DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Acknowledgment is made of Applicant's claim for domestic benefit under 35 U.S.C. 119(e). As such, the effective filing date of Claims 44 and 48-63 is 11/26/2020.
Election/Restrictions
Applicant’s election, without traverse, of Group I encompassing Claims 44, 48-51, and 60-63 in the reply filed on 10/20/2025 is acknowledged.
Status of the Claims
Amendments dated 10/20/2025 have been entered.
Claims 1-43 and 45-47 have been cancelled by Applicant.
Claims 44 and 48-63 are pending.
Claims 52-58 have been withdrawn from consideration as being directed to a non-elected invention.
Claims 44, 48-51, and 59-63 are examined herein.
Information Disclosure Statement
The Information Disclosure Statement filed on 05/23/2023 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”
In the current case, the view number for Figures 1A-10A are preceded by the word "Figure" instead
of the abbreviation "FIG.".
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office
action to avoid abandonment of the application. Any amended replacement drawing sheet should
include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is
being amended. The figure or figure number of an amended drawing should not be labeled as
“amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the
replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate
changes made to the brief description of the several views of the drawings for consistency. Additional
replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing
sheet submitted after the filing date of an application must be labeled in the top margin as either
“Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by
the examiner, the applicant will be notified and informed of any required corrective action in the next
Office action. The objection to the drawings will not be held in abeyance.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it is less than 50 words in length. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 44 is objected to because of the following informalities:
Claim 44 recites the term “MHC” which not a defined acronym in the claims. As Claim 44 is the first recitation of the term “MHC”, Applicant is advised to clearly define the full name of the abbreviation.
Appropriate correction is required.
Claim Interpretation
Claims 44, 48-51, 59, 60, and 63 recite, in part, the term “de-epitoped” which is defined in the instant specification in relation to glutenin molecules as when the antigenic units of the glutenin protein are mutated (pg. 19, paragraph 0093, line 34). As such the broadest reasonable interpretation of the term “de-epitoped” in relation to glutenin encompasses glutenin proteins that have any number or types of mutations in the antigenic units of the protein sequence.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 51 and 60-61 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 51 recites the limitation "the expression vector of claim 48" in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 48, from which Claim 51 depends, only explicitly recites an isolated polynucleotide encoding the de-epitoped HMW glutenin of Claim 44— not an expression vector. As such, the metes and bounds of the claimed invention are unclear. It is likely Applicant meant for Claim 51 to depend from Claim 49 which recites, in part, an expression vector. Therefore, for purposes of examination, "the expression vector of claim 48" recited in Claim 51 will be interpreted as the “the expression vector of claim 49”. This determination does not relieve Applicant of their duty to amend Claim 51 in any further correspondence.
Claim 60 recites, in part, “ A modified wheat…” which renders the claim indefinite. The term “wheat” recited in Claim 60— without expressly referring to a wheat plant, part thereof, or wheat plant cell— introduces ambiguity into the claim. It is unclear what exactly is expressing the de-epitoped HMW glutenin recited in Claim 44, therefore, one of ordinary skill in the art would not be able to determine the metes and bounds of the claimed invention. For purposes of examination, the “wheat” recited in Claim 60 will be broadly interpreted to encompass a wheat plant, part thereof, or wheat plant cell. This determination does not relieve Applicant of their duty to amend the claims in any further correspondence.
Claim 61 depends from Claim 60 and is therefore rejected for the same reasons as given above.
Claim Rejections - 35 USC § 112
Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 44, 48-51, 59 and 60-63 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 44, 48-51, and 60 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a de-epitoped high molecular weight (HMW) glutenin having reduced or abolished binding with HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, or HLA-DQ7.5 molecules compared to its wild-type counterpart, comprising the amino acid sequence set forth in any of SEQ ID NOs: 52, 55, 144, 145, 147, or 169 , does not reasonably provide enablement for a de-epitoped high molecular weight (HMW) glutenin having reduced or abolished binding with any MHC class II molecule known in the art compared to its wild-type counterpart, comprising the amino acid sequence set forth in any of SEQ ID NOs: 52, 55, 143-145, 147, or 169. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
In re Wands, 858 F.2d 731 (Fed. Cir. 1988) lists the following eight factors for determining
whether undue experimentation would be required to practice an invention: (1) quantity of
experimentation necessary; (2) amount of direction or guidance supplied; (3) presence or absence of
working examples; (4) nature of the invention; (5) state of the prior art; (6) relative skill of those in the
art; (7) predictability or unpredictability or the prior art; (8) breadth of the claims.
Claims 44, 48-51, 59 and 60-63 are broadly directed to de-epitoped high molecular weight (HMW) glutenin having reduced or abolished binding with MHC class II molecules compared to its wild-type counterpart, comprising the amino acid sequence set forth in any of SEQ ID NOs: 52, 55, 143-145, 147, or 169. The claims broadly encompass reduced or abolished binding to any MHC class II molecules known in the art.
Applicant teaches In-vitro testing of the designed modified gluten repeating antigenic subunits (SEQ ID NOs: 49-56) performed by a major histocompatibility complex (MHC II) binding assay to analyze the binding affinity of said repeating antigenic subunits (SEQ ID NOs: 49-56) to only a few MHC class II molecules denoted as HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5 (Example 1, pgs. 81-82; Table 3). Applicant also teaches additional In-vitro testing of the designed modified gluten repeating antigenic subunits (SEQ ID NOs: 143-147, 169, and 173-179) performed by a major histocompatibility complex (MHC II) binding assay to analyze the binding affinity of said repeating antigenic subunits (SEQ ID NOs: 143-147, 169, and 173-179) to only a few MHC class II molecules denoted as HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5 (Example 1, pgs. 83-84; Table 4). The results of the assay show that peptide variants comprising repeating antigenic subunits of claimed SEQ ID NO: 52 had undetectable (abolished) binding to HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5 (Table 3, 5th row). The results of the assay show that peptide variants comprising repeating antigenic subunits of claimed SEQ ID NO: 55 had undetectable (abolished) binding to HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5 (Table 3, 8th row). The results of the assay show that peptide variants comprising repeating antigenic subunits of claimed SEQ ID NO: 143 had undetectable (abolished) binding to only HLA-DQ8 (Table 4, 2nd row). The results of the assay show that peptide variants comprising repeating antigenic subunits of claimed SEQ ID NO: 144 had undetectable (abolished) binding to only HLA-DQ8, HLA-DQ2.5, and HLA-DQ2.2 (Table 4, 3rd row) and reduced binding to HLA-DQ7.5. The results of the assay show that peptide variants comprising repeating antigenic subunits of claimed SEQ ID NO: 145 had undetectable (abolished) binding to HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5 (Table 4, 4th row). The results of the assay show that peptide variants comprising repeating antigenic subunits of claimed SEQ ID NO: 147 had undetectable (abolished) binding to HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5 (Table 4, 5th row). The results of the assay show that peptide variants comprising repeating antigenic subunits of claimed SEQ ID NO: 169 had undetectable (abolished) binding to HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5 (Table 4, 6th row). As such, it is noted at even within the narrow species of MHC class II molecules disclosed by the instant specification, not all of the disclosed MHC class II molecules were described has having reduced or abolished binding to the instantly claimed repeating antigenic subunits (specifically, SEQ ID NO: 143).
Applicant does not teach a de-epitoped high molecular weight glutenin comprising SEQ ID NOs: 52, 55, 143-145, 147, or 169 that has reduced or abolished binding affinity to any MHC class II molecule known in the art relative to its wild-type counterpart. Even when looking at a narrow embodiment of the invention disclosed in the instant specification, Applicant has shown that not all of SEQ ID NOs: 52, 55, 143-145, 147, or 169 even have reduced or abolished binding to the four species of MHC class II molecules used in the working examples. As such, Applicant does not even teach in the instant disclosure if all of SEQ ID NOs: 52, 55, 143-145, 147, or 169 would actually be enabled for reduced or abolished binding to HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5, much less any known MHC class II molecule known in the art, without undue experimentation.
When looking at the broadest scope of the claims, it is unpredictable whether a de-epitoped high molecular weight glutenin comprising SEQ ID NOs: 52, 55, 143-145, 147, or 169 and its wild-type counterpart would have any structure/function relationship with any MHC class II molecule known in the art, much less reduced or abolished binding relative to the wild-type counterpart. The state of the art regarding MHC class II molecules teaches that because of MHC class II molecule’s extreme capacity for polymorphisms, there are around 3,000 known MHC class II alleles, wherein there are different MHC class II loci in most species [Rock et al. (2016): 724-737; pg. 733]. The prior art also teaches that different MHC II alleles have a high degree of binding specificity to particular peptides by virtue of their different anchor residues [Rock et al. (2016): 724-737; pg. 733].
The state of the art regarding MHC class II molecules and glutenin teach that modified glutenin molecules have some degree of binding specificity to specific MHC class II molecules denoted as HLA-DQ8 and HLA-DQ2 [van de Wal et al. (1999):3133-3139].
Given the teachings of Rock et al. and van de Wal et al., it is reasonable to conclude that the prior art does not provide evidence that all MHC class II molecules known in the art would be capable of binding to the wild-type high molecular weight glutenin required by the claims as a point of comparison to determine reduced or abolished binding affinities between de-epitoped high molecular weight glutenin relative to unmodified high molecular weight glutenin. It would require undue experimentation to determine if all MHC class II molecules known in the art, other than HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5, would have any degree of binding to the wild type high molecular weight glutenin and it would require further undue experimentation to then determine if the de-epitoped high molecular weight glutenin comprising SEQ ID NOs: 52, 55, 143-145, 147, or 169 would have reduced or abolished binding to any MHC class II molecule known in the art relative to the wild-type high molecular weight glutenin with any degree of binding to any known MHC class II molecule known in the art.
Based on the instant specification and the teachings of the prior art, it would be unpredictable whether any MHC class II molecule known in the art would be capable of binding to the wild-type high molecular weight glutenin required by the claims as a point of comparison to determine reduced or abolished binding affinities between de-epitoped high molecular weight glutenin relative to unmodified high molecular weight glutenin. The state of the prior art teaches that different MHC II alleles have a high degree of binding specificity to particular peptides by virtue of their different anchor residues [Rock et al. (2016): 724-737; pg. 733]— meaning not every MHC class II molecules would have a structure/function relationship with a wide variety of peptides, much less high molecular weight glutenin.
As such, it would require undue experimentation by one of ordinary skill in the art to determine if all MHC class II molecules known in the art, other than HLA-DQ8, HLA-DQ2.5, HLA-DQ2.2, and HLA-DQ7.5, would have any degree of binding to the wild type high molecular weight glutenin required by the instant claims and it would require further undue experimentation to then determine if the de-epitoped high molecular weight glutenin comprising SEQ ID NOs: 52, 55, 143-145, 147, or 169 would have reduced or abolished binding to any MHC class II molecule known in the art relative to the wild-type high molecular weight glutenin with any degree of binding to any known MHC class II molecule known in the art. Therefore, it would require undue experimentation to determine if a de-epitoped high molecular weight glutenin comprising SEQ ID NOs: 52, 55, 143-145, 147, or 169 has reduced or abolished binding affinity to any MHC class II molecule known in the art.
Given limited guidance supplied by Applicant, the breadth of the claims and the nature of the invention, as well as the unpredictability in the art, it would have required one skilled in the art undue trial and error experimentation to practice the claimed invention through the full scope of its claims.
Claim Rejections - 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 44 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over van de Wal et al. (European journal of immunology 29.10 (1999): 3133-3139) taken with evidence from the instant specification.
Regarding Claims 44 and 48, van de Wal et al. (herein referred to as van del Wal) teaches a glutenin fragment (glt04 residues 707–742, Swiss Prot. Accession Number P08489) with the sequence “SGQGQRPGQWLQPGQGQQGYYPTSPQQSGQGQQLGQ”, wherein van de Wal teaches that the minimal epitope required for optimal T cell stimulation for TCC S12 (from an HLA-DQ8 positive donor; See pg. 3137, right column, first full paragraph) comprises residues 724–734 (QGYYPTSPQQS, referred to as “glt peptide”) of the glt04 glutenin fragment (pg. 3134, left column; Fig. 2B). Residues 724–734 of Swiss Prot. Accession Number P08489 have 100% sequence identity relative to SEQ ID NO: 49 which is the wild-type high molecular weight glutenin required by the instant claims relative to instantly claimed SEQ ID NOs: 52, 55, 143-145, 147, and 169. Van de Wal teaches two different examples of mutating the residues 724–734 (QGYYPTSPQQS) of the glt04 glutenin fragment (de-epitoping the wild-type HMW glutenin; See Claim Interpretation section above) to decrease the antigenicity of the glt04 peptide relative to TCC S12 from an HLA-DQ8 positive donor (reduce or abolished binding with MHC class II molecules). Van del Wal teaches deamination of the residues 724–734 (QGYYPTSPQQS) of the glt04 glutenin fragment (de-epitoping the wild-type HMW glutenin; See Claim Interpretation section above), wherein Q to E substitutions in the glt04 peptide decreased the binding of residues 724–734 of the mutated glt04 glutenin fragment to PBMC from an HLA-DQ2/DQ8-positive donor (MHC class II molecules) relative to the wild-type glt04 glutenin fragment (pg. 3135, paragraph bridging left and right columns; Figure 4). Van de Wal also teaches peptide sequences that are mutated relative to residues 724–734 (QGYYPTSPQQS) of the wild-type glt04 glutenin fragment (de-epitoping the wild-type HMW glutenin; See Claim Interpretation section above), wherein 13 of the variants did not induce proliferation of TCC S12 (binding to an HLA-DQ8 positive donor) (pg. 3136, Table 1). Van de Wal teaches that variants carrying amino acids other than the glt peptide at positions 725 (p1), 727 (p3), 728 (p4) and 731 (p7) did not or only marginally stimulated TCC S12 (reduced or abolished binding with HLA-DQ8 molecules) relative to the wild-type glt04 glutenin fragment [residues 724–734 (QGYYPTSPQQS)] (paragraph bridging pgs. 3135-3136; Table 1).
Regarding Claim 44 and 48, based on the teachings of van de Wal which are directed to mutating HMW glutenin molecules (with the wild-type HMW glutenin having 100% sequence identity relative to the wild-type HMW glutenin required by the instant claims) to have decreased binding to HLA-DQ8 molecules for the purpose of decreasing antigenicity (T cell activity) of the glutenin subunit of gluten that is recognized by DQ8-restricted T cells from the small bowel of a CD patient, the prior art directs one of ordinary skill in the art to make any mutation in the wild-type HMW glutenin (SEQ ID NO: 49) that leads to HMW glutenin peptide variants with decreased antigenicity of the glutenin peptide in relation to HLA-DQ8 molecules relative to the wild-type HMW glutenin (SEQ ID NO: 49). Based on the experimental results of van de Wal, it would have been obvious to one of ordinary skill in the art, and well within the experience of one of ordinary skill in the art to mutate (de-epitope) any portion of residues 724–734 of Swiss Prot. Accession Number P08489 taught by van de Wal to determine the antigenic response of the mutated peptides in regards to binding with HLA-DQ8 molecules and to have mutated HMW glutenin subunits (de-epitoped HMW glutenin) comprising fewer anchoring residues resulting in a decrease of the glutenin specific T cell response. Examiner invites Applicant to submit evidence to show that the specific mutations encompassed by SEQ ID NOs: 52, 55, 143-145, 147, and 169, do anything other than what is reasonably expected (i.e., decrease or abolish binding of the HMW glutenin variant with MHC class II molecules) based on the disclosure of the prior art and evidence from the instant specification. Therefore, the instant invention is prima facie obvious in view of the prior art, taken with evidence from the instant specification.
Claims 49-51 are rejected under 35 U.S.C. 103 as being unpatentable over van de Wal et al. (European journal of immunology 29.10 (1999): 3133-3139) taken with evidence from the instant specification as applied to Claim 44 and 48 above, and further in view of Galili (Proceedings of the National Academy of Sciences 86.20 (1989): 7756-7760).
The teachings of van de Wal as applied to Claim 44 are set forth previously herein and are incorporated by reference.
However, van de Wal, taken with evidence of the instant specification, does not teach the features of Claim 49, encompassing an expression vector comprising the isolated polynucleotide of claim 48, operatively linked to a transcriptional regulatory sequence so as to allow expression of said de-epitoped high molecular weight glutenin in a cell; the feature of Claim 50, wherein the de-epitoped HMW glutenin is comprised within a cell; or the feature of Claim 51, wherein the de-epitoped HMW glutenin is incorporated into a method comprising a) culturing cells that comprise the expression vector of claim 48 under conditions allowing for expression of said de-epitoped HMW glutenin in said cells; (b) expressing said de-epitoped HMW glutenin; and (c) collecting said expressed de-epitoped HMW glutenin.
Galili teaches an entire DNA sequence encoding the mature wheat HMW glutenin subunit 1Dx2 which been subcloned into a bacterial expression vector. Galili reports the successful expression and purification of large amounts of an intact wheat HMW glutenin subunit in E. coli cells.
Regarding Claims 49, Galili teaches the construction of a plasmid comprising a gene encoding the wheat HMW glutenin subunit 1Dx2 of the cultivar Yamhill, wherein the bacterial expression vector (pEt-3a) comprises a promoter and a Shine-Dalgarno region derived from gene 10 of bacteriophage 17 as well as an initiator ATG codon situated within a unique Nde I site (pg. 7756, right column, Materials and Methods, Plasmid construction).
Regarding Claim 50, Galili teaches the expression of the bacterial expression vector denoted as pEt-3a, comprising the HMW glutenin 1Dx2 subunit, in E. coli cells (pg. 7757, Expression of the HMW Glutenin subunit in E. coli, See Figure 2).
Regarding Claim 51, Galili teaches the transformation of E. coli cells with the bacterial expression vector (pEt-3a) comprising the wheat HMW glutenin subunit 1Dx2 of the cultivar Yamhill, a promoter, and a Shine-Dalgarno region derived from gene 10 of bacteriophage 17 as well as an initiator ATG codon situated within a unique Nde I site (paragraph bridging pgs. 7756-7757, Materials and Methods, Plasmid construction). Galili then teaches the expression of the bacterial expression vector denoted as pEt-3a, comprising the HMW glutenin 1Dx2 subunit, in E. coli cells (pg. 7757, Expression of the HMW Glutenin subunit in E. coli, See Figure 2). After expression of the HMW glutenin subunit in E. coli cells, Galili teaches the extraction of the HMW glutenin from the cultured E. coli cells (pg. 7757, left column, Extraction of Proteins) and fractionation (collection) of the extracted HMW glutenin (pg. 7757, paragraph bridging left and right column, Fractionation of Proteins).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the claimed invention to use the de-epitoped HMW glutenin peptides taught by van de Wal, comprising any conceivable sequence variant of residues 724–734 of Swiss Prot. Accession Number P08489 rendered obvious by van de Wal in view of the instant specification, in the bacterial expression vector taught by Galili and subsequent methods of its use. Based on the teachings of Galili, one of ordinary skill in the art would have been motivated to use the de-epitoped HMW glutenin peptides taught by van de Wal, comprising any conceivable sequence variant of residues 724–734 of Swiss Prot. Accession Number P08489 rendered obvious by van de Wal in view of the instant specification, in the bacterial expression vector taught by Galili and subsequent methods of its use because the ability to produce large amounts of individual HMW glutenin subunits in heterologous systems will allow one of ordinary skill in the art to study the 3-D structure of the protein and structure-function relationships of the isolated protein (See Galili, pg. 7759, right column, 3rd full paragraph). Additionally, the teachings of Galili provide evidence that expressing HMW glutenin subunits in heterologous expression systems is routine and well known in the art at the time of the effective filing date of the claimed invention, and so it would be further obvious for one of ordinary skill in the art to use the de-epitoped HMW glutenin peptides taught by van de Wal, comprising any conceivable sequence variant of residues 724–734 of Swiss Prot. Accession Number P08489 rendered obvious by van de Wal in view of the instant specification, in the bacterial expression vector taught by Galili and subsequent methods of its use. The rationale to support a conclusion that the claims would have been obvious is that all the claimed elements were known in the prior art, and one of ordinary skill could have combined these elements as claimed with no change to their respective functions. Therefore, the instant invention is prima facie obvious in view of the prior art.
Claims 59-63 are rejected under 35 U.S.C. 103 as being unpatentable over van de Wal et al. (European journal of immunology 29.10 (1999): 3133-3139) taken with evidence from the instant specification as applied to claim 44 above, and further in view of Koning et al. (WO-2011157806-A1, published 12/22/2011).
The teachings of van de Wal as applied to Claim 44 are set forth previously herein and are incorporated by reference.
However, van de Wal, taken with evidence of the instant specification, does not teach the feature of Claim 59 encompassing a flour comprising the de-epitoped HMW glutenin of claim 44; the feature of Claim 60 encompassing a modified wheat (See 35 U.S.C. 112(b) rejection above) expressing the de-epitoped HMW glutenin of claim 44; the feature of Claim 61, encompassing a flour derived from the wheat of claim 60; the feature of Claim 62, encompassing dough comprising the flour of claim 44; and the feature of Claims 63, encompassing modified corn plant expressing the de-epitoped HMW glutenin of claim 44.
Koning et al. (herein referred to as Koning) teaches a modified gliadin polypeptide (pg. 59, Claim 1). Koning teaches modifying α-gliadin peptides, identifying those with reduced T cell recognition, testing for binding to the Celiac disease associated HLA-DQ2 and HLA-DQ8 molecules (pg. 42, lines 23-28), wherein mutation of a DQ8 epitope in the gliadin peptide results in eliminating or lowering the toxicity of the epitope (pg. 20, lines 14-17).
Regarding Claims 60, Koning teaches a wheat plant that is genetically modified to express the modified gliadin (Claim 15, pg. 61-62) and a grain therefrom (Claim 16, pg. 62).
Regarding Claims 59 and 61, Koning also teaches that the plants and grain of the invention comprising the modified gliadin can be used to create food products derived from grain, such as flour and bread. Bread would inherently comprise the dough that was baked to create the bread food product (paragraph bridging pgs. 23-24, and pg. 24, lines 7-11).
Regarding Claim 63, Koning teaches a plant that comprises in its genome a polynucleotide encoding the modified α-gliadins (pg. 61, Claim 14), wherein the plant is a cereal plant that naturally does not comprise harmful gluten, in particular tef, rice, maize or oats (pgs. 61-62, Claim 15).
Regarding Claims 59-63, throughout the disclosure of van de Wal, van de Wal teaches that the experimental procedures that utilized HMW glutenin in teachings of van de Wal as applied to Claim 44, were the exact experimental procedures used in an experiment involving gliadin peptides that are specifically recognized by HLA-DQ8 restricted gluten-specific T cell clones (pg. 3133, right column, Results, Identification of a DQ8-restricted glutenin-derived T cell epitope). Van del Wal also teaches that further mutation experiments using residues 724–734 of Swiss Prot. Accession Number P08489 were modeled from previous experiment using gliadin epitopes that are specifically recognized by HLA-DQ8 restricted gluten-specific T cell clones (pg. 3134, right column, Effect of deamidation of glt-specific recognition).
It is prima facie obvious to substitute known equivalents when the prior art element performs the identical function specified in the claim in substantially the same way, and produced substantially the same results as the corresponding element. Modifying gliadin polypeptides, wherein the mutation is of a DQ8 epitope in the gliadin peptide (as taught by Koning), would be expected to decrease or abolish binding of the gliadin variant with MHC class II molecules, providing a decrease in antigenicity with DQ8-restricted T cells from the small bowel of a CD patient, as taught by the modified HMW weight glutenin in van del Wal. As taught by van del Wal, gliadin peptides that are specifically recognized by HLA-DQ8 restricted gluten-specific T cell clones and HMW glutenin peptides that are specifically recognized by HLA-DQ8 restricted gluten-specific T cell clones were known obvious equivalents before the effective filing date of the claimed invention and therefore making a wheat plant, flour, dough, or modified corn plant comprising the de-epitoped HMW glutenin peptides taught by van de Wal, comprising any conceivable sequence variant of residues 724–734 of Swiss Prot. Accession Number P08489 rendered obvious by van de Wal in view of the instant specification, rather than the modified gliadin taught by Koning would have been obvious to one of ordinary skill in the art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KELSEY L. MCWILLIAMS whose telephone number is (703)756-4704. The examiner can normally be reached M-F 08:00-17:30.
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/KELSEY L MCWILLIAMS/Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663