Detailed Action
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-5, 7, 9, 11-12, 18, 23-27, 36, 46-47 and 49-50 are pending.
Claims 1-5, 7, 9, 11-12, 18, 46-47 and 49-50 are withdrawn.
Claims 23-27 and 36 are examined on the merits in the present Office action.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/25/2025 has been entered.
Withdrawn objections
The objection to the listing of references in the specification appearing from pages 47-49 is withdrawn in light of Applicant filing an IDS on 6/25/2025.
Withdrawn rejections
The rejection of claims 23-27 and 36 for having an improper Markush group is withdrawn in light of amendments made by Applicant.
Claim Rejections - 35 USC § 103
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.
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.
Claims 23-26 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Koning et al. (WO2011157806) in view of Shewry (Shewry and Tathum. Journal of Cereal Science. 67:12-21. 2016).
Due to Applicant's amendment of the claims, the rejection is modified from the rejection set forth in the Office action mailed 3/26/2025, as applied to claims 23-26 and 36.
Applicant claims an isolated glutenin or gliadin polypeptide which is mutated compared to a wild-type resulting in binding with lower affinity to the T-cells derived from a celiac patient than a non-mutated polypeptide binds to the T-cells derived from a celiac patient wherein the polypeptide comprises the amino acid sequence SEQ ID NO: 37-38, 41-43 or 46-48 (claim 23).
Applicant claims an isolated polynucleotide encoding the glutenin or gliadin polypeptide of claim 23 (claim 24).
Applicant claims an expression vector comprising the nucleotide of claim 24 operatively linked to a transcriptional regulatory sequence allowing expression in a plant cell (claim 25).
Applicant claims the transcriptional regulatory sequence of claim 25 comprises a plant promoter (claim 26).
Applicant claims a wheat being modified to express the glutenin or gliadin polypeptide of claim 23 (claim 36).
Regarding claim 23, Koning et al. teach a mutated gliadin polypeptide (claim 1). Koning et al. teach modifying α-gliadin sequences, identifying those with reduced T-cell recognition, testing for binding to the Celiac disease associated HLA-DQ2 molecules and for recognition by patient-derived α-gliadin specific T-cell clones (page 3, line 24 to page 4, line 6).
Regarding claim 24, Koning et al. teach a polynucleotide comprising a coding sequence for the modified α-gliadin (claim 11, page 61).
Regarding claim 25, Koning et al. teach the coding sequence and optional regulatory sequences form a vector or are part of a vector suitable for being transformed into a cell (page 26, line 27-30).
Regarding claim 26, Koning et al. teach the transcriptional regulatory sequence comprises a plant promoter, GBSS (page 50, lines 27-32).
Regarding claim 36, Koning et al. teach a wheat plant genetically modified to express the modified gliadin (claim 15, pages 61-62) and a grain therefrom (claim 16, page 62).
Koning et al. do not teach the mutated polypeptide comprises one of the sequences from the group consisting of SEQ ID NO: 37-38, 41-43 and 46-48 SEQ.
Koning et al. teaches a modified gliadin, DQ2-Glia-α1, which comprises an amino acid sequence with 33 residues, “33-mer with S”, which has almost no T-cell recognition compared to the unmodified sequence (Figure 5). Instantly claimed SEQ ID NO: 38 is the first 15 residues of the modified gliadin taught by Koning et al. with the exception of two substitutions, P8R and P10S. Note that each amino acid position is based on the description of the DQ2-Glia-α1 epitope P1(F/Y)2P3Q4P5(Q/E)6L7P8Y9 (see for example, Abstract). See alignment below.
Koning et al. do not teach the mutated polypeptide comprises a P8R and P10S substitution.
Shewry teaches that high levels of proline in the coeliac disease epitopes may reduce susceptibility to protease activity in the GI tract (Page 14, right column, first paragraph of “2.2. Identification of coeliac disease epitopes”). Therefore, a modified epitope with a reduced number of prolines is expected to have improved digestibility.
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to modify the glutenin or gliadin polypeptide of Koning et al. to comprise the full length of SEQ ID NO: 38 by substituting the prolines at positions 8 and 10 because Shewry teaches that high levels of proline in the coeliac disease epitopes may reduce susceptibility to protease activity in the GI tract. One of ordinary skill in the art would have been motivated to produce a modified polypeptide of Koning et al. to improve digestibility of wheat by people with Coeliac disease. A modified epitope with a reduced number of prolines is expected to have improved digestibility because it was known that high amounts of protein in epitope sequences reduced the ability to be digested by protease in the GI tract. Any property of lower affinity to T-cell recognition would have been inherent to the structure of the polypeptide. In addition, it would have been obvious to screen for lower T-cell affinity as taught by Koning et al.
Therefore, the teachings and suggestions of Koning et al. make obvious claims 23-26 and 36.
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Claim 27 remains rejected under 35 U.S.C. 103 as being unpatentable over Koning et al. (WO2011157806) in view of Shewry (Shewry and Tathum. Journal of Cereal Science. 67:12-21. 2016) as applied to claims 23-26 above and further in view of Herpen et al. (Annals of Botany 102: 331 –342, 2008).
Due to Applicant's amendment of the claims, the rejection is modified from the rejection set forth in the Office action mailed 3/26/2025, as applied to claims 23-27 and 36.
Claims 23-26 and 36 are obvious over Koning et al. as addressed by the rejection above.
Applicant claims the plant promoter of the transcriptional regulatory sequence is a wheat promoter (claim 27).
Koning et al. in view of Shewry do not teach expression of a modified α-gliadin with a wheat promoter.
Herpen et al. teach transforming a wheat plant with a wheat plant promoter, an α-gliadin promoter (page 335, left column, Results paragraph 1).
At time of filing, it would have been prima facie obvious to one of ordinary skill in the art to express the modified α-gliadin of Koning et al. with the α-gliadin promoter of Herpen et al. Given that Koning was able to successfully transform a wheat plant using the α-gliadin promoter, and the routine nature of the methods involved with expressing a gene in a wheat plant, one of ordinary skill in the art would have had reasonable expectation of success expressing a modified α-gliadin with an α-gliadin promoter.
Therefore, claim 27 is obvious over Koning et al. in view of Herpen et al.
Response to Arguments regarding rejection under 35 USC 103
Applicant's arguments filed 6/25/2025 have been fully considered but they are not persuasive.
Applicant’s arguments with respect to claims 23-27 and 36 have been considered but are moot because the rejection has been modified in response to Applicant’s amendment to remove SEQ ID NO: 36 from claim 23. does not rely on the substitution previously referred to by Koning et al.
Regarding Applicant’s argument that Koning et al. is teaching away from substituting other amino acids in the gliadin epitopes, this is not persuasive. MPEP 2143.01 provides that prior art suggestion of the claimed invention is not necessarily negated by desirable alternatives. While Koning et al. specifically point to positions 3, 7 and 8, this does not negate the motivation to combine the teachings of Koning et al. with the teachings of Shewry.
Conclusion
Claims 23-27 and 36 remain rejected.
Prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure, Mitea et al. (PLoS ONE 5(12): e15637. 2010), teaches expressing modified α-gliadins in wheat to eliminate antigenic properties of α-gliadins with celiac disease.
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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/DAVID R BYRNES/Examiner, Art Unit 1662