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 . 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.
Priority
The instant application is a 371 of PCT/CN2022/093339 filed on 05/17/2022 and claims foreign priority to CN202111593324.7 filed on 12/23/2021. The certified copy of the foreign priority application filed on 06/19/2024 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/19/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
The preliminary claim amendments filed on 06/19/2024 is acknowledged. Claims 11 and 14-15 are amended.
Accordingly, claims 1-15 are pending and being examined on the merits herein.
Drawings
The drawings are objected to because the x and y axis numbers and labels in FIGS. 1-4 have poor legibility. The additional text at the bottom of FIG. 1, and the texts within the data of FIG. 2 also have poor legibility.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 1 is objected to because of the following informalities:
The ATV014 formula structure has poor resolution, making it difficult to clearly see the chemical structures.
Appropriate correction is required.
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 11 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.
Claim 11 recites “a good solvent”.
The recited “good” is a term of degree, and as stated in MPEP 2173.05(b), “Acceptability of the claim language depends on whether one of ordinary skill in the art would understand what is claimed, in light of the specification”.
In this case, the disclosed specification does not define and does not provide a standard for determining what is considered a “good” solvent in the claimed process of making.
Claim Rejections - 35 USC § 112(a)
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.
Claims 11-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 11 recites a preparation method of the crystal form of ATV014 according to claim 1 comprising dissolving the ATV014 in a good solvent wherein the ATV014 is any solid form of ATV014, adding an antisolvent after dissolving clearly, precipitating out crystals, filtering, and drying to obtain the crystal form I of ATV014.
Claims 12 recites the preparation method according to claim 11, wherein the good solvent comprises/is selected from dimethylsulfoxide, N-methylpyrrolidinone, N,N-dimethylformamide, tetrahydrofuran, dichloromethane, methanol or a combination thereof; and the antisolvent comprises/is selected from water, methyl t-butyl ether or a combination thereof. further limit the good solvent and the antisolvent to the recited groups.
Claim 13 recites the preparation method according to claim 12, wherein the good solvent is dimethylsulfoxide, N-methylpyrrolidinone or a combination thereof, and the antisolvent is water; or the good solvent is tetrahydrofuran, and the antisolvent is water or methyl t-butyl ether or a combination thereof; or the good solvent is a mixed solvent of dichloromethane and methanol, and the antisolvent is methyl t-butyl ether.
Applicant has demonstrated the preparation of the recited ATV014 crystalline form in Example 2 (pages 13-15) of the instant specification.
Applicant has shown that the recited ATV014 crystalline can be formed by adding a certain amount of a good solvent to ATV014 compound and then slowly adding dropwise a certain amount of anti-solvent (poor solvent) as seen in Table 1 (page 13) and shown below.
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However, as seen in Table 1, not all combinations of a good solvent and an anti-solvent will lead to forming the recited ATV014 crystalline compound. Additionally, Table 1 also shows that not all amounts of the good solvent and the anti-solvent will lead to making the claim crystalline compound. For example, the combination of 0.2 mL dimethyl sulfoxide and 0.2 mL methyl tert-butyl ether resulted in no solids being formed.
Furthermore, CN’619 (CN113185519A in IDS filed 06/19/2024, an English translation is included in PTO-892) discloses that polymorphs typically have different X-ray diffraction patterns, infrared spectra, melting points, densities, hardness, crystal forms, optical and electrical properties, stability and solubility, and that different factors such as recrystallization solvent, crystallization rate and storage temperature may cause a single crystal form to dominate (paragraph n0028 pages 17-18 in English translated copy), which suggests that it would not be routine or predictable to determine which combination of solvents and their respective amounts are required in order to form the claimed ATV014 crystalline with the specified XRD peaks.
Therefore, claims 11-13 contain subject matter which was not described in the specification in such a way to reasonably convey to one skilled in the relevant art that the Applicant had possession of the invention because Applicant has demonstrated that not all amounts of any good solvent and any antisolvent, as currently recited in claim 11, will result in forming the recited crystalline ATV014 compound. Furthermore, claim 12 recites combinations, such as dimethyl sulfoxide as the good solvent and methyl tert-butyl ether as the anti-solvent, that Applicant has demonstrated will not result in forming the recited crystalline ATV014 compound. Lastly, while claim 13 recites combinations of a good solvent and antisolvent that will result in forming the recited crystalline ATV014 compound, claim 13 does not specify the amount of the good solvent and anti-solvent and also recites “or a combination thereof” for the good solvent and antisolvent, and Applicant has not demonstrated or suggested that a combination of any amount of dimethylsulfoxide and N-methylpyrrolidinone for the good solvent as well as a combination of any amount of water and methyl t-butyl ether of the antisolvent will result in the formation of the recited crystalline ATV014 compound.
Allowable Subject Matter
Claims 2-10 and 14-15 are allowable. Claim 1 is objected to but would be allowable if the claim objection described above is overcome.
The following is an examiner’s statement of reasons for allowance:
The instant claims are drawn to a crystal form of ATV014 having the recited X-ray powder diffraction peaks and pharmaceutical compositions thereof, method of making thereof, and method of treating SARS-CoV-2 using the pharmaceutical composition thereof.
Applicant has demonstrated the preparation of the recited ATV014 crystalline form in Example 2 (pages 13-15) of the instant specification. Applicant has shown that the recited ATV014 crystalline can be formed by adding a certain amount of a good solvent to ATV014 compound and then slowly adding dropwise a certain amount of anti-solvent (poor solvent) as seen in Table 1 (page 13).
The following reference is considered to be the closest prior art:
CN113185519A (in IDS filed 06/19/2024, an English translation is included in PTO-892)
CN’519 discloses nucleoside compounds and its applications for treating feline infectious peritonitis.
CN’519 discloses their compounds have several chemical structures (page 4 in original document) such as the structure shown below:
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The above compound in CN’519 is identical to the structure shown in the instant claims.
CN’519 further discloses that their compounds may be obtained in the form of their hydrates or in the form of solvents containing them (e.g., ethanol, DMSO, etc.) for their crystallization (paragraph n0027 page 16 in English translated copy). CN’519 discloses that their compounds can be in crystalline and polymorphic forms (paragraph n0028 page 17 in English translated copy).
CN’519 discloses that polymorphs typically have different X-ray diffraction patterns, infrared spectra, melting points, densities, hardness, crystal forms, optical and electrical properties, stability and solubility, and that different factors such as recrystallization solvent, crystallization rate and storage temperature may cause a single crystal form to dominate (paragraph n0028 pages 17-18 in English translated copy).
Even though CN’519 discloses crystalline forms of the same instant compound, CN’519 does not disclose the recited X-ray powder diffraction pattern (XRD) peaks as well as the processing steps and conditions that will result in forming the claimed crystal compound.
CN’077 (CN108659077A in PTO-892, an English translation is also included) discloses crystal forms, preparation methods, uses, and derivative compositions of nucleoside phosphoramide compounds (Description page 1).
CN’077 discloses their method of preparing the crystal form of the nucleoside compound involves dissolving the solid form of the compound in a good solvent, adding an anti-solvent to the solution, and stirring to precipitate out the crystal form of the compound (paragraphs 0041-0045).
CN’077 discloses that a good solvent includes several types of organic solvents including dimethyl sulfoxide, tetrahydrofuran, and others (paragraph 0046).
CN’077 discloses the anti-solvent include inorganic solvents and organic solvents such as water, n-hexane, n-heptane, and others (paragraph 0047).
CN’077 discloses that the weight-volume ratio (mg/mL) of the compound to a good solvent is (1-80):1, preferably (10-60):1 (paragraph 0048), and that the volume ratio of the antisolvent to the good solvent is 1: (1-20), preferably 1:(1-10) (paragraph 0049).
CN’077 demonstrates in Examples 1-5 (paragraphs 0128-0142) specific preparation steps for forming the crystal compound.
Example 1 involves adding 10 mL of ethyl acetate to 5 g of the compound, heating to 45-50C, adding n-hexane dropwise, and then cooling to 0-5C to form the crystal (paragraph 0129). Example 2 involves adding 60 mL of ethyl acetate and 30 mL of n-hexane to 10 gram of the compound and stirring at around room temperature to form the crystal (paragraph 0131). Example 3 involves adding 5 g of the compound to 25 mL of isopropanol and then heating/cooling to form the crystal (paragraph 0134). Example 4 involves adding 5 g of the compound to 14 mL of ethanol and heating/cooling to form the crystal (paragraph 0137). Example 5 involves adding 5 g of compound to 15 mL of acetonitrile and heating/cooling to form the crystal (paragraph 0140).
It would not have been prima facie obvious before the effective filing date of the claimed invention to have used prior art methods of making a crystalline form of a nucleoside compound such as disclosed in CN’077 to arrive at the recited XRD peaks for the crystalline form of the instant compound.
One of ordinary skill in the art would not have reasonable expectation of success because while CN’077 provides general guidance of the same processing steps and conditions such as using some of the same solvents such as DMSO and THF and anti-solvents such as water for crystallization of a nucleoside-based compound, the crystallization process examples provided in CN’077 do not use of any of the same combination of solvents and anti-solvents as well as the specific amounts of these solvents as shown in the Examples of the instant specification to form the claimed crystal compound, and there is no evidence to suggest that these crystallization methods in CN’077 will necessarily result in formation of the claimed crystal compound. Furthermore, Applicant has demonstrated that not all combinations and amounts of a “good” solvent and anti-solvent will result in the formation of the claimed crystal as shown in Table 1 (page 13). Therefore, it would also not be predictable for an ordinary skilled artisan to pick and choose solvents and anti-solvents and the amounts of these solvents from within the teachings of CN’077 in order to arrive at the claimed crystal compound.
Conclusion
Claims 2-10 and 14-15 are allowable. Claim 1 is objected to but would be allowable if the claim objection described above is overcome. Claims 11-13 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID H CHO whose telephone number is (571)270-0691. The examiner can normally be reached M-F 8AM-5PM.
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/D.H.C./Examiner, Art Unit 1693
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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