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 October 14, 2025 is pending. Claims 2-3, 10, 16, 23-25, and 27-28 are cancelled. Claims 1, 4-9, 11-15, 17, and 19-22 are amended. Claims 14-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species. Election was made without traverse in the reply filed June 4, 2025. Claims 1, 4-9, 11-13, 17-22, and 26 are examined upon their merits.
Information Disclosure Statement
The information disclosure statements filed on 08/14/2025 and 10/14/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Withdrawn Objections and Rejections
Applicant’s cancelation of Claim 10 has rendered all previous rejections directed to this claim moot.
Applicant’s amendments to the specification and claims have overcome all objections of record, and the specification objections and the claim objections are withdrawn.
The rejection of claims 1, 4-9, 11-13, 17-18, 21-22, and 26 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of Applicant’s amendments. The structures provided in Claim 1 overcome the indefinite functional language. Note, Claim 4 is interpreted as inherent functional properties of the structure of IL-2 fusion molecule outlined in Claim 1 (MPEP § 2112.01).
Claim Rejections - 35 USC § 112 (Maintained)
The rejection of Claims 1, 4-9, 11-13, 17-22, and 26 are rejected 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 claim(s) contains 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.
The claims are still directed to a genus of possible IL-2 fusion proteins. The IL-2 cytokine comprises at least 95% identity to SEQ ID NO: 1 or comprises the amino acid sequence set forth in SEQ ID NO: 2 (Claim 9); the carrier moiety can comprise any antibody or any antibody Fc domain (Claim 1); the ECD of IL-2Rβ comprises at least 95% identity to SEQ ID NO: 3 (Claim 7 and specification paragraph [0010]); the ECD of IL-2Rγ comprises at least 95% identity to SEQ ID NO: 6 (Claim 8 and specification paragraph [0010]); the fusion protein can further comprise an ECD of IL-2Rα comprising at least 95% identity to SEQ ID NO: 7 (Claims 21-22 and specification paragraph [0011]); the fusion can have linkers or not have linkers and the linkers can be cleavable or not cleavable and be various lengths (Claims 5, 11-13, and 17-18). Further, the IL-2 fusion molecule can comprise a first polypeptide comprising at least 99% identity to SEQ ID NO: 50 and a second polypeptide comprising at least 99% identity to SEQ ID NO: 53 (Claims 19-20).
Note, “an amino acid sequence set forth in” encompasses any fragment of two or more amino acid residues within the recited sequence. To instead claim a sequence in its entirety, appropriate claim language could recite “an amino acid sequence comprising SEQ ID NO:.”
Examiner acknowledges the corrected typographical error in specification Table 1 and recognizes that the specification teaches four species of IL-2 fusion proteins instead of two species. Species C1 comprises SEQ ID NO: 50 (IgG4 Fc – IL2(C125A)) and SEQ ID NO: 54 (IgG4 Fc – IL2Rγ – ILRβ); Species C2 comprises SEQ ID NO: 52 (IgG4 Fc – IL2(C125A/V69A/Q74P/T3A)) and SEQ ID NO: 54 (IgG4 Fc – IL2Rγ – ILRβ); Species D1 comprises SEQ ID NO: 50 (IgG4 Fc – IL2(C125A)) and SEQ ID NO: 53 (IgG4 Fc – ILRβ); and Species D2 comprises SEQ ID NO: 52 (IgG4 Fc – IL2(C125A/V69A/Q74P/T3A)) and SEQ ID NO: 53 (IgG4 Fc – ILRβ) (corrected Table 1 and paragraph [0027]).
Four species is still not a representative number of species to adequately represent the genus of IL-2 fusion molecules claimed. In the exemplified species, only one carrier moiety is used (IgG4 Fc domain), only two species of IL-2 cytokines are used (C125A and C125A/V69A/Q74P/T3A), only one species of IL-2Rβ ECD is used, only one species of IL-2Rγ ECD is used, no species of IL-2Rα ECD is used, only two species of linkers are evaluated in the first polypeptide, and only two species of linkers are evaluated in the second polypeptide. No experiments are performed to test how changing the linkers, carrier moieties, IL-2 variants, or masking ECD variants could alter IL-2 fusion molecule function. Similarly, no guidance is provided for how 5% or 1% of the amino acids could be added, deleted, or substituted such that the functional properties of the molecule are preserved.
Applicant's arguments filed October 14, 2025 have been fully considered but they are not persuasive.
Applicant argues that the disclosure of the instant application reasonable conveys to one skilled in the art that the inventors had possession of the subject matter of independent Claim 1 as amended. Examiner maintains that there is proper written description for species C1, C2, D1, and D2 as outlined above, but the disclosure does not provide adequate written description for the genus of IL-2 fusion molecules claimed that can vary substantially in IL-2 cytokines, masking moieties, carrier moieties, and linkers.
Applicant argues that the instant specification discloses a representative number of species of the claimed IL-2 fusion molecules, specifically teaching that the specification discloses four species instead of two. Upon evaluation of the four disclosed species (see above), a limited number of linkers, IL-2 variants, carrier moieties, and masking moieties are represented in the four species as compared to the broad genus of IL-2 fusion molecules claimed that comprises significant variation in each of these domains. Applicant is reminded that when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus (see MPEP § 2163.05.Ib of record). Applicant’s arguments are not persuasive and the rejection is maintained.
Claims 1, 4-9, 11-13, 17-22, and 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the specific species of IL-2 fusion molecules C1, C2, D1, and D2 (amended specification Table 1), does not reasonably provide enablement for the genus of IL-2 fusion molecules encompassed by the claims. 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.
Applicant's arguments filed October 14, 2025 have been fully considered but they are not persuasive.
Applicant argues that the amendments to Claim 1 and the disclosures of the instant specification (paragraph [0027] and Figs. 10A and 10B) have rendered the rejection moot. Examiner maintains that there is still substantial variation in the genus of IL-2 fusion molecules claimed (as outlined in the written description rejection above), and the four species of IL-2 fusion molecules taught by the disclosure do not provide proper enablement for the genus of IL-2 fusion molecules claimed. One of ordinary skill would have to perform further experimentation to make the variants encompassed by the claims (varying linkers/no linkers, cleavable/non-cleavable linkers, linker length, masking moiety sequences, IL-2 sequences, carrier moieties, and orientations) and screen their characteristics in order to practice the invention commensurate with the scope of the claims. This level of further experimentation is considered undue.
Applicant argues that enablement does not require the disclosure of every possible species within a genus, and instead, it is sufficient to provide representative species along with guidance allowing one skilled in the art to make others within the genus. Applicant further argues that the instant specification discloses four species of IL-2 fusion molecules, and the examples of the instant application provide adequate guidance no how to make the claimed IL-2 fusion molecules. Examiner maintains that no experiments are performed to test how changing the linkers, carrier moieties, IL-2 variants, or masking ECD variants could alter IL-2 fusion molecule function. Similarly, no guidance is provided for how 5% or 1% of the amino acids could be added, deleted, or substituted such that the functional properties of the molecule are preserved. There is no support that one of ordinary skill could make the variants encompassed by the claims and use them for their intended purpose, because there is no guidance on structure-to-function attributes for the entire genus of IL-2 fusion molecules. The claims are directed to a genus of IL-2 fusion molecules encompassing structural variation that is not enabled by the disclosure. Applicant’s arguments are not persuasive, and the rejection is maintained.
Double Patenting (Maintained)
1. The provisional rejection of Claims 1, 5, 7, 9, 11, and 26 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-8, 10, 16, and 19 of copending U.S. App. No. 17/787,741 is maintained.
2. The provisional rejection of Claims 1, 5, 9, and 26 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 9-10, 18, and 30 of copending U.S. App. No. 17/262,940 in view of Moya et al. J Chromatogr A. 2002 is maintained.
3. The provisional rejection of Claims 1, 5-7, 9, 11-13, 18, and 26 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 51-55, 61, and 68 of copending U.S. App. No. 18/960,740 in view of Moya et al. J Chromatogr A. 2002 is maintained.
4. The provisional rejection of Claims 1, 5, 7, 9, 11, 13, and 26 on the ground of nonstatutory double patenting as being unpatentable over claims 3, 19-21, 24, 30-32, and 38 of copending U.S. App. No. 19/133,147 is maintained.
Applicant's arguments filed October 14, 2025 have been fully considered but they are not persuasive. Applicant requests that the rejections be held in abeyance until the issuance of the referenced applications. MPEP § 804.I.B.1 states “As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance.” Therefore, the rejections are maintained.
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.
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