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 .
The prior art rejections are withdrawn in favor of the new grounds of rejection under this section, adding Schutz et al., Oncotarget. 2016 Oct 18; 7(42): 68503-68512, identified in the IDS dated 10/31/2025:
Claim Rejections - 35 USC § 103
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, 13, 14, 16, 19 and 20 remain rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 20050089519 based on an application by Kipriyanov et al. (Kipriyanov) in view of:
Arruebo et al., Journal of Nanomaterials, Volume 2009, January 2009, Article No.: 37, pp 1–24, previously cited (Arruebo); and
Schutz et al., Oncotarget. 2016 Oct 18; 7(42): 68503-68512, identified in the IDS dated 10/31/2025 (Schutz).
Kipriyanov teaches multivalent multimeric antibodies comprising at least two binding sites specific for the human B cell marker CD19 and human Fc gamma receptor III (CD16). Also described are polynucleotides encoding said antibodies as well as vectors comprising said polynucleotides, host cells transformed therewith and their use in the production of said antibodies. Finally, compositions are described comprising any of above mentioned antibodies, polynucleotides or vectors. The pharmaceutical compositions are useful for immunotherapy, preferably against B cell malignancies such as non-Hodgkin's lymphoma, see Abstract.
Kipriyanov may fail to explicitly teach conjugation to nanoparticles. However, the therapeutic benefits of conjugating antibodies to the recited nanoparticles were known, see Arruebo:
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Schutz (identified in the IDS dated 10/31/2025) also demonstrates that T-cell redirectors coupled to nanoparticles were known:
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In this way, those of ordinary skill could have applied anti-CD19/anti-CD18 antibodies to nanoparticles in the manner required and in a predictable fashion for the purposes of obtaining the recited conjugates. As outlined above, Kipriyanov teaches multivalent multimeric antibodies comprising at least two binding sites specific for the human B cell marker CD19 and human Fc gamma receptor III (CD16). The secondary references are added for the proposition that antibody-modified nanoparticles are applicable to these antibodies. Specifically, the secondary references demonstrate teaches that the technique of conjugating multi-specific antibodies to nanoparticles was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to multispecific antibodies, such as anti-CD19/anti-CD18 antibody taught by Kipriyanov, would have yielded predictable results. Accordingly, conjugating anti-CD19/anti-CD18 antibodies to nanoparticles for the purposes of providing the instant conjugates would have been prima facie obvious.
Claims 15 and 18 remain rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 2005089519 based on an application by Kipriyanov et al. (Kipriyanov) in view of:
Arruebo et al., Journal of Nanomaterials, Volume 2009, January 2009, Article No.: 37, pp 1–24, previously cited (Arruebo); and
Schutz et al., Oncotarget. 2016 Oct 18; 7(42): 68503-68512, identified in the IDS dated 10/31/2025 (Schutz); in further view of:
“Chemotherapy of Neoplastic Diseases” in Goodmann & Gilman's Manual of Pharmacology and Therapeutics, 2008, McGraw-Hill Medical 2008, previously cited (Goodmann & Gilman's).
The primary and secondary references may fail to explicitly teach that the additional therapeutic agents. However, it is for that proposition that the examiner joins Goodmann & Gilman's, which teaches that anti-cancer regimens are optimized with combination therapies in order to avoid common mechanisms of resistance:
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In this way, those of ordinary skill could have applied combination therapy in a predictable fashion for the purposes of treating the recited cancers. Specifically, Goodman & Gilman’s teaches that the particular known technique of combination therapy was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to the recited conjugates would have yielded predictable results, see MPEP 2144 (“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 reKerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”). Accordingly, including the recited conjugates in combination therapy for the purpose of treating cancer would have been prima facie obvious.
Applicant argues that the multivalent multimeric antibodies taught by Kipriyanov have structures quite different from those claimed in the instant application. Therefore, the antibodies of Kipriyanov do not fall into the scope of the claimed multispecific binding conjugate.
However, the claims recite that the first and second binding moieties are antibodies, or fragments thereof. As explicitly taught in the rejection, Kipriyanov teaches multivalent multimeric antibodies comprising at least two binding sites specific for the human B cell marker CD19 and human Fc gamma receptor III (CD16), and therefore, meets the reequipments of the recited first and second binding moieties.
Applicant also argues that Arruebo teaches that antibody-conjugated nanoparticles is useful for targeted drug delivery, wherein an antibody is used as a specific targeting moiety (e.g., tumor cell binding moiety) and conjugated to a nanoparticle, in order to deliver the drug loaded on or within the nanoparticle to the target cell with specificity (e.g., tumor cell). The Office cites Example (ii) of antibody-conjugated nanoparticles as showing that antibody-modified nanoparticles was recognized as part of the ordinary capabilities of one having skill in the art. However, while Arruebo teaches the conjugation of one antibody to a nanoparticle, Arruebo does so where the antibody is the targeting moiety, i.e., using the antibody's specificity to the target cell to deliver the chemotherapeutic drug formulated in the nanoparticle to the target cell allowing for the chemotherapeutic drug to kill the target cell. As such, the therapeutic effect is brought about by the drug delivered. The boost in therapeutic effect is a result of the specific targeting of the target cell by the antibody.
However, the claims do not exclude drug-loaded NP’s from the claims. In this manner, Arruebo is added for the proposition that the therapeutic benefits of conjugating antibodies to the recited nanoparticles were known, as outlined above.
Applicant argues that one of skill in the art would have no reasonable expectation of success in combining or modifying Kipriyanov and Arruebo. As demonstrated in Example 3 of the instant application, the conjugate of claim 1 enhanced the killing rate for tumor cells bound by NK cells, up to 80% or higher at E:T (i.e., NK cells : tumor cells) of 4:1, even more than 90%, with specific lysis window (the difference between the induced killing rate in the presence of the conjugate and the induced killing rate in the absence of the conjugate) of more than 60% (Table 2), even higher than that of the traditional BsAb taught by Kipriyanov (60% at 5ug/ml and E:T of 50:1) (Fig. 11).
However, Applicant’s remarks regarding Example 3 do not refute the known benefits of conjugating bispecific antibodies to NP’s as demonstrated by the references. In this manner, Applicant’s remarks do not refute that the references provide a reasonable expectation of success.
Nonetheless, Schutz (identified in the IDS dated 10/31/2025) also demonstrates that T-cell redirectors coupled to nanoparticles were known.
The double patenting rejections remain outstanding:
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 13-16, 18-20 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-9 of U.S. Patent No. 11000603;
Claims 11-17 of U.S. Patent No. 11525009;
Claims 1-6 of U.S. Patent No. 10758625.
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims also cover nanoparticle conjugates, wherein the conjugate comprises a first and second binding moieties connected by a nanomaterial which is a biodegradable nanomaterial. In this manner, the conflicting claims anticipate the scope of the instant claims.
Alternatively, the difference between the conflicting claims and the claimed inventions is that the conflicting claims may not teach the invention with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the instant conjugates with sufficient guidance and particularity, based on the structure of the recited bispecific antibody. In this manner, the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
In particular, the bispecific antibody conjugates of US 11525009 read on instant nanoparticle conjugates comprising a first and second binding moieties.
US 11525009:
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US 10758625:
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Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 10/31/2025 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). 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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646
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