Prosecution Insights
Last updated: April 19, 2026
Application No. 18/322,542

USE OF A COMBINATION COMPRISING A BTK INHIBITOR FOR TREATING CANCERS

Non-Final OA §103§DP
Filed
May 23, 2023
Examiner
STOICA, ELLY GERALD
Art Unit
1647
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
BEIGENE, LTD.
OA Round
1 (Non-Final)
67%
Grant Probability
Favorable
1-2
OA Rounds
2y 8m
To Grant
89%
With Interview

Examiner Intelligence

Grants 67% — above average
67%
Career Allow Rate
807 granted / 1211 resolved
+6.6% vs TC avg
Strong +23% interview lift
Without
With
+22.7%
Interview Lift
resolved cases with interview
Typical timeline
2y 8m
Avg Prosecution
31 currently pending
Career history
1242
Total Applications
across all art units

Statute-Specific Performance

§101
3.9%
-36.1% vs TC avg
§103
26.7%
-13.3% vs TC avg
§102
19.9%
-20.1% vs TC avg
§112
34.1%
-5.9% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1211 resolved cases

Office Action

§103 §DP
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 . Status of the claims Claims 79-96 are pending and are examined. Priority This application claims the benefit of priority of the International Application No. PCT/CN2016/096082, filed August 19, 2016. 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. Claims 79-82 and 85-96 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2014173289- cited by Applicant). The claims are drawn to a method for delay of progression or treatment of a B cell cancer in a subject, comprising administering to the subject in need thereof (S)-7-(1-acryloylpiperidin-4-yl)-2-( 4-phenoxyphenyl)-4,5,6, 7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide (zanubrutinib), or a pharmaceutically acceptable salt thereof, at a dose of 320 mg QD or 160 mg BID in 28-day cycles, in combination with rituximab. The B-cell cancer may be chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), non-CLL/SLL lymphoma, follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Waldenstr6m macroglobulinemia (WM), Hairy cell leukemia (HCL), Burkitt's-like leukemia (BL), B cell prolymphocytic leukemia (B-PLL), diffuse large B cell lymphoma (DLBCL), primary central nervous system lymphoma (PCNSL ), secondary central nervous system lymphoma (SCNSL) of breast or testicular origin, multiple myeloma, or marginal zone lymphoma (MZL). The B-cell cancer may also be a relapsed or refractory B-cell cancer (diffuse large B-cell lymphoma (DLBCL ), activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL), germinal center B-cell diffuse large B-cell lymphoma (GCB-DLBCL) or non-germinal center B-cell diffuse large B-cell lymphoma (non-GCB DLCBCL). Zanubrutinib may be administered orally while rituximab is to be administered intravenously. The Guo et al. teaches fused heterocyclic compounds as Bruton’s tyrosine kinase inhibitors and salts thereof, compositions thereof, and methods for treating disorders mediated thereby (abstract). The diseases treated comprise cancer, and in particular chronic lymphocytic lymphoma, non-Hodgkin's lymphoma, diffuse large B cell lymphoma, mantle cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia (claims 14 and 15), relapsed or refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) ([003]). One of the compounds is (S)-7-(1- acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6, 7-tetrahydropyrazolo[1,5-a]pyrimidine- 3-carboxamide, compound No. 103 (zanubrutinib [008]). The treatment may comprise administering the compound in combination with rituximab ([0120]). The dosage for the BTK inhibitor is between 0.1-2000 mg/day (in particular doses between 10-500 mg/day) ([0133]). The route of administration may be orally or intravenous (inter alia) ([0123]). The reference also acknowledges that that various modifications or changes will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims ([0141]). The reference is silent about the exact dosage and regimen of administration. Nevertheless, it would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have modified the teachings of Guo et al. with the general knowledge of a skilled artisan and arrive to the instant’s Application claims. This is because reference suggests routine variations known in the art. See In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980) "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Claims 83 and 84 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2014173289- cited by Applicant) in view of Autorino et al. (A complete response with Rituximab in metastatic diffuse large B-cell lymphoma of the testis: case report. Int. J. Immunopathol. & Pharmacol., 20, 401-403, 2007). The claims add the limitation that the B-cell cancer is a metastasized diffused large B-cell lymphoma. The teachings of Guo et al. were presented supra and they were silent about metastatic disease. Autorino et al. reflects a known fact in metastasized diffused large B-cell lymphoma, namely that the disease may be treated with rituximab every 3 weeks. After 3 months a complete response was observed in all sites of disease (abstract). It would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to treat metastatic DLBCL by combining the teaching of Guo et al. with the teaching of Autorino et al. with a reasonable expectation of success. This is because Guo et al. disclosed the use of Zanubrutinib and Rituximab for treating DLBCL. The fact that Autorino et al. disclosed the effect of Rituximab for metastatic DLBCL would have lead a skilled artisan to expect that the treatment of Guo et al. would be successful. 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 79-82 and 85-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,701,357 in view of Guo et al. (cited by Applicant). The instant claims differ from the claims of the Patent in the fact that the anti-CD20 antibody is Obinutuzumab which is an anti-CD20 antibody. Guo et al. teaches treating chronic lymphocytic lymphoma, non-Hodgkin's lymphoma, diffuse large B cell lymphoma, mantle cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia (claims 14 and 15), relapsed or refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) with (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6, 7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide, compound No. 103 (zanubrutinib).The treatment may comprise administering the compound in combination with rituximab (another CD20 antibody). It would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have tried to replace the Obinutuzumab with a functionally analog antibody (Rituximab) and treat B cell lymphomas with a reasonable expectation of success, since the both antibodies would bind and inhibit CD20. A person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. ELLY-GERALD STOICA Primary Examiner Art Unit 1647 /Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
Read full office action

Prosecution Timeline

May 23, 2023
Application Filed
May 23, 2023
Response after Non-Final Action
Jan 16, 2026
Non-Final Rejection — §103, §DP (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
67%
Grant Probability
89%
With Interview (+22.7%)
2y 8m
Median Time to Grant
Low
PTA Risk
Based on 1211 resolved cases by this examiner. Grant probability derived from career allow rate.

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