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 .
Claim Status – Response to Restriction/ Election
Claims 261-281 are currently pending. Applicant’s election without traverse of Group IV, claims 277-278 in the reply filed on March 12, 2026 is acknowledged.
Claims 277-278 and 281 are active and subject to examination. Claims 261-276 and 279-280 are withdrawn.
Claim Rejections – 35 USC § 112(b)
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.”
Claim 281 is 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.
One of ordinary skill in the art cannot determine the metes and bounds of claim 281 because it is unclear if the recited impurities are necessary elements of the compound of claim 277. Every one of (a)-(g) requires that the amount of impurity be equal to or less than a specified amount, with no absolute lower bound. For example, (a) purports to require < 0.01% of compound (VI-Cl-A), (b) purports to require about < 0.50% to about < 0.30% or about <0.01% or less of compound VI-Cl-B (g) purports to require about < 0.50% to about < 0.30% of a compound of Formula (IV). It is unclear if a compound of claim 277 having 0% of any of these compounds meets the requirements of the claim. It is also unclear for (g) how < 0.30% is further limiting when < 0.50% is already recited (e.g. 0.2% is less than both 0.5% and 0.3%). Similarly, (b) also contains a broader range or limitation followed by a narrow range or limitation and it is unclear if this narrower range is a limitation because 0.01% is less than 0.3% and 0.5%.
Claim Rejections – 35 USC § 102 – Previously Presented
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.”
The rejection of claim(s) 277-278 and 281 under 35 U.S.C. 102(a)(1) as being anticipated by Mudipalli et al. (US20030199515A1) is maintained.
Claim 281 is newly added but is rejected on the same grounds as previously presented.
Response to Arguments
The Applicant argues that Mudipalli does not disclose a compound of formula III with about 100% chiral purity (Remarks, p. 10). This argument was fully considered but is not persuasive. The compound of formula III of Mudipalli appears to be substantially identical to the compound of formula III of the instant invention, with an enantiomeric purity of about 100%. TMudipalli teaches a method for preparing maralixibat (a compound of formula III) with high enantiomeric purity and the same recrystallization step as in the instant invention. Mudipalli teaches optical resolution of the intermediates in maralixibat synthesis which results in optical purity of greater than 98% (about 100%):
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Mudipalli, Spec., para. [0392-0395].
Optically resolved compound 24 is then used for the synthesis of maralixibat (see examples 9-12) to obtain crude maralixibat which would necessarily have an enantiomeric purity of greater than 98% (about 100%). Mudipalli then teaches recrystallization of maralixibat in MEK/water/DABCO, to obtain highly pure maralixibat as in the instant invention (Example 116). The instant specification teaches a substantially identical process to obtain maralixibat with approximately 100% chiral purity: “Crude maralixibat is dissolved in MEK/water/DABCO, seeded with C-025325 and heated. To the solution, MEK is added to crystallize the product. The suspension is cooled, filtered and dried to form the recrystallized maralixibat in approximately 90% yield and > 99% purity and 100% chiral purity.” (Instant, Spec. para. [0330]). As the maralixibat is the same form as in the instant invention and is obtained under the same crystallization conditions with high purity, it is substantially identical to the claimed invention and can be presumed to have the same properties.
The Applicant argues that new claim 281 specifies that the compound of formula (III) to comprise one of more specific compounds (a) through (g). These arguments were fully considered but are not persuasive. Claim 281 does not require that the compound comprise any of the compounds (a) through (g) because claim 281 states that compound comprises one or more of (a) through (g), but (a) through (g) do not appear to require that the compound comprise one of the listed compounds, but just less than a threshold amount, including 0%. Mudipalli teaches that recrystallized maralixibat has a purity of 100% so is free of any impurities, meeting the claim limitation:
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Mudipalli, Spec., para. [0538], Example 117.
Reiterated Rejection
Claim(s) 277-278 and 281 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mudipalli et al. (US20030199515A1).
Claim 277 is a product-by-process claim directed towards a highly pure compound of Formula III, wherein the compound is prepared by a process comprising the step of converting a crystalline form of a compound of Formula I, or a pharmaceutically acceptable salt, hydrate or solvate thereof, to a crystalline form of a compound of Formula II or a pharmaceutically acceptable salt thereof, and wherein the purity of the compound of Formula III is at least about 98.5% and the chiral purity of the compound of formula III is about 100%.
The compound of formula III has the following structure:
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(claim 274).
Mudipalli teaches crystalline forms of the compound of Formula III, wherein the compound of Formula III has a purity of at least 90%, specifically 99.7%:
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Mudipalli, Specification, p. 47;
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Id., p. 49.
The patentability of a product-by-process claim is determined based on the patentability of the product, which does not depend on its method of production (MPEP § 2113).
As the product of Mudipalli is the same as the product of claim 277, claim 277 is anticipated.
Claim 278 is directed towards a compound of Formula III, wherein the compound is in crystalline Form II.
Mudipalli teaches a compound of Formula III, wherein the compound is in crystalline Form II:
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Mudipalli, Fig. 6.
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Id., Fig. 12.
Forms I and II disclosed by Mudipalli are the same Forms I and II as disclosed in the instant Application:
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Instant Fig. 11;
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Instant Fig. 13;
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Instant Fig. 14;
As shown in Mudipalli Fig. 6 and Instant Fig. 11, Mudipalli Form II and Instant Form II appear to be the same form because they have peaks in the same locations. Form II reference also appears to be the same form as the instant sample because the peak locations are substantially identical, seeming to be an admission by the Applicant of Form II in the prior art.
Mudipalli teaches a method for preparing maralixibat (a compound of formula III) with high enantiomeric purity and the same recrystallization step as in the instant invention. Mudipalli teaches optical resolution of the intermediates in maralixibat synthesis which results in optical purity of greater than 98% (about 100%):
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Mudipalli, Spec., para. [0392-0395].
Optically resolved compound 24 is then used for the synthesis of maralixibat (see examples 9-12) to obtain crude maralixibat which would necessarily have an enantiomeric purity of greater than 98% (about 100%). Mudipalli then teaches recrystallization of maralixibat in MEK/water/DABCO, to obtain highly pure maralixibat as in the instant invention (Example 116). As the maralixibat is the same form as in the instant invention and is obtained under the same crystallization conditions with high purity, it is substantially identical to the claimed invention and can be presumed to have the same properties.
Therefore, claim 278 is anticipated.
Claim 281 is directed towards the highly pure compound of claim 277, comprising one or more of about 0.01% or less of (a) through (f) and about 0.50% or less to about 0.30 or less of (g). Mudipalli teaches that the recrystallized maralixibat shown in Figs. 12 and 14 has a purity of 100% (Lab 2, Lab 3, Plant 2, Plant 4) and therefore has 0.01% or less of (a) through (f).
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Mudipalli, Spec., para. [0538], Example 117.
Therefore, claim 281 is anticipated.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
