. Patent Application No. 17/430,125.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of U.S. Patent Application No. 17/430,125 recite:
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The claims of U.S. Patent Application No. 17/430,125 recite a method for treating or ameliorating cholestatic liver disease in a subject in need thereof, wherein the subject has a BSEP deficiency with residual BSEP function comprising administering to the subject an ASBTI, such as maralixibat chloride (or a pharmaceutically acceptable alternative salt thereof), and the ASBTI is administered at a daily dose of about 1200 μg/kg (see claim 27).
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 7, 9, 18, 19, 21, 24, 25, 27, 29, 30, 37, 47, 54, 67, 68, 69, 75, 81 and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 8-19 and 38 of U.S. Patent Application No. 17/430,168.
The claims of U.S. Patent Application No. 17/430,168 recite a method for increasing growth in a pediatric subject having a cholestatic liver disease, comprising administering to the subject an effective amount of an ASBTI, including maralixibat (or a pharmaceutically acceptable salt thereof) in amount of about 400 to 800 μg/kg/day.
Further, the claims of U.S. Patent Application No. 17/430,168 recite:
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In the ‘168 disclosure, the applicant defines the term “cholestatic liver disease” as including PFIC, in particular, PFIC1, PFIC2 or PFIC3 (p.3, para. [0008]), thereby establishing that the methods of the ‘168 claims circumscribe the treatment of the cholestatic liver disease PFIC (including the specific subtypes PFIC1, PFIC2 and PFIC3).
The amounts of maralixibat ASBTI to be administered in the ‘168 claims overlap those instantly claimed, thus, render the instantly claimed ranges prima facie obvious over the ‘168 claims. See MPEP §2144.05.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 7, 9, 18, 19, 21, 24, 25, 27, 29, 30, 37, 47, 54, 67, 68, 69, 75, 81 and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 15-18, 48-50, 52-55, 58, 63, 71, 100-101 and 105 of U.S. Patent Application No. 17/430,210.
The claims of U.S. Patent Application No. 17/430,210 recite:
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Further, claim 18 of the ‘210 application specifies that the subject is a pediatric subject. Furthermore, claim 49 of the ‘210 application defines the ASBTI administration as twice daily.
The amounts of maralixibat ASBTI to be administered in the ‘210 claims clearly overlap those instantly claimed in claims, thus, render the instantly claimed ranges prima facie obvious over the ‘210 claims. See MPEP §2144.05.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 7, 9, 18, 19, 21, 24, 25, 27, 29, 30, 37, 47, 54, 67, 68, 69, 75, 81 and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-16, 21-24, 30, 32-33, and 35-36 of U.S. Patent Application No. 17/972,909 in view of Gedulin (U.S. Patent Application Publication No. 2014/0275090 A1).
The teachings of Gedulin have been discussed above and those teachings are incorporated herein by reference.
The claims of U.S. Patent Application No. 17/972,909 recite:
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Claims of ‘909 does not explicitly teach administration of maralixibat in an amount of “about 600 mg/kg/day to about 1200 mg/kg/day.
Gedulin 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 twice per day (p.10-11, para. [0059]; p.11, para. [0063]). Gedulin teaches that the compositions may also be employed to treat or ameliorate other cholestatic liver diseases, such as PFIC, including PFIC1, PFIC2 or PFIC3 (p.6, para. [0042]). Gedulin also teaches that the ASBTI is administered before ingestion of food (p.12, para. [0071]).
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 modify the ‘909 method to administer the ASBTI maralixibat therapy in an amount of “about 600 mg/kg/day to about 1200 mg/kg/day”.
The skilled artisan would have had a reasonable expectation of success in administering amounts within these ranges described by Gedulin prior to ingestion of food because Gedulin teaches such ranges as being suitable for administration for this therapeutic indication prior to ingestion of food.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 7, 9, 18, 19, 21, 24, 25, 27, 29, 30, 37, 47, 54, 67, 68, 69, 75, 81 and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 8, 13-14, 16, 24-26, 32-33, 39-43, 45-49 and 52-54 of U.S. Patent Application No. 17/973,194 in view of Gedulin (U.S. Patent Application Publication No. 2014/0275090 A1).
The teachings of Gedulin have been discussed above and those teachings are incorporated herein by reference.
The claims of U.S. Patent Application No. 17/973,194 recite:
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The ‘194 claims recite the pharmaceutical composition comprising propylene glycol (see claim 16), EDTA (see claim 25).
Further, the ‘194 claims recite:
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Furthermore, claim 48 of the ‘194 claims recite a method of treating or ameliorating a pediatric cholestatic liver disease comprising administering to a pediatric subject a therapeutically effective amount of a pharmaceutical composition comprising maralixibat (or pharmaceutically acceptable salt thereof) with a preservative and antioxidant. Claim 49 further defines the pediatric cholestatic liver disease as including PFIC, in particular, PFIC1, PFIC2 or PFIC3.
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Claims of ‘194 does not explicitly teach administration of maralixibat in an amount of “about 600 mg/kg/day to about 1200 mg/kg/day”
Gedulin 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 twice per day (p.10-11, para. [0059]; p.11, para. [0063]). Gedulin teaches that the compositions may also be employed to treat or ameliorate other cholestatic liver diseases, such as PFIC, including PFIC1, PFIC2 or PFIC3 (p.6, para. [0042]). Gedulin also teaches that the ASBTI is administered before ingestion of food (p.12, para. [0071]).
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 modify the ‘194 method to administer the maralixibat composition in an amount of “about 600 mg/kg/day to about 1200 mg/kg/day” because Gedulin teaches the administration of ASBTI therapy (including maralixibat) for the treatment of cholestatic liver disease, such as PFIC, in an amount of about 1 mg/kg/day and about 10 mg/kg/day (equivalent to 10,000 mg/kg/day) or about 5 mg/kg/day and about 1 mg/kg/day (equivalent to 1000 mg/kg/day), either as a once or twice daily administration, which are ranges that overlap the ranges recited in instant claims. See MPEP §2144.05.
The skilled artisan would have also found it prima facie obvious to administer amounts of the ‘194 maralixibat composition within these ranges described by Gedulin prior to ingestion of food because Gedulin teaches such ranges as being suitable for administration prior to ingestion of food by patients with cholestatic liver disease.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 7, 9, 18, 19, 21, 24, 25, 27, 29, 30, 37, 47, 54, 67, 68, 69, 75, 81 and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 21-24, 27-31, 48, 52, 58 and 60-63 of U.S. Patent Application No. 17/981,033.
Claims 1, 5, 21-22, 31 and 62-63 of the ‘033 claims recites a method of treating cholestatic liver disease in a subject in need thereof comprising administering to the subject an IBAT inhibitor that is maralixibat or volixibat (or a pharmaceutically acceptable salt thereof) orally at a dose of from about 280 mg/kg/day to about 1400 mg/kg/day, wherein the treatment increases event-free survival of the subject. Claim 58 further limits the IBAT inhibitor to maralixibat chloride. Claim 23 recites that administration of the IBAT inhibitor results in a reduction of cholestatic pruritus. Claim 27 specifies that the cholestatic liver disease is pediatric. Claims 29-30 define the cholestatic liver disease as including PFIC, in particular, PFIC1, PFIC2 or PFIC3.
The amounts of IBAT inhibitor (maralixibat) to be administered in the ‘033 claims clearly overlap those instantly claimed, thus, render the instantly claimed ranges prima facie obvious over the ‘033 claims. MPEP §2144.05.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
/I.S./Examiner, Art Unit 1621
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