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 .
Application Status
The amended claims filed April 16, 2026 in response to the non-final Office action mailed January 16, 2026 are acknowledged. Claims 3-11 and 13 have been canceled. Claim 1 has been amended.
Claims 1, 12, and 14-16 are pending and under examination herein.
The Declaration under 37 C.F.R. § 1.130(a), filed on April 16, 2026, is acknowledged.
Priority
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119
(a)-(d). The certification of the English translation of the foreign priority document, filed April 16, 2026, is accepted by the Examiner. Applicant is entitled to the foreign priority date of the CN202010305482.7 application filed on April 17, 2020.
Claim Objections and Rejections Withdrawn
All prior grounds of rejection of claims 3-11 and 13 are rendered moot by the cancelation of the claims.
The rejections of claims 1, 12, and 14-16 under 35 U.S.C. § 103 as being unpatentable over Xu (WO 2020/077635 A1) in view of Kang (BioProcess International (2016) 14(4): 40-45) or in view of Wang (US 2019/0284292 A1) and Akamatsu (US 2019/0194329 A1) are withdrawn in view of Applicant's declaration that the relevant disclosure in Xu is made by the co-inventors of the present application (i.e., subject to the exception under 35 U.S.C. § 102(b)(2)(A)) and Applicant’s statement on the record that the subject matter of Xu and the claimed invention were, not later than the effective filing date of the instantly claimed invention, owned by the same entity or subject to an obligation of assignment to the same entity (Dingfu Biotarget Co., Ltd.) (i.e., subject to the exception under 35 U.S.C. § 102(b)(2)(C)).
The rejection of claims 1, 12, and 14-16 under 35 U.S.C. § 103 as being unpatentable over Zhang (WO 2020/078149 A1) in view of Kang (BioProcess International (2016) 14(4): 40-45) or in view of Wang (US 2019/0284292 A1) and Akamatsu (US 2019/0194329 A1) are withdrawn in view of Applicant's statement on the record that the subject matter of Zhang and the claimed invention were, not later than the effective filing date of the instantly claimed invention, owned by the same entity or subject to an obligation of assignment to the same entity (Dingfu Biotarget Co., Ltd.) (i.e., subject to the exception under 35 U.S.C. § 102(b)(2)(C)).
The rejection of claims 1, 12, and 14-16 on the ground of non-statutory double patenting as being unpatentable over claims 1-9 and 19-20 of U.S. Patent No. 12,252,542 in view of Kang (BioProcess International (2016) 14(4): 40-45) is withdrawn in view of Applicant's amendments incorporating the subject matter of claim 13 (now canceled) into claim 1.
MAINTAINED CLAIM OBJECTIONS AND REJECTIONS
Claim Objections (Maintained)
Claim 1 is objected to because of the following informalities: It is suggested that “or” be placed at the end of list item 7, before the last list item (i.e., “the VL comprises an amino acid sequence as set forth in SEQ ID NO: 10, and the VH comprises an amino acid sequence as set forth in SEQ ID NO: 21; or”).
Appropriate correction is required.
Response to Arguments
Applicant's arguments filed April 16, 2026 have been fully considered but they are not persuasive.
Applicant submits that the requested amendment has been added.
However, claim 1 has not been amended to add “or” after the second-to-last list item.
Accordingly, the objection is maintained.
Double Patenting (Maintained)
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, 12, and 14-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 and 19-20 of U.S. Patent No. 12,252,542 (‘542 patent; cited in PTO-892 mailed July 24, 2025) in view of Wang (US 2019/0284292 A1; cited in PTO-892 mailed July 24, 2025) and Akamatsu (US 2019/0194329 A1; cited in PTO-892 mailed July 24, 2025). This is a maintained rejection that has been updated to reflect Applicant's amendments to the claims.
Relevant to claim 1, the ‘542 patent claims a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds to CD137 (see patented claims 1-9 and 19; Table 1, col 23-24), wherein the antibody or antigen-binding fragment thereof comprises a VL and a VH, wherein:
Said VL comprises the mutations V3A, D71N, V77I and the amino acid sequence set forth in SEQ ID NO: 104 (which shares 100% sequence identity to instant SEQ ID NO: 1), and said VH comprises the mutation N78K and the amino acid sequence set forth in SEQ ID NO: 128 (which shares 100% sequence identity to instant SEQ ID NO: 12);
Said VL comprises the mutation D71N and the amino acid sequence set forth in SEQ ID NO: 106 (which shares 100% sequence identity to instant SEQ ID NO: 3), and said VH comprises the mutations N78K, H84Q, and D86N and the amino acid sequence set forth in SEQ ID NO: 130 (which shares 100% sequence identity to instant SEQ ID NO: 14);
Said VL comprises the mutations D71N and V771I and the amino acid sequence set forth in SEQ ID NO: 108 (which shares 100% sequence identity to instant SEQ ID NO: 5), and said VH comprises the mutations N78K, H84Q, and D86N and the amino acid sequence set forth in SEQ ID NO: 132 (which shares 100% sequence identity to instant SEQ ID NO: 16);
Said VL comprises the mutations A10V, D71N, and V77I and the amino acid sequence set forth in SEQ ID NO: 110 (which shares 100% sequence identity to instant SEQ ID NO: 7), and said VH comprises the mutations N78K, H84Q, and D86N and the amino acid sequence set forth in SEQ ID NO: 134 (which comprises 100% sequence identity to instant SEQ ID NO: 18);
Said VL comprises the mutations A10V and D71N and the amino acid sequence set forth in SEQ ID NO: 111 (which shares 100% sequence identity to instant SEQ ID NO: 8), and said VH comprises the mutations Q13K, N78K, H84Q, and D86N and the amino acid sequence set forth in SEQ ID NO: 135 (which comprises 100% sequence identity to instant SEQ ID NO: 19);
Said VL comprises the mutations V3A, A10V, K44T, D71N, and V77I and the amino acid sequence set forth in SEQ ID NO: 112 (which shares 100% sequence identity to instant SEQ ID NO: 9), and said VH comprises the mutations Q13K and N78K and the amino acid sequence set forth in SEQ ID NO: 136 (which shares 100% sequence identity to instant SEQ ID NO: 20);
Said VL comprises the mutations A10V and V77I and the amino acid sequence set forth in SEQ ID NO: 113 (which shares 100% sequence identity to instant SEQ ID NO: 10), and said VH comprises the mutations Q13K, H84Q, D86N, A90T, and F97Y and the amino acid sequence set forth in SEQ ID NO: 137 (which shares 100% sequence identity to instant SEQ ID NO: 21); or
Said VL comprises the mutations A10V and V77I and the amino acid sequence set forth in SEQ ID NO: 114 (which shares 100% sequence identity to instant SEQ ID NO: 11), and said VH comprises the mutations Q13K, N78K, H84Q, D86N, A90T, and F97Y and the amino acid sequence set forth in SEQ ID NO: 138 (which shares 100% sequence identity to instant SEQ ID NO: 22).
Relevant to claims 15-16, the ‘542 patent further recites a method of treating colorectal cancer that comprises administering an effective amount of a composition comprising said antibody.
However, the ‘542 patent does not expressly claim that the preparation (pharmaceutical composition) comprises about 20 mM buffer salt including sodium dihydrogen phosphate and disodium hydrogen phosphate, about 3-7% sucrose by weight, about 10 mM sodium citrate, about 50 mM histidine, about 0.05% polysorbate 80 by weight, and water.
Wang discloses antibodies that specifically bind to 4-1BB (CD137) and pharmaceutical compositions comprising the same (e.g., Abstract; Summary). Wang teaches that antibodies of the invention formulated for parenteral administration may be prepared in a suitable buffer including sodium citrate, and contained in a flint or amber vial, ampule or pre-filled syringe (e.g., pages 21-22), relevant to claims 1 and 14. Further relevant to claim 1, Wang further teaches that sucrose (0-10%, optimally 0.5-1.0%) may be added to lyophilized formulations as a cryoprotectant (e.g., pages 21-22). Wang teaches that polysorbate 80 (0-0.05%) may be included as a surfactant (e.g., page 22). Wang further teaches that antibody formulations suitable for parenteral administration may be formulated in powder form for reconstitution with a suitable vehicle (e.g., sterile pyrogen-free water) before being administered to a subject (e.g., pages 21-22). Wang further teaches that the pharmaceutical compositions of the invention can comprise the buffer L-histidine (1-50 mM) (e.g., page 22).
Akamatsu also discloses anti-4-1BB antibodies and pharmaceutical compositions comprising the same (e.g., Abstract). Akamatsu teaches that pharmaceutical compositions of the invention may be prepared for storage as lyophilized formulations or as aqueous solutions by mixing an antibody of the invention with a pharmaceutically acceptable carrier, e.g., buffering agents (e.g., page 13). Akamatsu teaches that buffering agents help to maintain the pH of the formulation in the range simulating physiological conditions, and that buffering agents may be present in a wide range of concentrations from about 2 mM to about 50 mM (e.g., page 13). Suitable buffering agents for use in the formulations of the invention include phosphate buffers (e.g., monosodium phosphate (also known as sodium dihydrogen phosphate) and disodium phosphate (also known as disodium hydrogen phosphate) and citrate buffers (e.g., monosodium citrate-disodium citrate mixture) (e.g., page 13), relevant to claim 1. As understood by those of ordinary skill in the art, physiological pH typically ranges between 7.35 to 7.45, relevant to claim 12.
Further relevant to claim 1, Akamatsu teaches that stabilizers may be added which range in function from acting as a bulking agent, solubilizing the therapeutic agent, or helping to prevent denaturation or adherence to the container wall (e.g., page 13). Typical stabilizers include sucrose, trehalose, and mannitol, and may be present in amounts ranging from 0.5-10% (wt). Akamatsu teaches that non-ionic surfactants (e.g., polysorbate 80) may be added to help solubilize the glycoprotein or protect the glycoprotein from agitation-induced aggregation (e.g., pages 13-14).
Further relevant to claim 14, Akamatsu teaches that dry powder unit dosage forms may be packaged in a kit with a syringe and that liquid formulations may be pre-filled in a syringe in an amount suitable for a single administration (e.g., page 13).
In view of the teachings above, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive at a formulation comprising the anti-CD137 antibody preparation taught in the ‘542 patent, about 20 mM buffer salt (including sodium dihydrogen phosphate and disodium hydrogen phosphate), about 3-7% sucrose by weight, about 10 mM sodium citrate, about 50 mM histidine, about 0.05% polysorbate 80 by weight, and water, by trying various combinations of buffers, surfactants, and sugars in the process of routine optimization. The skilled artisan would have been motivated to do so because:
buffering agents (e.g., sodium citrate, monosodium phosphate, disodium phosphate) help to maintain the formulation at physiologically relevant pH conditions (as taught by Akamatsu);
stabilizers (e.g., sucralose) can be used to function as bulking agents, solubilize the therapeutic agent, or prevent denaturation or adherence to the container wall (as taught by Akamatsu and Wang);
surfactants (e.g., polysorbate 80) help to solubilize the glycoprotein and protect the glycoprotein against agitation-induced aggregation (as taught by Akamatsu), and
water acts as a suitable vehicle for (re)constituting antibody formulations into a liquid form suitable for parenteral administration (as taught by Wang).
There are a finite number of previously identified, predictably behaving options for buffers, surfactants, and sugars, and these excipients have been successfully incorporated into previously described anti-CD137 antibody formulations. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, buffers) have utility for the same respective purposes and are functionally equivalent.
Response to Arguments
Applicant's arguments filed April 16, 2026 have been fully considered but they are not persuasive.
Applicant asserts that Kang, Wang, and Akamatsu do not disclose the specific formulation of the instantly claimed preparation, in particular, the specific formulation of claim 1, which Applicant states showed good stability (e.g., Tables 4-1 to 4-7) and had relatively better binding activity (e.g., Table 4-10). Applicant argues that a skilled person “cannot get the specific formulation based on “Kang”, “Wang” or “Akamatsu” and cannot expect the stability and killing effect of preparations 13 and 14”. Remarks at pages 7-8.
In response, it remains held that one of ordinary skill in the art would have recognized that the buffers, surfactants, and sugars disclosed by Wang and Akamatsu are suitable for use in antibody formulations and have specific functions that are desirable for those formulating pharmaceutical compositions requiring a specific pH and stability. Wang and Akamatsu further provide that these specific pharmaceutically acceptable excipients are suitable for use in anti-CD137 antibody compositions. While Applicant emphasizes that none of the cited references teach the specific formulation recited in the present claims, the matter of anticipation (as is applicable under 35 U.S.C. § 102) is separate from that of obviousness (as is applicable under 35 U.S.C. § 103). MPEP § 2144.05 teaches, “"[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”. It was considered routine and conventional for those of ordinary skill in the art at the time of filing of the instantly claimed invention to optimize the concentration of buffers, sugars, and surfactants in a pharmaceutical composition to increase stability of the composition.
With respect to the “killing effect” of preparations 13 and 14, from which the presently claimed composition is modeled, it is generally expected that the active ingredient in such a pharmaceutical composition – namely, the anti-CD137 antibody – would have a greater influence on the killing effect of the pharmaceutical formulation than the pharmaceutically acceptable excipients included in the composition.
For the reasons above, the rejections are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Elizabeth A Shupe whose telephone number is (703) 756-1420. The examiner can normally be reached Monday to Friday, 9:30am - 6:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
Prosecution Insights