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
This application filed on 11/08/2023, is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/CN2022/092059, filed on 05/10/2022, which claims priority to Chinese Application No. 202110518999.9, filed 05/12/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 11/08/2023 and 12/23/2024, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Status of claims
The premilitary amendment filed on 11/08/2023, that amended claims 4, 6, 13, 15, 20, 22, 24, and 28-29, cancelled claims 5, 7-9, 14, 16-18, 21, 23, and 25-27, and added claims 30-33, is acknowledged.
Claims 1-4, 6, 10-13, 15, 19-20, 22, 24, and 28-33 are pending.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim interpretation of crystal form A, crystal for B and crystal form C:
Claim 1 recites “A crystal form A of a compound of formula (I), wherein the X-ray powder diffraction pattern of the crystal form A comprises characteristic diffraction peaks at the 2[Symbol font/0x71] angles of 16.16±0.20°, 16.60±0.20°, 22.02±0.20, and 23.08±0.20°. claims 2-4, and 6 further recite spectroscopic characterization. Instant specification defines the crystal form A as:
“In some embodiments of this application, the XRPD profile of the crystal form A is shown in Fig.1. [page 3]. Fig. 1 is the XRPD spectrogram of the Cu-Ka radiation of formula (I) compound crystal form A. [page 11].
The art teaches that compounds can exists in multiple crystalline forms, and the gold standard to distinguish these forms is through XRPD. The XRPD consider to be the fingerprint in determining and identifying the particular crystalline form. In view of the instant specification, the claimed crystalline form A is defined by XRPD peaks as shown in Figure 1, and in view of the art, crystalline form 1 is defined by Figure 1 and will be interpreted as the crystal form of Figure 1.
Similarly, crystal form B is defining by XRPD peaks as showing in Figure 4, and will be interpreted as the crystal form of Figure 4, and crystal form C is defining by XRPD peaks as showing in Figure 7, and will be interpreted as the crystal form of Figure 7 in view of the instant specification. [pages 4, 6, 11].
The claims are given their broadest reasonable interpretation in light of the specification. MPEP 2111. In particular, the reference to “Crystalline Form A, B or C” in the instant specification and in the claims is always associated with the language “comprising” regarding spectroscopic information i.e., XRPD peaks. Consistent with MPEP 2111.03, the claims are construed as being open-ended to allowing additional elements (“comprising” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps). In this case, the claims are construed as allowing other spectroscopic information as well as other solid forms “characterized” by additional information.
However, in view of the above interpretation, crystalline form A is not defined by the “open-ended” claims 1-4, and 6 and the recited XRPD peaks, instead, the crystalline form A is defined by Figure 1. Similarly, crystalline form B is not defined by the “open-ended” claim 10-13, and 15, and the recited XRPD peaks, instead, the crystalline form B is defined by Figure 4. And, crystalline form C is not defined by the “open-ended” claims 19-20, 22, and 24 and the recited XRPD peaks, instead, the crystalline form C is defined by Figure 7.
Specification
The disclosure is objected to for the following informalities:
The specification recites “in some embodiments of this application, the XRPD profile of the crystal form A is shown in Fig.4.” [page 5. 3rd para.]. However, Fig. 4 appears to show the XRPD of crystalline form B, as recited in the Description of Drawings, page 10 of instant specification. This objection can be overcome by amending the specification to recite that the XRPD profile of the crystal form B is shown in Fig. 4.
Appropriate correction is required.
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.
§ 103 Rejection over Zhang in view of Barth and Morissette
Claims 1-4, 6, 10-13, 15, 19-20, 22, 24, and 28-33 are rejected under 35 U.S.C. 103 as being obvious over Y. Zhang et al. (US PG PUB 2023/0357248A1, 11/09/2023, “Zhang” cited in the PTO-892) in view of W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892).
Prior Art Effect of Zhang
The earliest possible effective filing date of the subject claims is that of priority document Chinese Application No. 202110518999.9, filed 05/12/2021. Zhang is effective prior art under 35 USC § 102(a)(2) respecting the subject matter cited in this rejection as of the filing date of Zhang priority document CN202010096582.3 filed on 02/17/2020 because: (1) Zhang is U.S. patent application publication; (2) names another inventor; and (3) the subject matter of Zhang relied upon in this rejection is disclosed in Zhang’s priority document CN202010096582.3 (02/17/2020). See MPEP § 2154.01; 35 USC § 102(d). Thus, the effective filing date of the subject matter relied upon in this rejection is 02/17/2020, which is before the claims’ earlies possible effective filing date of 05/12/2021. See MPEP § 2154.01; 35 USC § 102(d).
Joint Inventorship
This application currently names joint inventors and assignee. 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.
Zhang teaches BTK inhibitors of formula (III) or a pharmaceutically acceptable salt thereof, [page 1, [0011]]. Zhang teaches compound 4 below as one of formula (III) species, [[0072], page 5, left col. 3rd comp., [page 12, [0148], Example 4]:
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Zhang teaches a method of treating a disease related to BTK protein kinase in a subject in need thereof, comprising administering to the subject the compound of formula (III) or pharmaceutically acceptable salt thereof. [page 1, [0006], claim 10].
Zhang teaches that the absolute configuration of the compound of formula III can be confirmed by conventional techniques in the art, such as single crystal X-Ray diffraction (SXRD). In the single crystal X-Ray diffraction (SXRD), the diffraction intensity data of the cultivated single crystal is collected using a Bruker D8 venture diffractometer with a light source of CuKa radiation in a scanning mode of q/o scan; after collecting the relevant data, the crystal structure is further analyzed by the direct method (Shelxs97) to confirm the absolute configuration. [page 8, [0101]]. Zhang teaches that compound 4 form crystalline forms [page 13, [0156]-[0163]].
However, Zhang does not specifically teach the crystalline forms A, B, or C of Zhang’s compound 4 or the spectroscopic characterization.
In the same art area, namely pharmaceutical preparations and their use in treating disease, Barth teaches the following:
“[c]rystalline forms of compounds are ordinarily preferable to the non-crystalline forms thereof. The crystalline materials have superior stability, appearance and handling characteristics when compared to their amorphous counterparts. For pharmaceutical use crystalline compounds are especially advantageous in manufacturing procedures and in formation and use of acceptable dosage forms such as solutions, suspensions, elixirs, tablets, capsules and various pharmaceutically elegant preparations required by the medical and pharmaceutical professions.” [Pg. 2, col. 1, ln. 60- col. 2, ln. 2].
Morissette teaches an automated high-throughput crystallization to form polymorphs, salts, co-crystals and solvate forms of pharmaceuticals [Title, abstract]. The prior art describes the successful application of the automated high-throughput technique to several known pharmaceuticals and details how thousands of crystallization conditions can be performed in parallel, computer analyzed and then used to produce the polymorphic forms of a given pharmaceutical [Page 296, para. 2].
At the time of invention, one of ordinary skill in the art would have been motivated to specifically pick compound 4 from Zhang’s BTK inhibitors of formula III for preparing crystalline forms. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Zhang teaches that the BTK inhibitors of formula (III) directed to the treatment of a disease related to BTK protein kinase [[0006], claim 10], and out of the BTK inhibitors of Zhang, compound 4 is the only compound that has strong inhibitory effect on a BTK with an IC50 of 7.3 nM [page 27, Table 6]; has good inhibitory effect on TMD8 cells [page 28, Table 7]; has superior solubility [page 28, Table 8]; has good plasma protein binding [page 28, Table 9], and has superior in vivo plasma protein binding and plasma concentration, [page 29, Tables 11-14]. One of ordinary skill in the art would have been motivated to prepare crystalline forms of the Zhang potent BTK inhibitor, compound 4 because Barth teaches that crystalline forms are preferred over non-crystalline forms; have superior stability; are preferred in formulation of dosage forms; and are advantageous in manufacturing procedures. [page 2, col. 1, ln. 60- col. 2, ln. 2].
One of ordinary skill in the art practicing the Zhang’s pharmaceutical compound 4 would form a crystalline form in accordance with the specific teaching of Zhang. Utilizing the routine “High-throughput salt selection” taught by Morissette [page 285-287] one of ordinary skill in the art would arrive at the claimed invention. Specifically, because Zhang teaches that compound 4 form crystals collected by Bruker D8 and the absolute configuration of the crystals is confirmed by SXRD. [[0101], [0156]-[0163]]. Thus, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed invention.
In the instant case one of ordinary skill in the art would have a reasonable expectation of success in following the teaching of Zhang and utilizing the well-known and routine automated high-throughput screening described by Morissette arrive at the claimed invention because such acts are conventional and routine in the art. One of ordinary skill in the art would be expected to apply methods within their technical grasp (such as automated high-throughput screening) to improve that which is already known in the art. The Supreme Court stated in KSR “if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person's skill.” KSR Intern. Co. v. Teleflex Inc., 127 S.Ct. 1727, 1731 (2007). Here, the use of an automated system to screen a pharmaceutical salt for crystallization is well known and specifically taught by Morissette. Therefore, the method is within the technical grasp of those of ordinary skill in the art and it would be obvious to one of ordinary skill in the art to use the same method and apply it to the Zhang’s compound.
Regarding the spectroscopic characterization of the obvious product, such properties are inherent in the product (MPEP 2112.02: "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.). In this case, one of ordinary skill in the art would have reasonably considered producing the crystalline salt form which would inherently show the same spectroscopic parameters as are in the claim. "[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. 102, or ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same." In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977).
Thus, claims 1-4, 6, 10-13, 15, 19-20, 22, and 24 are rejected as prima facie obvious.
With regard to claims 28-33, Zhang teaches a method of treating a disease related to BTK protein kinase in a subject in need thereof, comprising administering to the subject the compound of formula (III) or pharmaceutically acceptable salt thereof i.e., compound 4, wherein the disease related to BTK protein kinase is hematological neoplasm. [page 1, [0006], claims 10, 11].
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.
Non-Statutory Double Patenting over US Patent No. 12378253B2
Claims 1-4, 6, 10-13, 15, 19-20, 22, 24, and 28-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of US Patent No. 12378253B2 in view of W. Barth et al. (US Patent No. 4,432,987A, 02/21/1984, “Barth”, cited in the PTO-892) and S. Morissette, et al. Advanced Drug Delivery Reviews, Volume 56, Issue 3, 2004, Pages 275-300, “Morissette” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims are directed to crystalline forms A, B, and C of compound of formula (I), and methods of treating BTK protein kinase-related diseases by administering the crystalline forms of the compound of formula (I):
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US Patent No. 12378253B2 recites in claim 1 a compound represented by formula (III) or a pharmaceutically acceptable salt, and recites the claimed compound as species of formula (III), [claim 7]:
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US Patent No. 12378253B2 recites in claims 9-11 “A method of treating a lymphoma in a subject in need thereof. Lymphoma is a hematological neoplasm cancer mediated by BTK kinase, as described by US Patent No. 12378253B2 specification.
US Patent No. 12378253B2 does not recite the crystalline forms A, B, or C of US Patent No. 12378253B2 above compound or the spectroscopic characterization.
Barth and Morissette teach as discussed above, pages 6-7.
The obviousness rationale is similar to the obviousness of the 103 Rejection above, pages 8-9.
Conclusion
Claims 1-4, 6, 10-13, 15, 19-20, 22, 24, and 28-33 are rejected. No claim is allowed.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622