DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Request for Continued Examination (RCE), Amendments and Remarks, filed 1 July 2026, in the matter of Application N° 18/501,402. Said documents have been entered on the record. The Examiner further acknowledges the following:
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 1 July 2026 has been entered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
No claims have been canceled. Claims 128-135 have been added and are supported by the originally filed disclosure (see e.g., Spec., pp. 62-63, bridging paragraph).
Claim 54 has been amended with dosing ranges which that are designed to circumvent the disclosed dosages of the reference at issue. Support for the amended dosing ranges is present (see e.g., Spec., pp. 62-63, bridging paragraph).
No new matter has been added.
Thus, claims 54, 79, 82, 83, 101-104, 107-109, 111, 115, 117, 121, and 124-135 now represent all claims currently under consideration.
Information Disclosure Statement
One new Information Disclosure Statement (IDS) filed 1 July 2026 is acknowledged and has been considered.
Withdrawn Rejections
Rejection under 35 USC 102
Applicants’ amendment to claim 54 is persuasive in overcoming the previously maintained anticipation rejection. Said rejection is withdrawn.
Rejection under Nonstatutory Double Patenting
Applicants’ amendment to claim 54 is persuasive in overcoming the previously maintained double patenting rejection. Said rejection is withdrawn.
New Rejections
Applicants’ amendments and newly submitted IDS have necessitated the following grounds of rejection:
Claim Rejections - 35 USC §103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the Examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicants are advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the Examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 54, 79, 82, 83, 101-104, 107-109, 111, 115, 117, 121, and 124-135 are rejected under 35 U.S.C. 103 as being unpatentable over Gillberg et al. (US Pre-Grant Publication Nº 2022/0143043 A1; of record) in view of Jaecklin et al. (US Pre-Grant Publication Nº 2022/0160726 A1; new IDS reference) and Byröd et al. (US Pre-Grant Publication Nº 2021/0177767 A1).
The instantly claimed invention is directed to a method of treating pruritus associated with Alagille Syndrome (ALGS) in a subject in need thereof, comprising the oral administration of a therapeutically effective amount of a composition comprising odevixibat, or a pharmaceutically acceptable salt thereof, wherein the subject is administered a dosage of 19 µg/kg/day to 21 µg/kg/day, 28.5 µg/kg/day to 31.5 µg/kg/day, 47.5 µg/kg/day to 52.5 µg/kg/day, or 57 µg/kg/day to 105 µg/kg/day; and
wherein the subject exhibits a reduction in pruritus score relative to baseline following administration of the composition for at least eight (8) weeks.
In weighing the instantly recited method, the Examiner broadly and reasonably considers the claimed invention to be drawn to a method of treating pruritus (the presenting symptom) in a patient in need of such treatment comprising the oral administration of odevixibat. That the symptom is caused by or associated with such a condition as ALGS or progressive familial intrahepatic cholestasis (PFIC), for instance, is not considered to contribute to the overall patentability of the claimed method, notably in view of the recited functional limitation that the method exhibits a reduction in pruritis score. Thus, the broadest reasonable interpretation of the claimed method is that it is drawn to treating the symptom instead of the underlying genetic condition.
Gillberg discloses a method for treating pruritus associated with progressive familial intrahepatic cholestasis (PFIC) in a subject in need thereof, the method comprising orally administering to the subject a therapeutically effective amount of a pharmaceutical formulation comprising odevixibat, or a pharmaceutically acceptable salt thereof, wherein following administration of the pharmaceutical formulation, the subject exhibits a reduction in mean monthly pruritus score (see e.g., claims 1, 70, and 71).
Claim 75 further discloses that the mean monthly score occurs following the administration of the formulation for at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, or at least 24 weeks (see also claim 7).
Claim 110 discloses that the subject is a pediatric subject.
Claim 111 discloses administering the subject an amount of 120 µg/kg/day of odevixibat.
Claim 112 discloses administering the subject an amount of 40 µg/kg/day of odevixibat.
Claim 114 discloses that the pharmaceutical formulation of odevixibat, or a pharmaceutically acceptable salt thereof, comprises a plurality of particles, wherein each particle is between about 0.1 and about 1.5 mm in size and comprises odevixibat, or a pharmaceutically acceptable salt thereof, in an amount of from about 0.1% w/w to about 5.0% w/w based on the total weight of the particle.
Claim 115 discloses that each particle comprises odevixibat, or a pharmaceutically acceptable salt thereof, in an amount of from about 0.5% w/w to about 2.0% w/w based on the total weight of the particle.
Claims 132 and 133 respectively disclose that the administered odevixibat is in the form of a hydrate that is the sesquihydrate form.
Claim 134 discloses that the administered odevixibat is present as a crystalline hydrate form of the drug.
Claim 135 discloses that odevixibat is present as crystal modification 1 of odevixibat.
Claim 136 discloses that crystal modification 1 of odevixibat has an X-ray powder diffraction (XRPD) pattern, obtained with CuKα1-radiation, with at least specific peaks at °2θ positions 5.6±0.2, 6.7±0.2 and/or 12.1±0.2.
Claims 1-6 disclose that the odevixibat formulation, whose use is for treating pruritus, is orally administered and, per claim 3, is used to reduce the mean monthly pruritis score. Claims 4-6 disclose that the monthly mean reduction is, for instance, at least 2.0, or is about 1.2 to about 2.0, or is about 1.6.
Figure 5A depicts that patients that were administered odevixibat presented with a baseline pruritus score ranging from about 2.7-3.1, thereby meeting the range limitation of instant claim 111.
Claim 77 discloses a method for treating pruritus associated with progressive familial intrahepatic cholestasis (PFIC) in a subject in need thereof, the method comprising orally administering to the subject a therapeutically effective amount of a pharmaceutical formulation comprising odevixibat, or a pharmaceutically acceptable salt thereof, wherein following administration of the pharmaceutical formulation, the subject exhibits a reduction in mean serum bile acid concentration.
Claim 80 discloses further that the reduction in mean serum bile acid concentration is about 50 μmol/L to about 180 μmol/L relative to baseline.
Claims 34 and 102 disclose that odevixibat is orally administered for use in improving a liver parameter in the subject to whom it is administered (e.g., PFIC patient presenting pruritus).
Claims 35 and 103 disclose that the liver parameter that is improved is selected from the group consisting of autotaxin level, plasma C4 level, total bilirubin level, serum alanine aminotransferase (ALT) level, and serum aspartate transaminase (AST) level.
Claims 36 and 104 disclose that improvement in the liver parameter occurs following administration of the odevixibat formulation for at least 24 weeks, at least 28 weeks, at least 32 weeks, at least 36 weeks, at least 40 weeks, or at least 48 weeks.
Lastly, Figure 17B, ¶[0043], and ¶[0076] disclose that the subjects to whom odevixibat are administer demonstrate a reduction in pruritus score relative to baseline scores for about 36 weeks and longer.
Where Gillberg is deficient, is with respect to the instantly amended dosage ranges and values as set forth in claim 54 and new claims 128-135.
As discussed above, Gillberg discloses two specific doses of odevixibat to treat pruritus: 40 μg/kg/day and 120 μg/kg/day.
Applicants’ filed amendments are directed specifically at the recited doses of odevixibat in order to disclose those doses that are not the specific doses and not reachable by approximation of the instantly claimed doses (e.g., about 50 μg/kg/day).
The teachings of Jaecklin, however, are considered to bridge the gap between the recited doses and ranges and the disclosed dose of Gillberg.
Jaecklin is directed to a method of treating cholestatic liver disease in a subject comprising the administration of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) ranging in dose from about 10 μg/kg/day to about 400 μg/kg/day (see e.g., Abstract; claim 1).
Claims 2, 5, and 13 disclose that the administered ASBTI is odevixibat.
Claims 9 and 46 disclose that the cholestatic liver disease is ALGS. Claims 24, 36, and 37 disclose that pruritis is treated as a result of the administration of the ASBTI. Claim 36 discloses that the ASBTI results in a reduction in severity of pruritus, while claim 37 discloses the reduction in severity is measured as a reduction of at least 1.0 in an observer-reported itch reported outcome (ITCHRO(OBS)) score.
Claim 84 discloses that the administration of the ASBTI results in a reduction in the severity of pruritus.
Claim 85 additionally teaches that an ITCHRO score of the subject is reduced by at least 40% relative to baseline by 14 weeks.
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly administered odevixibat composition in the ranges recited and arrived at the recited method of treatment.
Though Gillberg does not disclose doses that are in the newly amended ranges or in approximation of the newly recited single-dose values, the Examiner advances that Jaecklin places within the purview of the ordinarily skilled artisan the requisite teachings to bridge this gap. Therein, Jaecklin discloses that administering ASBTI compounds such as odevixibat, in doses ranging from about 10 µg/kg/day to about 400 µg/kg/day are not only useful in treating pruritis, but also in reducing in the severity of pruritus within 14 weeks relative to the baseline measurement.
Added motivation for administering odevixibat in the ranges recited is found in other such teachings as Byröd et al. which state that “[o]devixibat exhibits high potency and should be administered in low doses, such as ranging from about 40 to about 120 μg/kg.” [emphasis added] See ¶[0005].
What this additionally conveys to the person of ordinary skill is that within the broader dosing range disclosed by Gillberg for such actives as odevixibat, that a range of about 40-120 µg/kg/day is not only known, but preferred, particularly for pediatric administration.
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, and absent a clear showing of evidence to the contrary.
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 54, 79, 82, 83, 107-109, 111, 124, and 126-135 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-37, 39-47, 49, 50 of copending Application No. 19/334,510 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations of instant claim 54 are presented above.
Reference claims 31, 32, 41, and 42 are considered to teach the recited method of claims 54 and 82. The limitations disclosed by reference claims 33-36 and 43-46, in view of other such teachings as claim 32, are considered to also read on instant claims 54, 82, and 128-135.
The limitations disclosed by reference claims 37, 47, and 49 read on the limitations of instant claims 107-109.
Reference claim 39 discloses the limitations recited by instant claims 54, 124, 126, and 127.
Reference claims 40 and 50 disclose the limitations recited by instant claim 79.
Were the reference application available as prior art, the Examiner submits that a person of ordinary skill in the art would possess clear motivation from it to arrive at the instantly claimed method of treating pruritus, whether associated with ALGS or not, absent a clear showing of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 54, 101-104, and 128-135 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31, 34-37, and 40-45 of copending Application No. 19/540,187 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations of the instantly claimed method are discussed above.
Reference claim 31 and 40-45 disclose the positively recited method steps of administering odevixibat in doses ranging from 40-120 µg/kg/day to treat a patient suffering from pruritus associated with ALGS.
The limitations disclosed by reference claims 34-37 teach the odevixibat limitations recited by instant claims 101-104.
Were the reference application available as prior art, the Examiner submits that a person of ordinary skill in the art would possess clear motivation from it to arrive at the instantly claimed method of treating pruritus, whether associated with ALGS or not, absent a clear showing of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 54, 79, 82, 83, 101, 107-109, 111, 115, 117, 121, and 124-135 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4-7, 12-14, 16, 17, 25, and 26 of Gillberg et al. (USPN 11,583,539 B2; of record) (reference claims) in view of Jaecklin et al. (US Pre-Grant Publication Nº 2022/0160726 A1; IDS reference).
The limitations of the claimed invention are discussed above.
Reference claim 2 discloses:
A method for treating pruritus associated with progressive familial intrahepatic cholestasis (PFIC) in a subject in need thereof, the method comprising orally administering to the subject a therapeutically effective amount of a pharmaceutical formulation comprising odevixibat, or a pharmaceutically acceptable salt thereof, wherein following administration of the pharmaceutical formulation, the subject exhibits a reduction in mean monthly pruritus score, and wherein the pharmaceutical formulation comprising odevixibat, or a pharmaceutically acceptable salt thereof, comprises a plurality of particles, wherein each particle is between about 0.1 and about 1.5 mm in size and comprises odevixibat, or a pharmaceutically acceptable salt thereof, in an amount of from about 0.1% w/w to about 5.0% w/w based on the total weight of the particle.
As further defined by the specification of the reference, PFIC is taught as being embodied by ALGS (see e.g., col. 1, line 65 to col. 2, line 2).
Claims 13 and 14 respectively disclose that the subject is administered 120 µg/kg/day and 40 µg/kg/day of odevixibat. As defined in the reference specification, these doses define the endpoints of the pediatric daily dosing range of about 40-120 µg/kg/day (see col. 19, line 66 to col. 20, line 3).
Added support in the prior art for the recited dosing range is taken from the teachings of Jaecklin, which as discussed above, discloses administering odevixibat to treat and reduce the severity of pruritus using a dosing range of about 10-400 µg/kg/day (see e.g., Abstract; claims).
The foregoing is considered to teach the limitations recited by instant claims 54, 82, and 128-135.
Claim 12 discloses the limitations of instant claim 79.
Claims 16 and 17 disclose the limitations of instant claim 83.
Claims 25 and 26 disclose the limitations of instant claim 101.
Claims 4-6 discloses the limitations of instant claims 107-109 and 111.
Claim 7 discloses the limitations of instant claims 126 and 127.
Were the reference patent available as prior art, the Examiner submits that a person of ordinary skill in the art would have been motivated, in view of the added teachings of Jaecklin, to arrive at the instantly claimed method of treating pruritus.
As noted above, the pediatric doses of 40 and 120 µg/kg/day are established endpoint doses for children weighing 5-20 kg as defined therein. Though the claims of Gillberg to do not appear to include other doses. The teachings of Jaecklin add that doses of odevixibat ranging from about 10-400 µg/kg/day are known to provide the requisite effect of reducing the severity of pruritus.
Thus, in view of the combined guidance, the skilled artisan would have possessed clear motivation to arrive at the instantly claimed method of treating pruritus, whether associated with ALGS or not, absent a clear showing of evidence to the contrary.
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
Prosecution Insights