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 .
Application Status
The preliminary amendment filed on 7/18/2024 is acknowledged. Claims 1-13 are currently pending and under consideration.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement filed on 7/18/2024 is acknowledged and has been considered except where lined through.
Specification
The disclosure is objected to because of the following informalities: When providing the crystallization methods, the specification teaches various dual solvent systems. However, there are instances when the ratio is not provided and/or the “second” solvent is not provided. For example, Example 8 provides the crystallization of VIII-C, wherein the API was added to DCM:MeOH (0.5 mL). However, it is unclear what the ratio is between DCM and MeOH. Similarly, Example 9 provides the preparation of hydrochloride crystal forms. Specifically, it sets forth that the API was added to tetrahydrofuran (1:1). Thus, the recitation of a ratio (1:1) insinuates that THF is combined with something else at a 1:1 ratio.
Appropriate correction is required.
Claim Objections
Claim 11 is objected to because of the following informalities: Claim 11 recites “afirst” in step (b). It is suggested that applicants add a “space” between “a” and “first”. Appropriate correction is required.
Claim Interpretation
Claim 9 recites a series of crystal forms of a compound of formula I, wherein the claim identifies these crystal forms by name, but does not provide any identifying characteristics for these names. For example, salt crystal forms I-A, I-B and I-C. A review of the specification appears to provide some initial identifying characteristics (see page 4/104, starting at line 22 to page 9/105 line 24). For examination purposes and prior art purposes, the examiner will be interpreting the named compounds to have the characteristics described in the specification. For example, for salt crystal form I-A, the examiner will interpret crystal form I-A to have an X-ray powder diffraction pattern including:
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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 2 and 6 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.
Regarding claims 2 and 6, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 9 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for how to make the numerous crystal forms recited in claim 9, does not reasonably provide enablement for how to make crystal forms referred to as VIII-C, IX-E or IX-F. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
The instant claims are crystal forms of a compound of formula I, wherein the crystalline forms are claimed by name, which in view of the claim interpretation above, are characterized by at least two or more X-ray diffraction patters as outlined within the specification (see page 4/104, starting at line 22 to page 9/105 line 24). Thus, the claims are limited to a specific crystal structure characterized by at least two or more X-ray diffraction patters as outlined within the specification.
Level of Skill in Art
The level of skill in the art is a clinician or an artisan with a PhD.
Working Examples
The instant specification provides a examples of the preparation of various “salt” crystal forms and free base crystal forms including vital information such as temperature, amount of API, solvent system used and reaction conditions (See Examples 1-31 of the specification). For example, the specification teaches the preparation of hydrocholoride crystal forms IXA, IXB, IX-C, IX-D, IX-E and IX-F:
At 0° C., approximately 25 mg of API was weighed and added to ethanol (0.5 mL), followed by the addition of 1.2 eq of hydrochloric acid. The mixture was reacted at 50° C. for 3 hours under magnetic stirring, and then cooled down to room temperature. After reacting overnight, the mixture was filtered to obtain the hydrochloride crystal form IX-A;
At 0° C., approximately 25 mg of API was weighed and added to tetrahydrofuran (0.5 mL), followed by the addition of 1.2 eq of hydrochloric acid. The mixture was reacted at 50° C. for 3 hours under magnetic stirring, and then cooled down to room temperature. After reacting overnight, the mixture was filtered to obtain the hydrochloride crystal form IX-B;
At 0° C., approximately 25 mg of API was weighed and added to 0.5 mL of ethyl formate, followed by the addition of 1.2 eq of hydrochloric acid. The mixture was reacted at 50° C. for 3 hours under magnetic stirring, and then cooled down to room temperature. After reacting overnight, the mixture was filtered to obtain the hydrochloride crystal form IX-C;
At 0° C., approximately 25 mg of API was weighed and added to DCM: MeOH (1:1) (0.5 mL), followed by the addition of 1.2 eq of hydrochloric acid. The mixture was reacted at 50° C. for 3 hours under magnetic stirring, and then cooled down to room temperature. After reacting overnight, the mixture was filtered to obtain the hydrochloride crystal form IX-D;
At 0° C., approximately 25 mg of API was weighed and added to tetrahydrofuran (1:1) (0.5 mL), followed by the addition of 2.2 eq of hydrochloric acid. The mixture was reacted at 50° C. for 3 hours under magnetic stirring, and then cooled down to room temperature. After reacting overnight, the mixture was filtered to obtain the hydrochloride crystal form IX-E;
At 0° C., approximately 25 mg of API was weighed and added to tetrahydrofuran (1:1) (0.5 mL), followed by the addition of 4.0 eq of hydrochloric acid. The mixture was reacted at 50° C. for 3 hours under magnetic stirring, and then cooled down to room temperature. After reacting overnight, the mixture was filtered to obtain the hydrochloride crystal form IX-F;
The crystal forms were subjected to various characterizations. From the analysis results, it can be seen that there are chemical shift deviations in the nuclear magnetic spectra, indicating that the free bases have undergone salt formation reaction. The XRPD data are shown in Tables 18-23.
Direction and Guidance
As noted above, the specification provides direction and guidance to make a number of different salt crystal forms and free base crystal forms. However, there are instances where the specification does not include ratios of the mixed solvent system or the second solvent in the mixed solvent system. Note: a solvent followed by a ratio (1:1) insinuates that the solvent system used for crystallization is a mixed solvent system. For example, Example 8 provides the crystallization of VIII-C, wherein the API was added to DCM:MeOH (0.5 mL). However, it is unclear what the ratio is between DCM and MeOH. Similarly, Example 9 provides the preparation of hydrochloride crystal forms. Specifically, it sets forth that the API was added to tetrahydrofuran (1:1). However, it is unclear what the second solvent is.
State of the Prior Art and Predictability of the Prior Art
The state of the prior art at the time was filing recognized the importance of the solvent system in designing solution crystallization processes. For example, Karunanithi and Achenie.(2007).”Solvent design for crystallization of pharmaceutical products”. Gani and Dam-Johansen (Eds), Chemical Product Design: Toward a Perspective through Case Studies (115-147). Elsevier B.V. teaches that one of the key decisions in designing solution crystallization processes is the selection of solvents (page 116, 2nd full paragraph). In particular, Karunanithi and Achenie teach that the design/selection of the optimal solvent for a given crystallization operation is not trivial, wherein solvent selection for crystallization process involves tradeoffs between numerous properties such as solubility, potential recovery of crystals, solvent effect on crystal morphology, solvent inflammability, solvent toxicity etc., which needs to be considered during design and selection (page 117, last paragraph). Regarding the crystal morphology, Karunanithi and Achenie teach that the type of solvent being used for crystallization can affect the morphology of the product crystals (page 119, Section 4.2.3). Wang et al. (Crystals 2017; 7: 357) reported out on how solvents play a role in crystallization by considering the viscosity of the solvent, wherein the viscosity of the solvent was changed by varying the volume ratio of alcohol in water (Abstract). Wang et al. found that diverse morphologies of silver particles are produced by varying the viscosity (page abstract).
Quantity of Experimentation
In view of the unpredictability of the art for solvent selection, and the lack of direction in the specification, the amount of experimentation required to determine which solvent or solvent ratio can be used to generate crystal forms referred to as VIII-C, IX-E or IX-F which have an X-ray diffraction patter having at least 2 or more peaks identified to be associated with said crystals.
Claim Rejections - 35 USC § 102
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)(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.
Claim(s) 9 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Wu et al. (US20230339936, 2023-10-26, English translation for WO2022017434 (PCT/CN2021/107759), filed on 2021-07-22), IDS).
The applied reference has a common inventor 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. 102(a)(2) 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) if the same invention is not being claimed; 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 in the reference 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.
As noted in the specification, the compound referred to as compound of formula 1 was first reported in PCT/CN2021/107759. Specifically, the FORM A was synthesized and separated according to the preparation method of PCT/CN2021/107759 (see specification page 30/105). Accordingly, it appears that Form A is the compound disclosed in the WO document.
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.
Claim 9 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1 and 12 of copending Application No. 17/999,295 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application teaches a compound having the formula
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referred to as compound 315 which is identical to the instantly claimed compound of formula I. While the reference application does not refer to this as Form A, the claimed limitation does not appear to result in a manipulative difference since the specification teaches that FORM A was synthesized and separated according to the preparation method of PCT/CN2021/107759 (see specification page 30/105).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Note: The issue fee has been paid on 5/08/2026, but the application has not yet issued.
Conclusion
Claim 11 is objected to.
Claims 2, 6 and 9 are rejected.
Claims 1, 3-5, 7-8, 10, and 12-13 are free of the prior art and in condition for allowance. Note: the closest prior art has been cited above. The prior art does not teach or suggest Form I or Form B as claimed.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at 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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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
Prosecution Insights