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 .
Claim Status
Claim listing filed on March 17, 2026 is pending. Claims 2, 6, 9, 12, 19, and 21-23 are cancelled. Claims 1, 4-5, 7-8, 10-11, 16, 20, and 26-27 are amended. Claim 18 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions or species. Claims 1, 3-5, 7-8, 10-11, 13-17, 20, and 24-27 are examined upon their merits.
Information Disclosure Statement
The information disclosure statement filed on 11/28/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections and Rejections
The amendments to the specification and claims overcome the objections of record, and the sequence compliance in drawings objection, specification objections, and claim objections are withdrawn.
The rejection of Claims 1, 3-5, 7-8, 10-11, 13-17, 20, and 24-27 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of Applicant’s amendments. Claims 1, 8, and 26 no longer recite “preferably” or “e.g.” Claim 26 provides specific Fc mutation structures in place of the previous indefinite functional language.
The rejection of Claims 4-5 under 35 U.S.C. 112(d) as being of improper dependent form is withdrawn in view of Applicant’s amendments.
The rejection of Claim 20 under 35 U.S.C. 112(a) as failing to comply with the written description and enablement requirements is withdrawn in view of Applicant’s amendments. Claim 20 no longer recites the genus of mutations comprising “a B’C’ loop sequence from IL-15.” There is proper written description and enablement for the method of amended Claim 20 which recites specific IL-2 mutations.
The rejection of Claims 1, 3-5, 7-8, 10-11, 13-17, 20, and 24-26 under 35 U.S.C. 103 as being unpatentable over Kang et al. US 2021/0213102 in view of Gu et al. US 12,269,855 is withdrawn in view of Applicant’s statement of common ownership under 35 U.S.C. 102(b)(2)(c) filed March 17, 2026. Applicant states that the subject matter disclosed in Kang, Gu, and the claimed invention were commonly owned by Innovent Biologics (Suzhou) Co., Ltd. not later than the effective filing date of the claimed invention. Therefore, neither Kang nor Gu qualify as prior art under 35 U.S.C. 102(a)(2).
The rejection of Claim 27 under 35 U.S.C. 103 as being unpatentable over Kang et al. US 2021/0213102 in view of Gu et al. US 12,269,855 as applied to Claims 1, 3-5, 7-8, 10-11, 13-17, 20, and 24-26, and further in view of Ast et al. US 2012/0244112 is withdrawn in view of Applicant’s statement of common ownership under 35 U.S.C. 102(b)(2)(c) filed March 17, 2026. Neither Kang nor Gu qualify as prior art under 35 U.S.C. 102(a)(2).
The provisional rejection of Claims 1, 3-5, 7-8, 10-17, 20, and 24-25 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 30, 32, 36, 43-44, 46-50, and 52 of copending U.S. App. No. 17/059,539 in view of Gu et al. US 12,269,855 is withdrawn in view of Applicant’s statement of common ownership under 35 U.S.C. 102(b)(2)(c) filed March 17, 2026. A secondary reference used to support an obviousness analysis for a nonstatutory double patenting rejection must be prior art (MPEP § 804.I.E), and Gu does not qualify as prior art under 35 U.S.C. 102(a)(2).
The rejection of Claims 1, 3-5, 7-8, 10-17, 20, and 24 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2, 4, and 7-12 of U.S. Patent No. 12,269,855 in view of Kang et al. US 2021/0213102 is withdrawn in view of Applicant’s statement of common ownership under 35 U.S.C. 102(b)(2)(c) filed March 17, 2026. A secondary reference used to support an obviousness analysis for a nonstatutory double patenting rejection must be prior art (MPEP § 804.I.E), and Kang does not qualify as prior art under 35 U.S.C. 102(a)(2).
Claim Rejections - 35 USC § 112 (New, necessitated by amendment)
Claims 1, 3-5, 7-8, 10-11, 13-17, 20, and 24-27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 20 recite wherein the shortened B’C’ loop region comprises a substitution of a sequence at position 73 to position 83 with AQSKNFH or a C-terminal truncation of a sequence at position 73 to position 83 wherein 4 amino acids are truncated from the C terminus (wherein the amino acid positions are numbered according to SEQ ID NO: 1). It is of record in the non-final rejection filed 12/18/2025 that the C-terminal truncation of 4 amino acids results in aa72-AQSKNFH-aa84 (page 8). Specifically, residues 73-83 of SEQ ID NO: 1 comprise AQSKNFHLRPR, and deleting 4 amino acids from the C terminus results in AQSKNFH. Therefore, it is unclear how a substitution of sequence AQSKNFH (Claims 1(ii)(a) and 20(i)(j)) differs from a C terminal truncation of 4 amino acids (Claims 1(ii)(b) and 20(i)(k)), as they would both result in aa72-AQSKNFH-aa84. Appropriate clarification is required. Claims 3-5, 7-8, 10-11, 13-17, and 24-27 are rejected for their dependence on Claim 1.
Claim 7 recites “wherein: (a) the IL-2 mutant protein has at least 85%, 86%, 87%, 88%, 89%, 90%, or 95% identity to the wild-type human IL-2; (b) the IL-2 mutant protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 22-26 or an amino acid sequence having at least 95%, 96%, 97% or 98% identity thereto.” There is no conjunction between limitation (a) and (b) which makes the claim scope unclear. For the purpose of compact prosecution, Claim 7 is interpreted with the broadest reasonable interpretation as (a) or (b).
Note, mutations L234A and L235A as recited in Claim 26 are interpreted with Kabat numbering as stated in the specification pages 6-7.
Note, “a wild-type IL-2” as recited in Claim 20 is interpreted with the broadest reasonable interpretation to encompass any wild-type IL-2 sequence known in the art prior to filing spanning different species, mature forms (e.g. biologically active), and non-mature forms (e.g. comprising the 20-amino acid leader sequence in human IL-2). It would be clear to one of ordinary skill how the recited mutations numbered according to SEQ ID NO:1 correspond to the appropriate wild-type IL-2 sequence by standard sequence alignment.
Claim Rejections - 35 USC § 112 (Maintained)
The rejection of Claims 1, 3-5, 7-8, 10-11, 13-17, and 24-27 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is maintained. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is of record in the non-final office action filed 12/18/2025 that Claims 7 and 27 are directed to a genus of possible IL-2 mutant protein sequences that lack proper written description (pages 9-10). Amended Claim 1 recites IL-2 mutations wherein residues 73 to 83 are replaced with a specific 7 amino acid sequence and wherein the CD25 binding interface mutations comprise 4-7 substitutions. Together, these limitations account for variation in 15-18 amino acid residues in IL-2 that are clearly defined and have proper written description. Claim 7(a) recites wherein the IL-2 mutant has at least 85% identity to the wild-type human IL-2 which is defined in Claim 1 as comprising SEQ ID NO: 1. 15% variation in SEQ ID NO: 1 means that any combination of 19 amino acids can be added, deleted, or substituted; however, Claim 1 only defines how to alter 15-18 amino acid residues. The limitations of Claim 7(a) still have variability in the amino acid sequence for which the disclosure lacks proper written description. Claim 7(b) recites wherein the IL-2 mutant protein comprises at least 95% identity to one of SEQ ID NOs: 22-26. Importantly, SEQ ID NOs: 22-26 comprise the mutations outlined in Claim 1. Therefore, 5% variation in SEQ ID NOs: 22-26 (each comprising 129 amino acid residues) means that any combination of 6 amino acid residues can be added, deleted, or substituted in addition to the mutations defined in Claim 1. Similarly, Claim 27 recites wherein the fusion protein comprises at least 95% identity to one of SEQ ID NOs: 15-19. SEQ ID NOs: 15-19 comprise 366 residues and already comprise the mutations outlined in Claim 1; therefore, 5% variation in SEQ ID NOs: 15-19 means that any combination of 18 amino acid residues can be added, deleted, or substituted in addition to the mutations defined in Claim 1. For these reasons, the claims are still directed to a genus of IL-2 mutant proteins for which there is insufficient recitation of distinguishing identifying characteristics or structure-to-function attributes in the disclosure.
Applicant's arguments filed March 17, 2026 have been fully considered but they are not persuasive.
Applicant argues that proper written description for the B’C’ loop region AQSDNFH is provided in Table 6 (molecule Y094). Examiner finds the supporting data in Table 6 persuasive and agrees that there is proper written description for the seven species of B’C’ loop regions recited in Claim 1(ii)(a) (AGDASIH, SGDASIH, AQSKNFH, AQSANFH, AQSDNFH, AGSKNFH, and AQSANIH). While Claim 1 is no longer directed to a genus of possible B’C’ loops, Applicant did not address the rejections of record pertaining to the genus of IL-2 mutant sequences (Claim 7) and the genus of IL-2 mutant fusion protein sequences (Claim 27) as reiterated above. To potentially overcome the written description rejection of record, Claim 1 could recite wherein the mutant IL-2 comprises SEQ ID NO: 1 and further comprises (1) a mutation at a binding interface of IL-2 to CD25 selected from (a)-(i) and (2) a substitution of a sequence at position 73 to position 83 with AGDASIH, SGDASIH, AQSKNFH, AQSANFH, AQSDNFH, AGSKNFH, or AQSANIH. This potential claim language would define the wild-type sequence and the specific mutations for which the specification provides proper written description and would remove the variation in sequence identity which is not supported by the specification.
The rejection of Claims 1, 3-5, 7-8, 10-11, 13-17, and 24-27 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is maintained because the specification, while being enabling for the specific species of B’C’ loop regions and CD25 binding interface mutations defined in Claim 1, does not reasonably provide enablement for the genus of IL-2 mutant sequences and the genus of IL-2 mutant fusion protein sequences encompassed by Claims 7 and 27. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
It is explained in detail in the written description rejection above how Claims 7 and 27 are directed to a genus of possible IL-2 mutant proteins with substantial structural variation.
Applicant's arguments filed March 17, 2026 have been fully considered but they are not persuasive.
Applicant argues that there is proper enablement for the B’C’ loop region AQSDNFH as demonstrated in Table 6 (molecule Y094). Examiner finds the supporting data in Table 6 persuasive and agrees that there is proper enablement for the seven species of B’C’ loop regions recited in Claim 1(ii)(a) (AGDASIH, SGDASIH, AQSKNFH, AQSANFH, AQSDNFH, AGSKNFH, and AQSANIH). While Claim 1 is no longer directed to a genus of possible B’C’ loops, Applicant did not address the rejections of record pertaining to the genus of IL-2 mutant sequences (Claim 7) and the genus of IL-2 mutant fusion protein sequences (Claim 27). It is of record in the non-final office action filed 12/18/2025 that there is unpredictability in how varying amino acid structures effects protein function, and the specification provides no guidance or direction for how 5% to 15% of the IL-2 amino acid structure can be varied such that the functional properties of the invention are preserved (reduced binding affinity to IL-2Rα, enhanced binding affinity to IL-2Rβγ, and improved expression yield and/or purity). A person having ordinary skill in the art would have to perform undue further experimentation to make the IL-2 structural variants encompassed by Claims 7 and 27 and screen their characteristics in order to practice the invention commensurate with the scope of the claims. The rejection is maintained.
Conclusion
No claim is 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 SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571) 272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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