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 .
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.
Status of the Claims
Claims 1-10, 13-24 and 26-28 are pending; claims 1-7 are withdrawn; claims 8, 9, 10, 13-14, 16, 18-24 and 26-28 are amended; claims 11-12 and 25 are canceled. Claims 8-10, 13-24 and 26-28 are examined below.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/EP2019/025002, filed 01/03/2019. Acknowledgment is also made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. 18000114.1, filed on 02/08/2018 with the European Patent Office.
Withdrawn Objections/Rejections
The previous objections of claim 8 and 9 are withdrawn in response to Applicant’s amendments to the claims.
The previous rejection of claims under 35 U.S.C. 112(a), regarding new matter, are withdrawn in response to Applicant’s amendments to the claims.
The previous rejection under 35 U.S.C. 112(b), regarding “wherein the gluten proteins in the sample comprise prolamine from rye…and HMW secaline from rye”, is withdrawn in response to Applicant’s amendments to the claims.
The previous rejection of claim 9 under 35 U.S.C. 112(b), regarding “when present at the same quantities”, is withdrawn in response to amendments to the claims.
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 8-11, 13-24 and 26-28 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.
The terms “LMW-glutenin”, “HMW-glutenin” and “HMW secalin” in claim 8 are each relative terms which render the claims indefinite. The terms “HMW” and “LMW” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For example, there does not appear to be a clearly limited molecular weight range accepted across the art which indicates what is an is not considered a high or low molecular weight for either of glutenin or secalin, and even further, as is supported by Applicant’s remarks filed 12/10/2025, there are other factors that go into classification beyond merely molecular weight, including each of their amino acid sequence, and as such genetic origin and modification (see evidence cited previously in rejection, Masci et al. and Li et al., as well as Applicant’s remarks and Schalk 12/10/2025, pages 16-17). Based on the evidence of record (previous rejection and referring to remarks), the boundaries regarding what species of proteins are encompassed by the claim are unclear, as there are many considerations that go into classifying a glutenin, or a secalin as low molecular weight or high molecular weight. It is not readily clear what species are encompassed by the claimed invention.
Claims 8 and 9 are amended such that claim 8 now recites functional language describing the claimed “respective dilutions” of the detection binding reagents in the mixture, see the claim recites, “wherein the detection binding reagents are present as a mixture at respective dilutions at which the gluten proteins gliadins, LMW-glutenin subunits and HMW-glutenin subunits each from wheat, HMW secaline from rye and other prolamines from rye and barley are measured with comparable signal strengths at the same mass fractions, the signal strengths of each detection binding reagent contributing to a total signal strength of gluten proteins in the sample according to the mass fraction of the gluten proteins they each detect present in the sample”. While not all claim terms that are described in terms of functional language are indefinite, in the present case the amounts of detection reagents (dilutions) recited in the mixture are still considered to be indefinite because in this instance (where the amounts are described in terms of function, namely the ability to allow all gluten proteins in the sample to be measured with comparable signal strengths at the mass fractions) the reliance on the functional language to describe the amount of detection binding reagent fails to provide a clear indication of the scope of the subject matter claimed in that one having ordinary skill cannot readily visualize what “dilutions” the claim is limited to (i.e., one cannot readily determine what respective dilutions are encompassed by the claimed language in order to properly compare that which is claimed to the closest prior art). It is not readily clear what limitation this language imposes on the claimed dilutions/mixture (i.e., what structural limitation does this language impose on the claimed invention which is a product invention), such that one can clearly visualize what is and what is not encompassed by the recited claim language.
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.
Claim(s) 8-10, 13-15, 18, 20, 22, 24, 26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Sorell et al., An innovative sandwich ELISA system based on an antibody cocktail for gluten analysis, FEBS Letters, 439, (1998), p. 46-50 in view of Mitea et al. Fine Specificity of monoclonal antibodies against celiac disease- inducing peptides in the gluteom, Am. J. Clin. Nutr., 88, (2008), p. 1057-1066.
Sorell et al. teach a test kit for the quantification of total amount of gluten proteins (claim 22) from a sample that is a food sample (see abstract) by means of specific affinity binding. The ELISA test kit (specific binding assay) of Sorell comprises a combination of two antibodies (i.e., specific detection binding reagents binding to prolamins, see abstract, in wheat, barley (hordein) and rye (secalin)). Sorell is reporting an ELISA system comprising three Mabs that recognize barley as well as wheat and rye gluten proteins (see page 46, end of col. 1 to col. 2). Sorell teach a combination of antibodies (i.e., a mixture comprising antibody 13B4 and Rye 5 MAbs (see page 47, col. 1, para 1, regarding cocktail sandwich ELISA, see also page 47, section 3.3, regarding recognition of all types of prolamin extracts, using a combination of 13B4 and Rye 5 antibodies, ELISA relying on a third HRP-conjugated MAb that binds those proteins in the prolamin family, see page 49, col. 2, Discussion paragraph 2).
Although Sorell is teaching a kit that specifically detects prolamin (i.e., prolamin proteins from wheat (gliadin), rye (secalin) and barley (hordein)) Sorell fails to teach detection binding reagent including detection reagent specific for glutelin in wheat, i.e., Sorell fails to teach their kit also for/capable of the detection of gluten proteins in the sample including, in addition to gliadins, LMW-glutenin subunits and HMW-glutenin subunits from wheat, as well as secalin that is HMW secalin.
Mitea et al. teach in celiac disease patients, peptides (peptides found in gliadins and glutenines) derived from dietary gluten are recognized by HLA-DQ2-restricted CD4+ T cells, which result in inflammation (abstract); Mitea teach antibodies against these peptides are usable for the purpose of screening food for their presence (abstract). As discussed in detail above, the specification of the present application indicates in wheat prolamin are called gliadins or in LMW and HMW (gluteline in wheat) (see specification at page 3). Mitea is teaching, during digestion, gluten proteins are broken down, but because of the high proline content of gluten, the degradation is not efficient and relatively large gluten peptides persist (page 1057, col. 1, last paragraph); that these peptides trigger an inflammatory immune response for those with CD. Mitea et al. teach these peptides originate from α and γ-gliadins and from the LMW and HMW glutenins (p. 1057, col. 2, para 1). Mitea teach that because intact gluten molecules and hydrolysates are used in the food industry, gluten detection assay should be able to detect both (para 2). Mitea teach they have developed mAbs against T cell stimulatory peptides present in α, γ- gliadin, LMW glutenin and HMW glutenin, Mitea teach some of these antibodies have already been used in the development of sensitive assays for detection. See table 1 disclosing the peptides used for generation of the specific MAb (see as discussed above, prolamine and gluteline). At table 2 (page 1060) Mitea teach comparison of minimal amino acid sequences recognized by the antibodies, the antibodies of Mitea are antibodies that bind include QPFPQPQ, RPQQPYP, QQRPFI, PPFSQQ, QSPF, QGQQGYYP (see also Table 3, peptides precipitated by the antibodies of Mitea).
Regarding claim 8, it would have been prima facie obvious to one having ordinary skill at the time the claimed invention was effectively filed, to have modified Sorell’s kit for detection of gluten by way of an antibody cocktail for detection of prolamin (from wheat, rye and barley) to further include in the cocktail, as the detection binding reagent for detection of gluten related peptides, a combination (mixture) of the antibodies of Mitea, specifically for the purpose of detecting total gluten (i.e., a combination of antibodies so not to miss gluten proteins present in the sample). Specifically, one would be motivated to make said modification because Mitea teach that because intact gluten molecules and hydrolysates are used in the food industry, gluten detection assay should be able to detect both (α and γ-gliadins and from the LMW and HMW glutenins, i.e. prolamin and glutelin), Mitea teach they have developed mAbs against T cell stimulatory peptides present in α, γ- gliadin, LMW glutenin and HMW glutenin. As a result, one would be motivated to make the modification in order to improve the kit for detection of gluten in a food sample in order to protect a person (for example with CD) from consuming a contaminated food (see as discussed, because Mitea specifically teach detection should be for both types of proteins).
One having ordinary skill in the art would have a reasonable expectation of success because Sorell teach using, for example, a cocktail (combination) of detection antibodies, and further because Mitea teach some of these antibodies (of Mitea) have already been used in the development of sensitive assays for this type of detection. As a result, because the art already supports the use of such antibodies for detection, particularly in combination as a mixture, one would expect success making the modification as indicated.
Further, regarding the recited limitations specific to the respective dilutions of each binding reagent present in the mixture, see as discussed above under 35 U.S.C. 112(b), the recited language fails to clearly impart any particular structural feature, such as a particular dilution/amount of each binding reagent to be present as part of the mixture provided as a kit. It is not possible, from the recited language, to envision the dilution/amount such to distinguish that which is claimed from that which is taught by the prior art. The combination of the cited teaches a structure (test kit) that is indistinguishable from that which is claimed (a test kit quantitatively detecting both prolamin and glutelin from wheat, and prolamin from rye and barley, i.e., total gluten protein). As such, it is expected from the cited art that the antibody binding reagents would be provided as dilutions that allow all proteins to be detected appropriately. See further as discussed above (under 35 U.S.C. 112(b)), it is not readily clear what is meant by “when present at the same quantities”.
Regarding claim 9, the kit of Sorell in view of Mitea comprises a microtiter plate (see as cited above), the combination of the cited art addresses wells coated with the mixture comprising more than two antibodies (those of Mitea in addition to the two antibodies from Sorell, see as indicated in detail above addressing the combination of specific detection binding reagents binding to prolamine and gluteline consistent with the present claims), as capture binding reagents. See further, Sorell describe a calibrator comprising gluten proteins from each of wheat, rye and barley (page 46, col. 2, section 2.2). The claim recites “optionally a colour reagent…, a stop solution, a sample dilution buffer and/or a wash buffer, and wherein the detection reagents are conjugated with reporter enzyme, a colour label, a fluorescence label or a chemiluminescence label. The detection reagents of Sorell are conjugated with reporter enzyme (see as cited in detail previously above). Further, the recited language “optional” indicates the additional reagents noted above (namely substrate, stop solution, dilution and/or wash buffer), are not specifically required as included as part of the claimed kit.
It would have been further prima facie obvious to one having ordinary skill in the art, when modifying Sorell’s ELISA with antibodies for capture of gluteline as in Mitea to further provide an antibody that is a labeled antibody for gluteline proteins in order to be able to detect the presence of the gluteline proteins (HMW and LMW glutenin). As discussed above, one would be motivated to modify the ELISA because Mitea teach suggest such tests should detect both families of gluten proteins, and because it would be necessary to provide antibody with label to produce the detectable signal (upon said modification). One having ordinary skill would have a reasonable expectation of success because Mitea is teaching antibodies to LMW and HMW glutenin (glutelines).
Regarding claim 10, see as cited in detail above, the kit of Sorell modified with Mitea is an ELISA (i.e., configured for use in an ELISA).
Regarding claim 13, see Sorell et al. at page 46, col. 2, section 2.2, gliadins, hordeins, secalins extracted from wheat, rye flours.
Regarding claims 14 and 15, see as cited in detail above (claim 8), the combination of the cited art addresses detection binding reagents conjugated to reporter enzyme (HRP).
Regarding claim 18, Sorell is teaching an ELISA, comprising detection reagent provided in solution (the combination of the cited art teach providing combination of antibodies for detection).
Regarding claim 20, Sorell et al. teach Rye 5 antibody as capture reagent (R5), and see Mitea at page 1064, end of col. 1, the art recognized commercially available antibody that binds QQPFP (SEQ ID NO. 1) for detecting gliadin is antibody R5 (R-Biopharm AG Darmstadt, Germany). As such, Sorell et al. and Mitea addresses the claim.
Regarding claim 22 (and duplicate claim 23), see the combination of the cited art above addresses testing for gluten in samples containing gluten proteins from wheat, rye and barley.
Regarding claims 24 and 26, see the combination of Sorell et al. in view of Mitea et al. as set forth above (claims 8-9 and 13), addressing all the limitations of claim 24.
Regarding claim 27, see as discussed previously, Sorell et al. teach Rye 5 antibody as capture reagent (R5), and see Mitea at page 1064, end of col. 1, the art recognized commercially available antibody that binds QQPFP (SEQ ID NO. 1) for detecting gliadin is antibody R5 (R-Biopharm AG Darmstadt, Germany). As such, Sorell et al. and Mitea addresses the claim.
Claim(s) 9, 16, 17, 19, 20 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Sorell et al. in view of Mitea et al., as applied to claim 8 above, and further in view of Sundvor et al., US PG Pub No. 2017/0003285A1 and Sousa Martin et al., US PG Pub No. 2016/0320385A1.
Regarding claims 9-10 and 24, see Sorell et al. in view of Mitea et al. are as cited in detail previously above, the combination of these references teach a kit substantially as claimed.
However, the combination of the cited art above fails to teach a test kit comprising a membrane device, namely a lateral flow assay (claims 8-10 and 24), fails to teach detection binding reagents conjugated with a colour label (claim 16), such as gold nanoparticles (claim 17), the detection binding reagents in a dried form on the membrane for use in a lateral flow assay (claim 19).
Sundvor et al. teach an example of a quantitative test strip (150, described at paras [0111]-[0112], capable of indicating amount), antibodies bound to labels (conjugate) at the substrate, analyte binding at a line/region/dot (or a set of regions for binding, i.e., more than one), active regions comprising antibody cocktails for a single analyte, a set of analytes, or for binding controls (see para [0111]). Sundvor does teach their device may comprise a combination of multiple (i.e., two or more) specific detection binding reagents binding to peptides indicative of gluten (e.g., for gliadin) (para [0111], refers to the use of antibody cocktails for detection, for example, for a set of analytes; para [0132] describes detecting multiple different analytes/allergens; see also paras [0136] and [0137]).
See further, Sousa Martin et al., at for example paras [0011], [0015], [0024], teaching detection of gluten polypeptides using either immunochromatographic test strips (membrane devices) or ELISA assay (ELISA in terms of providing components with a multi-well plate, antibodies immobilized on the wells of a plate or test strip).
Regarding claims 9, it would have been further prima facie obvious to have modified the ELISA as taught by the combination of Sorell et al. in view of Mitea, for detection of gluten proteins (namely prolamin and gluteline) to have modified the assay to be a membrane strip (lateral flow assay strip), as a simple substitution of one known assay substrate/technique for another, particularly because Sousa-Martin teach either as suitable for detection of gluten polypeptides. Further, one having ordinary skill in the art would have a reasonable expectation of success because in addition to Sousa-Martin teaching either alternative as suitable for detection of gluten, Sundvor also teach such test strips for the detection of gluten can include antibody cocktails (mixture) for the detection of different gluten proteins/peptides. As a result, one would expect success modifying the ELISA to be a lateral flow assay test device, because the test strip device could still accommodate the antibody cocktail for detection, as in the combination of Sorell and Mitea.
Regarding claims 16 and 17, see Sundvor teach label comprising coloured label, such as gold nanoparticles (para [0136]) (the combination as indicated above addresses the claim).
Regarding claim 19, see the combination of the cited art teaches the reagent dried in solution (coated on the device, see as cited above, the combination of the cited art teaching on a conjugate pad) .
Regarding claim 20, Sorell et al. teach Rye 5 antibody as capture reagent (R5), and see Mitea at page 1064, end of col. 1, the art recognized commercially available antibody that binds QQPFP (SEQ ID NO. 1) for detecting gliadin is antibody R5 (R-Biopharm AG Darmstadt, Germany). As such, Sorell et al. and Mitea addresses the claim.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Sorell et al. in view of Mitea et al., as applied to claim 8 above, and further in view of van Herpen et al., Detailed Analysis of the Expression of an Alpha-gliadin Promoter and the Deposition of Alpha-gliadin Protein During Wheat Grain Development, Annals. of Botany, 102, (2008), p. 331-342; and additionally, claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Sorell et al. in view of Mitea et al., Sundvor et al. and Sousa Martin et al., as applied to claim 9 above, and further in view of van Herpen et al.
Sorell et al. and the cited art teach an invention substantially as claimed (see as discussed in detail above).
Regarding claim 21 (as well as claim 28), reciting “wherein the capture binding reagent and/or detecting binding reagent binds to the epitope GYYPTS (SEQ ID No. 2)”, although Mitea et al. teach antibodies that bind substantially similar epitopes (see Mitea teach (Table 1) immunization peptides having sequences containing the claimed peptide “GYYPTS”, particularly sequences containing this peptides containing this sequence (shown in bold/underlined) are recognized as minimal amino acid sequences recognized by gluten-specific T-cells, further at Figure 1, Mitea teach minimal epitope sequences recognized by anti-HMW-glt mAb (see containing the claimed sequence GYYPTS, see also Table 2, and importantly table 3, epitopes shown in Bold, including QGQQGYYPT which substantially overlaps with the claimed GYYPTS)); Mitea et al. does not clearly teach an antibody which binds the epitope GYYPTS.
However, see van Herpen et al., a monoclonal antibody specific HMW (HMS 30-29 GYYPTS, page 335, col. 1, para 2, obtained from Koning, Leiden University Medical Center).
It would have been further prima facie obvious to one having ordinary skill to further modify the capture binding reagent and/or detection reagent of the device as taught by Sorell et al. and the cited prior art, such to further include in the combination, the HMW antibody of van Herpen, as an obvious matter of using an art recognized antibody for its intended purpose (detection of HMW proteins specific to gluten), one having ordinary skill motivated to further rely on the HMW antibody (in addition to those as taught by Mitea) to further improve, ensure binding to total gluten proteins (as another antibody capable of binding/detecting in a sample containing gluten proteins). One having ordinary skill would have a reasonable expectation of success incorporating an art recognized, available antibody reagent for its art recognized purpose, particularly considering the art (e.g., Mitea) recognized that a plurality of antibodies is capable of broad capture/detection.
Claims 23 is rejected under 35 U.S.C. 103 as being unpatentable over Sorell et al. in view of Mitea et al., as applied to claim 8 above, and further in view of Sundvor et al. (cited above) and Zuk et al., US Patent 4,208,479.
Regarding claim 23, Sorell does teach an extraction solution (a solution for extraction of proteins from wheat, see for example page 46, col. 2, section 2.2 comprising aliphatic short chain alcohol, namely ethanol), however fails to teach the extraction solution further comprises a chaotropic salt. Further, although Sorell is considered to address a kit since the reference teaches a cocktail sandwich ELISA (including reagents) together for assay, Sorell does not clearly teach the extraction solution/reagent as a part of their assay product.
Sundvor et al. teach an example of an assay device for detection of an analyte in a sample, for example to indicate gluten (quantitative test strip (150, described at paras [0111]-[0112], capable of indicating amount), antibodies bound to labels (conjugate) at the substrate, analyte binding at a line/region/dot (or a set of regions for binding, i.e., more than one), active regions comprising antibody cocktails for a single analyte, a set of analytes, or for binding controls (see para [0111]), teaching a combination of multiple specific detection binding reagents binding to peptides indicative of gluten (e.g., for gliadin) (para [0111], refers to the use of antibody cocktails for detection, for example, for a set of analytes; para [0132] describes detecting multiple different analytes/allergens; see also paras [0136] and [0137])).
Sundvor, also teaches extraction solution to extract an analyte from a homogenized sample (para [0082]). Regarding gluten, Sundvor teach extraction solution containing for example, 2-mercaptoethanol as a reducing disulfide prolamin crosslinking in a sample and solubilizes proteins, the solution additionally or alternatively containing guanidine hydrochloride as a disaggregating agent (para [0082]).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the extraction solution of Sorell to further include guanidine hydrochloride, one motivated to include this reagent as a disaggregating agent (Sundvor). Further, the modification would be applying a known technique to a known method, the prior art specifically teaching for extraction of gluten combining for example, component that reduces disulfide prolamin crosslinking, and component to promote disaggregation, namely by selecting from a finite list of suitable alternative reagents known to be combined for extraction to achieve gluten detection. One having ordinary skill would have a reasonable expectation because Sundvor specifically disclose this as a suitable combination for gluten extraction.
Although the prior art failed to teach included as part of the assay product (kit), an extraction solution, the advantages of packaging together necessary reagents in kit form were well known in the art at the time of the invention.
For example, Zuk et al. teach that in performing assays it is a matter of substantial convenience, as well as providing significant enhancement in accuracy to provide the reagents combined in a kit (column 22, lines 20-68).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art (and further one would expect success) to package together the reagents, including the extraction solution, in the form of a kit for convenience, improvement in accuracy, and/or for the purpose of commercial sale (Zuk).
Response to Arguments
Applicant's arguments filed 12/10/2025 have been fully considered but they are not persuasive for the following reasons.
Regarding remarks at page 13, see as indicated above, the previous objections to the claims are withdrawn in response to Applicant’s amendments to the claims.
Regarding remarks at page 13, see as indicated above, the previous rejection of claims under 35 U.S.C. 112(a), regarding new matter, are withdrawn in response to Applicant’s amendments to the claims.
Regarding remarks starting at page 14, the previous rejection under 35 U.S.C. 112(b), regarding “wherein the gluten proteins in the sample comprise prolamine from rye…and HMW secaline from rye”, is withdrawn in response to Applicant’s amendments to the claims. Similarly, the previous rejection of claim 9 under 35 U.S.C. 112(b), regarding “when present at the same quantities”, is withdrawn in response to amendments to the claims.
However, the rejection regarding the terms “LMW-glutenin”, “HMW-glutenin” and “HMW secalin” is maintained. Applicant argues (pages 15-17) that these terms are well-established terms in relation to gluten proteins, and that the metes and bounds of these terms would be readily understood by a person of ordinary skill in the art, Applicant referring to Appendix A (Schalk et al.), as supporting their argument. However there does not appear to be a clearly limited molecular weight range accepted across the art which indicates what is an is not considered a high or low molecular weight for either of glutenin or secalin, and even further, as is supported by Applicant’s remarks filed 12/10/2025, there are other factors that go into classification beyond merely molecular weight, including each of their amino acid sequence, and as such genetic origin and modification (see evidence cited previously in rejection, Masci et al. and Li et al., as well as Applicant’s remarks and Schalk 12/10/2025, pages 16-17).
Based on the evidence of record (previous rejection and referring to remarks), the boundaries regarding what species of proteins are encompassed by the claim are unclear, as there are many considerations that go into classifying a glutenin, or a secalin as low molecular weight or high molecular weight. It is not readily clear what species are encompassed by the claimed invention.
At remarks pages 17-18 Applicant further argues the previous rejection regarding the claimed dilution (see the grounds of rejection amended in detail above in response to Applicant’s amendments to the claims). Regarding the amended claim language, Applicant argues that claim 8, regardless of which gluten protein fraction is actually present in the sample, the same concentration (i.e., mass fraction) of any of these gluten proteins always produces the same signal as any other fraction when detected with the kit. Applicant remarks that for example, a sample comprising 10 mg/kg of prolamin will result in the same signal strength when using the claimed kit on a sample comprising 5 mg/kg prolamins, 3 mg/kg LMW-GS and 2 mg/kg HMW-GS (also in total 10 mg/kg proteins). In both cases, 10 mg/kg are detected. Applicant argues any detection and quantification of gluten proteins by the claimed kit are therefore possible for any mass fraction ratio of the different gluten proteins, that such detection and quantification of gluten proteins by the claimed kit thereby highly depends on the appropriate dilution the detection binding reagent.
This argument is not persuasive because, while emphasizing the importance on the “appropriate dilutions” for the detection binding reagent, this argument does not further clarify what that dilution would be. The claims do not appear to place a clear or definite limitation on the claimed dilution, beyond indicating the result it is to achieve. The arguments stress the importance of this dilution to the invention, but do nothing to further clarify or specify what the dilution claimed/encompassed would be.
Applicant argues the “appropriate dilutions” therefore depend on the specific detection binding reagents the conjugate method, and the detailed conjugation procedure, that they could vary from one test kit lot to the other even when the identical detection binding reagents are used and should be adjusted for each sample. Applicant asserts it is therefore not appropriate or possible to state a specific dilution amount for each agent, as these can only be determined by routine experimentation for each sample. In response, it is suggested that applicant amend the claims to omit the claimed functional language, as it appears that this argument supports that this language, although as recited appears to imply some structure (in terms of how much is present in the mixture), is actually directed to the intended use of the claimed product (the claimed invention being a product and not a method). Because the claimed language appears to suggest or imply an amount that is defined in terms of function, at this time the rejection is maintained.
Regarding the arguments specific to the rejection of claims under 35 U.S.C. 103, Applicant argues Sorell does teach a mixture of capture antibodies, and that Sorell teaches a single detection antibody, not a mixture of detection antibody (remarks page 20). Applicant argues providing a mixture of capture antibodies is less complex than a specific mixture of detection antibodies. However, it is maintained that it is the combination of the cited prior art which motivates one of ordinary skill to provide both antibodies to prolamin as well as gluteline.
Applicant argues Sorell has no specific adjustment of the mixture of capture antibodies disclosed, that in contrast, providing a dilution of detection binding reagents as claimed, produces the same signal for each protein in the fraction regardless of which is actually present. Applicant argues the preparation of these dilutions requires a more involved experimentation to avoid over or under determination of individual proteins and is substantially more complex than coating a plate with a mixture of capture antibodies at a first concentration. Applicant remarks that the adjusted dilution of the detection binding reagents is substantial for precise and reliable quantification of all gluten protein fractions in the sample.
Applicant’s arguments (page 20-23) are not persuasive. The arguments appear to both make the case that the claims are not limited to any particular dilution (binding reagent amounts), yet also argues this is a limitation important and which distinguishes the claimed product form the cited prior art. It is the combination of the cited art which addresses the claimed mixture of antibodies. See as noted in detail above (regarding the rejection under 35 U.S.C. 112(b)), Applicant’s remarks to the previous rejection under 35 U.S.C. 112(b) appear to support that the dilution may not be particularly limited and is a variable to be determined/adjusted at each experiment. It is not clear from remarks if it is the case that the dilution is not particularly limiting in terms of how much reagent for each is provided in the mixture, and rather is specific to the intended use of the combination when applied in methods of detecting.
In the interest of compact prosecution, the rejection under 35 U.S.C. 103 is maintained because the combination of the prior art provides motivation to provide, as a mixture, a kit as claimed, comprising both antibodies to prolamin and gluteline. The claimed invention is a product, not an invention, and therefore arguments that suggest that the cited references do not teach or disclose a step of precisely adjusting a mixture against different proteins to achieve detection is not persuasive that the claimed product is compositionally different or distinct from that which is taught by the cited prior art.
Conclusion
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLEN J MARCSISIN whose telephone number is (571)272-6001. The examiner can normally be reached M-F 8:00am-4:30pm.
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, Bao-Thuy Nguyen can be reached at 571-272-0824. 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.
/ELLEN J MARCSISIN/ Primary Examiner, Art Unit 1677