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 .
DETAILED ACTION
This office action is in reply to the Response to Election/Restriction filed 19 May 2026 for application 18/293,778 filed 31 January 2024, 371 of PCT/CN2022/109065 filed 29 July 2022, claiming priority from PCTCN2021110048 filed 02 August 2021. Claims 1 and 139 are amended. Claims 2-138, 140-147 and 149 are canceled. Claims 151-152 and 154 are withdrawn. Claims 155-164 are new. Currently, claims 1, 139, 148 and 150-164 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 31 January 2024 and 10 December 2025 was filed after the mailing date of the application on 31 January 2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because Fig. 2-8, Fig. 15-26, and Fig. 28-32 contain blurry images, plots, or texts. 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.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 19 May 2026 is acknowledged.
Applicant’s election without traverse of species of Crystalline Form B of compound I in the reply filed on 19 May 2026 is acknowledged.
As informed by the Applicant, claims 1, 139, 148, 150, 153, and 155-164 read upon the elected species.
Claims 151-152 and 154 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 19 May 2026.
The elected species was searched and found to be free of the prior art.
The closest match is example 52 described by Liu et al. (ERBB/BTK inhibitors, WO 2019/149164 A1, 2019 [same applicant as in the instant application]):
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While the compound itself has been disclosed (e.g. in Example 52 (pg. 182) and claim 9 on page 299, 2nd row, left compound), it is not described in a crystalline form, being obtained after prep-HPLC purification, possibly being a salt form with NH4+.
Claim 1 is directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 151-152 and 154, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 09 March 2026 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or non-statutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
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 non-obviousness.
Claim 154 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (ERBB/BTK inhibitors, WO 2019/149164 A1, 2019) in view of Braga et al. (Dealing with crystal forms (the kingdom of serendip?), Chem. Asian J. 2011, 6, 2214-2223) and Granberg et al. (Crystallization of paracetamol in acetone-water mixtures, J. Crystal Growth 1999, 198, 1999, 1287-1293).
Liu discloses example 52 which reads upon compound I:
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They do not, however, disclose a crystalline form of example 52 as the crude mixture is purified on prep-HPLC using NH3, NH4HCO3 additive in H2O/MeCN eluent followed by lyophilization.
Braga overcomes this deficiency by teaching that many crystal forms, salt forms, and polymorphs may exist with one specific molecule of interest (abstract), teaching desolvation/dehydration to obtain crystals (pg. 2), co-crystals (pg. 2), hydrates and multiple crystal forms (pg. 3), and the unpredictable nature of crystal formation. Braga also emphasizes that crystal forms have a significant impact on fundamental and applied science because the different forms may display a range of different physicochemical properties that can be exploited for different scopes and lead to different applications and utilizations, including drugs, pigments, agrochemicals, food additives, explosives, etc. (pg. 9).
Granberg focuses this specificity by teaching experimental work on obtaining crystals of paracetamol, an intermediate in the manufacture of azo-dyes and photographic materials and possessing antipyretic and analgesic properties (pg. 1288). Crystallization was optimized in a mixture of acetone-water containing 20-25% w/w. of water (abstract).
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider obtaining crystals of compound I with the aim of obtaining a form with better drug-like properties due to the varied physiochemical nature of different crystal forms, salts, and polymorphs, as taught by Braga, using any number of crystallizing conditions including acetone-water as taught by Granberg.
Double Patenting
The non-statutory 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 non-statutory 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, 139, 148, 150-153 and 155-164 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 9-11, 14 and 25 of co-pending Application No. 17/224,121 in view of Gardner et al. (Application of high throughput technologies to drug substance and drug product development, Computers and Chemical Engineering 2004, 28, 943-953). Although the claims are not identical, they are not patently distinct from one another because the claims of ‘121 recite compound I, a pharmaceutical composition containing compound I, a method of inhibiting ErbB or BTK using compound I, and a method also using a second therapeutic agent, that being an anti-tumor agent. A prima facie case of obviousness exists, to the person of ordinary skill in the art, in view of Gardner.
Gardner outlines the importance of high throughput physical-chemical technologies in the pharmaceutical discovery and development process as rapid target identification and libraries of hundreds of thousands of possible drug candidates require the support of an efficient high throughput synthetic process. Part of this process includes the rapid generation, characterization and testing of varying salt forms of small molecules and crystallization in a variety of polymorphs as these various forms of active pharmaceutical ingredients have a very broad range of pharmacokinetic, and therefore, therapeutic properties. Gardner also notes that, despite chemo-informatic programs, there is no means to determine the extent of polymorphism of any one compound and therefore the only developmental choice is to subject the active pharmaceutical ingredient to a wide variety of crystallization conditions. To that point, Gardner elevates their proprietary technology, capable of high throughput selection of forms and formulations of pharmaceutical candidates and products as a means to overcome the previously described limitation.
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The process, CrystalMax, is described as a unit capable of screening 18,000 crystallizations in parallel and can conduct thousands of studies on a single active pharmaceutical ingredient in parallel. Gardner demonstrates this process on the FDA approved drug Ritonavir by conducting 2000 parallel crystallization experiments, obtaining and identifying the two polymorphs published by Abbott in the drug’s developmental history.
Even if the polymorphs described in ‘121 are not identical to the claimed/recited polymorphs, it would have nonetheless been obvious to the person of ordinary skill in the art
at the time of Applicant’s earliest effective filing date to follow the teachings of Gardner and
obtain Applicant’s claimed/recited polymorphs. The person of ordinary skill in the art would
have had a reasonable expectation of successfully obtaining Applicant’s claimed/recited polymorphs by using Gardner’s high throughput technology which permits the person of
ordinary skill in the art to evaluate thousands of crystallization experiments in parallel and identify all polymorphs of a particular active agent. A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art
and one skilled in the art could have combined the elements as claimed by known methods
with no change in their respective functions, and the combination would have yielded nothing
more than predictable results to one of ordinary skill in the art.
This is a provisional non-statutory double patenting rejection.
Claims 151-152 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 1 of co-pending Application No. 18/045,838 in view of Gardner et al. (Application of high throughput technologies to drug substance and drug product development, Computers and Chemical Engineering 2004, 28, 943-953). Although the claims are not identical, they are not patently distinct from one another because the claims of ‘838 recite compound I and a method of inhibiting ErbB or BTK using compound I. A prima facie case of obviousness exists, to the person of ordinary skill in the art, in view of Gardner as outlined above.
Claims 1, 139, 148, 153 and 155-164 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1, 9, 11 and 23-24 of co-pending Application No. 16/910,208 in view of Gardner et al. (Application of high throughput technologies to drug substance and drug product development, Computers and Chemical Engineering 2004, 28, 943-953). Although the claims are not identical, they are not patently distinct from one another because the claims of ‘208 recite compound I, a pharmaceutical composition containing compound I, and a method also using a second therapeutic agent, that being an anti-tumor agent. A prima facie case of obviousness exists, to the person of ordinary skill in the art, in view of Gardner as outlined above.
Allowable Subject Matter
Claims 1, 139, 148, 150-153 and 155-164 contain allowable subject matter that would be allowed once the aforementioned provisional non-statutory double patenting rejections are overcome.
Reason For Allowance
The following is a statement of reasons for the indication of allowable subject matter: The elected species was not found in the prior art in a 100% embodiment. The closest match is example 52 described by over Liu et al. (ERBB/BTK inhibitors, WO 2019/149164 A1, 2019):
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While the compound itself has been disclosed, it is not described in a crystalline form, being obtained after prep-HPLC purification, possibly being a polymorph of salt form with NH4+. The free base form is also known as Sunvozertinib or Keytruda, sold by commercial vendors such as MedChemExpress under the catalog number HY-132842 (Sunvozertinib, MedChemExpress, medchemexpress.com/sunvozertinib.html?utm_source=bing&utm_medium=CPC&utm_campaign=US&utm_term=HY-132842&utm_content=DZD9008) and granted accelerated approval by the FDA for use with certain patients suffering from metastatic non-small cell lung cancer (FDA, fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sunvozertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20).
Summary
Claim 154 is rejected under 35 U.S.C. 103. Claims 1, 139, 148, 150-153 and 155-164 are rejected under non-statutory double patenting.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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