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 March 30, 2026 is acknowledged.
Claims 1-16 have been canceled.
Claims 17-36 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Claims 20 and 28-36 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.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 17-19 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
6. Claims 17, 19, and 24-27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jardetzky et al. (WO 2004/013158, 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):
PNG
media_image1.png
482
216
media_image1.png
Greyscale
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.
XX
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.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2004013158-A2.
XX
CC PD 12-FEB-2004.
XX
CC PF 01-AUG-2003; 2003WO-US024336.
XX
PR 01-AUG-2002; 2002US-00211948.
PR 02-AUG-2002; 2002US-0319446P.
XX
CC PA (NOUN ) UNIV NORTHWESTERN.
XX
CC PI Jardetzky TS, Wurzburg BA;
XX
DR WPI; 2004-169320/16.
DR N-PSDB; ADL01586.
XX
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
|||||| |||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 ADSNPRGVSAYLSRPSPFDLFIRKSPTITCLVVDLAPSKGTVNLTWSRASGKPVNHSTRK 61
Qy 61 EEKQRNGTLTVTSTLPVGTRDWIEGETYQCRVTHPHLPRALMRSTTKTSGPRAAPEVYAF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 EEKQRNGTLTVTSTLPVGTRDWIEGETYQCRVTHPHLPRALMRSTTKTSGPRAAPEVYAF 121
Qy 121 ATPEWPGSRDKRTLACLIQNFMPEDISVQWLHNEVQLPDARHSTTQPRKTKGSGFFVFSR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 ATPEWPGSRDKRTLACLIQNFMPEDISVQWLHNEVQLPDARHSTTQPRKTKGSGFFVFSR 181
Qy 181 LEVTRAEWEQKDEFICRAVHEAASPSQTVQRAVSVNPGK 219
|||||||||||||||||||||||||||||||||||||||
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).
Therefore, the reference teachings anticipate the instant invention.
7. 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.
8. Claims 17 and 18 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).
The teachings of Jardetzky et al. have been discussed, supra.
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 reduce levels of circulating pathogenic free IgE. The increased potency would result in lower doses required to achieve clinical benefits, lower volume of injection, 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 claims have been amended to recite “totality of the IgE Cε3 domain” and “the totality of IgE Cε3 and Cε4 domains” which will exclude portion of the IgE CH3 domain. Applicant asserts that the totality of the IgE Cε3 is represented by SEQ ID NO:10. Applicant asserts Champion et al. teaches short, truncated peptides but not uninterrupted Cε3 domain.
Applicant further argues that the instantly claimed product shows unexpected and superior results that could not have been predicted: no hIgE is detected in blood in mice vaccinated with the immunogenic product, see Figure 2E of the specification as-filed. Figure 3 discloses that mice vaccinated with the present invention are not protected from hIgE-mediated anaphylaxis. Thus, applicant asserts that the instant product demonstrated efficient to strongly neutralize hIgE and may be used to prevent or treat an inflammatory disorder. Applicant asserts that Champion teaches short peptides that are less than 20 amino acids long and fails to achieve this degree of efficiency. Applicant also asserts that Champion teaches away from the instant invention by using peptides rather than totality of the IgE Cε3 domain. Applicant argues that Jardetzky does not teach that the IgE mutant would be functional when conjugated to a carrier. Applicant asserts that there is no reasonable expectation of success because Champion’s peptide-carrier conjugates achieved only a marginal reduction in free IgE while the instant application achieved complete, undetectable clearance. Therefore, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
In contrast to applicant’s arguments relying upon unexpected superior results disclosed in Figure 2E, note that the results showing full length human IgE Cε3-4 domains consisting of G335C substitution conjugated with CRM197 is not commensurate in scope with the instant claims encompassing broadly an immunogenic product comprising at least one immunoglobulin or immunoglobulin fragment IgE Cε3 and a carrier protein.
Further, 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:
PNG
media_image2.png
114
648
media_image2.png
Greyscale
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).
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.
As such, applicant’s arguments have not been found persuasive.
9. No claim is allowed.
10. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
11. 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHUN W DAHLE/Primary Examiner, Art Unit 1641
Prosecution Insights