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 02/18/2026 are acknowledged.
Claims 1-5, 7-8, 17, and 21 are pending.
Claims 1 and 8 are amended.
Claims 6, 9-16, and 18-20 are canceled.
Claim 21 is new.
Claims 1-5, 7-8, 17, and 21 are under examination.
Withdrawn
The rejections of claims 1-12 and 15-19 under 35 U.S.C. 112(a) enablement are withdrawn. Applicant has amended claim 1 and provided persuasive arguments to overcome the rejections.
The rejections of claims 1-6, 8, and 16 under 35 U.S.C. 102 are withdrawn. Applicant has amended claim 1 to overcome the rejections.
The previous rejections of claims 1-12 and 15-19 under 35 U.S.C. 103 are withdrawn in view of Applicant’s amendment to claim 1 requiring that the anti-CD137 antigen-binding molecule be administered in combination therapy with an anti-PD-L1 antibody, and new claim 21 requiring that the anti-CD137 antigen-binding molecule be administered before or after administration of the anti-PD-L1 antibody.
The previous double patenting rejections of claims 1-12 and 15-19 are withdrawn in view of Applicant’s amendment to claim 1 requiring that the anti-CD137 antigen-binding molecule be administered in combination therapy with an anti-PD-L1 antibody, and new claim 21 requiring that the anti-CD137 antigen-binding molecule be administered before or after administration of the anti-PD-L1 antibody.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C.
119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55 and of the English translation of the Japanese foreign priority document JP 2020-021275. Priority is given with the effective filing date of 02/12/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/18/2026 and 03/20/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Maintained Rejection
Written Description
Claim 3 is 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. 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 claim is drawn to a method of treating cancer comprising administering an effective amount of an anti-CD137 antigen-binding molecule to a patient having cancer, wherein the anti-CD137 antigen-binding molecule comprises a HVR-H 1-3 and HVR-L 1-3 selected from (a) to (m), wherein the administered anti-CD137 antigen-binding molecule is a human antibody, humanized antibody, or chimeric antibody, or an antigen-binding fragment thereof.
The claim encompasses human antibodies. However, the specification teaches that the antibodies of the invention were obtained from an antibody phage display library constructed in WO2015083764 [see paragraph 0531 of the instant specification]. US20160304862 is referenced as being an accurate translation of WO2015083764 and teaches that the phage library utilized rabbit cells [see paragraphs 0824-0825 and 0849-0851].
There is no disclosure of a fully human antibody nor any expectation that a human antibody would comprise the same complementary determining regions (CDRs) as those disclosed in the instant application because the antibodies were made in rabbits. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian fibroblast growth factors (FGFs) were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. In the same manner, disclosure of a rabbit antibody sequences provides no salient information regarding the sequences produced in a human.
Accordingly, as applicant does not appear to be in possession of a fully human antibody with the claimed sequences, the disclosure as a whole fails to adequately describe a human antibody. Thus, a claim to such an antibody fails to meet the written description requirements.
Response to Arguments
The rejection of claim 3 under 35 U.S.C. 112 Written Description is maintained. Applicant argues that Reference Example 2 disclosed in US20160304862, corresponding to WO2015083784, provides construction of a rationally designed library containing human antibodies. This is not found persuasive because Example 2 in US20160304862 that Applicant points to for support of a “human antibody” produces antibodies by immunizing rabbits and rabbit B-cell cloning. There is no disclosure of a fully human antibody nor any expectation that a human antibody would comprise the same complementary determining regions (CDRs) as those disclosed in the instant application because the antibodies were made in rabbits.
Applicant’s arguments, see pages 15-17 of the remarks filed 02/18/2026, with respect to the rejections of claims 1-12 and 15-19 under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, in view of Applicant’s amendments adding new claim 21 requiring that the anti-CD137 antigen-binding molecule is administered before or after the administration of the anti-PD-L1 antibody, a new ground of rejection is made in view of Igawa (WO2020032230 and US Patent No. 12,304,960 (‘960); 11/28/2025 PTO-892,Tie et al., 2019 (instant PTO-892) and Dana-Farber, 2018 (instant PTO-892).
New Grounds of Rejection Necessitated by Amendment
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 1-5, 8, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Igawa (WO2020032230 and US Patent No. 12,304,960 (‘960); 11/28/2025 PTO-892) in view of Tie et al., 2019 (instant PTO-892). Note: The citations in the rejection are references to Igawa (US Patent No. 12,304,960 (‘960)), which also serves as an accurate English translation of WO2020032230.
Regarding claims 1 and 2, Igawa (‘960) teaches a method of treating an individual having a solid tumor (i.e. cancer) into which CD137 expressing immune cells have infiltrated comprising administering an effective amount of the anti-CD137 antigen-binding molecule [of claim 1] to the individual and the immune cells that have infiltrated the solid tumor may be CD8-positive T cells [see column 100 lines 1-22 and claim 10]. Igawa (‘960) further teaches an anti-CD137 antigen-binding molecule comprising a combination of HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 selected from (a) to (m) [see claim 1].
The sequences for each of the HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 set forth in options (a) to (m) of ‘960 are 100% identical to the sequences for each of the HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 set forth in options (a) to (m) of the instant claim.
Igawa (‘960) also teaches the anti-CD137 antigen-binding molecule of claim 1, which comprises a variable region that comprises a heavy chain variable domain (VH) and a light chain variable domain (VL) selected from (a) to (m) [see claim 13].
The sequences for each of the VH and VL set forth in options (a) to (m) of ‘960 are 100% identical to the sequences for each of the VH and VL set forth in options (a) to (m) of the instant claim.
However, Igawa does not specifically teach that the anti-CD137 antigen-binding molecule is administered in combination therapy with an anti-PD-L1 antibody.
Tie teaches atezolizumab, a high-affinity human IgG1 monoclonal antibody that binds selectively to PD-L1 and prevents the binding of PD-L1 to PD-1 and B7-1 (anti-PDL1 antibody), which enhances the magnitude and quality of the tumor-specific T-cell responses, resulting in improved antitumor activity (i.e. treats cancer), and thus, T-cell activation is enabled and tumor cell death is induced [page 524, left column, second paragraph]. Tie further teaches that atezolizumab is administered by i.v. infusion and has been approved for the treatment of UC and NSCLC (i.e. solid tumors) page 531, left column, third paragraph – right column, first paragraph].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the anti-CD137 antigen-binding molecule of Igawa with the atezolizumab of Tie in order to treat a solid tumor infiltrated with CD8+ T cells. One would have been motivated to have combined the anti-CD137 antigen-binding molecule of Igawa with the atezolizumab of Tie in a combination therapy with a reasonable expectation of success to treat a solid tumor infiltrated with CD8+ T cells because Igawa (‘960) teaches a method of treating an individual having a solid tumor (i.e. cancer) into which CD137 expressing immune cells, which may be CD8+ T cells, have infiltrated comprising administering an effective amount of the anti-CD137 antigen-binding molecule to the individual, and Tie teaches that atezolizumab is administered by i.v. infusion and has been approved for the treatment of UC and NSCLC (i.e. solid tumors). Thus, both are known treatments in the art for solid tumors. This follows the logic of MPEP 2144.06 which 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 for the same purpose of treating cancer (i.e. a solid tumor). One further would have been motivated to have combined the atezolizumab of Tie with the anti-CD137 antigen-binding molecule of Igawa because Tie teaches that the administration of atezolizumab enhances the magnitude and quality of the tumor-specific T-cell responses, resulting in improved antitumor activity, enabling T-cell activation and inducing tumor cell death.
Regarding claim 3, Igawa (‘960) teaches the antibodies are humanized [column 60, lines 16-17].
Regarding claim 4, claim 2 of Igawa (‘960) teaches the anti-CD137 antigen-binding molecule of claim 1, which comprises an altered Fc region, wherein the altered Fc region comprises any one combination of amino acid alterations
selected from the following:
L235W/G236N/H268D/Q295L/K326T/A330K/P343R/D413K;
K214RIL235W/G236N/H268D/Q295L/K326T/A330K/P343R/D413K;
L234Y /P238D/T250V/V264I/T307P/A330K/P343R/D413K;
L234Y/P238D/V264I/A330K/P343R/D413K;
L234Y/G237D/P238D/T250V/T307P/A330K/P343R/D413K;
L234Y/G237D/P238D/A330K/P343R/D413K;
L235W/G236N/H268D/Q295L/K326T/A330K/Q311R/P343R;
L234Y/P238D/T250V/V264I/T307P/A330K/Q311R/P343R;
L234Y/P238D/V264I/A330K/Q311R/P343R;
L234Y/G237D/P238D/T250V/T307P/A330K/Q311R/P343R;
L234Y/G237D/P238D/A330K/Q311R/P343R;
L235W/G236N/H268D/Q295L/K326T/A330K/P343R;
K214R/L235W/G236N/H268D/Q295L/K326T/A330K/P343R;
L235W/G236N/H268D/Q295L/K326T/A330K/D413K;
K214R/G236N/H268D/A330K/P343R;
K214R/L235W/G236N/H268D/A330K/P343R;
K214R/G236N/H268D/A330K/D413K;
K214R/G236N/H268D/A330K/P343R/D413K;
K214R/L235W/G236N/H268D/A330K/P343R/D413K;
K214R/G236N/H268D/A330K/Q311R;
K214R/L235W/G236N/H268D/A330K/Q311R;
K214R/G236N/H268D/A330K/Q311R/P343R;
K214R/L235W/G236N/H268D/A330K/Q311R/P343R;
K214R/G236N/H268D/A330K/Q311R/D413K;
K214R/L235W/G236N/H268D/A330K/Q311R/D413K; and
K214R/L235W/G236N/H268D/Q295L/K326T/A330K/Q311R.
Regarding claim 5, claim 14 of Igawa (‘960) teaches the anti-CD137 antigen-binding molecule of claim 1, which comprises an antibody variable region that comprises a heavy chain variable domain (VH) of SEQ ID NO: 51 and a light chain variable domain (VL) of SEQ ID NO: 60, claim 15 teaches an antibody comprising an antibody variable region that comprises a heavy chain variable domain (VH) of SEQ
ID NO: 51 and a light chain variable domain (VL) of SEQ ID NO: 60 and claims 16-27 of ‘960 teach various sequences for the CH and CL of the antibody.
SEQ ID NOs: 51 and 60 of Igawa (‘960) have 100% sequence identity to SEQ ID NOs: 51 and 60 of the instant claim, respectively, and the sequences disclosed in claims 16-27 of Igawa (‘960) for the CH and CL have 100% sequence identity to the sequences disclosed in options (xxvii-xxxviii) of the instant claim.
Regarding claim 8, Igawa (‘960) teaches a use of the anti-CD137 antigen-binding molecules or antibodies in the manufacture or preparation of a medicament, and teaches using the medicament for a method of treating cancer comprising administering to an individual having cancer an effective amount of the medicament [column 100, lines 44-54] and the anti-tumor activity of the antibodies can be measured using colon cancer cell lines (i.e. a method of treating colon cancer) [column 95, lines 45-65]. Further, Tie teaches that atezolizumab has been approved for the treatment of NSCLC (i.e. a lung cancer).
Regarding claim 21, the claimed subject matter is an obvious variation of the teachings of the art because the only difference between the claimed combination and the art is the order of steps performed. Altering the order of steps is obvious because changing the order of the steps does not change the end result (MPEP §2144.04(IV)(C).
Claims 1-5, 8, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Igawa (WO2020032230 and US Patent No. 12,304,960 (‘960); 11/28/2025 PTO-892) in view of Tie et al., 2019 (instant PTO-892), as applied to claims 1-5, 8, and 21 above, and further in view of Dana-Farber, 2018 (instant PTO-892).
The teachings of Igawa and Tie are above.
However, Igawa and Tie do not specifically teach that the anti-CD137 antigen-binding molecule is administered to a patient having a cancer refractory to treatment with an immune checkpoint inhibitor.
Regarding claims 7 and 17, Dana-Farber teaches that when a patient’s disease (i.e. cancer) is or becomes refractory, the next step may be to try another form of treatment [page 1, third paragraph].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the anti-CD137 antigen-binding molecule of Igawa to a patient that has a cancer refractory to treatment with any immune checkpoint inhibitor, such as an anti-CTLA-4 antibody. One would have been motivated to have administered the anti-CD137 antigen-binding molecule of Igawa to a patient that has a cancer refractory to treatment with any immune checkpoint inhibitor because Dana-Farber teaches that teaches that when a patient’s disease (i.e. cancer) is or becomes refractory, the next step may be to try another form of treatment.
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.
Claims 1-5, 8, and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 10, and 13-15 of U.S. Patent No. 12,304,960 (‘960), in view of Tie et al., 2019 (instant PTO-892) and Wolfl et al., 2008 (instant PTO-892).
Regarding claims 1 and 2 of the instant application, claim 10 of ‘960 teaches a method of treating an individual having a solid tumor (i.e. cancer) into which CD137 expressing immune cells have infiltrated comprising administering an effective amount of the anti-CD137 antigen-binding molecule of claim 1 to the individual and claim 1 of ‘960 teaches an anti-CD137 antigen-binding molecule comprising a combination of HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 selected from (a) to (m).
The sequences for each of the HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 set forth in options (a) to (m) of ‘960 are 100% identical to the sequences for each of the HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 set forth in options (a) to (m) of the instant claim.
Claim 13 of ‘960 teaches the anti-CD137 antigen-binding molecule of claim 1, which comprises a variable region that comprises a heavy chain variable domain (VH) and a light chain variable domain (VL) selected from (a) to (m).
The sequences for each of the VH and VL set forth in options (a) to (m) of ‘960 are 100% identical to the sequences for each of the VH and VL set forth in options (a) to (m) of the instant claim.
However, Igawa does not specifically teach that the anti-CD137 antigen-binding molecule is administered in combination therapy with an anti-PD-L1 antibody or that the solid cancer is infiltrated with CD8+ T cells.
Tie teaches atezolizumab, a high-affinity human IgG1 monoclonal antibody that binds selectively to PD-L1 and prevents the binding of PD-L1 to PD-1 and B7-1 (anti-PDL1 antibody), which enhances the magnitude and quality of the tumor-specific T-cell responses, resulting in improved antitumor activity (i.e. treats cancer), and thus, T-cell activation is enabled and tumor cell death is induced [page 524, left column, second paragraph]. Tie further teaches that atezolizumab is administered by i.v. infusion and has been approved for the treatment of UC and NSCLC (i.e. solid tumors) page 531, left column, third paragraph – right column, first paragraph].
Wolfl teaches that CD137 is expressed on the cell surface of antigen-specific CD8+ T-cells and promotes the proliferation and survival of the activated T-cells [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 combined the anti-CD137 antigen-binding molecule of ‘960 with the atezolizumab of Tie in order to treat a solid tumor infiltrated with CD8+ T cells. One would have been motivated to have combined the anti-CD137 antigen-binding molecule of ‘960 with the atezolizumab of Tie in a combination therapy with a reasonable expectation of success to treat a solid tumor infiltrated with CD8+ T cells because ‘960 teaches a method of treating an individual having a solid tumor (i.e. cancer) into which CD137 expressing immune cells have infiltrated comprising administering an effective amount of the anti-CD137 antigen-binding molecule to the individual, Tie teaches that atezolizumab is administered by i.v. infusion and has been approved for the treatment of UC and NSCLC (i.e. solid tumors), and Wolfl teaches that CD137 is expressed on the cell surface of antigen-specific CD8+ T-cells and it promotes the proliferation and survival of the activated T-cells. Thus, both are known treatments in the art for solid tumors and one would want to administer the agonist anti-CD137 antigen-binding molecule to the tumor infiltrated with CD8+ T cells in order to promote the proliferation and survival of the activated T-cells, as taught by Wolfl. This follows the logic of MPEP 2144.06 which 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 for the same purpose of treating cancer (i.e. a solid tumor). One further would have been motivated to have combined the atezolizumab of Tie with the anti-CD137 antigen-binding molecule of ‘960 because Tie teaches that the administration of atezolizumab enhances the magnitude and quality of the tumor-specific T-cell responses, resulting in improved antitumor activity, enabling T-cell activation and inducing tumor cell death.
Regarding claim 3 of the instant application, since claim 13 of ‘960 teaches anti-CD137 antigen-binding molecules with 100% sequence identity to those instantly claimed, including the framework regions, then the antigen-binding molecules of ‘960 are necessarily either human or humanized antibodies, as instantly claimed.
Regarding claim 4 of the instant application, claim 2 of ‘960 teaches the anti-CD137 antigen-binding molecule of claim 1, which comprises an altered Fc region, wherein the altered Fc region comprises any one combination of amino acid alterations
selected from the following:
L235W/G236N/H268D/Q295L/K326T/A330K/P343R/D413K;
K214RIL235W/G236N/H268D/Q295L/K326T/A330K/P343R/D413K;
L234Y /P238D/T250V/V264I/T307P/A330K/P343R/D413K;
L234Y/P238D/V264I/A330K/P343R/D413K;
L234Y/G237D/P238D/T250V/T307P/A330K/P343R/D413K;
L234Y/G237D/P238D/A330K/P343R/D413K;
L235W/G236N/H268D/Q295L/K326T/A330K/Q311R/P343R;
L234Y/P238D/T250V/V264I/T307P/A330K/Q311R/P343R;
L234Y/P238D/V264I/A330K/Q311R/P343R;
L234Y/G237D/P238D/T250V/T307P/A330K/Q311R/P343R;
L234Y/G237D/P238D/A330K/Q311R/P343R;
L235W/G236N/H268D/Q295L/K326T/A330K/P343R;
K214R/L235W/G236N/H268D/Q295L/K326T/A330K/P343R;
L235W/G236N/H268D/Q295L/K326T/A330K/D413K;
K214R/G236N/H268D/A330K/P343R;
K214R/L235W/G236N/H268D/A330K/P343R;
K214R/G236N/H268D/A330K/D413K;
K214R/G236N/H268D/A330K/P343R/D413K;
K214R/L235W/G236N/H268D/A330K/P343R/D413K;
K214R/G236N/H268D/A330K/Q311R;
K214R/L235W/G236N/H268D/A330K/Q311R;
K214R/G236N/H268D/A330K/Q311R/P343R;
K214R/L235W/G236N/H268D/A330K/Q311R/P343R;
K214R/G236N/H268D/A330K/Q311R/D413K;
K214R/L235W/G236N/H268D/A330K/Q311R/D413K; and
K214R/L235W/G236N/H268D/Q295L/K326T/A330K/Q311R.
Regarding claim 5 of the instant application, claim 14 of ‘960 teaches the anti-CD137 antigen-binding molecule of claim 1, which comprises an antibody variable region that comprises a heavy chain variable domain (VH) of SEQ ID NO: 51 and a light chain variable domain (VL) of SEQ ID NO: 60, claim 15 teaches an antibody comprising an antibody variable region that comprises a heavy chain variable domain (VH) of SEQ
ID NO: 51 and a light chain variable domain (VL) of SEQ ID NO: 60 and claims 16-27 of ‘960 teach various sequences for the CH and CL of the antibody.
SEQ ID NOs: 51 and 60 of ‘960 have 100% sequence identity to SEQ ID NOs: 51 and 60 of the instant claim, respectively, and The sequences disclosed in claims 16-27 for the CH and CL have 100% sequence identity to the sequences disclosed in options (xxvii-xxxviii) of the instant claim.
Regarding claim 8, Tie teaches that atezolizumab has been approved for the treatment of NSCLC (i.e. a lung cancer).
Regarding claim 21, the claimed subject matter is an obvious variation of the teachings of the art because the only difference between the claimed combination and the art is the order of steps performed. Altering the order of steps is obvious because changing the order of the steps does not change the end result (MPEP §2144.04(IV)(C).
Claims 1-5, 7-8, 17, and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 10, and 13-15 of U.S. Patent No. 12,304,960 (‘960), in view of Tie et al., 2019 (instant PTO-892) and Wolfl et al., 2008 (instant PTO-892), as applied to claims 1-5, 8, and 21 above, and further in view of Dana-Farber, 2018 (instant PTO-892).
The teachings of ‘960, Tie, and Wolfl are above.
However, ‘960, Tie, and Wolfl do not specifically teach that the anti-CD137 antigen-binding molecule is administered to a patient having a cancer refractory to treatment with an immune checkpoint inhibitor.
Regarding claims 7 and 17, Dana-Farber teaches that when a patient’s disease (i.e. cancer) is or becomes refractory, the next step may be to try another form of treatment [page 1, third paragraph].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the anti-CD137 antigen-binding molecule of ‘960 to a patient that has a cancer refractory to treatment with any immune checkpoint inhibitor, such as an anti-CTLA-4 antibody. One would have been motivated to have administered the anti-CD137 antigen-binding molecule of ‘960 to a patient that has a cancer refractory to treatment with any immune checkpoint inhibitor because Dana-Farber teaches that teaches that when a patient’s disease (i.e. cancer) is or becomes refractory, the next step may be to try another form of treatment.
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.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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