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
In the reply filed on 04/24/2025, Applicant’s election with traverse of Group I, claims 1-4, 6-8, 11-13, 18-19, 23-36, and 45, along with the species, first modification set T366W+K409A and claim 36, second modification set T366S+L368G+Y407A+F405K and claim 35, is acknowledged.
The traversal is on the ground that search and examination of the entire application as it currently stands would not place a serious burden on the Examiner. This is not found persuasive, because as noted in the Office Action dated 02/25/2025, the application contains claims with groups of inventions and a myriad of species with unique mutations which are not linked to form a single, general inventive concept under PCT 13.1 (see pgs. 4-6 of 02/25/2025 Office Action for further explanation).Until an elected species is found to be allowable, some claims may remain withdrawn. Therefore, the requirement is still deemed proper and is therefore made FINAL.
Claim 51 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction requirement in the reply filed on 04/24/2025.
Currently, claims 1-4, 6-8, 11-13, 18-19, 23-36, and 45 are pending and under examination.
Priority
This application is a 371 of PCT/CN2020/080848. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Priority date of 03/25/2019 is acknowledged.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 6-8, 11-13, 18-19, 23-36, and 45 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.
Claim 1 recites the limitation that the “proteinaceous heterodimer does not comprise any antibody heavy chain variable region or any antibody light chain variable region exhibiting binding specificity to a tumor antigen.” Similarly, claim 11 also recites the limitation “wherein said proteinaceous heterodimer does not comprise any targeting moiety exhibiting binding specificity to any tumor antigen.” It is unclear from the wording of these claims whether the proteinaceous heterodimer as currently constructed lacks variable regions with antigen binding regions or whether these are proteinaceous heterodimers that have VH/VL binding regions but do not exhibit binding specificity to tumor binding antigens. Therefore, the metes and bounds of the claims are unclear rendering the scope of the claims unascertainable.
Claims 2-4, 6-8, 12-13, 18-19, 23-36, and 45 depend from claim 1 but do not remedy the deficiencies introduced by claim 1 and are also therefore rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6-8, 11-13, 18-19, 23-36, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (WO2018228442, cited on pg. 1 of IDS filed on 10/25/2023) in view of Qu et al. (US10206980B2).
Xu teaches protein heterodimers and their use (see claims 1-39, Examples, and Table 2). Xu teaches a proteinaceous heterodimer composed of two different Fc-containing chains derived from IgG1 (claim 7). The first Fc chain bears a conventional antibody variable region, while the second chain is an Fc fusion protein wherein the C-terminus of an immunoregulator is fused to a N-terminus of the second Fc region, optionally via a linker (claims 1-2). Furthermore, Xu teaches embodiments with dual IL-10 fusions fused with each other via linker to the same Fc subunit (see paragraph 00348, Example 1.17). Xu teaches the modifications and substitutions of the two Fc subunits disclosed in claims 18-19, and 23-27 of the instant application, including the elected first modification set of T366W+K409A and the second modification set T366S+L368G+Y407A +F405K of the instant application (see group 10, Table 2). Finally, Xu also teaches the pharmaceutical composition of the proteinaceous heterodimer including a pharmaceutically acceptable excipient (paragraphs 00371 – 00394).
However, Xu does not teach the limitation of the heterodimer lacking an antibody heavy chain or light chain variable region exhibiting binding specificity to a tumor antigen as recited in claims 1 and 11.
Qu et al. (US10206980B2) address this deficiency in Xu by teaching a heterodimeric “knob in hole” Fc fusion protein in which two IL-15 Fc variants are combined with no antigen binding regions for tumor antigens, yet still express anti-tumor activity (see Abstract; Column 7, lines 29-49; Example 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the proteinaceous heterodimer as taught by Xu and combine it with the teachings of Qu which showed the anti-tumor efficacy of a proteinaceous heterodimer with combined Fc units lacking antigen binding regions for tumor antigens. One of ordinary skill in the art would have been motivated to do so because both Xu and Qu teach asymmetric knob in hole Fc fusion scaffolds to deliver therapeutic cytokines expressing anti-tumor activity while improving expression and optimizing drug delivery and dosage. Qu clearly teaches that these Fc only heterodimers lacking antigen binding regions show better stability, prolonged in vivo half-life and improved biological activity by increasing intramolecular interactions while still maintaining anti-tumor efficacy (Background). This gives one of ordinary skill in the art sufficient guidance to use the teachings of Xu’s IL-10 fused heterodimer without antigen binding regions to optimize for cytokine mediated anti-tumor activity. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
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.
1. Claims 1-4, 6-8, 11-13, 18-19, 23-36, 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 above). The teachings of Xu and Qu are summarized above. Patent ‘149 claims teach a Fc heterodimer with many of the same mutations for the first and second Fc chains as recited in the instant application claims including the elected mutation set of T366W+K409A for the first Fc chain and the modification set T366S+L368G+Y407A +F405K for the second Fc chain (claim 1(2)). However, Patent ‘149 does not specifically teach the addition of IL-10 as a fused immunoregulator to the heterodimer nor the lack of variable binding regions for tumor antigens. Xu and Qu, as discussed previously, address these deficiencies. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the heterodimer as described in Patent ‘149 and combine it with the teachings of IL-10 fused Fc heterodimer of Xu and the negative VH/VL heterodimer of Qu to create an IL-10 fused, Fc only heterodimer with anti-tumor activity as described in the instant application. As described previously, one would be motivated to do so due to the anti-tumor efficacy of an immunoregulator such as IL-10 and the increased stability and optimized drug stability and delivery afforded by a Fc only heterodimer lacking variable binding regions. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
2. Claims 1-4, 6-8, 11-13, 18-19, 23-36, and 45 are 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 (cited above) for the reasons mentioned above.
3. Claims 1-4, 6-8, 11-13, 18-19, 23-36, 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 (cited above) for the reasons mentioned above.
4. Claims 1-4, 6-8, 11-13, 18-19, 23-36, 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 (cited above). Patent ‘124 claims teach a proteinaceous heterodimer with IL-10 fused as an immunoregulator. However, Patent ‘124 does not teach the heterodimer as lacking variable binding regions for tumor antigens. As discussed previously, Qu addresses this deficiency by teaching a Fc only IL-15 heterodimer lacking antigen binding regions showing anti-tumor efficacy. Thus, when combined with the teachings of Patent ‘124 claims, the current invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
5. Claims 1-4, 6-8, 11-13, 18-19, 23-36, 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 (cited above) for the same reasons discussed above.
6. Claims 1-4, 6-8, 11-13, 18-19, 23-36, 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 (cited above) for the same reasons discussed above.
7. Claims 1-4, 6-8, 11-13, 18-19, 23-36, 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 (cited above) for the reasons mentioned above.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowable.
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/DENNIS GEORGE/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644
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