DETAILED ACTION
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
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Application Status
The claim set filed on 1/26/2023 is acknowledged. Claims 1-20 are currently pending and under consideration.
Information Disclosure Statement
The information disclosure statements filed on 7/6/2023 and 2/23/2024 have been considered except where lined through.
Specification
The specification is objected to because it contains an embedded hyperlink and/or other form of browser executable code (see for example, page 4). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser executable code. See MPEP 608.01.
Claim Interpretation
The claim language of a number of independent claims is confusing. For example, Claim 8 recites “A pharmaceutically acceptable salt of the crystal form of the compound of formula (I) according to claim 1 and a crystal form of the pharmaceutically acceptable salt.” As such, the claim appears to imply two (2) components. One (1) is a pharmaceutically acceptable salt of the crystal form of the compound of formula (I) according to claim 1 AND the second (2) is a crystal from of the salt itself. The first pharmaceutically acceptable salt appears to imply that this is a salt of the crystal form recited in claim. However, in view of the specification, it appears that the compound of formula (I) as prepared from preparation 12 is used and NOT the crystal form of claim 1 to make the pharmaceutically acceptable salt of a compound of formula (I). (beginning on page 30, example 5 of the specification). In view of this, it is the examiners interpretation that what Applicants are attempting to claim is a crystal form of a pharmaceutically acceptable salt of a compound of formula (I). Additionally, Claims 17 and 18 are both confusing in that they recite a pharmaceutical formulation/composition comprising what appears to be at least three components: 1) the crystal form of the compound of formula (I) of claim 1, 2) the pharmaceutically acceptable salt of the crystal form of the compound of formula (I), and 3) the crystal from of the pharmaceutically acceptable salt. It is the examiners interpretation that what Applicants are attempting to claim is a pharmaceutical composition/formulation comprising at least a crystal form of the compound of formula (I) of claim 1 OR a crystal form of a pharmaceutically acceptable salt of a compound of formula (I).
Claim Rejections - 35 USC § 112
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.
Claims 8-18 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.
As noted above, the claims are confusing. The claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
Claim 15 recites the limitation "second alcohol solvent" or “second ester solvent”. There is insufficient antecedent basis for this limitation in the claim since the claim does not appear to recite a “first alcohol solvent” or “first ester solvent”.
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.
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.
Claims 8-9 and 14-18 is/are rejected under 35 U.S.C. 103 as being obvious over Liu et al. (US2022/0106299 A1, 2022-04-07) in view of Ohannesian and Streeter (2001, Handbook of Pharmaceutical Analysis, Marcel Dekker, Inc. Chapter 1) and Stahl and Wermuth (2002, Handbook of Pharmaceutical Salts Properties, Selection and Use, Wiley-VCH) and Bastin et al. (Organic Process Research & Development 2000, 4, 427-435).
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Liu et al. teach a compound represented by the general formula (I)
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, a pharmaceutically acceptable salt, an ester or stereoisomer thereof which are ketohexokinase inhibitors, pharmaceutical formulations/compositions comprising said compounds and the manufacture of a medicament for treating and/or preventing KHK-mediated diseases and related conditions (Abstract). Specifically, Liu et al. teach a compound having the formula
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referred to as Compound 1 which showed good inhibitory activity against KHK-C (Table 1 and paragraph 0187 (Table 3)). With regards to the pharmaceutical composition, the PG Pub teaches that the pharmaceutical compositions comprise a compound of general formula I, the pharmaceutically acceptable salt, the ester or stereoisomer thereof, and one or more second therapeutic agents and optionally one ore more pharmaceutically acceptable carriers (paragraph 0127). With regards to the pharmaceutical formulation, the PG Pub teaches that the pharmaceutical formulation comprises compound of general formula I, the pharmaceutically acceptable salt, the ester or stereoisomer thereof, and one or more pharmaceutically acceptable carrier, wherein the formulation is in any dosage form that is clinically or pharmaceutically acceptable (paragraph 0128).
Liu et al. does not specifically teach a pharmaceutical salt of
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, wherein the salt is a potassium salt, sodium salt, magnesium salt or calcium salt. Nor does Liu et al. teach the preparation of the pharmaceutical salts in a polar solvent.
Ohannesian and Streeter teach that salt selection is a critical part of the drug development process because selection of an appropriate salt can significantly reduce time to market (page 12, 1st full paragraph). Moreover, Ohannesian and Streeterteach that the major consideration is the relative acidity and/or basicity of the chemical species involved and provides a number of common anions and cations that can be used including, but not limited to, sodium, potassium, calcium, lithium, magnesium and zinc (page 17, Counterions and Table 4). Furthermore, Ohannesian and Streeterteach that many examples can be found in the literature that demonstrate the applicability of examining a number of salts to obtain the necessary properties needed for development and marketing of the drug substance (page 16, last paragraph). Lastly, Ohannesian and Streeterteach that salt can be produced on a small scale using a variety of methods, wherein there must be adequate solubility of each reactant in the solvent system chosen (page 20, Salt Preparation).
Stahl and Wermuth teach that the choice of salt former (counter-ion) depends on several factors including, but not limited to, crystal formation and largely by the acidity and basicity of the ionizable group and provides common pharmaceutical salt formers such as sodium, potassium, calcium, magnesium and zinc (page 167, 3.1 Choice of the Salt Former (Counter Ion) and Table 1). Moreover, Stahl and Wermuth teach that while the preparation of pharmaceutical salts is usually not a matter of university teaches, the authors provide a collection of preparation methods from the literature (page 250, Introduction). For example, the authors teach that for potassium or sodium salts the preferred preparations make sue of rather anhydrous sodium or potassium carboxylates, which are well soluble in organic solvents such as methanol, ethanol, or ether (page 258 to 261, 3.1 Potassium and Sodium salts)
Bastin et al. teach that the selection of an appropriate salt form for a new chemical entity provides the pharmaceutical chemist and formulation scientist with the opportunity to modify the characteristics of the potential drug substance and to permit the development of dosage forms with good bioavailability, stability, manufacturability and patient compliance (abstract). Moreover, Bastin et al. teach that where possible, a range of salts should be prepared for each new substance and their properties compared during a suitable preformulation program (abstract). The reference further teaches that the choice of salt is governed largely by the acidity or basicity of the ionizable group and provides some of the most frequently used including organic amines, fatty acids and metallics such as sodium, potassium, calcium, magnesium and zinc (page 428, 2nd column, 2nd full paragraph and Table 1).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to prepare a variety of salt form of the compound taught by Liu et al. in view of the teachings above. One of ordinary skill in the art would have been motivated to make such a library, with a reasonable expectation of success, because:
- Bastin et al teach that where possible, a range of salts should be prepared for each new substance and their properties compared during a suitable preformulation program and,
- that the selection of an appropriate salt form for a new chemical entity provides the pharmaceutical chemist and formulation scientist with the opportunity to modify the characteristics of the potential drug substance and to permit the development of dosage forms with good bioavailability, stability, manufacturability and patient compliance.
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 8-9 and 14-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-9 of U.S. Patent No. 12,331,038 B2 to Lui et al. (2025-06-17) in view of in view of Ohannesian and Streeter (2001, Handbook of Pharmaceutical Analysis, Marcel Dekker, Inc. Chapter 1) and Stahl and Wermuth (2002, Handbook of Pharmaceutical Salts Properties, Selection and Use, Wiley-VCH) and Bastin et al. (Organic Process Research & Development 2000, 4, 427-435).
US Patent No 12,331,038 claims a compound represented by the general formula (I)
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, a pharmaceutically acceptable salt, an ester or stereoisomer thereof (claim 1). Specifically, the US Patent claims a compound having the formula
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(Claim 7). With regards to the pharmaceutical composition, the US Patent claims that the pharmaceutical compositions comprise a compound of general formula I, the pharmaceutically acceptable salt, the ester or stereoisomer thereof, and one or more second therapeutic agents and optionally one or more pharmaceutically acceptable carriers (claim 9). With regards to the pharmaceutical formulation, the US Patent claims that the pharmaceutical formulation comprises compound of general formula I, the pharmaceutically acceptable salt, the ester or stereoisomer thereof, and one or more pharmaceutically acceptable carrier, wherein the formulation is in any dosage form that is clinically or pharmaceutically acceptable (Claim 8).
Liu et al. does not specifically teach a pharmaceutical salt of
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, wherein the salt is a potassium salt, sodium salt, magnesium salt or calcium salt. Nor does Liu et al. teach the preparation of the pharmaceutical salts in a polar solvent.
Ohannesian and Streeterteach that salt selection is a critical part of the drug development process because selection of an appropriate salt can significantly reduce time to market (page 12, 1st full paragraph). Moreover, Ohannesian and Streeterteach that the major consideration is the relative acidity and/or basicity of the chemical species involved and provides a number of common anions and cations that can be used including, but not limited to, sodium, potassium, calcium, lithium, magnesium and zinc (page 17, Counterions and Table 4). Furthermore, Ohannesian and Streeterteach that many examples can be found in the literature that demonstrate the applicability of examining a number of salts to obtain the necessary properties needed for development and marketing of the drug substance (page 16, last paragraph). Lastly, Ohannesian and Streeterteach that salt can be produced on a small scale using a variety of methods, wherein there must be adequate solubility of each reactant in the solvent system chosen (page 20, Salt Preparation).
Stahl and Wermuth teach that the choice of salt former (counter-ion) depends on several factors including, but not limited to, crystal formation and largely by the acidity and basicity of the ionizable group and provides common pharmaceutical salt formers such as sodium, potassium, calcium, magnesium and zinc (page 167, 3.1 Choice of the Salt Former (Counter Ion) and Table 1). Moreover, Stahl and Wermuth teach that while the preparation of pharmaceutical salts is usually not a matter of university teaches, the authors provide a collection of preparation methods from the literature (page 250, Introduction). For example, the authors teach that for potassium or sodium salts the preferred preparations make sue of rather anhydrous sodium or potassium carboxylates, which are well soluble in organic solvents such as methanol, ethanol, or ether (page 258 to 261, 3.1 Potassium and Sodium salts)
Bastin et al. teach that the selection of an appropriate salt form for a new chemical entity provides the pharmaceutical chemist and formulation scientist with the opportunity to modify the characteristics of the potential drug substance and to permit the development of dosage forms with good bioavailability, stability, manufacturability and patient compliance (abstract). Moreover, Bastin et al. teach that where possible, a range of salts should be prepared for each new substance and their properties compared during a suitable preformulation program (abstract). The reference further teaches that the choice of salt is governed largely by the acidity or basicity of the ionizable group and provides some of the most frequently used including organic amines, fatty acids and metallics such as sodium, potassium, calcium, magnesium and zinc (page 428, 2nd column, 2nd full paragraph and Table 1).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to prepare a variety of salt form of the compound as claimed by the US Patent in view of the teachings above. One of ordinary skill in the art would have been motivated to make such a library, with a reasonable expectation of success, because:
- Bastin et al teach that where possible, a range of salts should be prepared for each new substance and their properties compared during a suitable preformulation program and,
- that the selection of an appropriate salt form for a new chemical entity provides the pharmaceutical chemist and formulation scientist with the opportunity to modify the characteristics of the potential drug substance and to permit the development of dosage forms with good bioavailability, stability, manufacturability and patient compliance.
Conclusion
Claims 8-18 are rejection. Claims 1-7 and 19-20 are free of the prior art and allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joseph McKane can be reached at 571-272-0699. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626