DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 3/6/26, are acknowledged.
Claims 1-2, 13, 20, 28, 50-51, 53, 57, 60, 62-64, 68, 70 and 116 have been amended.
Claims 1-2, 13, 20, 28, 32, 50-51, 53, 57, 60, 62-64, 68, 70 85, 99 and 116 are pending and are under examination.
In view of Applicant’s claim amendments, only the following rejections remail.
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.
Claims 53 and 57 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.
The term “about” in claims 53 and 57 is a relative term which renders the claims indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Applicant’s arguments filed 3/6/26 have been fully considered, but they are not persuasive.
Applicant argues that according to MPEP 2173.05(b), when a term of degree is presented in a claim, a determination is first to be made as to whether the specification provides some standard for measuring the degree, and if it does not, a determination is made as to whether one of ordinary skill in the art, in view of the status of the art, would be nevertheless reasonably apprised of the claim scope. Applicant argues that the term “about”, when viewed in light of the specification, would not be indefinite.
Applicant cites no teachings of the specification that shed light on the scope of “about”. The ordinary artisan, even in view of the status of the art, would not be reasonably apprised of the claim scope, and Applicant presents no evidence to the contrary.
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.
Claims 1-2, 13, 20, 28, 32, 50-51, 53, 57, 60, 62-64, 68, 70, 85, 99, and 116 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20160257752, in view of WO2019025545 (of record),
The ‘752 application teaches a method of treating cancer comprising administering to an individual having cancer a human PD-1 axis binding antagonist and a taxane (see page 1, in particular). The ‘752 application teaches that the PD-1 axis binding antagonist can be a PD-L1 binding antagonist such as a PD-L1 antibody (see paragraphs 7-8 and 127-128, in particular). The ‘752 application teaches that the taxane can be administered before, simultaneously with, or after the PD-1 axis antagonists (see paragraph 14, in particular). The ‘752 application teaches that the taxine is paclitaxel (see paragraph 14, in particular). The ‘752 publication teaches a composition comprising said PD-1 axis binding antagonist and the taxane (See paragraph 308 and 316, in particular). The ‘752 application discloses the antibody can be a bispecific antibody (See paragraph 87 and 210-211, in particular). The ‘752 application also teaches that the taxane and PD-1 axis antagonist can be administered in conjunction with an antibody that binds and activates CD137 (see paragraph 325 and 328, in particular). The ‘752 application teaches that inhibiting PD-L1 axis in combination with a taxane provides a synergistic anti-tumor effect (See paragraph 350, in particular). The ’752 publication teaches that the antibody and the taxane can be administered in treatment cycles (see pages 318-319, in particular). The ‘752 publication teaches that the dose of antibody can range from 0.01 to 15 mg/kg and that the dose of taxane can be about 25 to about 100 mg/m2 (see paragraphs 318-319, in particular). The ‘852 publication teaches intravenous administration (see paragraphs 21, 319-322, in particular). The ‘752 publication teaches treatment cycles of 21 days (see paragraph 318-319, 322), and also teaches an embodiment wherein the antibody and taxane are administered on the same day (see paragraph 14, 318-319, in particular). The ‘752 publication teaches administration every three weeks, Q3W, see paragraph 318-319, 322, in particular). The ‘752 publication teaches that in some embodiments the patient can be one who has been treated with a cancer therapy before the treatment with the PD-1 axis inhibitor and the taxane (See paragraph 315, in particular). However, the, 752 publication also teaches that the combination treatment can result in complete response and it would also be obvious that it could be given as a first treatment for cancer (see paragraph 13, in particular). The ‘752 publication teaches further administering other agents such as dexamethasone (see paragraph 81-82, in particular). The ’752 publication in particular teaches that in a clinal setting, treatment with paclitaxel typically involves premedication with dexamethasone to lower hypersensitivity reactions (See paragraph 349). Thus, it would be obvious that when using paclitaxel as the taxane, as explicitly taught in the ‘752 publication, one should use a prior treatment with dexamethasone to lower hypersensitivity. For example, one could envision in the sequential treatment method embodiment taught by the reference, giving dexamethasone, followed by paclitaxel, and at a sequential, later time point giving the PD-1 axis antagonism, in a treatment cycle.
The reference differs from the claimed invention in that it does not explicitly teach a binding agent comprising a first binding region binding to human CD137 and a second binding region binding to human PD-L1.
WO2019025545 teaches a method of treating cancer comprising administering a bispecific antibody comprising a first binding arm that binds to human CD137 and a second binding art that binds to human PD-L1 (see pages 1-4, in particular). WO2019025545 teaches that the bispecific antibody functions to activate CD137, and also to block PD-L1 binding, leading to increased anti-tumor T cell responses (see page 3, in particular). WO2019025545 teaches that the antibody is particularly useful in therapeutic settings where stimulation of CD137 and blocking pf the PD-1/PD-L1 axis is needed, since it can be achieved simultaneously resulting in higher magnitude of T cell proliferation (See page 4, in particular). WO2019025545 teaches that the PD-L1 binding arm comprises a VH and VL of SEQ ID NO: 17 and 21, respectively, which comprise the CDRs of SEQ ID NO: 9-11, 13, DDN, and 14 of the instant application. WO2019025545 teaches that the CD137 binding arm comprises a VH and VL of SEQ ID NO: 15 and 16, which comprises CDRS of SEQ ID NO: 2-4, 6, GAS, and 7 of the instant application (see Table 1 on pages 83-84, in particular). WO2019025545 teaches that the bispecific antibody comprises each VH having a CH comprising a CH3 having asymmetrical mutations (see pages 60-69, in particular). WO2019025545 teaches that the CH regions comprise a first and second IgG1 CH with different substitutions such as in T366, L368, K370, F405, Y407, or K409 (see pages 60-69, in particular). WO2019025545 teaches both CH regions having substitution of L234, L235, or D265, with F, E, and A, respectively, and wherein F405 of the first heavy chain is L, and K409 of the second heavy chain is R (See pages 74-75, in particular). Thus, the antibodies in WO2019025545 have the same VH/VL and CH domains and are therefore within the scope of acasunlimab. WO2019025545 teaches effective dosages range from 0.1 to 20 mg/kg and administration intravenously and administering repeated dosage over a period of time, i.e. cycles (See pages 81-82, in particular). WO2019025545 teaches administration of the bispecific antibody in combination with a chemotherapeutic agent (see page 83, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the bispecific PD-L1 and CD137 binding antibody of WO2019025545, as the PD-L1 antagonist and CD137 agonist antibodies in the method of the ‘752 application. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because WO2019025545 teaches that the antibody is particularly useful in therapeutic settings where stimulation of CD137 and blocking pf the PD-1/PD-L1 axis is needed, since it can be achieved simultaneously resulting in higher magnitude of T cell proliferation.
Alternatively, it also would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to further administer a taxane as the chemotherapeutic agent, as taught by the ‘752 publication, in the method of treating cancer with the bispecific antibody of WO2019025545. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘752 application teaches that inhibiting PD-L1 axis in combination with taxane provides a synergistic anti-tumor effect.
Applicant’s arguments filed 3/6/26 have been fully considered, but they are not persuasive.
Applicant argues that the ‘752 publication teaches synergy and therapeutic benefit from blocking PD-1/PD-L1 signaling in combination with taxanes, but that nothing in Kim indicates this synergy would be maintained if PD-1 blockage/antagonism was replaced with an agent that stimulates CD137/4-1BB.
The rejection does not rely on replacing PD-1 blockade, since multispecific PD-1/CD137 antibody of WO 2019/025545 also functions to as a PD-1/PD-L1 antagonist. Moreover, the ‘752 publication explicitly teaches that the taxane and PD-1 axis antagonist can be administered in conjunction with an antibody that binds and activates CD137 (see paragraph 325 and 328, in particular. WO 2019/025545 also teaches that the bispecific PD-L1/CD137 antibody can be combined with chemotherapy to treat cancer. The references provide a reasonable expectation of success in combining the bispecific antibodies with chemotherapy such as a taxane to treat cancer. The references also provide a reasonable expectation that synergy could be achieved, since the multispecific antibody of WO 2019/025545 functions to block PD-1/PD-L1 and activate CD137, and the ‘752 publication teaches synergy between a combination of a taxane and PD-1/PDL-1 blockade, and that the combination can further include an antibody that activates CD137.
Applicant further argues that WO 2019/025545 teaches PD-L1x CD137 bispecific antibody that blocks PD-1/PD-L1 signaling and activates CD137, and this dual engagement is not contemplated by the ‘752 publication. Applicant argues that therefore nothing would suggest that the synergy of the ‘752 publication could be preserved.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Obviousness does not require absolute predictability or conclusive proof of efficacy is not required (see MPEP 2143.02). The prior art references provide a reasonable expectation of success for the reason set forth above.
Applicant further argues that WO 2019/025545 is directed to 4-1BB/CD137 agonists and not chemotherapy combinations, and therefore dos not suggest synergy with taxanes and there would be no motivation to combine a taxane with the bispecific antibody of WO 2019/025545 with a reasonable expectation of success.
WO 2019/025545 explicitly teaches that the bispecific PD-L1/CD137 antibody can be combined with chemotherapy for treating cancer, and the ordinary artisan would be motivated to select a taxane as the chemotherapeutic to enhance treatment based on the teachings of the cited references with a reasonable expectation of success.
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 1-2, 13, 20, 28, 32, 50-51, 53, 57, 60, 62-64, 68, 70, 85, 99, and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-6, 9-10, 12-13, 15, 18, 22, 25-26, 44, 48, 66, 68-69, 71, 76, 60, 86, and 89 of copending Application No. 18/570,257, in view of US 20160257752.
The ‘257 application claims a method of treating cancer in a subject comprising administering a binding agent comprising a first binding region to human CD137 and a second binding region to human PD-L1 in the dosages and regimens encompassed by the instant claims, and also claims that the binding agent has the same CDRs, CH region mutations as recited in the instant claims. The ‘257 application does not claim administering in combination with a taxane, however it would be obvious to do so based on the teachings of the ‘752 publication because the reference teaches that inhibiting PD-L1 axis and activation of CD137 in combination with taxane provides a synergistic anti-tumor effect. Furthermore, the dosing parameters and other limitations would also be obvious based on the teachings of the ‘752 application (see above).
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 13, 20, 28, 32, 50-51, 53, 57, 60, 62-64, 68, 70, 85, 99, and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 94-115 of copending Application No. 17/172,700, in view of US 20160257752.
The ‘700 application claims a method of treating cancer in a subject comprising administering a binding agent comprising a first binding region to human CD137 and a second binding region to PD-L1 in the dosages and regimens encompassed by the instant claims, and also claims that the binding agent has the same CDRs, CH region mutations as recited in the instant claims. The ‘700 application does not claim administering in combination with a taxane, however it would be obvious to do so based on the teachings of the ‘752 publication for the same reasons set forth above. Furthermore, the dosing parameters and other limitations would also be obvious based on the teachings of the ‘752 application for the same reasons set forth above.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 13, 20, 28, 32, 50-51, 53, 57, 60, 62-64, 68, 70, 85, 99, and 116 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10,968,280, or claims 1-19 of 11,459,395 in view of US 20160257752.
The patents claim a binding agent comprising a first binding region to human CD137 and a second binding region to PD-L1, wherein the binding agent has the same CDRs, CH region mutations as recited in the instant claims. The patents disclose the use of the claimed antibodies is for treating cancer and the present claims merely claim the same anti-cancer use of the antibodies patented in the above applications, in combination with a taxane. However, it would be obvious to use PD-L1 and CD137 binding antibodies in combination with a taxane for treating cancer based on the ‘752 publication for the same reasons set forth above. Furthermore, the dosing parameters and other limitations would also be obvious based on the teachings of the ‘752 application for the same reasons set forth above.
Claims 1-2, 13, 20, 28, 32, 50-51, 53, 57, 60, 62-64, 68, 70, 85, 99, and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 87, 90, 92, 94, 96, 98, 100, 102, 104-139 of copending Application No. 17/172,698, or claims 89, 92-94, 97-98, 101-102, 104-128 of 17/821,837, in view of US 20160257752.
The applications claim a multispecific antibody, or a method of producing a multispecific antibody that binds CD137 and PD-L1, and the present claims merely claim the same anti-cancer use of the antibodies patented in the above applications, in combination with a taxane. However, it would be obvious to use PD-L1 and CD137 binding antibodies in combination with a taxane for treating cancer based on the ‘752 publication for the same reasons set forth above. Furthermore, the dosing parameters and other limitations would also be obvious based on the teachings of the ‘752 application for the same reasons set forth above.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 13, 20, 28, 32, 50-51, 53, 57, 60, 62-64, 68, 70, 85, 99, and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-98 of copending Application No. 18/698,354, in view of US 20160257752.
The ‘354 application claims a method of treating cancer in a subject comprising administering a binding agent comprising a first binding region to human CD137 and a second binding region to PD-L1 and also claims that the binding agent has the same CDRs, CH region mutations as recited in the instant claims. The ‘354 application does not claim administering in combination with a taxane, however it would be obvious to do so based on the teachings of the ‘752 publication for the same reasons set forth above. Furthermore, the dosing parameters and other limitations would also be obvious based on the teachings of the ‘752 application for the same reasons set forth above.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 13, 20, 28, 32, 50-51, 53, 57, 60, 62-64, 68, 70, 85, 99, and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/696,689, 17/289,602, 17/759,906, or 17795318, in view of US 20160257752.
The copending applications claim the same CD137 and PD-L1 binding antibody of the instant claims, or method of treating cancer in a subject comprising administering a said antibody. It would be obvious to administer the antibody to treat cancer in combination with a taxane based on the teachings of the ‘752 publication for the same reasons set forth above. Furthermore, the dosing parameters and other limitations would also be obvious based on the teachings of the ‘752 application for the same reasons set forth above
This is a provisional nonstatutory double patenting rejection.
Applicant argues that the claims are not obvious for the same reasons set forth above.
The claims stand rejected for the same reasons set forth above.
No claim is allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 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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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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