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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 December 15, 2025, has been entered.
Election/Restrictions
Applicant’s election of Group I (i.e., 1-3, 7-13, 36, 39, and 43 drawn to a surrogate peptide) in the reply filed on May 20, 2024, is acknowledged. Additionally, Applicant’s election of Species A (i.e., eCry3.1Ab as a single and specific target transgenic protein, root tissue as a single and specific biological sample, maize as a single and specific transgenic plant, valine as a single and specific stable isotope labeled amino acid, and SEQ ID NO: 27 as a single and specific surrogate peptide) in the reply filed on September 26, 2024, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Please note that in light of the Examiner search, Species A is expanded to include where the target transgenic protein is Cry1Ab protein, leaf tissue as a biological sample, rice as a transgenic plant, and SEQ ID NOs: 1-2 are surrogate peptides. Also please note that the single and specific stable isotope labeled amino acid of Species A is hereby withdrawn.
Status of Claims
Claims 1-55 were originally filed on February 26, 2021.
The amendment received on February 26, 2021, canceled claims 4-6, 14-35, 37-38, 40-42, 44-45, 49-50, and 53-55; amended claims 1 and 36; and added new claims 56-57. The amendment received on April 30, 2025, amended claim 1.
Claims 1-3, 7-13, 36, 39, 43, 46-48, 51-52, and 56-57 are currently pending and claims 1-3, 7-9, 39, and 43 are under consideration as claims 46-48, 51-52, and 56-57 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, and claims 10-13 and 36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the replies filed on May 20, 2024, and September 26, 2024.
Priority
The present application claims status as a 371 (National Stage) of PCT/US19/46438 filed August 14, 2019, and claims priority under 119(e) to U.S. Provisional Application No. 62/723,164 filed on August 27, 2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 15, 2025, is being considered by the examiner.
Sequence Interpretation
For claim 1, please note that the Examiner is interpreting the scope of the amino acid sequence of the surrogate peptide as open-ended requiring 100% identity to one of the recited sequences with any N- and/or C-terminal residues.
For claim 7, please note that the Examiner is interpreting the scope of the amino acid sequence of the surrogate peptide as open-ended requiring 100% identity to one of the recited sequences with any N- and/or C-terminal residues.
For claim 8, please note that the Examiner is interpreting the scope of the amino acid sequence of the transition ion as open-ended requiring 100% identity to one of the recited sequences with any N- and/or C-terminal residues. However, as will be further articulated in rejections below, the peptide produces this transition ion amino acid sequence. Thus, the structure of the claimed labeled surrogate peptide does not require one of the sequences recited in claim 8 since the recited sequences are part of the intended use of the claimed labeled surrogate peptide.
For claim 9, please note that the Examiner is interpreting the scope of the amino acid sequence of the surrogate peptide as open-ended requiring 100% identity to one of the recited sequences with any N- and/or C-terminal residues.
Response to Amendment
The Declaration under 37 CFR 1.132 filed 11/25/25 is insufficient to overcome the rejection of claims 1, 7-9, 39, and 43 based upon Park WO 01/98523 A2 published on December 27, 2001 as set forth in the last Office action for the following reasons.
The Declarant’s assertions are acknowledged. However, in response to the Declarant’s argument that the peptide discussed by Park would not allow for detection and quantitation in mass spectrometry because selecting a peptide for use in mass spectrometry detection verses selecting a peptide for antibody production requires a different set of selection criteria including (1) peptide length ideally should be between 6 to 25 amino acids, (2) peptide selection requires good chromatography separation with well resolved peaks and consistent retention time, (3) cleavage sites for tryptic peptides need to be efficient and reliable (i.e., need to avoid peptides with proline or regions prone to missed cleavages), (4) peptide selection should avoid instability of peptides that may be prone to chemical modifications or degradation leading to variable quantitative results such as methionine and tryptophan, asparagine, and glutamine, and (5) peptide selection should avoid post-translation modifications such as phosphorylation, glycosylation and acetylation (See Declaration received on 11/25/25, paragraphs 3, 6, and 9), it is found unpersuasive. Here, it appears the Declarant is focused on the claimed intended use of the labeled surrogate peptide, and how Park’s labeled peptide is not capable of being used as instantly claimed. However, as stated in the Action mailed on 7/31/25, the Declarant is respectfully reminded that the claimed invention is directed to a product and not a method of using the product. As such, the first question is what structure is being claimed. The structural requirements of claim 1 are a peptide comprising a label and an amino acid sequence selected from a Markush group of peptide sequences including elected SEQ ID NO: 27 (i.e., TDVTDYHIDQV). Next, an interpretation of the scope/breadth of the claimed structural requirements is made. Pursuant to MPEP 2113.03(I), the transitional term "comprising" is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. As discussed in the “Sequence Interpretation” section supra, the scope of claim 1 with respect to the peptide amino acid sequence is being interpreted as open-ended requiring 100% identity to SEQ ID NO: 27 but with any N- and/or C-terminal additions. This interpretation is in light of the transitional phrase “comprising” a label and an amino acid sequence. As such, the scope/breadth of the claimed peptide amino acid sequences requires 100% identity to instant SEQ ID NO: 27, but encompasses any amino acid sequence regardless of length that contains instant SEQ ID NO: 27. In contrast to “comprising”, the transitional phrase, “consisting” would be interpreted as closed-ended requiring 100% identity and the same length to SEQ ID NO: 27 thereby excluding any amino acid sequence that contains instant SEQ ID NO: 27 within a larger sequence. In light of these first two steps, as discussed in the rejection below, the Park reference expressly suggests a peptide comprising an a label and an amino acid sequence of SEQ ID NO: 27. More specifically, Park’s SEQ ID NO: 57 has the amino acid sequence of TDVTDYHIDQVSNLVECLSDEFCLDE where residues 1-11 are 100% identical to instant SEQ ID NO: 27. Thus, in light of the interpretation of claim 1, Park’s SEQ ID NO: 57 reads on the scope of the claimed peptide amino acid sequence of instant SEQ ID NO: 27. Declarant does not dispute this finding, i.e., that Park’s SEQ ID NO: 57 reads on the claimed amino acid sequence of instant SEQ ID NO: 27, or that Park’s SEQ ID NO: 57 is indirectly conjugated to a label.
Furthermore, it is noted that of the five criteria identified by the Declarant, 4 of them involve the structure of the peptide; more specifically, criteria 1 and 3-5. With respect to the first criteria, i.e., peptide length ideally should be between 6 to 25 amino acids, it is acknowledged that Park’s SEQ ID NO: 57 is slightly larger than Declarant’s identified peptide length range of 6 to 25 amino acids, i.e., Park’s SEQ ID NO: 57 is 27 amino acids in length. However, such a criteria cannot be considered a per se structural requirement since several other amino acid sequences recited in the claimed Markush have amino acid sequence lengths greater than 25 amino acids; for example, SEQ ID NO: 23 has 28 total amino acids, SEQ ID NO: 25 has 34 total amino acids, and SEQ ID NO: 77 has 31 total amino acids. Presumably, these claimed sequences would function as claimed. Otherwise, a question of whether the claimed invention is fully enabled would arise. As such, notwithstanding that the scope/breadth of the claimed amino acid sequence encompasses Park’s SEQ ID NO: 57, the fact that Park’s SEQ ID NO: 57 is 27 amino acids in length does not per se exclude it as constituting a claimed amino acid sequence comprising instant SEQ ID NO: 27 capable of functioning in a mass spectrometry assay.
With respect to the third criteria, i.e., cleavage sites for tryptic peptides need to be efficient and reliable (i.e., need to avoid peptides with proline or regions prone to missed cleavages), it is noted that Park’s SEQ ID NO: 57 does not contain any tryptic cleavage sites, nor does it contain a proline residue. Slechtova et al. teaches that trypsin is a highly specific protease that cleaves peptide bonds at the C-terminal side of lysine or arginine residues except when followed by proline (See Slechtova et al., Anal. Chem. 87:7636-7643 (2015) at pg. 7636, col. 2, 1st paragraph). Slechtova et al. also teaches that the presence of glutamate or aspartate acidic residues near the cleavage site also reduces the proteolysis speed (See Slechtova, pg. 7637, col. 1, 1st paragraph). Similar inhibition was reported for scissile sites flanked by phosphorylated serine and threonine residues, which also carry a negative charge (See Slechtova, pg. 7637, col. 1, 1st paragraph). However, Park’s SEQ ID NO: 57 does not contain any arginine or lysine residues, and therefore, this third criteria is not applicable. Thus, consideration of the third criteria does not exclude Park’s SEQ ID NO: 57 as constituting a claimed amino acid sequence comprising instant SEQ ID NO: 27 capable of functioning in a mass spectrometry assay.
With respect to the fourth and fifth criteria, i.e., peptide selection should avoid instability of peptides that may be prone to chemical modifications or degradation leading to variable quantitative results such as methionine and tryptophan, asparagine, and glutamine, and peptide selection should avoid post-translation modifications such as phosphorylation, glycosylation and acetylation, it is noted that there are many amino acid residues susceptible to chemical modifications including post-translation modifications and/or degradation. Li et al. teaches that oxidation is one of the major chemical degradation pathways for protein pharmaceuticals where methionine, cysteine, histidine, tryptophan, and tyrosine are the amino acid residues most susceptible to oxidation due to their high reactivity with various reactive oxygen species (See Li et al., Biotechn. Bioeng. 48:490-500 (1995) at abstract). Similarly, Grassi et al. identifies that methionine, cysteine, histidine, tyrosine, tryptophan, and phenylalanine are susceptible to oxidation (See Grassi et al., Amino Acids 51:1409-1431 (2019) at abstract; Table 1). Moreover, Grassi et al. teaches that aspartate, glutamate, asparagine, glutamine and N-terminal dipeptidyl motifs are susceptible to intra- and inter-residue cyclization (See Grassi, abstract). Serine, threonine, cysteine and cystine are susceptible to β-elimination (See Grassi, abstract). In the instant case, Park’s SEQ ID NO: 57, i.e., TDVTDYHIDQVSNLVECLSDEFCLDE (note: bold residues represent instant SEQ ID NO: 27), does not contain any methionine or tryptophan residues. Although Park’s SEQ ID NO: 57 contains 2 threonine residues, 2 serine residues, 1 asparagine residue, 3 glutamate residues, 2 cysteine residues, 1 tyrosine, 1 glutamine, 1 histidine, and 5 aspartate residues, instant SEQ ID NO: 27 contains some of these residues, i.e., 2 threonine residues, 3 aspartate residues, 1 tyrosine, 1 glutamine, and 1 histidine. In fact, 8 of the 11 residues of instant SEQ ID NO: 27 constitute residues susceptible to chemical modification including post-translation modifications and/or degradation. Moreover, many of the peptides recited in the claimed Markush group contain residues susceptible to chemical modifications or degradation, e.g., instant SEQ ID NO: 3 contains 2 threonine residues, 2 serine residues, and 1 tyrosine residue, and instant SEQ ID NO: 23 contains 1 methionine residue, 1 aspartate residue, 6 asparagine residues, 4 glutamate residues, 1 serine, residue, 1 tyrosine residue, and 2 cysteine residues. The Declarant has not offered any explanation why the claimed peptide sequences including instant SEQ ID NO: 27 are capable of performing the claimed intended use, but yet would not meet the Declarant’s fourth and fifth criteria. It is acknowledged that there are many amino acids susceptible to chemical modifications including post-translation modifications and/or degradation, but without any specific evidence demonstrating why Park’s SEQ ID NO: 57 is not capable (See Action mailed on 7/31/25, “Response to Arguments” section, response to Applicant’s first argument: a prior art’s sequence need not perform the claimed use, but rather, be capable of such use when a product claim recites an intended use in the preamble of a claim) of functioning in a mass spectrometry assay, the presence of these residues in a sequence, especially given that the claimed sequences also contain these residues, does not exclude Park’s SEQ ID NO: 57 as constituting a claimed amino acid sequence comprising instant SEQ ID NO: 27 capable of functioning in a mass spectrometry assay.
With respect to Declarant’s second criteria, i.e., peptide selection requires good chromatography separation with well resolved peaks and consistent retention time, the Declarant has not provided any evidence to demonstrate that Park’s SEQ ID NO: 57 would not exhibit the property of good chromatography separation with well resolved peaks and consistent retention time. The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether Declarants’ SEQ ID NO: 27 exhibits different properties and, if so, to what extent, from that of Park’s SEQ ID NO: 57. Notably, the Declaration provides no specific evidence that Park’s SEQ ID NO: 57 is incapable of functioning in a mass spectrometry assay. Therefore, with the showing of the reference, the burden of establishing non-obviousness by objective evidence is shifted to the Declarant. Thus, even when considering the Declarant’s five identified criteria for selecting a peptide for use in mass spectrometry detection, Park’s SEQ ID NO: 57 complies with the stated criteria without evidence to the contrary and when comparing Park’s SEQ ID NO: 57 with the claimed sequences.
However, even if the Declarant provides evidence demonstrating that Park’s SEQ ID NO: 57 is incapable of functioning in a mass spectrometry assay, an evaluation of the structural scope of the claimed invention with respect to the enablement requirement would need to be conducted. This is because a chemical composition and its properties are inseparable. As stated in the Action mailed on 11/25/25, pursuant to MPEP 2112.01(I),
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433.
Pursuant to MPEP 2112.01(II), “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. In the instant case, as discussed supra, Park’s SEQ ID NO: 57 constitutes an amino acid sequence of instant SEQ ID NO: 27 in light of the broadest reasonable interpretation of the claimed sequence. As such, Park suggests the claimed structural limitations of a labeled peptide derived from a transgenic protein comprising a label and an amino acid sequence of SEQ ID NO: 27. Thus, given that the teachings of Park render the claimed structure of the labeled peptide obvious, the teachings of Park would also necessarily render the claimed function/intended use obvious.
Additionally, for completeness, the Examiner would like to acknowledge that once the scope of the claimed structural limitations has been determined, the final step is to consider any remaining functional properties and/or intended uses. As stated in the Action mailed on 7/31/25, pursuant to MPEP 2111.02(II), the question is whether these functional/intended use limitations impart structure to the claimed labeled peptide. As discussed in the rejection below, the instant specification defines a surrogate peptide as one that is derived from a target transgenic protein via proteolytic digestion that functions in a mass spectrometry assay to produce one or more transition ions that in combination with the surrogate peptide differentially detects and/or quantitates the target transgenic protein when the target transgenic protein is in the presence of one or more other transgenic proteins and/or non-transgenic proteins in a complex biological matrix and does not detect and/or quantitate the one or more other transgenic proteins or the non-transgenic proteins in the biological matrix (See instant specification, [080]). Park expressly teaches that the peptides are derived from genetically modified organisms, i.e., recombinant proteins derived from genetically modified organisms include BT recombinant proteins (See Park specification, pg. 7, 3rd paragraph). As such, Park expressly teaches that the peptide is derived from a transgenic protein. Therefore, the structure imparted from the claimed functional/intended use limitations is taught by the prior art. The remaining functional/intended use limitations do not impart a structural limitation for the claimed labeled peptide, and thus, are of no structural significance in determining whether Park renders obvious the claimed invention. However, even if the functional/intended use limitations are considered limiting, as discussed in the MPEP supra, the question is whether a prior art structure is capable of performing the intended use as recited in the preamble meets the claim. Given the structure of the Park’s labeled peptide is encompassed by the scope of the claimed labeled peptide, it would then follow that Park’s labeled peptide is capable of performing the claimed functional property/intended use without evidence to the contrary.
Accordingly, the Declarant’s argument is found unpersuasive.
Maintained Rejections
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1, 7-9, 39, and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Park WO 01/98523 A2 published on December 27, 2001.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claims 1, 7, and 9, with respect to a peptide comprising an amino acid sequence of SEQ ID NO: 27:
Park teaches detection of genetically modified organisms and foodstuff prepared from genetically modified organisms (See Park specification, pg. 4, 2nd to 6th paragraphs; pg. 6, last paragraph to 1st paragraph). To do so, Park teaches an antibody that combines specifically with a recombinant protein by analyzing a protease cleavage map or recombinant proteins expressed in transformed DNA in genetically modified organisms, selecting peptides that do not have homology with peptides prepared from the same protease cleavage map for a wild-type plant protein among peptides analyzed from the cleavage map, preparing synthetic peptides from amino acids of the selected peptides, and preparing an antibody from the synthetic peptides (See Park specification, pg. 4, last paragraph to pg. 5, 1st paragraph). Then, the prepared antibody specifically with a recombinant protein with food and confirming an antigen-antibody reaction to distinguish foodstuff prepared from a wild-type plant from foodstuff prepared from a genetically modified organism (See Park specification, pg. 5, 3rd paragraph). The recombinant proteins derived from genetically modified organisms include BT recombinant proteins (See Park specification, pg. 7, 3rd paragraph). The selected BT peptides are depicted in Table 3 as SEQ ID NOs: 55-162 where SEQ ID NO: 57 has the amino acid sequence of TDVTDYHIDQVSNLVECLSDEFCLDE (See Park specification, pg. 11, last paragraph; Table 3). When comparing Park’s SEQ ID NO: 57 with instant SEQ ID NO: 27, there is 100% identity with resides 1-11. As discussed in the “Sequence Interpretation” section supra, Park’s SEQ ID NO: 57 is encompassed by the scope of instant claim 1. This peptide was used to prepare antibodies against it that can be used to detect the same sequence in a biological sample containing plants such as corn thereby indicating the presence of a genetically modified organism. In Example 7, Park teaches that BT amino acid sequences were analyzed and identified as SEQ ID NOs: 55-162 (See Park specification, pg. 25, 3rd paragraph; Example 7). Park took the peptides of SEQ ID NOs: 160-162 and raised antibodies against them (See Park specification, pg. 25, last paragraph to pg. 26, 1st paragraph; Example 7). Then the prepared antibodies and labeled (See discussed below) secondary antibodies were added in vitro to biological samples containing genetically modified foodstuff such as rice, corn or beans and wild-type foodstuff in order to determine whether the prepared antibodies bind to the recombinant proteins in the genetically modified organism (See Park specification, pg. 19, last paragraph to pg. 20, 1st paragraph; pg. 26, 2nd paragraph; Examples 1 and 7). Thus, an ordinary skilled artisan would utilize any identified BT derived peptide including Park’s SEQ ID NO: 57 as further articulated below. Therefore, the teachings of Park satisfy the claim limitation with respect to a peptide comprising instant SEQ ID NO: 27 as recited in instant claims 1, 7, and 9.
For claim 1, with respect to where the peptide is a labeled peptide:
As discussed supra, Park teaches a peptide comprising instant SEQ ID NO: 27 that is used to prepare antibodies where the prepared antibodies will react with the peptide sequence in a biological sample containing plants such as corn thereby indicating the presence of a genetically modified organism. Additionally, Park teaches that confirmation of antigen-antibody reaction (i.e., note: the antigen is the peptide sequence identified above) of recombinant protein can be achieved by a conventional method in a lab by using a coloring protein or showing fluorescence by preparing a secondary antibody conjugated with an inactive fluorescent protein that binds only with the antigen-antibody complex, binding the secondary antibody to the antigen-antibody complex, and adding an enzyme and activating the inactive florescence protein (See Park specification, pg. 15, 2nd paragraph). It is more preferable to conjugate colloidal gold with the secondary antibody and binding this antibody-colloidal gold conjugate to an antigen-antibody complex (See Park specification, pg. 7, 3rd paragraph). Given that the claimed labeled peptide does not require any specific label or how the peptide is labeled thereby including indirect labeling of the peptide, the resulting conjugate of the labeled secondary antibody with the antigen-antibody complex constitutes where the antigen, e.g., an identified peptide such as SEQ ID NO: 57, is labeled. Thus, the teachings of Park suggest the claim limitation with respect to where the peptide is a labeled peptide as recited in instant claim 1.
For claim 1, with respect to where the labeled peptide is a surrogate peptide:
It is noted that the instant specification defines a surrogate peptide as one that is derived from a target transgenic protein via proteolytic digestion that functions in a mass spectrometry assay to produce one or more transition ions that in combination with the surrogate peptide differentially detects and/or quantitates the target transgenic protein when the target transgenic protein is in the presence of one or more other transgenic proteins and/or non-transgenic proteins in a complex biological matrix and does not detect and/or quantitate the one or more other transgenic proteins or the non-transgenic proteins in the biological matrix (See instant specification, [080]). As such, structurally speaking, the definition requires the peptide to be derived from a target transgenic protein. In this, as discussed below, Park teaches that the recombinant proteins (note: the identified peptides are fragments of the recombinant proteins) derived from genetically modified organisms include BT recombinant proteins (See Park specification, pg. 7, 3rd paragraph). BT induces the resistance to harmful insects by transferring cryIA and cryIIIA genes of Bacillus thuringiensis to plants including cryIA(b) from corn (i.e., maize), and cryIIIA from potatoes (See Park specification, pg. 8, 2nd paragraph). Although Park does not expressly teach that that eCry3.1Ab is a BT transgenic protein in which peptides are derived from, since Park teaches a species of peptide that falls with the claimed subgenus of peptides that are derived from eCry3.1Ab (i.e., Park’s SEQ ID NO: 57), it must follow that Park’s SEQ ID NO: 57 constitutes a peptide that is derived from eCry3.1Ab. Thus, the teachings of Park satisfy where the peptide is derived from a transgenic protein.
The means by which the peptide is derived from a target transgenic protein, i.e., proteolytic digestion, constitutes a product-by-process limitation. Regarding product-by-process claims, the Federal Circuit has found that "[e]ven through product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim in the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." See MPEP 2113 and In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Furthermore, the Federal Circuit found that “[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes.” See MPEP 2113 and Amgen, Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). Therefore, the process by which the peptide is derived does not impart a structural limitation to the resulting peptide fragment, and thus, does not aid in the patentability of a labeled peptide.
Furthermore, the definition encompasses the intended use of the peptide, i.e., functions in a mass spectrometry assay to produce one or more transition ions….
Pursuant under MPEP 2111.02(II):
statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim. See, e.g., In re Otto, 312 F.2d 937, 938, 136 USPQ 458, 459 (CCPA 1963) (The claims were directed to a core member for hair curlers and a process of making a core member for hair curlers. The court held that the intended use of hair curling was of no significance to the structure and process of making.); In re Sinex, 309 F.2d 488, 492, 135 USPQ 302, 305 (CCPA 1962) (statement of intended use in an apparatus claim did not distinguish over the prior art apparatus). To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board’s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant’s claim 1 (a dispensing top for dispensing popcorn in a specified manner)) and cases cited therein. (emphasis added).
As such, a labeled peptide is intended to function in a mass spectrometry assay to produce one or more transition ions that in combination with the surrogate peptide differentially detects and/or quantitates the target transgenic protein when the target transgenic protein is in the presence of one or more other transgenic proteins and/or non-transgenic proteins in a complex biological matrix and does not detect and/or quantitate the one or more other transgenic proteins or the non-transgenic proteins in the biological matrix. Thus, the claimed labeled peptide being a labeled surrogate peptide encompasses the intended use of the labeled peptide. Although Park does not expressly teach using the labeled peptide to differentially detect and/or quantitate eCry3.1Ab as a target transgenic protein in a biological matrix in a mass spectrometry assay (See Zhang article; abstract; pg. 2700, col. 1, 2nd paragraph), the labeled peptide functioning as defined renders the Park labeled peptide being capable of performing the defined intended use. Thus, the disclosure of Park et al. satisfies the claim limitation with respect to Park’s labeled peptide being a labeled surrogate peptide as recited in instant claim 1.
For claims 1 and 7, with respect to where the labeled peptide functions in a mass spectrometry assay to selectively detect or quantitate a target transgenic protein such as eCry3.1Ab protein in a mixture of transgenic proteins and non-transgenic proteins in one or more biological samples from one or more transgenic plants as recited in instant claim 1; and with respect to where the peptide selectively detects or quantitates an eCry3.1Ab protein as recited in instant claim 7:
As discussed supra for claim 1, Park teaches that the recombinant proteins derived from genetically modified organisms include BT recombinant proteins (See Park specification, pg. 7, 3rd paragraph). BT induces the resistance to harmful insects by transferring cryIA and cryIIIA genes of Bacillus thuringiensis to plants including cryIA(b) from corn (i.e., maize), and cryIIIA from potatoes (See Park specification, pg. 8, 2nd paragraph). However, although Park does not expressly teach that the method of detection is a mass spectrometry assay or that the transgenic protein is an eCry3.1Ab protein, such limitations do not impart a structural limitation that a prior art reference needs to teach. Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Additionally and/or alternatively, the discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02. Moreover, “[t]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is necessarily present in the prior art does not necessarily make the claim patentable. As such, claim 1 recites an intended use of the claimed labeled peptide such that the labeled peptide is used in a mass spectrometry assay to selectively detect or quantitate a target transgenic protein such as Cry1Ab protein in a mixture of transgenic proteins and non-transgenic proteins in one or more biological samples from one or more transgenic plants. A recitation of an intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Accordingly, although Park did not expressly teach the claimed function/intended use, since Park discloses a labeled peptide as instantly claimed, the intended use of the labeled peptide is also rendered obvious.
For claim 8, with respect to where the peptide produces a transition ion having an amino acid sequence selected from SEQ ID NOs: 142-150, DGR, IEF, and LER:
It is noted that Park does not teach where SEQ ID NO: 57 produces a transition ion having an amino acid sequence selected from SEQ ID NOs: 142-150, DGR, IEF, and LER. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02. Moreover, “[t]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is necessarily present in the prior art does not necessarily make the claim patentable. As such, claim 8 recites an intended use of the claimed labeled peptide such that the labeled peptide produces a transition ion having an amino acid sequence selected from SEQ ID NOs: 142-150, DGR, IEF, and LER. A recitation of an intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Accordingly, although Park did not expressly teach the claimed function/intended use, since Park discloses a labeled surrogate peptide as instantly claimed, the intended use of the labeled peptide is also rendered obvious.
Additionally and/or alternatively, although Park does not teach where SEQ ID NO: 57 produces a transition ion having an amino acid sequence selected from SEQ ID NOs: 142-150, DGR, IEF, and LER, it is unnecessary for a prior art reference to teach this limitation because a functional property of the peptide (i.e., producing a transition ion having an amino acid sequence selected from SEQ ID NOs: 142-150, DGR, IEF, and LER) does not state a condition that is material to patentability or provide a structural limitation that would further limit the claimed peptide. The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the functional property of the peptide (i.e., producing a transition ion having an amino acid sequence selected from SEQ ID NOs: 142-150, DGR, IEF, and LER) is an intended result of the claimed peptide that gives little meaning and purpose to the structure of the claimed peptide. Accordingly, claim 8 recites an intended result that does not render material to patentability.
For claims 39 and 43, with respect to where the transgenic plant is corn or rice as recited in instant claim 39; and with respect to where the biological sample is from leaf tissue or root tissue as recited in instant claim 43:
The detection of genetically modified organisms in foodstuff include agricultural crops (See Park specification, pg. 7, 2nd paragraph) such as corn, beans, rice and potatoes (See Park specification, pg. 7, 2nd paragraph; pg. 19, last paragraph to pg. 20, 1st paragraph; pg. 26, 2nd paragraph; Examples 1 and 7). Moreover, Park teaches that the crop plant is dried, ground, filtered, and dissolved in buffer solution (See Park specification, pg. 19, last paragraph). As such, the teachings of Park satisfy the claim limitation as recited in instant claim 39. However, even if Zhang et al. did not expressly teach that the transgenic plant is corn or the biological sample is from leaf tissue or root tissue, the limitations recited in instant claims 39 and 43 further limit the function and/or intended use of the claimed labeled peptide. Thus, the limitations recited in instant claims 39 and 43 do not further limit the structure of the claimed labeled peptide. Therefore, the teachings of Park satisfies the claim limitations as recited in instant claims 39 and 43.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Park does not expressly teach a specific embodiment of a labeled surrogate peptide comprising instant SEQ ID NO: 27 as recited in instant claims 1, 7, and 9. However, the teachings of Park suggest this deficiency by constituting simple substitution of one known element for another to obtain predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to a specific embodiment of a labeled surrogate peptide comprising instant SEQ ID NO: 27 as recited in instant claims 1, 7, and 9, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to follow the teachings of Park and utilize Park’s SEQ ID NO: 57 derived from a transgenic BT protein instead of Park’s SEQ ID NOs: 160-162 to raise antibodies against it, add the prepared antibodies and labeled secondary antibodies that bind the prepared antibodies in vitro to biological samples containing genetically modified foodstuff such as rice, corn or beans and wild-type foodstuff where the prepared antibodies bind to the recombinant BT transgenic protein containing Park’s SEQ ID NO: 57 and the labeled secondary antibodies bind to the prepared antibody-recombinant protein complex where such binding detects the presence of genetically modified organisms in the foodstuff. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because Park’s SEQ ID NOs: 55-162 were known to be derived from a transgenic BT protein, were known to be used to prepare antibodies against them, and were known to be targeted for binding by the prepared antibodies and labeled secondary antibodies in order to detect genetically modified organisms in foodstuff as taught by Park. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that SEQ ID NOs: 160-162 of Park were derived from a transgenic BT protein and used to prepare antibodies against them, and then targeted in an in vitro biological sample of genetically modified and non-genetically modified organisms such as corn, rice or beans where the prepared antibodies and labeled secondary antibodies to the prepared antibodies are added to the sample and bind to recombinant protein containing one of SEQ ID NOs: 160-162 thereby forming a labeled secondary antibody-prepared antibody-recombinant protein complex in order to detect a genetically modified organism that contains the recombinant protein in the biological sample. Therefore, substituting Park’s SEQ ID NO: 57 instead of Park’s SEQ ID NOs: 160-162 as the peptide derived from a transgenic BT protein used to prepare antibodies and then targeted in an in vitro biological sample of genetically modified and non-genetically modified organisms would support the detection of genetically modified organisms containing SEQ ID NO: 57 once the prepared antibodies and labeled secondary antibodies bind to SEQ ID NO: 57 by constituting simple substitution of one known element for another to obtain predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Park WO 01/98523 A2 published on December 27, 2001, as applied to claim 1 above, and further in view of Croote et al., Systems Biol. Appl. 2:1-10 (2016), and Pepscan, “Stable isotope labeled peptides,” Pepscan, available online at https://www.pepscan.com/fr/synthese-peptidique-a-facon/modification-des-peptides/stable-isotope-labeled-peptides/, 4 pages (first available May 19, 2015 per Google), as applied to claims 2-3 herewith.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claim 1, please see discussion of Park supra.
For claim 2, with respect to where the peptide is labeled by incorporation of a SIL amino acid as recited in instant claim 2; and with respect to where the SIL amino acid is isoleucine or valine as recited in instant claim 3:
As discussed supra for claim 1, Park teaches using an immunoassay with a coloring antibody to detect genetically modified organisms in foodstuff. Park also teaches using an ELISA kit with a coloring antibody in order to perform the detection method (See Park specification, pg. 17, 2nd paragraph to pg. 18, 1st paragraph). However, Park does not expressly teach where the peptide is labeled by incorporation of a SIL amino acid such as isoleucine or valine.
Croote et al. sought to develop assays that can sensitively and reliably detect trace amounts of allergen in manufactured food where mass spectrometry (MS) is a promising alternative to commonly employed antibody-based assays owing to its ability to quantify multiple proteins in complex matrices with high sensitivity (See Croote article, abstract). Although Croote discusses some advantages to antibody-based assays such as ELISA (See Croote article, pg. 1, col. 2, last paragraph), Croote also identifies several disadvantages of ELISA including little to no sensitivity for foods subjected to thermal processing, which can denature or degrade epitopes, false-positives can occur due to antibody cross-reactivity, inability to be multiplexed thereby adding cost to food manufacturers, and differences in antibody composition, target analyte(s), sample preparation procedures, and standards used for calibration between ELISAs can result in large quantitative differences when testing identical foods (See Croote article, pg. 2, col. 1, 2nd paragraph). In comparison, liquid-chromatography-mass spectrometry (MS) has a key advantage; namely, sensitive multiplexed quantitation of allergenic proteins (See Croote article, pg. 2, col. 1, 3rd paragraph). Croote also teaches that selected reaction monitoring is the most extensively used targeted technique (See Croote article, abstract; pg. 2, col. 1, 4th paragraph).
One promising improvement for MS-SRM assays is the use of proteotypic peptides, which are peptides whose presence appears robust to variations in food matrix (See Croote article, abstract). Croote suggests proteotypic peptides for a subset of allergenic milk, egg and peanut proteins, but also soy, wheat, and tree nuts (See Croote article, abstract). Once an SRM assay has been developed, quantitation can be achieved using synthetic, stable isotope-labeled (SIL) peptides that behave identically to their unlabeled target analogues chromatographically and in fragmentation profile, but differ in mass (See Croote article, pg. 6, col. 2, last paragraph to pg. 7, col. 1, 1st paragraph). Utilizing the SIL amino acid approach offers several advantages including having benefits of linearity over four orders of magnitude, coefficients of variation typically below 10%, and inter-laboratory comparability, all characteristics that are required for developing a standardized analytical workflow capable of quantifying allergens present in trace amounts in commercial foods (See Croote article, pg. 7, col. 1, 1st paragraph). Croote further teaches a specific approach of using SIL peptides including where allergen quantitation can be achieved by using the highest intensity peptide for each protein, while other peptides are confirmatory (See Croote article, pg. 7, col. 1, 2nd paragraph). Thus, when combining the teachings of Croote with those of Park, an ordinary skilled artisan would be motivated with a reasonable expectation of success to detect genetically modified organisms in foodstuff by using the MS-SRM assay instead of the antibody-based assay where the identified peptides, e.g., SEQ ID NO: 57, of Park as one of the peptides determined to be those of highest intensity would be labeled, and in particularly, an SIL amino acid incorporated into one of the identified peptides.
However, the teachings of Park and Croote do not expressly teach where isoleucine or valine is the SIL amino acid.
Pepscan teaches peptides labeled with stable, non-radioactive isotopes are increasingly used for convenient detection in research (See Pepscan reference, pg. 1, 1st paragraph). Isotope-labeled, or ‘heavy’ amino acids, are derived from natural amino acids by substitution of certain atoms (N, C, H) with their ‘heavy isotope’ variant (See Pepscan reference, pg. 1, 1st paragraph). Although the SIL peptides display identical physiochemical properties and chemical reactivity as their non-labeled counterparts, there is a minute mass difference constituting the basis for using the SIL peptides in a variety of absolute quantification applications such as quantitative proteomics, the quantification of complex protein mixture at very low concentration or NMR studies (See Pepscan reference, pg. 1, last paragraph to pg. 2, 1st paragraph). Pepscan also teaches eight of the most common SIL amino acids including isoleucine and valine (See Pepscan reference, pg. 3, 1st paragraph; Table 2). Given that Park’s SEQ ID NO: 57, i.e., TDVTDYHIDQVSNLVECLSDEFCLDE, has one isoleucine residue, three leucine residues, one phenylalanine residue, and three valine residues, an ordinary skilled artisan would be motivated to incorporate a SIL amino acid at one of these 8 residues, and at a minimum, be motivated to try to incorporate a SIL isoleucine or valine given the finite number of amino acids most commonly incorporated as SIL amino acids.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Park does not expressly teach where the peptide is labeled by incorporation of a SIL amino acid as recited in instant claim 2 where the SIL amino acid is isoleucine or valine as recited in instant claim 3. However, the teachings of Croote et al. and Pepscan cure these deficiencies by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to where the peptide is labeled by incorporation of a SIL amino acid as recited in instant claim 2; and with respect to where the SIL amino acid is isoleucine or valine as recited in instant claim 3, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of Park and detect a genetically modified organism such as corn, rice, beans or potatoes in foodstuff by using the MS-SRM assay of Croote et al. instead of the antibody-based assay where the identified peptides, e.g., SEQ ID NO: 57, of Park is one of the peptides determined to be those of highest intensity, and thus, would be labeled via incorporation of an SIL amino acid where the SIL amino acid is isoleucine or valine. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the MS-SRM assay was known to offer advantages over antibody-based assays when detecting allergens in foodstuff; namely, improved sensitivity and reliability to detect trace amounts of allergen in manufactured food, and where the MS-SRM assay was known to use SIL peptides based on the highest intensity peptide for a protein and that offer several advantages including having benefits of linearity over four orders of magnitude, coefficients of variation typically below 10%, and inter-laboratory comparability, all characteristics that are required for developing a standardized analytical workflow capable of quantifying allergens present in trace amounts in commercial foods as taught by Croote et al.; and because SIL amino acids such as isoleucine and valine were known to be increasingly used for convenient detection in research given that SIL amino acids display identical physiochemical properties and chemical reactivity as their non-labeled counterparts with a minute mass difference constituting the basis for using the SIL peptides in a variety of absolute quantification applications such as quantitative proteomics, the quantification of complex protein mixture at very low concentration or NMR studies as taught by Pepscan.
One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that SEQ ID NO: 57 of Park was derived from a transgenic BT crop protein and used in antibody-based assays such as ELISA to detect a genetically modified organism such as corn, rice, beans or potatoes that contains the identified peptide in a biological sample of foodstuff. Therefore, substituting the antibody-based detection method with the MS-SRM assay method including where an isoleucine or valine are substituted with an SIL isoleucine or valine would support the detection of a genetically modified organism such as corn, rice, beans or potatoes that contains the identified peptide in a biological sample of foodstuff by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Applicants’ Arguments
Applicants contend that the cited reference does not support a prima facie case of obviousness because (1) an ordinary skilled artisan would not be motivated to take the detection method disclosed in Park, i.e., an indirect analysis requiring antibodies to detect the presence of a protein in a sample, and modify it to arrive at the claimed invention, i.e., a direct analysis using mass spectrometry assay to not only detect but to quantify proteins in a biological sample, with any expectation of success (See Applicant’s Response received on 4/30/25, pg. 2-3); (2) the cited art does not expressly teach or suggest every claim limitation, in particular, with respect to where the method of detection is a mass spectrometry assay or that the transgenic protein is an eCry3.1Ab protein (See Applicant’s Response received on 4/30/25, pg. 3); and (3) an ordinary skilled artisan would not be motivated to select only the first 11 amino acids of SEQ ID NO: 57 taught by Park that was used in an ELISA assay and arrive at the specific SIL peptide used in MS-MRM disclosed in the instant claims (See Applicant’s Response received on 4/30/25, pg. 4).
Response to Arguments
Applicant's arguments filed 11/25/25 for claims 1-3, 7-9, 39, and 43 have been fully considered but they are not persuasive. It is noted that Applicant’s arguments mirror those provided in the Declaration. Thus, these arguments have been addressed in the “Response to Amendment” section supra. Applicant’s attention is directed to the response to the Declaration supra. The response to those arguments are incorporated herewith.
Accordingly, the rejections of claims 1-3, 7-9, 39, and 43 are maintained as Applicants’ arguments are found unpersuasive.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm.
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, Lianko Garyu can be reached on 571-270-7367. 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.
/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654