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
Applicant’s amendments received 06NOV2025 are acknowledged.
Claims 2-11, 14, 18-19, 23-27, 30-43, 46-54, 56-164, and 167-177 have been canceled.
Claims 1, 12-13, 15-16, 21, and 28-29 have been amended.
Claims 178-179 are new.
Claims 1, 12-13, 15-17, 20-22, 28-29, 44-45, 55, 165-166, and 178-179 are pending and examined on the merits in the instant application (i.e., claim 1 is independent).
Priority
The present application is a 371 National Stage of PCT International Application No. PCT/US2020/52764, filed 25SEP2020, which claims the benefit of US Provisional Patent Application No. 62/906447, filed 26SEP2019. Applicant’s claim for the benefit of prior-filed application is acknowledged.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 06NOV2025 is/are acknowledged and the references cited therein have been considered.
Drawings
Applicant’s arguments, see p 7, Amendments to the drawings section, filed 06NOV2025, with respect to objections to the drawings for minor informalities have been fully considered and said objections to the drawings have been withdrawn in view of new drawings filed as part of said response.
Upon further evaluation, the drawings are objected to because the CDR3 of Fig 1 and 2 are not annotated. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
Applicant’s arguments, see p 7, Amendments to the specification section, filed 06NOV2025, with respect to objections to the specification for minor informalities have been fully considered and said objections to the specification have been withdrawn in view of amendments to the specification filed as part of said response.
Upon further evaluation, the disclosure is objected to because of the following informalities:
The brief description of Fig 1 and 2 should include sequence identifiers for amino acid sequences (i.e., “SEQ ID NO:” notation).
Table 6 appears to contain both “,” and “.” as decimal markers.
Appropriate correction is required.
Claim Objections
Applicant’s arguments, see p 7-8, Response to claim objections section, filed 06NOV2025, with respect to objections to claim(s) 12-13, 15, and 21-22 for informalities have been fully considered and said objections to claim(s) 12-13, 15, and 21-22 have been withdrawn in view of claim amendments filed as part of said response.
Upon further consideration, claim 22 is objected to because of the following informalities: Claim 22 contains an error: “and” should be removed between “L153A” and “with respect” in line 2 of the claim. Appropriate correction is required.
Withdrawn Rejections
Indefiniteness
Applicant’s arguments, see p 8, Response to rejection under 35 USC §112(b) section, filed 06NOV2025, with respect to the rejection(s) of claim(s) 1-2, 6-7, 12-13, 15-17, 20-22, 28-29, 44-45, 55, 165-166, and 168 (claims 2, 6-7, and 168 have been cancelled) under 35 USC §112(b) have been fully considered and said rejections of claims 1, 12-13, 15-17, 20-22, 28-29, 44-45, 55, and 165-166 have been withdrawn in view of the claim amendments filed as part of said response.
Enablement
Applicant’s arguments, see p 8-10, Response to rejection under 35 USC §112(a) section, filed 06NOV2025, with respect to the rejection(s) of claim(s) 1-2, 6-7, 12-13, 15-17, 20-22, 28-29, 44-45, 55, 165-166, and 168 (claims 2, 6-7, and 168 have been cancelled) under 35 USC §112(a) - enablement have been fully considered and said rejections of claims 1, 12-13, 15-17, 20-22, 28-29, 44-45, 55, and 165-166 have been withdrawn in view of the claim amendments filed as part of said response.
Double Patenting
Applicant’s arguments, see p 10-13, Response to double patenting rejection section, filed 06NOV2025, with respect to the rejection(s) of claim(s) 1, 7, 16-17, 20-22, and 28 (claim 7 has been cancelled) under non-statutory double patenting and claim(s) 1, 7, 12, 15-16, 20-22, 28-29, 44-45, 55, and 168 (claims 7 and 168 have been cancelled) under provisional non-statutory double patenting have been fully considered and said rejections of said claims have been withdrawn in view of the claim amendments filed as part of said response.
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.
Applicant’s claim amendments received as part of the 06NOV2025 response have necessitated the following new grounds of rejection.
Claims 1, 12, 16-17, 20-21, 28-29, and 165-166 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,440,943, herein referred to as “’943.” Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed chimeric construct especially in instant claims 16 and 29 are obvious variations of the chimeric protein in claim 1 of the ‘943 patent.
The ’’943 patent claims recite:
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SEQ ID NO: 24 is not claimed in the issued ‘943 patent. However, the construct of claim 1(b) of the ‘943 patent is a generic term for one or more of a PDL1 VHH targeting moiety set forth in SEQ ID NO: 24 as recited in the instant application. In order to determine the scope of the structures of claim 1(b), the specification of the ‘942 patent was consulted and the species of SEQ ID NO: 24 and SEQ ID NO: 24-linker-SEQ ID NO: 24 were disclosed. In Example 8, the ‘943 patent teaches PDL1 targeted IFNα1 and variants thereof comprising PDL1 VHH (i.e., SEQ ID NO: 301) or PDL1 VHH x PDL1 VHH (i.e., SEQ ID NO: 303), which are 100% query match to SEQ ID NO: 24 of the instant application) (see OA.APPENDIX). Therefore, claim 1(b) of the ‘943 patent claims SEQ ID NOs: 301 and 303 (i.e., 100% query match to the anti-PDL1 VHH targeting moiety set forth in SEQ ID NO:24 of the instant application).
In this instance, because the targeting moiety of the chimeric protein complex of the ‘943 patent claims SEQ ID NO: 301 or 303, which are 100% query match to SEQ ID NO: 24 (i.e., anti-PDL1 VHH or anti-PDL1 VHH-linker-anti-PDL1 VHH, respectively) of the instant application (see OA.APPENDIX) and because the chimeric protein complex of the ‘943 patent claims the Fc-based chimeric protein complex comprising SEQ ID NOs: 301 or 303, a signaling agent and a Fc domain, there is no clear difference in the scope between the products of the instant application and the ’943 patent.
Claims 13, 15, 22, and 179 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,440,943, herein referred to as “’943” as applied to claims 1, 12, 16-17, 20-21, 28-29, and 165-166 and in further view of WO 2017/134306 A1 (ORIONIS BIOSCIENCES NV, 10AUG2017), herein referred to as “’306.”
The issued claims of the ‘943 patent are summarized above.
However, they do not claim: wherein the anti-PDL1 TM further comprises a recognition domain which recognizes an antigen on an immune cell, or which recruits cytotoxic T cells to the tumor environment, or wherein the signaling agent is IFNα2, the signaling agent comprises one or more mutations (i.e., R149A) of IFNα2, or pharmaceutical compositions of the Fc-based chimeric protein complex.
Nevertheless, ‘306 teaches chimeric structures comprising anti-CD8 (i.e., antigen on an immune cell and cytotoxic T cell recruiter), anti-PDL1 VHH, R149A mutant of IFNα2 signaling agent, Fc domain and pharmaceutical compositions thereof (see entire document, specifically see p 29, lines 8-11; p 43, line 40 through p 61, line 32, p 19, line 5-8, p 71-72, and p 77). Specifically, ‘306 teaches that the constructs are of interest because CD8+ T lymphocytes (i.e., cytotoxic T cells or CTLs) play an important role in host defense against a wide gamut of viral, protozoan, and bacterial infections, and are important effectors in antitumor immunity; however, cancers have developed methods to evade CTLs and as such there is a need for improved immunotherapeutic agents that effectively derail tumor evasion and enhance anti-tumor immunity as mediated by CTLs (p 1-2). The combination of a CD8 targeting moiety for recruiting CD8-expressing T cells to cells which express PDL1 (i.e., cancer cell), and a signaling agent that may be modified to attenuate activity, provides agents that can be used to treat various diseases or disorders such as cancer (p 2). With regard to the signaling agents, ‘306 teaches that the signaling agents bear mutations that affect affinity and/or activity at one or more interferon receptors (p 18, lines 5-8 and lines 12-15). Furthermore, ‘306 teaches that the pharmaceutical compositions comprise the chimeric constructs and pharmaceutically acceptable excipients which provide the proper form for administration to a subject (p 77).
It would have been obvious to artisans to modify the issued Fc-based chimeric protein complex comprising an IFNα1 signaling agent, one or more targeting moiety (i.e., at least anti-PDL1 VHH set forth in SEQ ID NO: 301), and an Fc region as claimed by the ‘943 patent to include an additional targeting moiety which binds an antigen on an immune cell and/or recruits cytotoxic T cells (i.e., CD8), to modify the signaling agent to a mutant IFNα2 sequence, and to include said chimeric protein structure in a pharmaceutical composition as taught by ‘306. This is because ‘306 teaches that the combination construct allows for recruitment of cytotoxic CD8+ T cells to a cancer environment via a PDL1 targeting moiety, that the signaling agent may be modified to attenuate activity, and because the pharmaceutical compositions are comprised of the constructs and a pharmaceutically acceptable excipient providing a form for proper administration. One would have been motivated to do so, given the direction by the ‘943 patent that the structure could be modified with regard to the inclusion of additional targeting moieties and that the construct was to be administered. Furthermore, one would have been motivated to do so, given that ‘306 teaches a variety of signaling agent options for attenuating the activity of the constructs inclusive of IFNα1 or IFNα2 and mutations thereof as well as pharmaceutical compositions which provide an appropriate form of administration. There would have been a reasonable expectation of success, given the knowledge that by modifying chimeric protein of the ‘943 patent by including an additional CD8 targeting moiety, a signaling agent which attenuates activity, and a pharmaceutical composition for proper forms of administration, which could be used to recruit cytotoxic T cells to a tumor microenvironment for enhanced immunotherapeutic activity, as taught by ‘306.
Claim 178 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,440,943, herein referred to as “’943” as applied to claims 1, 12, 16-17, 20-21, 28-29, and 165-166 and in further view of JP 2018/531039 A6 (Suzhou AlphaMab Co., LTD., et al. 13DEC2018), herein referred to as “’039.”
The issued claims of the ‘943 patent are summarized above.
However, they do not claim: pharmaceutical compositions of the anti-PDL1 TM.
Nevertheless, ‘039 teaches a pharmaceutical composition comprising a single domain antibody which binds to PDL1 and a pharmaceutically acceptable carrier which includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible, which are suitable for administration by injection or infusion and the antibody or fragment thereof may be coated with a material to protect the compound from the action of acids and other natural conditions that may inactivate the antibody or fragment thereof (see entire document, specifically see claims 1 and 20 and “pharmaceutically acceptable carrier” definition).
It would have been obvious to artisans to modify the issued VHH targeting moiety which specifically binds to PDL1 (i.e., SEQ ID NO: 301 or 303, which is 100% query match to SEQ ID NO: 24 of the instant application, see discussion supra) as claimed by the ‘943 patent to include a pharmaceutical composition comprising a pharmaceutically acceptable carrier, as taught by ‘039. This is because ‘039 teaches that a pharmaceutically acceptable carrier provides a form that is suitable for administration to a patient. One would have been motivated to do so, given the direction by ‘039 that such PDL1 targeting moieties were to be administered to a subject and therefore would require pharmaceutically acceptable excipients to provide the proper form for administration. There would have been a reasonable expectation of success, given the knowledge that the PDL1 targeting moiety taught by the ‘943 patent could be modified to include a pharmaceutically acceptable carrier as taught by ‘039 for providing the proper administration form.
Conclusion
No claims are 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 SAMANTHA L. HOPKINS whose telephone number is (703)756-4666. The examiner can normally be reached Mon-Thurs 6:00 AM to 4:00 PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571)272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641