Detailed Action
The present office action is in response to the arguments filed 04 Jun 2025.
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
Claims 1-2 and 21-22 of the pending application have been examined on the merits. Claims 20 and 23 remain withdrawn. Acknowledgement is made of the cancellation of claims 3-19.
Priority
The instant application still has the effective filing date of March 7, 2019.
Response to Applicant Arguments
Examiner acknowledges applicant remarks filed 04 Jun 2025.
The double-patenting rejections of claims 4-6, 8-14, and 16-19 are rendered moot following applicant’s cancellation of claims 3-19 in the amendments filed 04 Jun 2025.
Applicant’s arguments filed 04 Jun 2025 with respect to claim(s) 1-2 and 21-22 for the double-patenting rejection over U.S. Patent No. 11,358,950 and the provisional double-patenting rejection over copending Application No. 17/594,737 have been fully considered but are not persuasive for the following reasons:
Applicant argues the formula and anti-PD-1 antibody provide unexpected results, evidenced by the comparative data presented in the specification (pg. 6). Applicant argues that the claimed combination produced a decrease in tumor volume that was greater than the sum of the effects achieved by administering an anti-PD-1 antibody or the compound of example 2 by itself and the evidence shows a greater than expected effect which could not have been predicted based on the teachings of the applied references (pg. 7). Applicant argues that Kearney et al. (Cell Death Diff, 2017, 24:1705-1716; provided in IDS 12/28/22), hereinafter Kearney, teaches that the mechanisms by which Smac-mimetics display anti-tumor efficacy in vivo are complex (pg. 1714, column 2) and thus it would have been unpredictable that the compound of the recited formula and anti-PD-1 antibody would show improved anti-tumor efficacy. Applicant further argues that the Smac-mimetic tested in Kearney is structurally distinguishable from the compound of the recited formula.
Applicant argues that the mechanisms by which Smac-mimetics display anti-tumor efficacy in vivo are complex which makes it unpredictable that the compound of the recited formula found in U.S. Patent No. 11,358,950, hereinafter ‘950, and co-pending Application No. 17/594,737, hereinafter ‘737, which is the IAP inhibitor in the instant claims, would display synergy with anti-PD-1 antibodies. However, this is arguing limitations which do not exist in the claims, mainly that this combination needs to be applied in vivo. See MPEP § 2145(VI). Kearney teaches combination therapies that boost immunity likely synergize with Smac-mimetics and that administering the Smac-mimetic birinapant in combination with Anti-PD-1 antibodies exhibited synergy and reduced the viability of target cells to 28% (pg. 1714, column 1). Both ‘950 and ‘737 teach the instant compound of Example 2 as a Smac-mimetic. A person of ordinary skill in the art would have the expectation that the Smac-mimetic taught in ‘950 and ‘737 would exhibit synergy with anti-PD-1 antibodies as taught in Kearney when combined in cells.
In light of the discussion above, the rejection of claims 1-2 and 21-22 under obviousness-type double-patenting as obvious over ‘950 and Kearney, and ‘737 and Kearney is maintained for the reasons of record and restated below.
Because the double-patenting rejection of claims 1-2 and 21-22 over co-pending Application No. 17/594,737 is not the only rejection remaining in the application, it is maintained for the reasons of record and restated below.
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- 2 and 21-22 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,358,950, hereinafter ‘950, in view of Kearney et al. (Cell Death Diff, 2017, 24:1705-1716; provided in IDS 12/28/22), hereinafter Kearney.
Claim 17 of ‘950 claims the elected compound of Formula (I):
Instantly elected compound
‘950 claim 17 compound (column 100)
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Claim 18 of ‘950 claims a composition of a generic Formula (I):
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according to reference claim 1 and a pharmaceutically acceptable carrier. The reference generic Formula (I) found in reference claim 1 can include the instant compound in reference claim 17. The compounds of the reference claims are defined as IAP inhibitors (Title and Abstract). However, the copending claims do not encompass a combination comprising the elected compound and an anti-PD-1 antibody.
Kearney teaches that synthetic IAP antagonists, such as Smac-mimetics can promote apoptosis upon interaction with IAP BIR domains (pg. 1705, column 1). Furthermore, Kearney teaches that combination therapies that boost immunity are likely to synergize with Smac-mimetics. Kearney teaches that the Smac-mimetic birinapant in combination with Anti-PD-1 immune checkpoint therapy reduced the viability of target cells to 28% (pg. 1714, column 1). Kearney teaches that AIPs and PD-L1 protect tumors cells from apoptosis and that co-inhibition of IAP and PD-L1 markedly sensitizes tumor cell to killing (pg. 1715, column 1).
It would be obvious to a person of ordinary skill in the art to combine a compound of Formula (I) claimed in ‘950 with the anti-PD-1 antibody described in Kearney. A person having ordinary skill in the art would be motivated to create this combination to reduce the viability of target cancer cells.
Claims 1-2 and 21-22 are provisionally rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1 and 10 of copending Application No. 17/594,737, hereinafter 737, in view of Kearney.
Claim 1 of ‘737 claims the crystalline compound of the instantly elected invention:
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Claim 10 of ‘737 claims a composition of the reference compound and a pharmaceutically acceptable carrier. Furthermore, ‘737 defines the reference compound as a Smac mimic used as an IAP inhibitor (Title and pg. 1, lines 9-11 in the specification). However, neither of claims 1 or 10 require an anti-PD-1 antibody.
Kearney teaches that synthetic IAP antagonists, such as Smac-mimetics can promote apoptosis upon interaction with IAP BIR domains (pg. 1705, column 1). Furthermore, Kearney teaches that combination therapies that boost immunity are likely to synergize with Smac-mimetics. Kearney teaches that the Smac-mimetic birinapant in combination with Anti-PD-1 immune checkpoint therapy reduced the viability of target cells to 28% (pg. 1714, column 1). Kearney teaches that AIPs and PD-L1 protect tumors cells from apoptosis and that co-inhibition of IAP and PD-L1 markedly sensitizes tumor cell to killing (pg. 1715, column 1).
It would be obvious to a person of ordinary skill in the art to combine a compound of Formula (I) claimed in ‘737 with the anti-PD-1 antibody described in Kearney. A person having ordinary skill in the art would be motivated to create this combination to reduce the viability of target cancer cells.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed. THIS ACTION IS MADE FINAL. 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.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625