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
The present Application, filed June 22, 2023, is a national stage entry under 35 U.S.C. § 371 of International Patent Application No. PCT/CN2021/143219, filed December 30, 2021, which claims priority to Chinese Patent Application Nos. CN202110829596 and CN202011642452, filed July 22, 2021 and December 31, 2020, respectively.
Status of the Claims
In the amendment filed June 22, 2023, claims 1, 4, 8-10, 14, 16, and 19 are canceled and new claim 21 is added. Claims 2-3, 5-7, 13, 15, and 20 are amended. Claims non-patent are currently pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 22, 2023 is acknowledged.
Claim Rejections - 35 USC § 103
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.
Claims 2, 5-7, and 20-21 are obvious over Yang, Palcsó, and Gupta :
Claims 2, 5-7, and 20-21 are rejected under 35 U.S.C. § 103 as being unpatentable over U.S Patent No. 9,096,601 to Yang et al. (hereinafter, “Yang”), in view of the non-patent publication, Different types, applications and limits of enabling excipients of pharmaceutical dosage forms, Drug Discovery Today: Technol., 27, pgs. 21-39 (2018) by Palcsó et al, (hereinafter, “Palcsó”), and further in view of the non-patent publication, Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations, Molecules, 23, art. 1719, pgs. 1-15 (2018) by Gupta et al. (hereinafter, “Gupta”).
Claim 2 recites a pharmaceutical composition, comprising a compound represented by Formula B as an active ingredient, and an excipient,
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wherein the active ingredient has a weight percentage of 1% to 90%; and the remainder being the excipient.
Yang teaches arylamino purine derivatives of formula (I)
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(col. 2, lines 43-63) that are multi-kinase inhibitors (col. 44, lines 28-32). In particular, Yang teaches compound 8-29 (Example 90)
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which has substantial multi-kinase inhibitory activity and cancer cell growth inhibitory activity (Table 3-5). Compound 8-29 is also one of only two compounds evaluated for in vivo anti-tumor effect (Assay 4, col. 127, line 53 through col. 128, line 35). The results showed that compound 8-29 had a substantial in-vivo growth inhibition of FLT3-ITD mutated human acute myelogenous leukemia cell strain MV4-11 in transplanted mice.
Yang also discloses a pharmaceutical composition containing a arylamino purine derivative compound, which can be present as a pharmaceutically acceptable salt (col. 44, lines 23-27). While Yang does not expressly refer to an “excipient,” however one of skill in the art would understand that a “pharmaceutical composition,” as taught by Yang, by definition would include one or more excipients. See, for example, Palcsó, which states that therapeutic compounds are never used alone, but are always used as part of a pharmaceutical formulation. The active ingredient of the pharmaceutical composition is generally present in a negligible amount relative to other substances that are most commonly used as excipients (Introduction, first two sentences). One would therefore have understood that, by definition, the “pharmaceutical composition” of Yang includes the API (e.g. compound 8-29) and one or more excipients.
Yang does not explicitly disclose the specific hydrate-salt of instant claim 2. However, the hydrated chloride salt of compound 8-29 would have been an obvious variant because formation of such hydrated salts was well-known in the art for the purpose of improving properties such as solubility of pharmaceutical free base compounds like compound 8-29. See, for example, Gupta.
Gupta teaches a review of the formation of salts and alternative solid forms of pharmaceutical compounds, particularly to modify pharmacodynamics, and the like (Abstract). Gupta teaches that salt formation is widely used to increase solubility and dissolution rate of a drug, and that hydrochloride is among the most common counterions used for basic (alkaline) chemical entities (pgs. 5-6, 2.8 Solubility and Dissolution Rate). Gupta further teaches that hydrate forms of APIs are quite common, noting that about one-third of APIs are thought to form hydrates if exposed to conditions conducive to hydrate formation, such as by having the API come into contact with water during crystallization (pg. 4, 2.5 Water of Hydration). Gupta further notes that water molecules in pharmaceutical hydrates influence properties such as solubility and stability (pg. 4, 2.5 Water of Hydration). It would have been obvious to try to form a salt of compound 8-29 of Yang in order to improve properties such as solubility/bioavailability, and one would have had a reasonable expectation of success forming such a salt with the hydrochloride counterion, as one of the most common counterions to be used with basic APIs like compound 8-29. Furthermore, one would have reasonably expected water of hydration in the salt crystal when performing the crystallization in the presence of water.
Claim 2 is therefore obvious over Yang, Palcsó, and Gupta. With respect to claim 5, Palcsó teaches a variety of actual pharmaceutical formulations/compositions with their excipients, and teaches sorbitol as one that is used, for example with the API, Ritonavir (Table 1). As shown in claim 7, sorbitol is a filler of the instant claims. With respect to claims 6 and 7, only the filler is required, other excipients being optional, and so claims 6 and 7 are obvious for the same reason as is claim 5.
With respect to claims 20 and 21, Yang teaches a method of treating tumors, selected from the group consisting of human non-small cell lung carcinoma and others, the method comprising administering an effect amount of a disclosed multi-kinase inhibitor (Yang claim 8). It would have been obvious to perform this method by administering the composition of Yang, Palcsó, and Gupta.
Claims 11, 13, 15, and 17-18 are obvious over Yang, Palcsó, Gupta, and Codallos Jr.:
Claims 11, 13, 15, and 17-18 are rejected under 35 U.S.C. § 103 as being unpatentable over Yang, in view of Palcsó and Gupta, further in view of U.S. Patent No. 10,398,693 to Codallos Jr., et al. (hereinafter, “Codallos Jr.”).
Claim 11 recites the pharmaceutical composition of claim 6 wherein the filler is one of pregelatinized starch and a number of other individual or combination fillers. None of Yang, Palcsó, or Gupta explicitly teaches this limitation, but the use of such fillers would have been obvious, because these fillers were well-known, conventional fillers in the art. See, for example, Codallos Jr.
Codallos Jr. teaches pharmaceutical compositions of pharmaceutical compositions of N-[5-(3,5-difluorobenzyl)-1H-indazol3-yl)-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide (Abstract), a known multi-kinase inhibitor (col. 1, lines 24-40). Codallos Jr. teaches the composition can include a pharmaceutically acceptable excipient carrier or diluent (col 49, lines 6-10), which can be a filler (col. 56, lines 42-45), and can be gelatinized starch (col. 56, lines 53-54). It would have been obvious to use the gelatinized starch of Codallos Jr. as an excipient (filler) in the composition of Yang, Palcsó, and Gupta.
With respect to claims 13, 15, and 18, Codallos Jr. teaches multiple working examples (col. 116-123), such as Example 8, in which the active ingredient constitutes ~45 by weight of the composition, fillers constitute ~44%, and additional excipients constitute <10% of the total mass. With respect to claim 17, Codallos Jr. teaches that the pharmaceutical composition is a oral solid formulation that is a capsule (e.g. Example 8).
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 2, 5-7, 11, 13, 15, 17-18, and 20-21 are rejected for nonstatutory double patenting over Yang, Palcsó, Gupta, and Codallos Jr.:
Claims 2, 5-7, 11, 13, 15, 17-18, and 20-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-9 of U.S. Patent No. U.S Patent No. 9,096,601 (Yang), in view of Palcsó, Gupta, and Codallos Jr. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 8 of Yang is directed to a pharmaceutical composition comprising a genus of arylamino purine derivatives that includes the compound of instant claim 2. The compositions of the instant claims are obvious variants of this composition of claim 8 of Yang for the reasons addressed above in the rejections for obviousness under 35 U.S.C. § 103. Claim 9 of Yang recites a method of treating tumors such as non-small cell lung carcinoma, comprising administering a compound from a genus that includes the compound of instant claim 2, and the methods of instant claims 20-21 are obvious variants of this method of Yang, as described above. The compositions of the instant dependent claims are further obvious variants of the composition of claim 8 of Yang, in view of the secondary references, as described above.
Allowable Subject Matter
Claim 3 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629