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 Claims
Following Applicant’s amendment filed on 11/04/2025, claims 1, 11, and 35 are currently amended. Claim 36 is cancelled. Claims 1-4, 6-8, 11-13, 18-19, 23-35, and 45 are currently pending and under examination.
Claim Rejections - 35 USC § 112
Applicant’s arguments, see pg. 9, filed 11/04/2025, with respect to rejection of claims 1-4, 6-8, 11-13, 18-19, 23-36, and 45 under 35 U.S.C. 112(b) have been fully considered and are persuasive. The rejection of 08/05/2025 has been withdrawn.
Claim Rejections - 35 USC § 103
Claims 1-4, 6-8, 11-13, 18-19, 23-34, and 45 remain rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (cited in previous Office Action dated 08/05/2025) in view of Qu et al. (cited in Office Action dated 08/05/2025).
Applicant's arguments filed 08/05/2025 have been fully considered but are persuasive only to the extent that Xu does not expressly disclose IL-10 fused to a carboxy terminal amino acid of an Fc subunit. Xu instead places the immunoregulator N-terminal the second Fc region. Xu nevertheless teaches the remaining heterodimer structure, tandem IL-10 arrangement, elected Fc modifications T366W/K409A and T366S/L368G/Y407A/F05K, and pharmaceutical compositions.
Qu addresses the identified deficiencies. Qu teaches non targeted knob in hole Fc heterodimers lacking tumor antigen binding variable regions and expressly discloses both cytokine Fc orientations, including Fc-Knob-linker-IL-15 paired with Fc-Hole and Fc-Hole-linker-IL-15 paired with Fc-Knob (pg. 9). Thus, Qu expressly teaches a cytokine fused to the carboxy terminal side of an Fc subunit. Qu further produced and tested these constructs, establishing that the Fc cytokine orientation retains biological activity.
Although Qu reports a preference for the opposite orientation in certain IL-15 proliferation assays, Qu does not teach away from the Fc cytokine constructs. Rather, Qu expressly identifies and successfully produces such constructs. Accordingly, Qu’s preference does not teach away from the claimed orientation.
Applicant’s comparative results have also been considered. The Specification reports improved yield, cellular proliferation, TNF-α inhibition, and tumor suppression for particular C-terminal IL-10 constructs. However, claims 1-34, and 45 encompass substantially broader subject matter, including different Fc subunits and modification sets, one more IL-10 molecules, fusion to either Fc chain, unspecified linkers, and additional structural components. Applicant has not established that the observed improvements would reasonably extend throughout this scope or that the improvements result solely from the broadly claimed C-terminal orientation. Therefore, the evidence is not commensurate in scope with claims 1-34 and 45 and does not outweigh the evidence of obviousness.
Double Patenting
Applicant's arguments filed 11/04/2025 have been fully considered but they are not persuasive.
1. Claims 1-4, 6-8, 11-13, 18-19, 23-24, and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, and 8 of U.S. Patent No. 11168149 (‘149) in view of Xu et al. and Qu et al. (cited in previous Office Action dated 08/05/2025).
2. Claims 1-4, 6-8, 11-13, 18-19, 23-34, and 45 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 12281177 (‘177) in view of Xu et al. and Qu et al.
3. Claims 1-4, 6-8, 11-13, 18-19, 23-34, and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11357826 (‘826) in view of Xu et al. and Qu et al.
4. Claims 1-4, 6-8, 11-13, 18-19, 23-34, and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10471124 (‘124) in view of Qu et al.
5. Claims 1-4, 6-8, 11-13, 18-19, 23-34, and 45 are rejected on the ground of nonstatutory
double patenting as being unpatentable over claims 1-2, and 4-6 of U.S. Patent No. 11845806 (‘806) in view of Qu et al.
6. Claims 1-4, 6-8, 11-13, 18-19, 23-35, and 45 are rejected on the ground of nonstatutory
double patenting as being unpatentable over claims 1-2 U.S. Patent No. 11987609 (‘609) in view of Qu et al.
7. Claims 1-4, 6-8, 11-13, 18-19, 23-34, and 45 are provisionally rejected on the ground of
nonstatutory double patenting as being unpatentable over claims 1-9, and 13 of copending Application No. 19/084,362 in view of Xu et al and Qu et al.
This is a provisional nonstatutory double patenting rejection.
Regarding the rejections based on U.S. Patents 11168149; 12281177; 11357826; 10471124; 11845806, and copending Application No. 19/084,362, Applicant principally argues that the cited patent claims and Xu disclose an immunoregulator or IL-10 fused N-terminal side of an Fc region, whereas the instant claims require IL-10 fused directly or indirectly to a carboxy-terminal amino acid of an Fc subunit. Although this distinction is acknowledged, Qu expressly teaches asymmetric Fc-cytokine heterodimers in which a cytokine is fused to the carboxy-terminal side of an Fc subunit, as well as Fc heterodimers lacking tumor antigen binding variable regions. Accordingly, Qu provides the teaching for the structural orientation and absence of tumor targeting variable regions not expressly recited in the patent claims or Xu. It would therefore have been obvious to employ the known Fc-cytokine orientation taught by Qu in the Fc heterodimer/IL-10 constructs of the cited patent claims and Xu.
Applicant’s evidence of increased yield and biological activity for certain reverse IL-10/Fc constructs has also been considered. However, the evidence is limited to particular Fc6/Fc9 constructs and has not been shown to be reasonably commensurate in scope with the substantially broader subject matter of claims 1-34 and 45. The Specification confirms that the reported improvements concern particular reverse-(IL-10)2-Fc9 constructs relative to selected comparison constructs (pgs. 24-26). Accordingly, the evidence does not outweigh the evidence of obviousness for the broadly claimed subject matter.
Applicant’s argument concerning U.S. Patent No. 11987609 is likewise not persuasive. Amended claim 35 encompasses a first monomer having SEQ ID NO: 17 together with a second monomer having SEQ ID NO: 60, which the instant Specification identifies as the Fc6-(IL-10)2 construct. Thus, Applicant’s reliance on differences between other sequence alternatives does not establish patentable distinctness of the full scope of claim 35.
Accordingly, the nonstatutory double patenting rejections are maintained, and the rejection based on copending Application No: 19/084,362 remains provisional.
Allowable Subject Matter
Amended claim 35 is limited to SEQ ID NOs: 55, 60, or 62 paired with SEQ ID NO: 17 and is found free of the prior art. However, claim 35 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claim is allowable.
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.
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/DENNIS GEORGE/Examiner, Art Unit 1644
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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