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 .
Election/Restriction
Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Claims 1 and 3-20, drawn to a crystalline maleate salt of a compound of Formula I and pharmaceutical composition comprising the crystalline maleate salt.
II. Claim 21, drawn to a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 20.
The inventions are independent or distinct, each from the other because:
Inventions I and II are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case, method of treating a disease or disorder in a subject can be practiced with materially different compounds that are not instant claimed crystalline maleate salt of a compound of Formula I, and instant claimed compound could be used in different type of assay.
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because one or more of the following reasons apply: Groups I and II are drawn to different inventions which require different classification and different searching strategies. The method of treating disease in Group II invention needs different search that are not required for search of product in Group I invention.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
During a telephone conversation with the attorney on the record, Lin Yu, on 06/26/2026, a provisional election was made without traverse to prosecute the invention of Group I, claims 1 and 3-20. Affirmation of this election must be made by applicant in replying to this Office action. Claim 21 is withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claim Status
Claims 1 and 3-21 are pending.
Claim 21 is withdrawn.
Claims 1 and 3-20 are currently under examination in this office action.
Priority
This instant application 18/813,917, filed on 08/23/2024 , is continuation of 18/409,608 ( now abandoned) filed on 01/10/2024, which is a continuation of 17/516,420 (now abandoned) filed on 11/01/2021, which claims priority benefit of U.S. provisional application Nos. 63/108,803 filed 11/02/2020, and 63/190,107 filed on 05/18/2021.
It’s noted instant Example 10 and 11 are NOT disclosed in US provisional application No. 63/108,803.
Information Disclosure Statement
The information disclosure statements dated 01/18/2025 and 01/19/2025 are in compliance with the provisions of 37 CFR1.97. Accordingly, the reference listed in IDS are being considered by the Examiner.
Claim Objections
Claims 1 and 3-7 are objected to because of the following informalities:
Claims 1 and 3- 7 recite XRPD peaks followed by multiple “± 0.2º 2θ”, which is not concise.
Duplicative claims
Claims 1 and 3-8 are objected as being significantly duplicative claims. Claims 1 and 3-8 are not identical, but they are not patentably distinct from each other. Claims 1 and 3-8 recites crystalline maleate salt of compound of formula I characterized by different peaks of the same X-ray powder diffraction (XRPD) pattern as set forth in FIG. 5.
Claims 9-12 are objected as being significantly duplicative claims. Claims 9-12 recite crystalline maleate salt of compound of formula I characterized by the same DSC as set forth in FIG. 4.
Claims 16-18 are objected as being significantly duplicative claims. Claims 16-18 recite crystalline maleate salt of compound of formula I characterized by the same TGA as set forth in FIG. 6.
It’s noted XRPD peaks, DSC, TGA are characteristic description and/or property of crystalline maleate salt of compound of Formula I, which do not further contribute to the structural limitation of crystalline maleate salt.
Drawings
The drawings are objected to because Figures 1-6 are blurry and illegible.
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 interpretation
According to PubChem database, instant claimed compound, (R)-2-((1-(2-(4-methoxy-3-(2-morpholinoethoxy) phenyl)-5-methylthiazol-4-yl)ethyl)thio)pyrimidine-4,6-diamine (CAS# 2107280-55-5) is also known as DI-87, TRE-515, etc. (retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/122491414).
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Instant claims are drawn to crystalline maleate form of compound of Formula I charactered by X-ray diffraction pattern, melting point, DSC, TGA, etc. Please note X-ray diffraction pattern, melting point, DSC, TGA , etc. are properties of the crystalline form that do not necessarily further contribute to the structure limitation of the crystalline maleate form of compound of Formula I. Once the crystalline form is obtained, XRPD, DSC and TGA could be easily measured by a person skilled in the art through a normal measurement method.
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.
Claims 1 and 3-20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 1 recites a crystalline maleate salt form of a compound of Formula I, wherein the crystalline maleate salt is characterized by an X-ray powder diffraction pattern comprising a peak at 7.6 ± 0.2 º 2θ , 8.7± 0.2 º 2θ, 10.8± 0.2 º 2θ, 12.2 ± 0.2 º 2θ, 13.4 ± 0.2 º 2θ, 16.0 ± 0.2 º 2θ, or 19.5 ± 0.2 º 2θ as measured by X-ray powder diffraction using an X-ray wavelength of 1.5406 A.
Claim 1 is indefinite because it recites XRPD peaks in the alternative, and it’s unclear which peaks are required to characterize instantly claimed crystalline maleate salt form. Thus, the scope of claim 1 cannot be determined with reasonable certainty.
Claims 3, 5 and 6 are indefinite because they also recite XRPD peaks in the alternative, 7.6 ± 0.2 º 2θ , 8.7± 0.2 º 2θ, or 16.0± 0.2º 2θ.
Claims 5 and 6 recite XRPD peaks in the alternative, 7.6 ± 0.2 º 2θ , 8.7± 0.2 º 2θ, or 16.0± 0.2º 2θ and “at least one peak selected from ...” . A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In instant claims, XRPD pattern comprising peaks at 7.6 ± 0.2 º 2θ , 8.7± 0.2 º 2θ, or 16.0± 0.2º 2θ is broad limitation of XRPD peaks, the limitation comprising the alternative peak and “at least one peak selected from ...” is narrower limitation of XRPD peaks. It’ not clear which peaks are required to characterize instantly claimed crystalline maleate salt form.
Claim 7 recites “at least five peaks selected from ...” .It’ not clear which five peaks are required to characterize instantly claimed crystalline maleate salt form.
Claims 9-20 are rejected due to dependency on claim 1.
Claim 8 recites the crystalline maleate salt is characterized by an X-ray powder diffraction pattern substantially as set forth in FIG. 5. Claim 12 recites the crystalline maleate salt is characterized by DSC thermogram substantially as set forth in FIG. 4. Claim 18 recites the crystalline maleate salt is characterized by TGA thermogram substantially as set forth in FIG. 6. It’s not clear what threshold of peaks are considered as substantially as set forth in the figures. As stated in MPEP § 2173.05(s): “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)”.
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 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 1 and 3-20 are rejected under 35 U.S.C. § 103 as unpatentable over Radu et al. (US 2019/0016714, hereafter Radu ‘714, corresponding to US 10,570,124, Applicant’s IDS dated 01/18/2025), in view of LU et al. (US 20120289545, Applicant’s IDS dated 01/18/2025).
Regarding instant compound of Formula I, Radu ‘714 teaches preparation of deoxycytidine kinase binding compounds or a pharmaceutically acceptable salt or solvate thereof, method of modulating deoxycytidine kinase (dCK) and treating disease associated with deoxycytidine kinase (e.g. cancer) (See abstract, [0237], [0245], [0253]; claims 1-47, Embodiments P1 to P43 and Embodiments 1-43, Tables 1 and 2, Examples 2-5). Radu ‘714 explicitly teaches preparation of compound 9R, which is instant compound of Formula I as illustrated in the structure below, and activity thereof (Example 2, [0356], [0359], Examples 6-8, Tables 4-8). Radu‘714 teaches recrystallization of the enantiomers with MeOH/acetone solvent system gave compound 9R with 93% ee.
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Radu’ 714 teaches embodiments in crystalline diastereomeric salt form (See [0192]. Radu’ 714 teaches pharmaceutical composition comprising deoxycytidine kinase binding compounds and a pharmaceutically acceptable carrier (See [0212]-[0232]; claim 35).
Radu’ 714 is silent about the crystalline maleate salt of Compound 9R( i.e. instant compound of Formula I).
Lu teaches variety of crystalline salt forms (e.g. maleate) of an anticancer compound (E)-N-{4-3-chloro-4-(2-pyridinylmethoxy)anilinol-3-cyano-7-ethoxy-6-quinolinyl)-4-(dimethylamino)-2-butenamide, and pharmaceutical compositions comprising the crystalline salt forms (See abstract, [0005]-[0017], Examples 1-2, Table 1- 10; Figures 1-8; claims 1-12, 15-35).
Lu teaches variety of process/conditions for preparing crystalline maleate salt forms characterized by XRPD pattern, DSC, TGA, etc. ( See Examples 1-2, Table 1-10; Figures 1-8).
Regarding claims 1 and 3-8, Lu teaches crystalline maleate form I characterized by XRPD pattern peaks (2θ ±0.2θ), wherein 7.38, 8.75, 10.20, 12.24, 19.99, 21.32 are close to instant claimed peaks (See Figure 1, 5, 6, 7, 8; [0007] and [0009] ).
Regarding claims 9-12, Lu teaches crystalline maleate forms characterized by DSC (See [0006], [0010], [0057], Figure 3, Table 1).
Regarding claims 14-15, Lu teaches crystalline fine needles with particle size raging about 5-50 µm( See Table 4).
Regarding claims 16-19, Lu teaches crystalline maleate form exhibits water loss at about 50°C., as measured by DSC, and is characterized by a water content of about 2.5 to 2.7% by weight, as measured by thermal gravimetric analysis (TGA) (See [0051], [0058], Figure 4).
It is common practice in the pharmaceutical industry to explore different crystalline salt form of compounds for purpose of solubility, stability, and bioavailability etc. as illustrated by Lu.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of instant invention to explore different crystalline salt form for Compound 9R( i.e. instant compound of Formula I) taught by Radu’ 714 based on combined teachings of Lu and general knowledge of crystalline pharmaceutical salt and pharmaceutical composition thereof. At the time of instant invention was made, it was already known that Compound 9R ( i.e. instant compound of Formula I) could be prepared by recrystallization and have good anticancer activity. Lu teaches crystalline maleate salt forms of anticancer amine compound that’s stable with improved water solubility. A skilled artisan would be motivated to explore crystalline salt form of Compound 9R( i.e. instant compound of Formula I) based on combined teachings of Radu’ 714, Lu and optimization based on general knowledge of crystalline pharmaceutical salt, and reasonably expect the crystalline salt form of Compound 9R( i.e. instant compound of Formula I) would provide improved stability and desirable property. Once the crystalline form of compound of Formula I is obtained, it would be easily measured/charactered by XRPD pattern, DSC, etc. through routine experiment as taught by Lu and general knowledge of crystalline salt.
As stated in MPEP 2144.05, " It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions".
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art, together with optimization based on general knowledge of crystalline pharmaceutical salt. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1, and 3-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,446,307. Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claims are directed to a composition comprising a crystalline form II of maleate salt of compound of Formula I charactered by X-ray diffraction pattern, DSC, TGA, etc. that are identical or very similar as instant claims.
Reference claims 1-6 recite X-ray diffraction pattern comprising peaks at 7.6±0.2° , 8.7±0.2°, 16.0±0.2° , 12.2±0.2° , 17.6±0.2° , 19.5±0.2° , 21.7±0.2°, 10.8±0.2°, and 13.4±0.2° as set forth in FIG. 5 (which read on instant claims 1 and 3-8).
Reference claims 7-10 recite DSC thermogram as in Fig. 4 (which read on instant claims 9-12).
Reference claims 11 recite melting point in the range of about 150 to about 155° C (which read on instant claim13).
Reference claims 12-13 recite needle-like particles ranging in size from about 1 μm to about 100 μm (which read on instant claims 14-15).
Reference claims 14-17 recite DSC thermogram as in Fig. 6 (which read on instant claims 16-19). Reference claim 18 recites pharmaceutical composition comprising crystalline form and a pharmaceutically acceptable excipient (which reads on instant claim 20).
A skilled artisan would have known a crystalline maleate salt form of compound of Formula I with instant characterization was already taught by reference claims. Based on the continuity data on the record, instant applications and reference patent are continuation of US application 17/526,420, and no 35 USC 121 shield exists.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on (571)272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.M./Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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