Prosecution Insights
Last updated: April 19, 2026
Application No. 17/998,521

DOSING AND ADMINISTRATION OF ACTIVATABLE ANTI-CTLA-4 ANTIBODY

Non-Final OA §103§DP
Filed
Nov 11, 2022
Examiner
PETERS, ALEC JON
Art Unit
1641
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Bristol-Myers Squibb Company
OA Round
1 (Non-Final)
69%
Grant Probability
Favorable
1-2
OA Rounds
3y 10m
To Grant
99%
With Interview

Examiner Intelligence

Grants 69% — above average
69%
Career Allow Rate
22 granted / 32 resolved
+8.8% vs TC avg
Strong +59% interview lift
Without
With
+58.7%
Interview Lift
resolved cases with interview
Typical timeline
3y 10m
Avg Prosecution
38 currently pending
Career history
70
Total Applications
across all art units

Statute-Specific Performance

§101
2.2%
-37.8% vs TC avg
§103
25.6%
-14.4% vs TC avg
§102
10.7%
-29.3% vs TC avg
§112
31.7%
-8.3% vs TC avg
Black line = Tech Center average estimate • Based on career data from 32 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 . Applicant’s amendment, filed on 11/11/2022, is acknowledged. Claims 1-14 are currently pending. Election/Restrictions Applicants’ election without traverse of the Species of: 1) a method of treatment comprising an activatable CTLA-4 antibody monotherapy; 2) Q8W; and 3) 1600mg, filed on 1/16/2026 is acknowledged. Claims 7-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected Species. Claims 1-6 are under examination as reading on a method of treatment comprising administration of an activatable anti-CTLA-4 antibody at a dose of 1600mg and an interval of Q8W. Claim Interpretation Claim 1 currently recites an activatable antibody comprising the heavy chain variable domain of SEQ ID NO: 9, and the light chain variable domains of SEQ ID NOL 21, 22, or 23 each of SEQ ID NO: 21, 22, and 23 comprises the light chain variable domain sequence of ipilimumab with a N-terminal masking moiety and protease cleavable domain, which are the specific structures that give rise to the function of “activatable”, satisfying 112(a) requirements. This is also disclosed in Table 1 of the instant specification. 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. 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 1-3 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Weber et al. (J Clin Oncol 27, 9023-9023(2009) doi: 10.1200/jco.2009.27.15_suppl.9023) in view of Tipton et al. (WO201808555, on IDS filed on 8/25/2023), as evidenced by Schadendorf et al. (Lancet. 2018 Sep 15;392(10151):971-984. doi: 10.1016/S0140-6736(18)31559-9). Weber et al. teaches a method of treating melanoma comprising administration of ipilimumab every 8 weeks (Abstract): “Ipilimumab is a human anti-CTLA-4 antibody shown to have clinical activity in melanoma…Ipilimumab at 3 or 10 mg/kg intravenously every 8 weeks for 12 months…” Weber et al. additionally teaches treatment of patients with stage IV melanoma (Abstract): “…46 patients had stage IV…” Schadendorf et al. is provided as an evidentiary reference to demonstrate that stage IV melanoma is metastatic (Tables 1 and 2, cropped below): PNG media_image1.png 629 626 media_image1.png Greyscale PNG media_image2.png 242 626 media_image2.png Greyscale Weber et al. as evidenced by Schadendorf et al. teaches a method of treating metastatic melanoma comprising administration of ipilimumab every 8 weeks. Weber et al. in view of Schadendorf et al. does not teach administration of an activatable ipilimumab. Tipton et al., in the same field of endeavor, teaches activatable anti-CTLA4 ipilimumab antibodies (Abstract): “[p]rovided herein are activatable anti-human CTLA-4 antibodies comprising a heavy chain comprising a VH domain and a light chain comprising a masking moiety (MM), a cleavable moiety (CM), and a VL domain…”. Tipton et al. additionally teaches the activatable ipilimumab comprising the heavy chain of SEQ ID NO: 353 and the light chain of SEQ ID NO: 448 (¶[0014] and [0111]). SEQ ID NO: 353 of Tipton et al. is 100% identical to instant SEQ ID NO: 11: Qy 1 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYY 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYY 60 Qy 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSAS 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSAS 120 Qy 121 TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL 180 Qy 181 YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPS 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 181 YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPS 240 Qy 241 VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST 300 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 241 VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST 300 Qy 301 YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT 360 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 301 YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT 360 Qy 361 KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ 420 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 361 KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ 420 Qy 421 GNVFSCSVMHEALHNHYTQKSLSLSPG 447 ||||||||||||||||||||||||||| Db 421 GNVFSCSVMHEALHNHYTQKSLSLSPG 447 SEQ ID NO: 448 of Tipton et al. is 100% identical to instant SEQ ID NO: 24 (i.e., the limitations of instant claim 2): Qy 1 QGQSGSCRTQLYGYNLCPYGGGSSGGSISSGLLSGRSDNPGGGSEIVLTQSPGTLSLSPG 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 QGQSGSCRTQLYGYNLCPYGGGSSGGSISSGLLSGRSDNPGGGSEIVLTQSPGTLSLSPG 60 Qy 61 ERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTI 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 ERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTI 120 Qy 121 SRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 SRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL 180 Qy 181 LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 181 LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE 240 Qy 241 VTHQGLSSPVTKSFNRGEC 259 ||||||||||||||||||| Db 241 VTHQGLSSPVTKSFNRGEC 259 Tipton et al. additionally teaches administration of pharmaceutical compositions comprising the activatable ipilimumab (claims 19 and 25), including melanoma (claims 26 and 27). Tipton et al. teaches that the activatable antibodies have reduced side effects compared to the parent antibody (¶[0007]): “[s]uch activatable anti-human CTLA-4 antibodies have CTLA-4 binding activity in the tumor microenvironment, where the masking moiety is removed by proteolytic cleavage of the cleavable moiety by tumor specific proteases, but exhibit greatly reduced binding to CTLA-4 outside the tumor. In this way, the activatable anti-human CTLA-4 antibodies of the present invention retain anti-tumor activity while reducing the side effects associated with anti-CTLA-4 activity outside the tumor. It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of treating metastatic melanoma with ipilimumab taught by Weber et al. to use the activatable ipilimumab taught by Tipton et al. with a reasonable expectation of success, as both references teach methods of treating melanoma comprising administration of ipilimumab. One would have been motivated to make this change for the purposes of treating metastatic melanoma with an activatable ipilimumab that has less side effects than the parent antibody. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. Claims 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Weber et al. (supra) in view of Tipton et al. (supra), as evidenced by Schadendorf et al. (supra) as applied to claims 1-3 and 6 above, and further in view of Conejo-Garcia et al. (U.S. PGPub 20190201526). The combined teachings of Weber et al. and Tipton et al., as evidenced by Schadendorf et al., has been discussed supra. The combined references do not teach administration of 1600mg of activatable ipilimumab. Conejo-Garcia et al., in the same field of endeavor, teaches administration dosages of ipilimumab, including 1600mg (¶[0098]): “…an anti-CTLA-4 antibody selected from the group consisting of ipilimumab…a dose selected from the group consisting of about 10mg, …1600mg…”. It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have modified the combined teachings of Weber et al. and Tipton et al., as evidenced by Schadendorf et al., further in view of Conejo-Garcia et al. to have tried a dose of 1600mg for the activatable ipilimumab to treat metastatic melanoma in a patient though routine optimization. Conejo-Garcia et al. teaches doses of ipilimumab, including 1600mg, that one with ordinary skill in the art would be able to apply to the activatable ipilimumab taught by Tipton et al. "[I]t is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456 (CCPA 1955); see also In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003). "Only if the 'results of optimizing a variable' are 'unexpectedly good' can a patent be obtained for the claimed critical range." In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997) (quoting In re Antonie, 559 F.2d 618, 620 (CCPA 1977)). "[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. 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 1-3 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over: Claims 1-17 of U.S. Patent No. 9,320,811 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1-3) Claims 1-10 of U.S. Patent No. 8,685,394 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1-3) Claims 1-11 of U.S. Patent No. 8,119,129 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 2) Claims 1-5 of U.S. Patent No. 8,449,886 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1) Claims 1-8 of U.S. Patent No. 8,475,790 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 7) Claims 1-30 of U.S. Patent No. 10,377,824 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 13) Claims 1-37 of U.S. Patent No. 10,266,591 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 28) Claims 1-28 of U.S. Patent No. 10,072,082 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 20, and 21) Claims 1-22 of U.S. Patent No. 9,856,320 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 3) Claims 1-15 of U.S. Patent No. 10,688,180 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1, SEQ ID NO: 19 and 20 are the ipilimumab variable regions) Claims 1-29 of U.S. Patent No. 11,612,654 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1) Claims 1-29 of U.S. Patent No. 10,512,689 (claims are drawn to pharmaceutical compositions comprising ipilimumab, see claim 1) Claims 1-20 of U.S. Patent No. 10,174,113 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 13) Claims 1-15 of U.S. Patent No. 12,152,075 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 13-15) Claims 1-18 of U.S. Patent No. 11,078,278 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 5, and 6) Claims 1-16 of U.S. Patent No. 10,983,128 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1, SEQ ID NO: 1 and 2 are the ipilimumab variable regions) Claims 1-18 of U.S. Patent No. 10,081,681 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 2, and 18) Claims 1-20 of U.S. Patent No. 12,528,865 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 4) Claims 1-11 of U.S. Patent No. 11,072,657 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 4) Claims 1-11 of U.S. Patent No. 10,196,445 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1-3, SEQ ID NO: 9 and 10 are the ipilimumab variable regions) Claims 1-11 of U.S. Patent No. 11,623,965 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 4) Claims 1-11 of U.S. Patent No. 11,332,529 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 7) Claims 1-15 of U.S. Patent No. 11,767,361 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 6) Claims 1-14 of U.S. Patent No. 12,441,799 (claims are drawn to methods of treatment comprising administration of activatable ipilimumab, see claims 1 and 7) Claims 1-20 of U.S. Patent No. 11,117,968 (claims are drawn to methods of treatment comprising administration of activatable ipilimumab, see claims 1, 5, and 18) Claims 1-18 of U.S. Patent No. 11,400,094 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 10-13) Claims 1-76 of U.S. Patent No. 12,077,584 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 60 and 75) Claims 1-113 of U.S. Patent No. 11,274,150 (claims are drawn to ipilimumab, see claim 15) Claims 1-19 of U.S. Patent No. 12,466,888 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 2, and 18) Claims 1-19 of U.S. Patent No. 11,274,150 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 2, and 18) Claims 1-28 of U.S. Patent No. 11,572,405 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 28) Claims 1-20 of U.S. Patent No. 12,479,917 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 3) Claims 1-10 of U.S. Patent No. 12,478,674 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 3) each in view of Weber et al. (J Clin Oncol 27, 9023-9023(2009) doi: 10.1200/jco.2009.27.15_suppl.9023, supra) and Tipton et al. (WO201808555, on IDS filed on 8/25/2023, supra), as evidenced by Schadendorf et al. (Lancet. 2018 Sep 15;392(10151):971-984. doi: 10.1016/S0140-6736(18)31559-9, supra). Although the claims at issue are not identical, they are not patentably distinct from each other. Each of the above patents claims the anti-CTLA-4 antibody ipilimumab, or methods of treatment comprising administration of ipilimumab. The patents do not claim administration of an activatable ipilimumab at an interval of Q8W to treat metastatic melanoma (the limitations of instant claims 1, 2 and 3-6). Weber et al., in the same field of endeavor, teaches a method of treating melanoma comprising administration of ipilimumab every 8 weeks (Abstract): “Ipilimumab is a human anti-CTLA-4 antibody shown to have clinical activity in melanoma…Ipilimumab at 3 or 10 mg/kg intravenously every 8 weeks for 12 months…” Weber et al. additionally teaches treatment of patients with stage IV melanoma (Abstract): “…46 patients had stage IV…” Schadendorf et al. is provided as an evidentiary reference to demonstrate that stage IV melanoma is metastatic (Tables 1 and 2). Tipton et al., in the same field of endeavor, teaches activatable anti-CTLA4 ipilimumab antibodies (Abstract): “[p]rovided herein are activatable anti-human CTLA-4 antibodies comprising a heavy chain comprising a VH domain and a light chain comprising a masking moiety (MM), a cleavable moiety (CM), and a VL domain…”. Tipton et al. additionally teaches the activatable ipilimumab comprising the heavy chain of SEQ ID NO: 353 and the light chain of SEQ ID NO: 448 (¶[0014] and [0111]). SEQ ID NO: 353 of Tipton et al. is 100% identical to instant SEQ ID NO: 11, and SEQ ID NO: 448 of Tipton et al. is 100% identical to instant SEQ ID NO: 24 (i.e., the limitations of instant claim 2). Tipton et al. additionally teaches administration of pharmaceutical compositions comprising the activatable ipilimumab (claims 19 and 25), including melanoma (claims 26 and 27). Tipton et al. teaches that the activatable antibodies have reduced side effects compared to the parent antibody (¶[0007]): “[s]uch activatable anti-human CTLA-4 antibodies have CTLA-4 binding activity in the tumor microenvironment, where the masking moiety is removed by proteolytic cleavage of the cleavable moiety by tumor specific proteases, but exhibit greatly reduced binding to CTLA-4 outside the tumor. In this way, the activatable anti-human CTLA-4 antibodies of the present invention retain anti-tumor activity while reducing the side effects associated with anti-CTLA-4 activity outside the tumor. It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have modified the inventions of the above patents to treat metastatic melanoma with an activatable ipilimumab administered at an interval of Q8W with a reasonable expectation of success, as Weber et al. teaches method of treating metastatic melanoma with ipilimumab every 8 weeks, and Tipton et al. teaches activatable forms of ipilimumab that can be used to treat melanoma. One would have been motivated to make this change for the purposes of treating metastatic melanoma with an activatable ipilimumab that has less side effects than the parent antibody. Therefore, the invention encompassed by the instant claims is a prima facie obvious variant of the patents listed supra, each in view of Weber et al. and Tipton et al., as evidenced by Schadendorf et al., especially in absence of evidence to the contrary. Claims 4 and 5 are rejected on the ground of nonstatutory double patenting as being unpatentable over: Claims 1-17 of U.S. Patent No. 9,320,811 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1-3) Claims 1-10 of U.S. Patent No. 8,685,394 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1-3) Claims 1-11 of U.S. Patent No. 8,119,129 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 2) Claims 1-5 of U.S. Patent No. 8,449,886 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1) Claims 1-8 of U.S. Patent No. 8,475,790 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 7) Claims 1-30 of U.S. Patent No. 10,377,824 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 13) Claims 1-37 of U.S. Patent No. 10,266,591 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 28) Claims 1-28 of U.S. Patent No. 10,072,082 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 20, and 21) Claims 1-22 of U.S. Patent No. 9,856,320 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 3) Claims 1-13 of U.S. Patent No. 10,688,180 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1, SEQ ID NO: 19 and 20 are the ipilimumab variable regions) Claims 1-29 of U.S. Patent No. 11,612,654 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1) Claims 1-29 of U.S. Patent No. 10,512,689 (claims are drawn to pharmaceutical compositions comprising ipilimumab, see claim 1) Claims 1-20 of U.S. Patent No. 10,174,113 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 13) Claims 1-15 of U.S. Patent No. 12,152,075 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 13-15) Claims 1-18 of U.S. Patent No. 11,078,278 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 5, and 6) Claims 1-16 of U.S. Patent No. 10,983,128 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1, SEQ ID NO: 1 and 2 are the ipilimumab variable regions) Claims 1-18 of U.S. Patent No. 10,081,681 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 2, and 18) Claims 1-20 of U.S. Patent No. 12,528,865 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 4) Claims 1-11 of U.S. Patent No. 11,072,657 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 4) Claims 1-11 of U.S. Patent No. 10,196,445 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1-3, SEQ ID NO: 9 and 10 are the ipilimumab variable regions) Claims 1-11 of U.S. Patent No. 11,623,965 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 4) Claims 1-11 of U.S. Patent No. 11,332,529 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 7) Claims 1-15 of U.S. Patent No. 11,767,361 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 6) Claims 1-14 of U.S. Patent No. 12,441,799 (claims are drawn to methods of treatment comprising administration of activatable ipilimumab, see claims 1 and 7) Claims 1-20 of U.S. Patent No. 11,117,968 (claims are drawn to methods of treatment comprising administration of activatable ipilimumab, see claims 1, 5, and 18) Claims 1-18 of U.S. Patent No. 11,400,094 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 10-13) Claims 1-76 of U.S. Patent No. 12,077,584 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 60 and 75) Claims 1-113 of U.S. Patent No. 11,274,150 (claims are drawn to ipilimumab, see claim 15) Claims 1-19 of U.S. Patent No. 12,466,888 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 2, and 18) Claims 1-19 of U.S. Patent No. 11,274,150 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1, 2, and 18) Claims 1-28 of U.S. Patent No. 11,572,405 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 28) Claims 1-20 of U.S. Patent No. 12,479,917 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 3) Claims 1-10 of U.S. Patent No. 12,478,674 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 3) each in view of Weber et al. (supra) and Tipton et al. (supra), as evidenced by Schadendorf et al. (supra), as applied to claims 1-3 and 6 above, and further in view of Conejo-Garcia et al. (U.S. PGPub 20190201526, supra). Although the claims at issue are not identical, they are not patentably distinct from each other. The invention encompassed by the instant claims is a prima facie obvious variant of the invention of each of the patents listed supra in view of Weber et al. and Tipton et al., as evidenced by Schadendorf et al., and further in view of Conejo-Garcia et al. for the same reasons discussed in the 35 USC 103 rejection supra. Claims 1-3 and 6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over: Claims 1-4 of copending U.S. Application 19/030,567 (claims are drawn to ipilimumab, see claims 1 and 2) Claims 52, 66, 84, and 104-109 of copending U.S. Application 18/190,822 (claims are drawn to ipilimumab, see claims 151 and 109) Claims 2, 8, 14-18, 20, 21, 46, 48, and 49 of copending U.S. Application 17/523,702 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1) Claims 1, 2, 4-6, 8-11, 34-36, 38, 40, 41, 43, 44, 46, 47, and 49 of copending U.S. Application 19/172,371 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 8) Claims 1, 2 5, 8, 10, 11, 13-15, 21-23, 26, 27, 31, 34, 36, 37, 41, 44, and 48 of copending U.S. Application 18/778,430 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 34) Claims 1-3, 8, 11, 15, 16, 18, 22, 24, 26-31, 38, 43, 52, and 53 of copending U.S. Application 18/531,312 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 22) Claims 1, 61, 62, 66, 67, 69-71, 73, 80, 85, 90, 91, 96, 97, 99-101, 103, 104 of copending U.S. Application 18/916,385 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 99) Claims 1, 11-14, 16-21 of copending U.S. Application 19/025,586 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 11) Claims 24-43 of copending U.S. Application 18/787,822 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 30) Claims 1-20 of copending U.S. Application 18/450,219 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 6) Claims 1-4, 6, 7, 9, 13, 16-27 of copending U.S. Application 19/025,613 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 9) Claims 1-47 of copending U.S. Application 18/780,867 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 41) Claims 1-23 of copending U.S. Application 18/468,097 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 22) Claims 1, 7, 16, 22-30 of copending U.S. Application 17/818,298 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 26) Claims 167-186 of copending U.S. Application 19/025,264 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 179) Claims 1, 9, 11, 14-18, 24, 25, 27, 29, 33, 34, 41, 44, 52, 53, 67 of copending U.S. Application 19/199,098 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 41) Claims 1, 15-17, 56, 57, 61, 64, 66, 72 of copending U.S. Application 17/599,433 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 64) Claims 125, 126, 128-130, 132, 134-144 of copending U.S. Application 17/762,576 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 141) Claims 1-20 of copending U.S. Application 17/793,174 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 16) Claims 21-29, 31-35, 37, 39, 41, 42, 44, 46-54 of copending U.S. Application 17/786,442 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 54) Claims 1-20 of copending U.S. Application 17/793,162 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 18) Claims 93-111 of copending U.S. Application 18/841,061 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 111) Claims 1-4, 8, 12, 18, 25, 28, 33, 39, 47, 48, 53, 68, 84, 88, 99, 103, 109, and 110 of copending U.S. Application 19/006,029 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 48(ii)) each in view of Weber et al. (J Clin Oncol 27, 9023-9023(2009) doi: 10.1200/jco.2009.27.15_suppl.9023, supra) and Tipton et al. (WO201808555, on IDS filed on 8/25/2023, supra), as evidenced by Schadendorf et al. (Lancet. 2018 Sep 15;392(10151):971-984. doi: 10.1016/S0140-6736(18)31559-9, supra). Although the claims at issue are not identical, they are not patentably distinct from each other. The invention encompassed by the instant claims is a prima facie obvious variant of the invention of each of the co-pending Applications listed supra in view of Weber et al. and Tipton et al., as evidenced by Schadendorf et al., for the same reasons discussed in the double patenting rejection supra. This is a provisional double patenting rejection. Claims 4 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over: Claims 1-4 of copending U.S. Application 19/030,567 (claims are drawn to ipilimumab, see claims 1 and 2) Claims 52, 66, 84, and 104-109 of copending U.S. Application 18/190,822 (claims are drawn to ipilimumab, see claims 151 and 109) Claims 2, 8, 14-18, 20, 21, 46, 48, and 49 of copending U.S. Application 17/523,702 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 1) Claims 1, 2, 4-6, 8-11, 34-36, 38, 40, 41, 43, 44, 46, 47, and 49 of copending U.S. Application 19/172,371 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claims 1 and 8) Claims 1, 2 5, 8, 10, 11, 13-15, 21-23, 26, 27, 31, 34, 36, 37, 41, 44, and 48 of copending U.S. Application 18/778,430 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 34) Claims 1-3, 8, 11, 15, 16, 18, 22, 24, 26-31, 38, 43, 52, and 53 of copending U.S. Application 18/531,312 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 22) Claims 1, 61, 62, 66, 67, 69-71, 73, 80, 85, 90, 91, 96, 97, 99-101, 103, 104 of copending U.S. Application 18/916,385 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 99) Claims 1, 11-14, 16-21 of copending U.S. Application 19/025,586 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 11) Claims 24-43 of copending U.S. Application 18/787,822 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 30) Claims 1-20 of copending U.S. Application 18/450,219 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 6) Claims 1-4, 6, 7, 9, 13, 16-27 of copending U.S. Application 19/025,613 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 9) Claims 1-47 of copending U.S. Application 18/780,867 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 41) Claims 1-23 of copending U.S. Application 18/468,097 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 22) Claims 1, 7, 16, 22-30 of copending U.S. Application 17/818,298 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 26) Claims 167-186 of copending U.S. Application 19/025,264 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 179) Claims 1, 9, 11, 14-18, 24, 25, 27, 29, 33, 34, 41, 44, 52, 53, 67 of copending U.S. Application 19/199,098 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 41) Claims 1, 15-17, 56, 57, 61, 64, 66, 72 of copending U.S. Application 17/599,433 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 64) Claims 125, 126, 128-130, 132, 134-144 of copending U.S. Application 17/762,576 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 141) Claims 1-20 of copending U.S. Application 17/793,174 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 16) Claims 21-29, 31-35, 37, 39, 41, 42, 44, 46-54 of copending U.S. Application 17/786,442 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 54) Claims 1-20 of copending U.S. Application 17/793,162 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 18) Claims 93-111 of copending U.S. Application 18/841,061 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 111) Claims 1-4, 8, 12, 18, 25, 28, 33, 39, 47, 48, 53, 68, 84, 88, 99, 103, 109, and 110 of copending U.S. Application 19/006,029 (claims are drawn to methods of treatment comprising administration of ipilimumab, see claim 48(ii)) each in view of Weber et al. (supra) and Tipton et al. (supra), as evidenced by Schadendorf et al. (supra), as applied to claims 1-3 and 6 above, and further in view of Conejo-Garcia et al. (U.S. PGPub 20190201526, supra). Although the claims at issue are not identical, they are not patentably distinct from each other. The invention encompassed by the instant claims is a prima facie obvious variant of the invention of each of the co-pending Applications listed supra in view of Weber et al. and Tipton et al., as evidenced by Schadendorf et al., and further in view of Conejo-Garcia et al. for the same reasons discussed in the double patenting rejection supra. This is a provisional double patenting rejection. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm 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, Misook Yu can be reached at (571) 272-0839. 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. /ALEC JON PETERS/Examiner, Art Unit 1641 /MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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Prosecution Timeline

Nov 11, 2022
Application Filed
Feb 13, 2026
Non-Final Rejection — §103, §DP (current)

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