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. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 28, 2026 has been entered.
Claims 1-16 and 19 have been canceled.
Claims 17, 18, and 20-36 are pending.
Claims 20 and 28-36 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 21, 2025.
Claims 17, 18, and 21-27 are currently under consideration as they read on the elected invention.
3. In view of applicant’s amendment, following rejections are set forth.
4. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
5. 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.
6. Claims 17, 18, and 21-27 are rejected under 35 U.S.C. 103 as being unpatentable over Jardetzky et al. (WO 2004/013158, reference on IDS) in view of Champion et al. (WO 2011/154878, reference on IDS).
Jardetzky et al. teach a mutant IgE protein comprising G335C substitution that is a closed conformation having the full length ε3 and ε4 domains (e.g. see Fig. 1 and lines 31-33 of page 8, or copy below):
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Jardetzky et al. teach that IgE antibody interact with the cellular receptor FcεRIα and FcεRII through the constant domain of the heavy chain (e.g. see pages 13-15 in page 6) and is glycosylated (e.g. see lines 10-15 in page 8 and lines 4-7 in page 12). Jardetzky et al. further teach unmodified IgE-Fc that is 99% identical to the instantly recited SEQ ID NO:7 (see sequence alignment below):
Human mutant immunoglobulin E (IgE) protein SEQ ID NO:11.
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KW mutant immunoglobulin E; mutant IgE; mutant IgE heavy chain;
KW mutant IgEHC; reduced spatial mobility; Fc-epsilon-RI; IgE receptor;
KW Fc-epsilon-RI-alpha; IgE-mediated disease; allergy; immune response;
KW human; mutant; IgE.
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OS Homo sapiens.
OS Synthetic.
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CC PN WO2004013158-A2.
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CC PD 12-FEB-2004.
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CC PF 01-AUG-2003; 2003WO-US024336.
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PR 01-AUG-2002; 2002US-00211948.
PR 02-AUG-2002; 2002US-0319446P.
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CC PA (NOUN ) UNIV NORTHWESTERN.
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CC PI Jardetzky TS, Wurzburg BA;
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DR WPI; 2004-169320/16.
DR N-PSDB; ADL01586.
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Query Match 99.0%; Score 1153; Length 220;
Best Local Similarity 99.5%;
Matches 218; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 ADSNPRCVSAYLSRPSPFDLFIRKSPTITCLVVDLAPSKGTVNLTWSRASGKPVNHSTRK 60
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Db 2 ADSNPRGVSAYLSRPSPFDLFIRKSPTITCLVVDLAPSKGTVNLTWSRASGKPVNHSTRK 61
Qy 61 EEKQRNGTLTVTSTLPVGTRDWIEGETYQCRVTHPHLPRALMRSTTKTSGPRAAPEVYAF 120
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Db 62 EEKQRNGTLTVTSTLPVGTRDWIEGETYQCRVTHPHLPRALMRSTTKTSGPRAAPEVYAF 121
Qy 121 ATPEWPGSRDKRTLACLIQNFMPEDISVQWLHNEVQLPDARHSTTQPRKTKGSGFFVFSR 180
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Db 122 ATPEWPGSRDKRTLACLIQNFMPEDISVQWLHNEVQLPDARHSTTQPRKTKGSGFFVFSR 181
Qy 181 LEVTRAEWEQKDEFICRAVHEAASPSQTVQRAVSVNPGK 219
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Db 182 LEVTRAEWEQKDEFICRAVHEAASPSQTVQRAVSVNPGK 220
Jardetzky et al. teach working example of construction of IgE cysteine mutant by substituting a cysteine into an unmodified IgG protein of SEQ ID NO:11 (e.g. see Example 1 in page 31). As such, this IgE cysteine mutant would be identical to the instant SEQ ID NO:7 recited in instant claim 22.
Jardetzky et al. further teach that the IgE can be fused to another segment for desired function including increased stability, increased immunogenicity and the fusion segment can be metal binding domain (e.g. poly-histidine segment), Fc receptor, or complement protein, antibody-binding domain (e.g. see paragraph spanning pages 24-25). The compound that increased immunogenicity is considered adjuvant. Jardetzky et al. teaches composition comprising the IgE domains and a pharmaceutically acceptable excipient, and a carrier; and nonaqueous vehicles including oil which would be emulsion (e.g. see pages 29).
Jardetzky et al. teach that the mutant IgE protein having the full length ε3 and ε4 domains and consisting of G335C substitution can be used to produce and isolate therapeutic compounds that will inhibit the binding of IgE protein to FcεRI and FcεRIα (e.g. see Abstract).
The reference teachings differ from the instant invention by not describing CRM197 as a carrier, and at least one adjuvant, and emulsion.
Champion et al. teach IgE Cε3 domain vaccine comprising part of the Cε3 domain conjugated with a carrier including CRM197 (e.g. see Summary of the Invention). Champion et al. teach that the IgE CH3 (Cε3) domain is able to form loops participating the interaction of CH3-CH4 region with it high affinity receptor FcεRI and is immunogenic and anaphylactogenic (e.g. see page 5). Champion et al. further teach a pharmaceutical composition comprising the antigenic IgE peptide conjugated with an immunogenic carrier coupled with one or more adjuvants together with a pharmaceutically acceptable excipient, and additionally emulsifying agent (e.g. see lines 25-40 in 61).
Furthermore, Champion et al. teach the immunogenic carrier CRM197 protein is nontoxic form of diphtherial toxin (e.g. see lines 24-30 in page 19) and can be linked to immunogenic IgE peptide either directly or via a peptide linker (e.g. see page 20).
Champion et al. teach that the antigenic IgE peptide coupled with the immunogenic carrier when administered with one or more adjuvants, can induce potent anaphylactogenic anti-IgE antibodies capable of significantly reducing levels of circulating pathogenic free IgE. The increased potency would result in lower doses required to achieve clinical benefits, lower volume of injections, lower cost of treatment, decreased frequency of administration (e.g. see tope paragraph in page 3).
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 Jardetzky et al. and Champion et al., to conjugate the IgE-Fc mutant comprising full length Cε3 and Cε4 and also containing G335C substitution to the carrier protein CRM197 disclosed. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, because Champion et al. teach IgE Cε3 domain can be used as a vaccine conjugated with a carrier including CRM197 for treating Ig-E mediated disorder (see Champion @Abstract) or to induce anti-IgE antibody and Jardetzky et al. teach Cys-IgE-Fc mutant is stable and is useful in producing new monoclonal anti-IgE antibody. Substituting the known IgE-Fc Cε3 domain in the immunogenic compound disclosed in Champion et al. with another known immunogenic Cys-335 IgE-Fc taught by Jardetzky et al. would have yielded predictable results of inducing immune response against pathogenic IgE. Given that it was well known that protein carrier CRM197 is nontoxic and can be conjugated to IgE Cε3 peptide to induce potent anaphylactogenic anti-IgE antibodies, and given that the IgE-Fc mutant comprising full length Cε3 and Cε4 is readily available, one of ordinary skill in the art would have been motivated to conjugate the IgE-Fc mutant comprising full length Cε3 and Cε4 to carrier protein such as CRM197 to induce potent anaphylactogenic anti-IgE antibody production with a reasonable expectation of success.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant asserts that the prior art SEQ ID NO:11 are different from the instant SEQ ID NO:7 in that the prior art SEQ ID NO:11 does not show cysteine mutation in position 7 and also in the first amino acid residue.
This is not found persuasive for following reasons:
In contrast to applicant’s reliance on the sequence alignments, note that the only claim recites SEQ ID NO:7 is instant claim 22. Further, the instant claims cite “wherein the IgE fragment comprises the totality of Cε3 and Cε4” without recited amino acid sequences. Thus, the species of the prior art SEQ ID NO:11 having an additional amino acid residue at the N-terminus read on the instantly recited IgE fragments.
Furthermore, given that Jardetzky specifically teaches G335C substitution which corresponds to the single amino acid difference shown in the sequence alignment above, Jardetzky teaches IgE fragment comprising species of the IgE fragment comprises the totality of Cε3 and Cε4, the instantly recited SEQ ID NO:7 in dependent claim 22.
Applicant further argues that Jardetzky does not teach CRM197 carrier, adjuvant, and emulsion and does not teach an immunogenic product comprising IgE or fragment thereof for treating inflammatory disorder. Applicant acknowledges that Jardetzky teaches SEQ ID NO:11 and a cysteine substitution shown in the sequence alignments about asserts that the prior art does not teach that the IgE mutant induce neutralizing anti-IgE antibodies. Applicant asserts that Champion does not teach the instantly recited IgE mutant and Table 5 teaches 4 IgE CH3 peptides that would be expected to induce different anti-IgE antibody responses. Thus, applicant asserts that Champion teaches away from the adding protein carrier such as CRM197.
Applicant asserts that the instant application shows surprising results such as polyclonal anti-IgE neutralizing antibodies in IgE humanized mice, e.g. in Figure 2 and page 8 and Figure 3 in the specification as-filed. The full length of IgE domain would enable the generation of anti-IgE antibodies with conformational epitopes. Applicant asserts that the instant product is efficient in inducing strong neutralizing IgE leading to undetectable IgE levels in circulation, indicating that the instant product can be used to prevent or treat inflammatory disorders such as severe allergic reactions
As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
In contrast to applicant’s reliance on the unexpected and surprising results shown in Figures 2 and 3 in the instant specification, note that these results are not commensurate in scope with the instant claims. Specifically, the results relying upon by applicant were done using specific structure of IgE Cε3 and Cε4 and specific CRM197 conjugate. The instant claims encompass genus of IgE Cε3 and Cε4 without specific structures, e.g. amino acid sequences, and a laundry list of carrier proteins that differ in structures.
Thus, the unexpected and surprising results is not sufficient to provide evidence of nonobviousness for the entire genus of the immunogenic products recited in the instant claims.
Further, any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. The claimed combination showed an additive result when a diminished result would have been expected. See MPEP 716.02.
Here, contrary to applicant’s assertion that smaller peptides do not work the same way as the totality of IgE Cε3 or IgE Cε3 and IgE Cε4, note that the instant specification explicitly states that the invention encompass fragments, not just totality of IgE Cε3 and IgE Cε4, e.g. see lines 6-8 in page 15 of the specification as-filed or see copy below for convenience:
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Furthermore, the unexpected and surprising results disclosed in Figure 2 was from the species of human IgE Cε3-4 containing G335C substitution (identical to the human IgE fragment disclosed in Jardetzky et al.) conjugated to well-known nontoxic carrier CRM197 (disclosed by Champion et al.).
Therefore, the marked superiority, e.g. no hIgE is detected in blood in mice vaccinated with the human IgE Cε3-4 consisting G335C substitution conjugated to CRM197 carrier would be expected from the combined teachings of the prior art.
Moreover, in contrast to applicant’s arguments that Champion teaches away from the instant invention by teaching CRM197 conjugated to fragment rather than full length IgE Cε3-4, note that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Alson note that the mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979).
Once again, 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 re Kerkhoven, 626 F.2d 846, 850, 205USPQ 1069, 1072 (CCPA 1980) (see MPEP 2144.06). The superior results achieved from the combination of the compounds would be expected by one skilled in the art.
Here, given the teachings of Jardetzky regarding the use of human IgE Cε3-4 domains consisting G335C substitution to generate therapeutic compounds and the teachings of Champion with respect to conjugating nontoxic CRM197 carrier proteins to human IgE fragments to enhance the antibody production, an ordinary skill in the art would have been motivated to conjugate the well-known carrier protein CRM 197 to the readily available human IgE Cε3-4 domains consisting G335C substitution to further enhance the production of therapeutic compounds that can inhibit the binding of IgE to its receptor.
Therefore, applicant’s arguments have not been found persuasive.
7. No claim is allowed.
8. 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.
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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
