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 .
Claims Status
The amendments and remarks filed 11/27/2025 are acknowledged.
Claims 1, 8-9, 11, 14-15, and 17-22 are pending.
Claims 1, 8, 11, 14, 17-18, and 20 are amended.
Claims 2-7, 10, 12-13, and 16 are canceled.
Claims 9 and 15 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/31/2025.
Therefore, claims 1, 8, 11, 14, and 17-22 are under examination.
Withdrawn
The objection to the drawings are withdrawn. Applicant has submitted replacement black and white drawings to overcome the objection.
The rejections of claims 1-2, 4-8, 10-14, and 16-22 under 35 U.S.C. 112(b) are withdrawn. Applicant has amended claim 1 in order to overcome the rejections.
The rejection of claim 20 under 35 U.S.C. 112(a) are withdrawn. Applicant has amended the claim to overcome the rejection.
The rejections of claims 1-2, 4-8, 10-14, and 21-22 under 35 U.S.C. 103 are withdrawn. Applicant has amended claim 1 to overcome the rejections.
Terminal Disclaimer
The joint research agreement terminal disclaimer (JRA TD) filed 11/27/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. has been reviewed and is disapproved. The JRA TD was not approved for the following reasons:
The reference(s) listed in the terminal disclaimer must have been disqualified as
prior art as required by 37 CFR 1.321 (d). If the reference(s) has not been disqualified as prior art, a grantable petition under 37 CFR 1.183 requesting waiver of the prior art requirement in 37 CFR 1.321(d) would be needed.
The statement under 37 CFR 1.104(c) (i.e. the JRA statement) uses pre-AIA
language. See MPEP 717.02(a)(II) for AIA language.
The amendment to the specification uses pre-AIA language.
Maintained Rejections
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.
These rejections have been modified solely to address the amendments to claim 1 requiring the specific structure of formula (I) or formula (II) and the specific amino acid substitutions for the IL-2 variant.
Claims 1, 8, 11, 14, and 17-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No.11,492,384 (‘384) in view of Kosaka et al., 2007 (08/27/2025 PTO-892) and Du et al., 2019 (08/27/2025 PTO-892).
Regarding claims 1, 11, 19 and 22 of the instant application, claim 1 of ‘384 teaches a fusion protein of the following structural formula (I) or (II):
N'-X-[linker (1)]n-Fc domain-[linker (2)]m-Y-C' (Formula I)
N'-Y-[linker (1)]n-Fc domain-[linker (2)]m-X-C' (Formula II)
wherein N' is the N-terminus of the fusion protein, C' is the C-terminus of the fusion protein, X is a CD80 protein, Y is an IL-2 protein, the linkers (1) and (2) are peptide linkers, and n and m are each independently 0 or 1, claim 10 of ‘384 teaches that the CD80 protein is a CD80 fragment, claim 11 of ‘384 teaches that the CD80 fragment consists of the 35th amino acid to the 242nd amino acid in the amino acid sequence of SEQ ID NO: 11, claim 4 of ‘384 teaches that the IL-2 protein is an IL-2 variant, claim 5 of ‘384 teaches that the IL-2 variant 38th, 42nd, 45th, 61st, and, 72nd amino acids in the amino acid sequence of SEQ ID NO: 10, claim 6 of ‘384 teaches that the IL-2 variant
comprises at least one substitution selected from the group consisting of R38A, F42A, Y45A, E61R, and L72G in the amino acid sequence of SEQ ID NO: 10, and claim 7 of ‘384 teaches that the IL-2 variant comprises any one selected from the following substitution combinations (a) to (d) in the amino acid sequence of SEQ 40 ID NO: 10:
(a) R38A/F42A, (b) R38A/F42A/Y45A, (c) R38A/F42A/E61R, (d) R38A/F42A/L72G.
SEQ ID NO: 11 of ‘384 has 100% sequence identity to SEQ ID NO: 11 of instant claim 11.
However, ‘384 does not teach that the fusion protein is administered to a subject to treat cancer in combination with a NK cell.
Kosaka teaches that gastric cancer decreased the expression of CD80, which results in the failure of immune recognition, and that CD80 infection combined with IL-2 addition significantly increased the activation cytotoxicity of mononuclear cells, and increased the survival of subjects with intraperitoneal tumor [see Abstract]. Kosaka further teaches that the combination of CD80 and IL2 may contribute to improved outcomes for subjects with peritoneal metastasis of gastric carcinoma [see Abstract]. Kosaka teaches that mice with OCUM-2MD3 (gastric cancer) tumors implants were injected with IL-2 and AdCD80 [page 1948, right column, first paragraph], and also teaches that CD80 and IL-2 synergistically activate CTLs to gastric cancer cells in vitro and in vivo [page 1952, left column, second paragraph].
Du teaches that gastric cancer (GC) is one of the most common cancers, with a high incidence of cancer death [see Abstract]. Natural Killer (NK) cells, which are known as important lymphocytes in innate immunity, play vital roles in suppressing GC initiation, progression, and metastases, and that NK cell adoptive therapy is a safe, and well-tolerated method, which can enhance NK cell cytotoxicity against GC [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have treated the subject with gastric cancer, as taught by Kosaka, by administering the fusion protein of ‘384. One would have been motivated to have treated this subject with the fusion protein of ‘384 because ‘384 teaches a fusion protein comprising an IL2 protein and a CD80 protein, and Kosaka teaches that the combination of CD80 and IL2 may contribute to improved outcomes for subjects with peritoneal metastasis of gastric carcinoma, and that CD80 and IL-2 synergistically activate CTLs to gastric cancer cells in vitro and in vivo. Thus, there would be a reasonable expectation of success in treating the subject with gastric cancer of Kosaka with the fusion protein of ‘384.
It further would have been obvious to have treated the subject with gastric cancer of Kosaka, by administering NK cells, as taught by Du, in combination with the fusion protein of ‘384. One would have been motivated to have combined the NK cells of Du with the fusion protein of ‘384 because Du teaches that NK cells play vital roles in suppressing gastric cancer (GC) initiation, progression, and metastases, and that NK cell adoptive therapy is a safe, and well-tolerated method, which can enhance NK cell cytotoxicity against GC. MPEP 2144.06 states “it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, it would have been obvious to combine the separate, known compositions (i.e. the fusion protein and NK cells) for the same purpose of treating gastric cancer. Thus, there would be a reasonable expectation of success in treating the subject with gastric cancer of Kosaka with the fusion protein of ‘384 and the NK cells of Du.
Claims 8, 14, 17-18, and 20-21 of the instant application are included in this rejection because claims 8-18 of ‘384 teach each of the instant claim limitations, respectively.
Claims 1, 8, 11, 14, and 17-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-8, 10, 14-16, 18-23, and 29-31 of copending Application No. 17/912,403 (‘403; reference application) in view of Du et al., 2019 (08/27/2025 PTO-892).
Regarding claims 1 and 19 of the instant application, claim 1 of ‘403 teaches a fusion protein comprising an IL-2 protein and a CD80 protein fragment or a variant thereof, claim 29 of ‘403 teaches a pharmaceutical composition comprises as an active ingredient, the fusion protein of claim 1, claim 30 of ‘403 teaches a method for preventing or treating cancer or an infectious disease in a subject in need thereof comprising administering an effective amount of the pharmaceutical composition to the subject, claim 18 of ‘403 teaches a fusion protein of the following structural formula (I) or (II):
N'-X-[linker (1)]n-Fc domain-[linker (2)]m-Y-C' (Formula I)
N'-Y-[linker (1)]n-Fc domain-[linker (2)]m-X-C' (Formula II)
wherein N' is the N-terminus of the fusion protein, C' is the C-terminus of the fusion protein, X is a CD80 protein, Y is an IL-2 protein, the linkers (1) and (2) are peptide linkers, and n and m are each independently 0 or 1, claim 4 of ‘403 teaches that the IL-2 proteins is an IL-2 variant, claim 5 of ‘403 teaches wherein the IL-2 variant is obtained by substitution of at least one selected from the 38th, 42nd, 45th, 61st, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10, claim 6 of ‘403 teaches that the IL-2 variant is obtained by at least one substitution selected from the group consisting ofR38A, F42A, Y45A, E61R, and L72G in the amino acid sequence of SEQ ID NO: 10, and claim 7 of ‘403 teaches that the IL-2 variant is obtained by any one selected from the following substitution combinations (a) to (d) in the amino acid sequence of SEQ ID NO: 10: (a) R38A/F42A (b) R38A/F42A/Y45A (c) R38A/F42A/E61R (d) R38A/F42A/L72G.
SEQ ID NO: 10 of ‘403 has 100% sequence identity to SEQ ID NO: 10 of instant claim 1.
However, ‘403 does not teach that the fusion protein is administered in combination with a natural killer cell.
Du teaches that gastric cancer (GC) is one of the most common cancers, with a high incidence of cancer death [see Abstract]. Natural Killer (NK) cells, which are known as important lymphocytes in innate immunity, play vital roles in suppressing GC initiation, progression, and metastases, and that NK cell adoptive therapy is a safe, and well-tolerated method, which can enhance NK cell cytotoxicity against GC [see Abstract].
It would have been obvious to have treated a subject with cancer, specifically gastric cancer, by administering the fusion protein, as taught by ‘403, in combination with NK cells, as taught by Du. One would have been motivated to have combined the NK cells of Du with the fusion protein of ‘403 because Du teaches that NK cells play vital roles in suppressing gastric cancer (GC) initiation, progression, and metastases, and that NK cell adoptive therapy is a safe, and well-tolerated method, which can enhance NK cell cytotoxicity against GC. MPEP 2144.06 states “it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, it would have been obvious to combine the separate, known compositions (i.e. the fusion protein and NK cells) for the same purpose of treating gastric cancer. Thus, there would be a reasonable expectation of success in treating a subject with gastric cancer of with the fusion protein of ‘403 and the NK cells of Du.
Claims 8, 11, 14, 17-18, and 20-22 are included in this rejection because claims 2, 8, 10, 14-16, 18-23, 29, and 31 of ‘403 teach each of the instant claim limitations, respectively.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 8, 11, and 17-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-10, and 12-13 of copending Application No. 17/948,894 (‘894; reference application) in view of Kosaka et al., 2007 (08/27/2025 PTO-892) and Du et al., 2019 (08/27/2025 PTO-892).
Regarding claims 1, 19 and 21-22 of the instant application, claim 1 of ‘894 teaches a fusion protein dimer, comprising: two monomers, each of which contains the following structural formula (I) or (II):
N'-X-[linker (1)]n-Fc domain-[linker (2)]m-Y-C' (Formula I)
N'-Y-[linker (1)]n-Fc domain-[linker (2)]m-X-C' (Formula II)
wherein N' is the N-terminus of the fusion protein, C' is the C-terminus of the fusion protein, X is a CD80 protein, Y is an IL-2 protein, the linkers (1) and (2) are peptide linkers, and n and m are each independently 0 or 1, claim 2 of ‘894 teaches the n and m are each independently 1, claim 3 of ‘894 teaches that the IL-2 protein is an IL-2 variant, claim 4 teaches that the IL-2 variant is obtained by substitution of at least one selected from the 38th, 42nd, 45th, 61st, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10, claim 5 of ‘894 teaches that the IL-2 variant comprises at least one substitution selected from the group consisting of R38A, F42A, Y45A, E61R, and L72G in the amino acid sequence of SEQ ID NO: 10, and claim 6 of ‘894 teaches that the IL-2 variant comprises any one selected from the following substitution combinations (a) to (d) in the amino acid sequence of SEQ ID NO: 10: (a) R38A/F42A (b) R38A/F42A/Y45A
(c) R38A/F42A/E61R (d) R38A/F42A/L72G.
However, ‘894 does not teach that the fusion protein is administered to a subject to treat cancer in combination with a NK cell.
Kosaka teaches that gastric cancer decreased the expression of CD80, which results in the failure of immune recognition, and that CD80 infection combined with IL-2 addition significantly increased the activation cytotoxicity of mononuclear cells, and increased the survival of subjects with intraperitoneal tumor [see Abstract]. Kosaka further teaches that the combination of CD80 and IL2 may contribute to improved outcomes for subjects with peritoneal metastasis of gastric carcinoma [see Abstract]. Kosaka teaches that mice with OCUM-2MD3 (gastric cancer) tumors implants were injected with IL-2 and AdCD80 [page 1948, right column, first paragraph], and also teaches that CD80 and IL-2 synergistically activate CTLs to gastric cancer cells in vitro and in vivo [page 1952, left column, second paragraph].
Du teaches that gastric cancer (GC) is one of the most common cancers, with a high incidence of cancer death [see Abstract]. Natural Killer (NK) cells, which are known as important lymphocytes in innate immunity, play vital roles in suppressing GC initiation, progression, and metastases, and that NK cell adoptive therapy is a safe, and well-tolerated method, which can enhance NK cell cytotoxicity against GC [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have treated the subject with gastric cancer, as taught by Kosaka, by administering the fusion protein of ‘894. One would have been motivated to have treated this subject with the fusion protein of ‘894 because ‘894 teaches a fusion protein comprising an IL2 protein and a CD80 protein, and Kosaka teaches that the combination of CD80 and IL2 may contribute to improved outcomes for subjects with peritoneal metastasis of gastric carcinoma, and that CD80 and IL-2 synergistically activate CTLs to gastric cancer cells in vitro and in vivo. Thus, there would be a reasonable expectation of success in treating the subject with gastric cancer of Kosaka with the fusion protein of ‘894.
It further would have been obvious to have treated the subject with gastric cancer of Kosaka by administering NK cells, as taught by Du, in combination with the fusion protein of ‘894. One would have been motivated to have combined the NK cells of Du with the fusion protein of ‘894 because Du teaches that NK cells play vital roles in suppressing gastric cancer (GC) initiation, progression, and metastases, and that NK cell adoptive therapy is a safe, and well-tolerated method, which can enhance NK cell cytotoxicity against GC. MPEP 2144.06 states “it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, it would have been obvious to combine the separate, known compositions (i.e. the fusion protein and NK cells) for the same purpose of treating gastric cancer. Thus, there would be a reasonable expectation of success in treating the subject with gastric cancer of Kosaka with the fusion protein of ‘894 and the NK cells of Du.
Claims 8, 11, 17-18, and 20 of the instant application are included in this rejection because claims 7-10, and 12-13 of ‘894 teach each of the instant claim limitations, respectively.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
The double patenting rejections of claims 1, 8, 11, and 17-22 over U.S. Patent No.11,492,384, copending Application No. 17/912,403, and copending Application No. 17/948,894 are maintained. Regarding the double patenting rejections over U.S. Patent No.11,492,384, and copending Application No. 17/948,894, on page 21 of the remarks, Applicant argues that a Joint Research Agreement Terminal Disclaimer (JRA TD) has been filed to overcome the double patenting rejections. This is not found persuasive because the JRA TD was disapproved and therefore, these double patenting rejections are maintained. Regarding the double patenting rejections over copending Application No. 17/912,403, on page 21 of the remarks, Applicant states that it is requested that this provisional ejection be held in abeyance and does not provide any arguments otherwise. Therefore, this double patenting rejection is maintained.
Conclusion
No claims are 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.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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