Prosecution Insights
Last updated: April 19, 2026
Application No. 17/993,567

COMBINATION THERAPIES OF HDAC INHIBITORS AND PD-L1 INHIBITORS

Final Rejection §103§DP
Filed
Nov 23, 2022
Examiner
WU, JULIE ZHEN QIN
Art Unit
1643
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Huyabio International LLC
OA Round
2 (Final)
62%
Grant Probability
Moderate
3-4
OA Rounds
3y 4m
To Grant
99%
With Interview

Examiner Intelligence

Grants 62% of resolved cases
62%
Career Allow Rate
211 granted / 343 resolved
+1.5% vs TC avg
Strong +52% interview lift
Without
With
+51.6%
Interview Lift
resolved cases with interview
Typical timeline
3y 4m
Avg Prosecution
27 currently pending
Career history
370
Total Applications
across all art units

Statute-Specific Performance

§101
6.9%
-33.1% vs TC avg
§103
29.4%
-10.6% vs TC avg
§102
22.9%
-17.1% vs TC avg
§112
19.9%
-20.1% vs TC avg
Black line = Tech Center average estimate • Based on career data from 343 resolved cases

Office Action

§103 §DP
The Examiner of your application in the USPTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Supervisory Patent Examiner Julie Wu. 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 . Claims 1, 8, and 14-21 are pending and being examined on the merit. Rejections - 35 USC § 103 All previous rejections of claims 6, 7, and 13 are moot in view of claim cancellation. All previous rejections of claims 1, 8, and 13-15 under 35 USC 112a for lacking written description is withdrawn in view of claim amendments. Previous rejection of claims 1, 8, and 14 under 35 USC 102a2 over Pinheiro et al. (WO2016153839) is withdrawn in view of claim amendments. Previous rejection of claims 1, 8, and 14 under 35 USC 102a2 over Goodenow et al. (WO2017004092) is withdrawn in view of claim amendments. Previous rejection of claims 1, 8, and 14 under 35 USC 102a2 over Ordentlich et al. (WO2017117196) is withdrawn in view of claim amendments. Previous rejection of claim 1 under 35 USC 102a2 over Woods et al. (Cancer Research, 2014, 74:abstract 4090) is withdrawn in view of claim amendments. Previous rejection of claims 1, 8, and 14 under 35 USC 103 over Pinheiro et al. (WO2016153839) in view of Appendix A, B and C is withdrawn in view of claim amendments. Previous rejection of claims 1, 8, and 14 under 35 USC 103 over Pinheiro et al. (WO2016153839) in view of Dubinett (WO2016073759) and Feldman (US20160200815), and Murriel et al. (US20160176962) and Appendix A, B and C is withdrawn in view of claim amendments. Previous rejection of claim 1 and 8 under 35 USC 103 over Woods et al. (Cancer Research, 2014, 74:abstract 4090) in view of Dubinett (WO2016073759) and Feldman (US20160200815), and Murriel et al. (US20160176962) and Appendix A, B and C is withdrawn in view of claim amendments. New Rejections Necessitated by Claim Amendments/Rejections Maintained 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. 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. 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, 8, 14, and 16-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pinheiro et al. (WO2016153839, of record) and Dong et al. (Cancer Chemother Pharmacol vol. 69 p. 1413 (2012), of record). Pinheiro teaches a method of treating cancer comprised of administering a combination of PD-1 antagonists and HDAC inhibitor SAHA (vorinostat), wherein the cancer includes renal cell carcinoma (instant claim 20), melanoma (instant claim 18), NSCLC (instant claims 16 and 17), colorectal cancer, bladder cancer (instant claim 21), and urothelial cancer (instant claim19) (abstract, summary; para 0076; pages 32-33, points 1 and 20). Pinheiro teaches that the PD-1 antagonist inhibits the binding of PD-L1 to PD1 or PD-L1 to PD1 (para 0011). Regarding claim 8, Pinheiro teaches a method of treating cancer comprised of administering a PD-L1 antibody, including BMS-936559 or AMP-514, as the PD-1 antagonist in combination with vorinostat (para 00100; page 34, point 9, 10 and 12). Pinheiro teaches that administration of vorinostat and an anti-PD-1 antibody synergistically reduced tumor volume of colon cancer (example 1; figure 8), and renal cortical adenocarcinoma (example 2; figure 9). Regarding claim 14, Pinheiro further teaches that administration of the PD-1 antagonist and vorinostat is given following prior radiation therapy (para 00134). Pinheiro does not teach that the method of treating NSCLC, melanoma, urothelial cancer, renal cell carcinoma, and bladder cancer comprised of administering an HDAC inhibitor of formula I and BMS-936559 or AMP-514. Dong et al. teaches that chidamide (which has a structure which reads on applicant’s formula I) is a HDAC inhibitor that has enhanced metabolic stability when compared to other family of HDAC inhibitors (page 1415, left column, last paragraph). Dong et al. teaches a method of treating solid tumor comprised of administering chidamide (title, abstract, page 1417 and discussion). Dong et al. teaches that chidamide treatment of colorectal cancer, lung adenocarcinoma, and renal cell carcinoma resulted in stable disease (page 1418, left column, 2nd paragraph). Dong et al. teaches that chidamide is a promising candidate to sue in combination with other anti-cancer agents (page 1420, right column, last paragraph). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the PD-1 antagonist and vorinostat in the method of treating cancer, including NSCLC, melanoma, urothelial cancer, and renal cell carcinoma, comprised of administering PD-1 antagonist and vorinostat of Pinheiro et al. with another PD-1 antagonist, BMS-9936559 or AMP-514 (PD-L1 antibody) of Pinheiro, and chidamide of Dong et al. Pinheiro et al. disclose that PD-L1 antibody, BMS-9936559 or AMP-514, is an PD-1 antagonist that can be administered with Vorinostat for treating cancer. Dong et al. teaches that chidamide is a stable HDAC inhibitor that is effective at treating a variety of solid tumors, and can be used with other anti-tumor agents. It would be obvious to one of ordinary skill in the art before the effective filing date to have had a reasonable expectation of success for forming a method of treating a variety of cancers, including NSCLC, melanoma, urothelial cancer, and renal cell carcinoma, comprised of administering BMS-9936559 or AMP-514 and chidamide, because Pinheiro teaches that combining a PD-1 antagonist with an HDAC inhibitor resulted in synergistic inhibition of tumor growth and that BMS-9936559 or AMP-514 is also an PD-1 antagonist, and Dong et al. teaches that Dong et al. teaches that chidamide is a stable HDAC inhibitor that is effective at treating a variety of solid tumors, and can be used with other anti-tumor agents. Claim(s) 14 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pinheiro et al. (WO2016153839, of record) and Dong et al. (Cancer Chemother Pharmacol vol. 69 p. 1413 (2012), of record) as applied to claim 1 and 14 above, and further in view of Massari et a (Cancer Treatment Reviews, 2015, 41:114-121). The teachings of Pinheiro et al. and Dong et al. are described above. Pinherio The combined teachings of Pinheiro et al. and Dong et al. does not teach that the subject being treated was previously treated with a PD-1 inhibitor. Massari et al. teaches that subjects with renal carcinoma are being treated with both anti-PD-1 antibody, MEDI0680, and Anti-PD-L1 antibody (MEDI4736 or AMP-514) (page 117, table 3). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating renal carcinoma comprised of administering AMP-514 and chidamide of Pinheiro et al. and Dong et al. to include administering MDI0680 of Massari in order to aggressively treat renal carcinoma. The combined teachings of Pinheiro et al. and Dong et al. teaches a method of treating renal carcinoma comprised of administering AMP-514 and chidamide. Massari teaches that renal cell carcinoma can be treated with both anti-PD-1 antibody, MEDI0680, and anti-PD-L1 antibody (MEDI4736 or AMP-514). It would be obvious to one of ordinary skill in the art before the effective filing date to have had a reasonable expectation of success for forming an aggressive method of treating renal cell carcinoma comprised of administering MEDI0680, AMP-514 and chidamide, because the combined teachings of Pinheiro et al. and Dong et al. teaches a method of treating renal carcinoma comprised of administering AMP-514 and chidamide; and Massari teaches that renal cell carcinoma can be treated with both anti-PD-1 antibody, MEDI0680, and AMP-514. 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, 8, 14, and 16-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10385131B2. Although the claims at issue are not identical, they are not patentably distinct from each other. The patented claims are directed to a method of treating cancer comprised of administering formula 1 (claims 1 and 7) and a PD-L1 antibody (claim 1), wherein the PD-L1 antibody is BMS-936559 (claim 6), and wherein the cancer that is being treated in the patented method is NSCLC, melanoma, urothelial cancer, renal cell carcinoma, or bladder cancer (claim 8). The patented claim is a species of the instant claimed method. A species anticipates a genus (MPEP 2131.02). Claims 1, 8, 16, 17 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18421171 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The copending claims are directed to a method of treating cancer, including melanoma, renal cell carcinoma, NSCLC, comprised of administering chidamide (claim 8) and a PD-L1 antibody (claims 17 and 18), which is overlapping in scope with the instant claims 1, 16, 17 and 20. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claims 1, 8, 14, and 16-21 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11535670B2 in view of Pinheiro et al. (WO2016153839). The patented claims are directed to a method of treating colorectal cancer comprised of administering formula 1 and a PD-L1 antibody (claim 1), wherein the PD-L1 antibody is BMS-936559 (claim 9). The patented claimed method does not teach treating NSCLC, melanoma, urothelial cancer, renal cell carcinoma, or bladder cancer. The teachings of Pinheiro et al. are described above. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the patented method of treating colon cancer comprised of administering BMS-9936559 and formula I to treat other types of cancer including, including NSCLC, melanoma, urothelial cancer, and renal cell carcinoma of Pinheiro et al. Pinheiro et al. disclose treating NSCLC, melanoma, urothelial cancer, and renal cell carcinoma with a PD-1 antagonist and Vorinostat. It would be obvious to one of ordinary skill in the art before the effective filing date to have had a reasonable expectation of success for forming a method of treating a variety of cancers, including NSCLC, melanoma, urothelial cancer, and renal cell carcinoma, comprised of administering BMS-9936559 and formula, because the patented claims are directed to a method of treating colorectal cancer comprised of administering formular I and an anti-PD-L1 antibody, including BMS-9936559, and Pinheiro et al. teaches that NSCLC, melanoma, urothelial cancer, and renal cell carcinoma can be treated with a PD-1 antagonist with an HDAC inhibitor, vorinostat. Claims 14 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11535670B2 and Pinheiro et al. (WO2016153839) as applied to instant claim 1 above and further in view of Massari et a (Cancer Treatment Reviews, 2015, 41:114-121). The modified patented claims of are described above. The modified patented claims are not directed to further administering a PD-1 antibody. However, this deficiency is made up in Massari. Massari et al. teaches that subjects with renal carcinoma are being treated with both anti-PD-1 antibody, MEDI0680, and Anti-PD-L1 antibody (MEDI4736 or AMP-514) (page 117, table 3). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the modified patented claimed method of treating renal carcinoma comprised of administering BMS-9936559 and formula I, to include administering the anti-PD-1 antibody, MEDI0680 of Massari in order to aggressively treat renal carcinoma. The modified patented method is directed to method of treating renal carcinoma comprised of administering BMS-9936559 and formula I, and Massari teaches that renal cell carcinoma can be treated with both PD-1 and PD-L1 antibodies. It would be obvious to one of ordinary skill in the art before the effective filing date to have had a reasonable expectation of success for forming an aggressive method of treating renal cell carcinoma comprised of administering MEDI0680, AMP-514 and chidamide. Claims 14 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10385131B2 as applied to instant claim 1 above and further in view of Massari et a (Cancer Treatment Reviews, 2015, 41:114-121). The modified patented claims of are described above. The modified patented claims are not directed to further administering a PD-1 antibody. However, this deficiency is made up in Massari. Massari et al. teaches that subjects with renal carcinoma are being treated with both anti-PD-1 antibody, MEDI0680, and Anti-PD-L1 antibody (MEDI4736 or AMP-514) (page 117, table 3). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the modified patented claimed method of treating renal carcinoma comprised of administering BMS-9936559 and formula I, to include administering the anti-PD-1 antibody, MEDI0680 of Massari in order to aggressively treat renal carcinoma. The modified patented method is directed to method of treating renal carcinoma comprised of administering BMS-9936559 and formula I, and Massari teaches that renal cell carcinoma can be treated with both PD-1 and PD-L1 antibodies. It would be obvious to one of ordinary skill in the art before the effective filing date to have had a reasonable expectation of success for forming an aggressive method of treating renal cell carcinoma comprised of administering MEDI0680, AMP-514 and chidamide. Claims 14 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18421171 as applied to instant claim 1 above and further in view of Massari et a (Cancer Treatment Reviews, 2015, 41:114-121). The copending claims of are described above. The copending claims are not directed to further administering a PD-1 antibody. However, this deficiency is made up in Massari. Massari et al. teaches that subjects with renal carcinoma are being treated with both anti-PD-1 antibody, MEDI0680, and Anti-PD-L1 antibody (MEDI4736 or AMP-514) (page 117, table 3). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the modified copending claimed method of treating renal carcinoma comprised of administering BMS-9936559 and formula I, to include administering the anti-PD-1 antibody, MEDI0680 of Massari in order to aggressively treat renal carcinoma. The copending method is directed to method of treating renal carcinoma comprised of administering BMS-9936559 and formula I, and Massari teaches that renal cell carcinoma can be treated with both PD-1 and PD-L1 antibodies. It would be obvious to one of ordinary skill in the art before the effective filing date to have had a reasonable expectation of success for forming an aggressive method of treating renal cell carcinoma comprised of administering MEDI0680, AMP-514 and chidamide. Claims 18 and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18421171 as applied to instant claim 1, and further in view of Pinheiro et al. (WO2016153839). The copending claimed method is described above. The copending claimed method does not teach treating urothelial cancer, or renal cell carcinoma. The teachings of Pinheiro et al. are described above. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the copending method of treating cancer comprised of administering BMS-9936559 and formula I to treat other types of cancer, including urothelial cancer, and renal cell carcinoma of Pinheiro et al. Pinheiro et al. disclose treating urothelial cancer, and renal cell carcinoma with a PD-1 antagonist and Vorinostat. It would be obvious to one of ordinary skill in the art before the effective filing date to have had a reasonable expectation of success for forming a method of treating a variety of cancers, including urothelial cancer, and renal cell carcinoma, comprised of administering BMS-9936559 and formula I, because the patented claims are directed to a method of treating different types of solid cancer comprised of administering formular I and an anti-PD-L1 antibody, including BMS-9936559, and Pinheiro et al. teaches that urothelial cancer, and renal cell carcinoma can be treated with a PD-1 antagonist with an HDAC inhibitor, vorinostat. Conclusion No claims allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIE WU whose telephone number is (571)272-5205. The examiner can normally be reached on M-F 9-5PM. 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, Bonnie Eyler can be reached on (571) 272-1200. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /JULIE WU/Supervisory Patent Examiner, Art Unit 1643
Read full office action

Prosecution Timeline

Nov 23, 2022
Application Filed
Mar 17, 2025
Examiner Interview Summary
Mar 17, 2025
Examiner Interview (Telephonic)
Apr 03, 2025
Response after Non-Final Action
May 19, 2025
Non-Final Rejection — §103, §DP
Sep 18, 2025
Response Filed
Mar 05, 2026
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

3-4
Expected OA Rounds
62%
Grant Probability
99%
With Interview (+51.6%)
3y 4m
Median Time to Grant
Moderate
PTA Risk
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