DETAILED OFFICE ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The request filed on 02 January 2026 for a Continued Examination (RCE) under 37 CFR 1.114 based on parent Application No. 16/771,948 is acceptable, and an RCE has been established. An action on the RCE follows.
Applicant’s response filed on 02 January 2026 is acknowledged and entered.
Note, the status identifier of claim 4 indicates “Previously Presented”; however, a limitation of “43, 47, 51, 55, 59, 63, 64, 71, 76, 80 and 84.” appeared in line 3 of the claim, after the “103.” (period), was not present in the immediate prior version filed on 3/18/2025. Thus, the response is not in compliance with 37 C.F.R. 1.121 (c)(2), which requires that all claims being currently amended must be presented with markings to indicate the changes that have been made relative to the immediate prior version; and that the text of any added subject matter must be shown by underlining the added text. See also, MPEP 714 II. C. (B). Appropriate correction is required.
Currently, claims 4 and 11-23 are pending, and claims 4, 11-13, 22 and 23 are under consideration to the extent that they read on the elected sequences. Claims 14-21 remain withdrawn from further consideration as being drawn to a non-elected invention.
Formal Matters:
Claims
Claims 4 and 22 are objected to for the following informalities, appropriate correction is required:
Claim 4 recites “wherein the peptide immunogen construct is selected from the group consisting of …”; the following is suggested: “wherein the peptide immunogen construct comprises an amino acid sequence selected from the group consisting of …”.
Claim 22 recites “wherein the IL-31 peptide immunogen construct is SEQ ID NOs: 43, 47, 51, 55, 59, 63, 64, 71, 76, 80 and 84”; the following is suggested: “wherein the IL-31 peptide immunogen construct comprises the amino acid sequence of SEQ ID NO: 43, 47, 51, 55, 59, 63, 64, 71, 76, 80 or 84”.
Prior Art Rejections
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 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.
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 of this title, 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 4, 11, 12 and 22 remain rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Vaccine 23 (2005): 2049-2056), and Bammert et al. (US 2013/0022616, 1/24/2013; provided previously), for the reasons of record set forth in the previous Office Actions mailed on 12/19/2024, and 7/1/2025.
Claims 4, 11-13, 22 and 23 remain rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Vaccine 23 (2005): 2049-2056, “Wang 1”), and Bammert et al. (US 2013/ 0022616, 1/24/2013; provided previously), as applied to claims 4, 11, 12 and 22 above, and further in view of C. Wang (US 2014/0271690, 9/18/2014, “Wang 2”; provided previously), for the reasons of record set forth in the previous Office Actions mailed on 12/19/2024, and 7/1/2025.
Applicants argument filed on 02 January 2026 has been fully considered, but is not deemed persuasive for the reasons below.
At pages 5-6 of the response, the applicant made similar argument as previously: none of the cited reference and the Office Action provides a motivation to combine Wang 1 and Bammer; Wang 1 is a platform paper describing UBI's strategy for designing peptide vaccines, but it does not teach that one may simply take any arbitrary fragment of a target protein and "drop it" into a UBITh@-linker-B-cell epitope format; and emphasizes that, for each target, a specific functional site must first be identified by epitope mapping and functional antigenicity assays, and then optimized in sequence and conformation, before fusion to a UBITh@T-helper epitope; Bammert is not a vaccine reference at all, its invention is monoclonal antibodies against IL-31 and their therapeutic use, in which IL-31 truncations are used only as antigens to map the antibody binding region and to assess signaling, not as immunogens for vaccination; there is no suggestion in Bammert to use any IL-31 fragment as an active peptide vaccine, much less in a Th- spacer-B construct as claimed; and Wang 1 and Bammert do not provide a concrete motivation to select the precise IL-31 segments of SEQIDNOs: 3-12 and 96, to pair them specifically with UBITh@1 or UBITh@3.
This argument is not persuasive for the reasons of record. In addition, in response to applicant’s argument that there is no motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, as acknowledged by applicant previously, Wang 1 discloses that the core technologies developed by UBI lead to the products of various vaccines (a collection of UBITh® T helper cell epitopes). Also, as discussed previously, Wang teaches a framework for the GMP-compliant manufacture of UBITh® immunotherapeutics and vaccines, which can be used for preparing various vaccines including vaccines for immunotherapy of allergy (such as asthma, anaphylactic reactions to bee sting or peanuts, and other allergic diseases), wherein Wang’s framework is the same as that of the present invention; and Bammert teaches that IL-31 is involved in dermatitis, pruritic skin lesions, allergy and airway hypersensitivity; and teaches
the specific target epitope (Fig. 15) of the IL-31 (SEQ ID NO: 32), which is comprised in the IL-31 B cell epitopes in the present claims, for example, the IL-31 epitopes in the present SEQ ID NO: 43-46 and 63-86; or comprises those in the present SEQ ID NO: 47-58, with 100% sequence identity (see Office Action mailed on 12/19/2024). Therefore, it would be instantly obvious to one skilled in the art to combine the two references to make an IL-31 vaccine using UBITh® T helper cell epitope platform, and to use the epitope for generation the antibody to the IL-31 for disease treatment, following the combined teachings of Wang 1 and Bammert. Furthermore, as discussed previously, Bammert teaches that this epitope is identified/assayed by its ability to bind the IL-31 monoclonal antibodies (alanine scanning mutagenesis), which is one of the art-recognized ways for epitope mapping. Therefore, it is unclear as to why applicant ignores or dismisses this method/assay; and what “concrete” motivation is meant or needed in the instant case.
At pages 6-7 of the response, the applicant argues that the combined teachings do not provide a reasonable expectation of success for the specific constructs of claim 4, as Bammert's epitope mapping is performed on full-length IL-31 and large C-terminal truncations such as 20-122 and 20-100, with loss of binding observed only when truncated further to 20-80 (see Fig. 14 and p. 25, [0340]-[0341]; SEQ ID NO: 63, 65, 67); loss of binding in the 20-80 construct and disruptions caused by alanine substitutions in residues 76-122 lead Bammert to conclude that a region roughly corresponding to amino acids "between about 95 and 125" or more narrowly" between about 102 and 122" of canine IL-31 SEQ ID NO: 32 is important for binding the disclosed monoclonal antibodies (see Bammert, p. 3, [0032]; claims 27-28); that these experiments does not define what isolated peptide sequence, of what length and boundaries, will function as a stand-alone B-cel vaccine epitope; and a person of ordinary skill would thus understand Bammert as identifying an antibody epitope on native IL-31, but would not reasonably expect that lifting that region into a linear peptide would yield a functional vaccine B-cell epitope.
This argument is not persuasive because, while Bammert teaches a monoclonal antibody that specifically binds to a region between about amino acid residues 95 and 125, or between about amino acid residues 102 and 122 of the canine IL-31 of SEQ ID NO: 32, the amino acids 98-125 within said amino acid residues 95-125 of SEQ ID NO: 32 equal to amino acids 76-103 in Bammert’s Fig. 15. Note, amino acids 76-122 of the IL-31 fragment (which seems numbered based on the mature sequence) shown in Bammert’s Fig. 15 equal to amino acids 98-144 of SEQ ID NO: 32 in the Bammert reference. In addition, Bammert also specifically teaches that truncation analysis of canine IL-31 revealed amino acid residues (annotated in FIG. 15 between positions 80 and 122) are involved in binding 11E12 and 34D03 antibodies; and that fine mutational analysis using alanine scanning revealed that ASP77, LYS78, ILE81, ASP82, and ILE85 of the full-length IL-31 construct all impact binding of 11E12 or 34D03 indicating this region most likely defines the epitope responsible for recognition by these antibodies; and that this region of the human IL-31 protein was shown to be involved with binding to the GPL subunit of its co-receptor; these observations, along with the ability of mAbs 11E12 and 34D03 to neutralize IL-31 mediated pSTAT activity in monocytes, support the hypothesis that these mAbs bind to residues on canine IL-31 that are essential for binding of this cytokine to its receptor, thereby inhibiting its ability to induce signaling (page 25, [0343]). Note, amino acids 76-122 of the IL-31 fragment (based on the mature sequence) shown in Bammert’s Fig. 15 equal to amino acids 98-144 of SEQ ID NO: 32 of the Bammert reference. Note, it is noted that the IL-31 fragment in Bammert’s Fig. 15 comprises 47 amino acids, which fragment comprises the 47 residues of the B epitope (48 amino acids) in the present SEQ ID NO: 43-46 with 100% sequence identity. It is therefore clear that Bammert defines a region in the canine IL-31, which is “most likely defines the epitope responsible for recognition by these antibodies”; and almost completely overlaps the B epitope of the present invention. In addition, linear peptides as B cell epitopes have been well known and well established in the art. Thus, merely further testing/assaying the linear epitope in a region of the IL-31 polypeptide, which region is identified/indicated by the prior art as “most likely defines the epitope” responsible for the antibody recognition, does not constitute a novel inventive concept.
At page 7 of the response, the applicant repeatedly argues that it is well established that B-cell epitopes are often conformational and discontinuous, mapping by truncation and alanine scanning can identify residues that influence antibody binding without defining a peptide that is suitable as a vaccine epitope; and short linear sequences often fail to adopt the native three-dimensional conformation outside the full protein context; that the literature of record cautions that epitope predictions based on mutagenesis should be treated carefully in vaccine design and that proper epitope-based vaccines must position critical contact residues in an appropriate spatial orientation an inherently non-trivial task; that Wang 1 underscores that the target epitope must be functionally validated and optimized before becoming part of a UBITh@ construct, explicitly teaching that candidate target sites are first identified by functional antigenicity assays and then optimized; and neither Wang l nor Bammert suggests that the IL-31 region identified for antibody binding in Bammert can simply be cut out, converted into a linear peptide of specific length, fused to UBiTh l or UBITh®3 through s-lysine, and expected to function as a therapeutic immunogen without extensive design and optimization.
This argument is not persuasive for the reasons of record and above. The common general knowledge does not outweigh the specific factual evidence taught by the prior art reference (Bammert). As applicant acknowledges previously, Wang 1 reference and Bammert gives general guidance to prepare the IL-31 peptide immunogen constructs of claim 4, testing the epitope would be routine in the art. Once again, merely further testing/verifying/assaying the linear epitope in a region of the IL-31 polypeptide, which region is identified/indicated by the prior art as “most likely defines the epitope” responsible for the antibody recognition, does not constitute a novel inventive concept. Further, obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988) (see also, MPEP 2144.08, II.A.4.(e)); i.e., verifying, assaying and confirming a suitable vaccine, which represents absolute predictability, is not required for a prior art reference; and efficacy is not a requirement for prior art enablement (see MPEP 2121 III.). Clearly, applicant applied the improper standards for the argument, and applicant is reminded that the standards for patentability differ from that for FDA vaccine approval, and it is the latter that would require that the target epitope must be functionally validated and optimized before becoming part of a UBITh@ construct (vaccine).
At page 8 of the response, the applicant argues that the rejection ultimately rests on impermissible hindsight reconstruction, as neither Wang 1 nor Bammert, nor their combination, discloses or points the skilled person to the particular IL-31B-cell epitopes of SEQIDNOs: 3-12 and 96, their pairing precisely with UBITh l or UBITh@3, the s-lysine spacer, or the exact ordering of these elements embodied in SEQ ID NO: 43-66, 71-86, 102, and 103; and those are the result of Applicant's own design and optimization work in the face of the very uncertainties described above; that the fact that Applicant has successfully carried out this non-trivial design work does not render the resulting constructs obvious; and the rejection uses the invention as a blueprint for the prior art, rather than asking where the prior art would have led on its own; accordingly, when Wang 1 and Bammert are viewed together and in light of the state of the art, there is no specific motivation to construct the IL-31 peptide immunogens of claim 4 as claimed, no reasonable expectation of success that such constructs would function without undue experimentation, and teachings that actually caution against the simplistic epitope substitution theory advanced in the rejection.
This argument is not persuasive for the reasons of record and above. Additionally, in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, none of the teachings is from applicants own disclosure. Further, again, applicant's argument is against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. As discussed previously, Wang teaches a framework for the GMP-compliant manufacture of UBITh® immunotherapeutics and vaccines, which can be used for preparing various vaccines [including vaccines for immunotherapy of allergy (such as asthma, anaphylactic reactions to bee sting or peanuts, and other allergic diseases), wherein Wang’s framework is the same as that of the present invention; and Bammert teaches the specific target epitope (Fig. 15), which fragment comprises 47 amino acids that are 100% identical to the 47 residues of the present B epitope (48 amino acids) of SEQ ID NO: 3 in the present constructs of SEQ ID NO: 43-46. It is the combined teachings of Wang and Bammert, which render the claimed invention obvious. Furthermore, again, as applicant acknowledges previously, Wang 1 reference and Bammert gives general guidance to prepare the IL-31 peptide immunogen constructs of claim 4, thus, further testing/verifying/assaying the linear epitope in a region of the IL-31 polypeptide, which region is identified/indicated by the prior art as “most likely defines the epitope” responsible for the antibody recognition, would be routine in the art, and would not be considered undue experimentation, or constitute a novel inventive concept.
Conclusion:
No claim is allowed.
Advisory Information:
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication should be directed to Examiner DONG JIANG whose telephone number is 571-272-0872. The examiner can normally be reached on Monday - Friday from 9:30 AM to 7:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DONG JIANG/
Primary Examiner, Art Unit 1674
3/6/26