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 rejection under section 103 is maintained:
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, 8, 9, 19, 22, 24, 28-30 remain rejected under 35 U.S.C. 103 as being unpatentable over:
WO 2017025033 (WO 033) and GenCore version 6.4.2 , Biocceleration Ltd. Database Accession No. BDO13634, 2015 and GenCore version 6.4.2 , Biocceleration Ltd. Database Accession No. BDO13635, 2015 (collectively “sequences”);
in view of:
Schutz et al., Oncotarget. 2016 Oct 18; 7(42): 68503–68512 (Schutz); or
U.S. Publication No. 20150366991 based on an application by Schneck et al. (Schneck); or
Tang et al., 2015, Expert Opinion on Biological Therapy, 15:9, 1251-1255 (Tang); or
Xu et al., Nanoscale, 2019, 11, 9661-9678 (Xu);
in further view of
Nobs et al., Bioconjugate Chem. 2006, 17, 139−145 (Nobs); or
Shargh et al., Nanomedicine, 11(1), 2016, 63–79 (Shargh).
WO 033, demonstrates that the anti-CD16/CEA bispecific antibody was known, see claims 4 and 5, SEQ ID NOS: 1 and 2. See also, sequences:
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WO 033 may fail to explicitly teach conjugation of the bispecific antibody to a nanoparticle.
However, nanoparticles conjugated with both an antigen-specific T cell binding moiety and a tumor cell binding moiety, were known.
See Schutz:
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See also Schneck:
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See Tang, teaching nanoparticle bispecific T cell engagers (BITE’s) were known,
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Tang also teaches magnetic bispecific cell engager (MagBICE), that combines BiAbs with biodegradable iron nanoparticles. Tang teaches that in treating cancer, the advantages of MagBICE over traditional BiTE could even extend beyond magnetic targeting and imaging; alternating current electromagnetic field could be applied to generate hyperthermia at MagBICE particles to enhance cancer cell death.
Regarding conjugating a bispecific antibody with a nanoparticle, the secondary references teach that a nanoparticle conjugated with two types of antibodies can achieve the same function as a traditional bispecific antibody (e.g., co-localization of immune effector cell/therapeutic cell and target cell). This is emphasized by Applicant:
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See Applicant’s remarks dated 12/11/2023.
In this regard:
(1) the prior art contained a conjugated nanoparticle which differed from the claimed nanoparticles by the substitution with a bispecific antibodies, instead two monospecific antibodies;
(2) the substituted bispecifc antibody and its functions were known in the art;
(3) one of ordinary skill in the art could have substituted the bispecific antibodies for the monospecific antibodies, and the results of the substitution would have been predictable; as admitted by Applicant, see above.
Here the claim would have been obvious because the substitution for the bispecific antibody yielded a reasonable expectation of success.
The claims require conjugation to specific biodegrable nanoparticle (NP’s). However, antibody conjugation to these NP’s was known.
See Nobs teaching biodegradable poly(lactic acid) (PLA) conjugated to anti-HER2 antibodies.
See Shargh:
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In this way, those of ordinary skill could have applied the required NP’s in the manner required and a predictable fashion for the purposes of providing the recited multi- specific antibody conjugates. As outlined above, the primary references teach the required anti-CD16/CEA bispecific antibody as bispecific T cell engagers. The secondary references are added for the proposition that these bispecific antibodies are applicable to antigen-specific nanoparticles for cancer therapy. Specifically, the secondary references teach that the particular known technique of using biodegradable NP’s conjugated with bispecific T-cell engagers 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 of conjugating nanoparticles with bispecific antibodies, such as those taught by the primary references, to provide bispecific T cell engagers, would have yielded predictable results. Accordingly, conjugating biodegradable NP’s with the claimed CD16/CEA bispecific antibody conjugates would have been prima facie obvious.
Significantly, the prior art teaches anti-CD16/CE bispecific antibodies conjugated to a nanomaterial. It is for this proposition that the following are combined in the rejection:
Xu:
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See page 9662.
The benefits of using biodegradable nanoparticles were known, see Nobs and Shargh, above. Any characteristics, including the alleged unexpected results, would have been a necessary aspect of this nanoparticle.
Applicant argues that the references do not render the instant invention obvious or teach each and every aspect of the claimed invention.
However, the rejection is a combination of references, not taken singly, as represented in Applicant’s remarks. The combination of references teaches teach every aspect of an anti-CD16/CEA bispecific antibody conjugated to a biodegradable nanoparticle.
Applicant argues that the cited references teach away from the claimed composition and fail to provide one of ordinary skill in the art with a reasonable expectation of success.
However:
WO 033 teaches that the instant anti-CD16/CEA bispecific antibodies were known.
The secondary references demonstrate that biodegradable NP-conjugated antibodies were known, see Nobs, for example.
As discussed above, those of ordinary skill would have recognized that applying the known technique of conjugating the recited bispecific antibodies to biodegradable NP’s would have yielded predictable results, in view of at least these disclosures. Also, none of the references clearly teach that the recited NP-conjugated antibodies are unlikely to provide a reasonable expectation of success. Therefore, the references do not teach away from the instant invention.
Applicant's reiterates arguments regarding Tang disclosing "MagBICE agents are iron nanoparticles conjugated with two types of antibodies." Tang, page 1253, col.1, para. 2 (emphasis added). Applicant also argues that the Office Action also fails to consider Applicant's arguments regarding Schutz and Schneck not disclosing increased tumor killing rates.
Again, these references demonstrate that bispecific T cell redirector NP’s were known. The difference between these references and the invention is the use of bispecific antibodies on biodegradable NP’s, which were known, see WO 033 and Nobbs.
Also, as argued above, Applicant suggests that the secondary references show interchangeability with bispecific antibodies:
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See Applicant’s remarks dated 12/11/2023.
Nonetheless, arguments regarding these references have been addressed.
Regarding any alleged unexpected result, Applicant has not demonstrated that the instant NP’s have a superior effect over other NP’s with bispecific antibodies. Therefore, any alleged unexpected effect is not probative of non-obviousness.
Regarding the eligibility of Xu as prior art against the instant application, Applicant has not shown support for the instant application in priority document PCT/CN2016/101984. Specifically, an English translation of PCT/CN2016/101984 indicating support for the instant application has not been provided. Therefore, Xu remains eligible as prior art against the instant application.
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.
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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