DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions. Claims 56-77 filed May 01, 2025 are currently pending.
Priority
Acknowledgement is made of the continuation of Application 17951326, now U.S. Patent 12,145,959. Application 17951326 is a continuation of Application 16696196 filed 11/26/2019, now abandoned. Application 16696196 is a continuation of Application 16031889, now abandoned. Application 16031889 is a continuation of Application 14354553, now abandoned. Application 14354553 is a national stage entry of PCT/US2012/062303 filed 10/26/2012, which claims priority to U.S. Provisional Application 61553094 filed 10/28/2011 and U.S. Provisional Application 61607487 filed 03/06/2012.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/19/2024 and 09/04/2025 are 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 § 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 factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 56-76 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over the combination of Gillberg (US2013/0225511 published 08/29/2013 with priority to U.S. Provisional Application 61410957 filed 11/8/2010), Reagan-Shaw (FASEBJ Vol. 22 pages 659-661 published 2007) and Gedulin (US2011/0294767 published 12/1/2011).
Gillberg teaches ilial bile acid transport inhibitors of Formula (I) (abstract, [0004]). Said ileal bile acid inhibitors are also referred to as the claimed genus of apical-sodium dependent bile acid transport inhibitors ([0038]). Said bile acid transport inhibitors of Formula (I) may be administered in pharmaceutically acceptable salt forms as well as solvated and hydrated forms ([0295]). Primary sclerosing cholangitis is one of 45 disorders to be effectively treated by the administration of an ilial bile acid transport inhibitors of Gillberg ([0301]-[0302], claims 1, 3).
Regarding claims 75-76, oral administration of said bile acid transport inhibitor to human patients is embodied in the methodology of Gillberg, wherein said oral formulation is co-formulated with an enteric polymer targeted for the gastrointestinal tract in order to reduce systemic exposure ([0396], [0405], [0415]). Regarding claim 71, administration with a bile acid binder such as cholestipol is embraced within the methodology of Gillberg ([0332]). Regarding claim 72, combinations comprising said bile acid transport inhibitor with ursodeoxycholic acid to treat the disclosed disorders are also embraced in the methodology of Gillberg ([0375], [0383]). Gillberg teaches that said bile acid inhibiting compound can be a low permeability drug as defined by the FDA ([0408]). Gillberg teaches that said inhibitor is administered in a daily dosage of 0.02-20 mg ([0411]-[0413]).
Reagan-Shaw teaches that the average weight of a human patient is 60 kg, (Table 1) and the range taught in Gillberg above corresponds to a range of 0.33 mg/kg per day to 0.33 mg/kg per day, which overlaps with the amounts in the instant claims 62-66. Applicant is reminded of MPEP 2144.05 wherein 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).
However, neither Gillberg nor Reagan-Shaw explicitly teach administering the disclosed bile acid transport inhibitor in the claims. Nor does Gillberg nor Reagan-Shaw explicitly teach administering said ASTBI inhibitor before the ingestion of food.
Gedulin teaches that the elected species of Formula (II) shown above is a potent bile acid transport inhibitor, effective for reducing intraenterocyte bile acids ([0207],claims 1, 10, 14). Gedulin teaches that said compound is orally administered and systemically absorbed and that doses of 0.001-50 mg per day are therapeutically effective to treat disclosed disorders, which overlaps with the amount of Gillberg and the instant claims ([0090], [0380]) and [0492]).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to administer the disclosed bile acid transport inhibitor of Gedulin in order to treat primary sclerosing cholangitis in a subject in need in view of Gillberg.
MPEP 2143 provides rationale for a conclusion of obviousness including (B): Simple substitution of one known element for another to obtain predictable results;
Appellant is reminded that “[I]t is well settled that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985).” Applicant is also reminded of MPEP 2144.07 wherein the selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)
In the present case, it was known in the art of Gillberg that primary sclerosing cholangitis is one of 45 disclosed disorders effectively treated by the administration of an ilial bile acid transport inhibitor to a subject in need. Considering Gedulin teaches that the elected species of Formula (II) shown above is a potent bile acid transport inhibitor, said artisan would have readily predicted that substitution of the ASTBI inhibitor of Formula (I) in the regimen of Gillberg to an ASTBI inhibitor of Formula (II) in view of Gedulin, said resulting ASTBI therapeutic regimen would have effectively treated primary sclerosing cholangitis in the afflicted patient.
Regarding the limitation wherein the bile acid transport inhibitor regimen of Gillberg, Reagan-Shaw and Gedulin effectively decreases serum bile acid or hepatic bile acid in the patient by at least 20% (claims 58-60, 66), or wherein less than 10% of the bile acid transport inhibitor is systemically absorbed upon oral administration (claim 61) or wherein the regimen reduces the level of serum bile acids (claim 67), reduces pruritis (claim 68), reduces fatigue (claim 69) reduces inflammation in small bile ducts (claim 70), the combination of Gillberg, Reagan-Shaw and Gedulin is silent as to the reduction of these properties. However, Applicant is reminded that properties that accrue from the process step of administering a therapeutically effective amount of the bile acid transporter inhibitor to a patient comprising primary sclerosing cholangitis patient as taught by the combination of Gillberg, Reagan-Shaw and Gedulin are considered characteristic features of the claimed therapeutic regimen.
It is noted that MPEP 2112 discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on". Gillberg teaches that doses of 0.33 mg/kg per day to 0.33 mg/kg per day (0.02-20 mg per day to a human patient) of said bile acid transport inhibiting compounds are therapeutically effective at treating primary sclerosing cholangitis ([0301]-[0302], [0380], [0411]-[0413], [0492], claims 1, 3). This is the same therapeutically effective dosing of the bile acid transport inhibiting compound of Gedulin [0492], as well as same therapeutically effective amount embraced within [0272] of the instant specification and claims. In the instant case, the burden is shifted to Applicant to prove that the therapeutically effective amount of bile acid transport inhibitor administered in regimen of Gillberg, Reagan-Shaw and Gedulin to a patient comprising primary sclerosing cholangitis does not yield the disclosed properties.
In addition, regarding the limitation wherein said regimen is administered before the ingestion of food, such as 30-60 minutes before a meal (claims 73-74), the optimum dosing cycle of the bile acid transport inhibitor to the patient comprising primary sclerosing cholangitis would have been a matter well within the insight of one of ordinary skill in the art. Such a determination would have been made in accordance with a variety of factors, such as the route of administration, pharmacological considerations, such as activity, efficacy, pharmacokinetics and toxicology profiles of the combined regimen, as well as the age, weight, diet and severity of the medical condition of the patient. Thus, the dosing cycle that would have been employed would have varied widely and, in the absence of evidence to the contrary, the current claimed specific administration regimen is not seen to be inconsistent with one that would have been determined by the skilled artisan. Furthermore, absent and evidence demonstrating a patentable difference between the compositions administered and the criticality of the claimed frequency and dosing cycles, the determination of the optimum or workable frequency of administration given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. 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 workable ranges by routine experimentation.”).
Claim 77 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over the combination of Gillberg (US2013/0225511 published 08/29/2013 with priority to U.S. Provisional Application 61410957 filed 11/8/2010), Reagan-Shaw (FASEBJ Vol. 22 pages 659-661 published 2007) and Gedulin (US2011/0294767 published 12/1/2011) as applied to claims 56-76 above, in view of Housset (WO2009/115398 published 09/24/2009).
As disclosed above, the combination of Gillberg, Reagan-Shaw and Gedulin render obvious the administration of the art-recognized apical sodium dependent bile acid transport inhibitor of Formula (II) to treat primary sclerosing in a subject in need, as apical sodium dependent bile acid transport inhibitors were established in the art as being effective at treating primary sclerosing cholangitis in an afflicted subject.
However, the combination of Gillberg, Reagan-Shaw and Gedulin does not specifically teach wherein the bile acid transport inhibitor is administered with a vitamin supplement.
Housset teaches treating the biliary disease primary sclerosing cholangitis comprising administering a therapeutically effective amount of a vitamin D formulation (abstract, page 3 lines 1-15, claims 1-6). Housset teaches that said vitamin D formulation further comprises the art-recognized primary sclerosing cholangitis treating ursodeoxycholic acid (page 1 line 30-page 2 line 10, claims 1-4). As shown in Figures 4-5, compositions comprising Vitamin D and ursodeoxycholic acid increased cathelicidin expression, thereby neutralizing deleterious effects of bacterial products in the patient (page 21-22, Figures 4-5).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to administer the primary sclerosing cholangitis treating bile acid inhibitor of Formula (II) of Gillberg, Reagan-Shaw and Gedulin in combination with vitamin D and ursodeoxycholic acid in view of Housset in order to arrive at the presently claimed methodology.
Motivation to administer the bile acid transport inhibitor Formula (II) of Gillberg, Reagan-Shaw and Gedulin with vitamin D and ursodeoxycholic acid flows logically from the fact that each agent was individually taught in the prior art as being effective at treating primary sclerosing cholangitis, which in turn, raises the reasonable expectation of success, that when combined, a composition comprising a bile acid of Formula (II), vitamin D and ursodeoxycholic acid would be efficacious at treating primary sclerosing cholangitis. The instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose (MPEP 2144.06).
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 56-61, 64-70 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,576,079.
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following. Claims 1-15 are directed to treating a cholestatic liver disease in a subject in need comprising administering the same apical sodium-dependent bile acid transporter inhibitor of the present claims in a dose of 40 mg/day to 200 mg/day. Primary sclerosing cholangitis is one of 6 liver disorders to be treated with the claimed apical sodium-dependent bile acid transporter inhibitor. The methodology of claims 1-15 of U.S. Patent 12,576,079 lies inside the presently claimed methodology of administering any dose of the same apical sodium-dependent bile acid transporter inhibitor to treat primary sclerosing cholangitis in a subject in need, as well as the doses embodied within claims 64-66. The reduction of serum bile acid by at least 30% embodied within claim 1 of U.S. Patent 12,576,079 reads on the reduction of serum bile acid in claims 58-60. Claim 15 of U.S. Patent 12,576,079 further embraces the reduction of pruritis, which reads on the methodology of present claim 68.
Regarding the limitation wherein apical sodium-dependent bile acid transporter inhibitor administered in a dose of 40 mg/day to 200 mg/day as taught in claims 1-15 of U.S. Patent 12,576,079 reduces fatigue (claim 69) reduces inflammation in small bile ducts (claim 70), or wherein less than 10% of the bile acid transport inhibitor is systemically absorbed upon oral administration (claim 61), claims 1-15 of U.S. Patent 12,576,079 are silent as to the reduction of these properties. However, Applicant is reminded that properties that accrue from the process step of administering the same therapeutically effective amount of the same bile acid transporter inhibitor to same patient comprising primary sclerosing cholangitis patient as taught by the combination of claims 1-15 of U.S. Patent 12,576,079 are considered characteristic features of the claimed therapeutic regimen.
It is noted that MPEP 2112 discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on”. In the instant case, the burden is shifted to Applicant to prove that the therapeutically effective amount of bile acid transport inhibitor administered in regimen of U.S. Patent 12,576,079 to a patient comprising primary sclerosing cholangitis does not yield the disclosed properties.
Claims 56-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 23, 27-30, 59 of copending Application 17981033.
Claim 1 of copending Application 17981033 are directed to treating a cholestatic liver disease in a subject comprising orally administering the same claimed apical sodium-dependent bile acid transporter inhibitor as presently claimed for a duration of at least 5 years in a dose of 0.280-1.40 mg/kg/day. Said oral administration and therapeutically effective amount of apical sodium-dependent bile acid transporter inhibitor overlaps with the methodology embodied within present claims 56-62. Treatment of the claimed primary sclerosing cholangitis is embodied within claims 29-30 of copending Application 17981033. Reduction of pruritus by administration of the claimed apical sodium-dependent bile acid transporter inhibitor is embodied within claim 23 of copending Application 17981033, which overlaps with the subject matter of present claim 68.
Regarding the limitation wherein apical sodium-dependent bile acid transporter inhibitor administered in a dose of 0.280-1.40 mg/kg/day as taught in claims 1, 23, 27-30, 59 of copending Application 17981033 reduces serum bile acid (claims 58-60), reduces fatigue (claim 69) reduces inflammation in small bile ducts (claim 70), or wherein less than 10% of the bile acid transport inhibitor is systemically absorbed upon oral administration (claim 61), claims 1, 23, 27-30, 59 of copending Application 17981033 are silent as to the reduction of these properties. However, Applicant is reminded that properties that accrue from the process step of administering the same therapeutically effective amount of the same bile acid transporter inhibitor to same patient comprising primary sclerosing cholangitis patient as taught by claims 1, 23, 27-30, 59 of copending Application 17981033 are considered characteristic features of the claimed therapeutic regimen.
It is noted that MPEP 2112 discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on”. In the instant case, the burden is shifted to Applicant to prove that the therapeutically effective amount of bile acid transport inhibitor administered in regimen of claims 1, 23, 27-30, 59 of copending Application 17981033 to a patient comprising primary sclerosing cholangitis does not yield the disclosed properties.
Conclusion
In view of the rejections set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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