DETAILED ACTION
Applicant’s amendments to the claims filed 5/20/2026 are acknowledged and entered into the record.
Accordingly Claims 31-50 are pending and will be examined on the merits.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections Maintained - 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.
Claim(s) 31-50 are rejected under 35 U.S.C. 103 as being unpatentable over Bell et al. (US Patent 9,718,880) in view of Chamberlain et al. (US Patent 8,088,376).
The claims are drawn to the anti-C5 antibody eculizumab comprising a VH and VL having SEQ ID NOs: 7 and 8, respectively having a variant human Fc constant region with greater affinity to FcRn than that of a native human Fc constant region. The claims are further drawn to specific Fc mutations, nucleic acid encoding said antibody, expression vector and host cell and methods of producing said anti-C5 antibody and methods of treatment.
Bell et al. teach eculizumab, a humanized monoclonal antibody against C5 that inhibits terminal complement activation. Bell et al. teach the anti-C5 antibody having 100% identity to instantly claimed VH and VL regions having instant SEQ ID NOs: 7 and 8 (see column 30). Bell et al. teach nucleic acids encoding the eculizumab anti-C5 antibody, expression vectors comprising said nucleic acid and a host cell used to produce said anti-C5 antibody. Bell et al. further disclose methods of treatment comprising administering the eculizumab anti-C5 antibody in patients with paroxysmal nocturnal hemoglobinuria (PNH) as well as prior art teachings showing the beneficial effect of anti-C5 antibodies in systemic lupus, rheumatoid arthritis, autoimmune disease, cardiopulmonary bypass and acute myocardial infarction (see column 8). Bell et al. do not teach wherein the antibody has a variant Fc constant region with greater affinity to FcRn than that of the native human Fc constant region. This deficiency is made up for by Chamberlain et al.
Chamberlain et al. teach optimized IgG immunoglobulin variants directed to Fc variants of a parent polypeptide including at least one modification in the Fc region of the polypeptide and pharmaceutical compositions comprising said polypeptides for therapeutic purposes. Chamberlain et al. disclose the variant polypeptides exhibit enhanced binding to FcRn as compared to the parent as well as increased half-life. Chamberlain et al. disclose some of the following Fc variant modifications: 252Y, 259I, 307Q, 308F, 428L, 434S/A/H. Chamberlain et al. disclose the engineered variants bind with great affinity to human FcRn binding at pH6.0 relative to wild-type IgG1.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the Fc constant region of the eculizumab anti-C5 antibody taught by Bell et al. to improve FcRn binding affinity for a better therapeutic antibody based on the teachings of Chamberlain et al. Combining the teachings of Bell et al. and Chamberlain et al. to make an anti-C5 antibody having a VH and VL comprising SEQ ID NOs: 7 and 8 respectively as taught by Bell et al. with Fc constant region mutations as taught by Chamberlain et al. and recited in the instant claims would result in an antibody having instantly claimed SEQ ID NO: 11, 13, 15, and 16. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the teachings of Bell et al. of therapeutic treatment comprising administering the anti-C5 antibody eculizumab and Chamberlain et al. teaching variant Fc constant regions to improve FcRn binding affinity and enhance in vivo half-life.
Response to Arguments
Applicant's argue in the response filed 5/20/2026 that the “references cited fail to specifically disclose an isolated antibody comprising a triple substitution comprising M252Y, S254T, and T256E, or a double substitution comprising M428L and N434S” and “without specific guidance on which amino acids can be substituted in the IgG2/IgG4 hybrid Fc antibody, the skilled artisan would not have had a reasonable expectation of success.” Applicants further argue Chamberlain does not disclose Fc variants which specifically bind to C5. These arguments have been fully considered but they are not persuasive.
Chamberlain et al. specifically teach state in their abstract “The present application relates to variant Fc region comprising the double mutation 428L/434S that increases serum half-life and the numbering is according to the EU index.” Chamberlain et al. further discloses “The results show that the variants enhanced the in vivo half-life of antibody up to 3.2-fold. In the best case (the 428L/434S variant) half-life was extended from 9.7 days to 31.1 days.” Chamberlain et al. teaches the antigen targeted by the IgG variants can be virtually any antigen and specifically recite the “anti-complement (C5) antibodies.” Chamberlain et al. additionally teach the variants can included a hybrid IgG sequence.
All other previous rejections are hereby withdrawn in view of applicants amendments and arguments in the response filed 5/20/2026.
Conclusion
Claims 31-50 are rejected.
No Claim is 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.
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/Meera Natarajan/Primary Examiner, Art Unit 1643
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