DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment filed on January 12, 2026 is acknowledged.
Claims 2-8, 11, 13, 17, 20, 22, 23, 35, 36, 39-45, and 51-53 have been canceled.
Claims 1, 9, 10, 12, 14-16, 18, 19, 21, 34, 37, 38, and 46-50 are pending.
Claims 9, 10, 37, and 46-49 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 30, 2025.
Claims 1, 12, 14-16, 18, 19, 21, 34, 38, and 50 are currently under consideration as they read on the elected invention of a polypeptide and the species of E435R/P329R and OX40.
3. In view of applicant’s amendment, following rejections are set forth.
4. 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 1, 12, 14-16, 18, 19, 21, 34, 38, and 50 stand 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 for the reasons of record.
Independent claim 1 recites “an Fc region of a human IgG …. E345R and P329R in human IgG1” The preamble recites human IgG which encompass human IgG1-IgG4, wherein the body of the claims recites human IgG1. As such, the limitation of human IgG1 does not appear to have antecedent basis in that the preamble recited human IgG, not human IgG1.
Amending claim 1 by replacing “human IgG1” in line 4 to “the Fc” or “said Fc” would obviate this rejection.
6. 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.
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.
7. Claims 1, 12, 14-16, 18, 19, 21, 34, 38, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Hoffman et al. (US2014/0051834) in view of Randall et al. (WO 2016/164480, reference on IDS) for the reasons of record.
Hoffman et al. teach a polypeptide comprising a human Fc variant comprising at least one amino acid mutation with reduced effector function. Hoffman et al. teach:
“[0010] In other instances, for example, where blocking the interaction of a widely expressed receptor with its cognate ligand is the objective, it would be advantageous to decrease or eliminate all antibody effector function to reduce unwanted toxicity. Also, in the instance where a therapeutic antibody exhibited promiscuous binding across a number of human tissues it would be prudent to limit the targeting of effector function to a diverse set of tissues to limit toxicity. Last but not least, reduced affinity of antibodies to the Fc.gamma.RII receptor in particular would be advantageous for antibodies inducing platelet activation and aggregation via Fc.gamma.RII receptor binding, which would be a serious side-effect of such antibodies”
Hoffman et al. teach a polypeptide comprising a human IgG Fc variant comprising P329R substitution to destroy the proline sandwich within the Fc-region (e.g. see [0026]-[0031]). In examples, Hoffman et al. teach human anti-CD20 IgG antibody having P329R amino acid substitution leads to markedly reduced cytosolic activity; and teach that P329R destroys the function of proline sandwich in the human IgG antibody similar to P329G Fc variant (e.g. see FIG. 3b, copied below and [0487]).
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Hoffman et al. teach composition comprising the polypeptide (e.g. see [0418]) and articles of manufacture in a container such as vials (e.g. see [0447]).
The reference teachings differ from the instant invention by not describing E345R substitution and an antibody that binds TNFR-SF including OX40.
Randall et al. teach a polypeptide comprising an antigen binding region that binds to a cell surface receptor that is a member of receptor family TNFR-SF including
OX40 (e.g. see [0008]-[0021]), and an modified Fc region from human IgG1 Fc region comprising amino acid modification including E345R for diminished CDC activity (e.g. see [0013]-[0014] and [0056]). Randall et al. teach human IgG1 Fc region comprising amino acid substitution E345R (e.g. see Table 4 in page 72). Randall et al. teach additional substitutions in human IgG1 Fc region including substitution in position 329 including P329G ([0417]-[0418]). Randall et al. teach single variant E345R (e.g. see [0578]).
It would thus be obvious to one of ordinary skill in the art at the time the invention was filed to combine the teachings of Hoffman et al. and Randall et al. to produce an human IgG Fc variant comprising combination substitutions in position E345 including E345R and position P329 including P329R. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, since Hoffman et al. teach P329R substitution in the Fc region of a human IgG1 antibody would provide the benefit of reduced effector functions thereby limit antibody toxicity and Randall et al. teach E345R and substitution in P329G in the Fc region of human IgG1 would diminish CDC. As such, combining E345R and P329R by the methods of making point mutation in the Fc region disclosed by both Hoffman et al. and Randall et al. would have yielded predictable result of an IgG antibody with E345R and P329R substitutions in the Fc region for reduced effector functions and reduced toxicity.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that the claims have been amended to incorporated the limitation of previous claim 11 (now canceled). As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Now canceled claim 11 encompass the first mutation E345R and the second mutation P329R. The E345R and P329R double mutations were found obvious for the reasons stated in the previous Office Action mailed on July 11, 2025 and reiterated above. As such, applicant’s arguments have not been found persuasive.
8. No claim is allowed.
9. 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.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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, Misook Yu can be reached at 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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/CHUN W DAHLE/Primary Examiner, Art Unit 1641