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 .
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 SEQ ID NOs: 29-31. Also, as stated in the Action mailed on 2/11/26, the single and specific stable isotope labeled amino acid of Species A is hereby withdrawn.
Additionally please note that SEQ ID NOs: 27 and 29-30 are free of the art as there is no teaching or suggestion in the art for an amino acid sequence consisting of SEQ ID NO: 27 or comprising either SEQ ID NO: 29 or 30.
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. The amendment received on May 19, 2026, canceled claims 10-13, 36, 46-48, 51-52, and 56-57; and amended claims 1 and 7-9.
Claims 1-3, 7-9, 39, and 43 are currently pending and are under consideration.
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 statements (IDSs) submitted on July 27, 2026, are being considered by the examiner. Please note that both IDSs received on 7/27/26 cite identical references.
Sequence Interpretation
For claims 1 and 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 any one of SEQ ID NOs: 29-31 with any N- and/or C-terminal residues; and as closed-ended requiring 100% identity and the same length to SEQ ID NO: 27.
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 closed-ended requiring 100% identity and the same length to SEQ ID NO: 27; and as closed-ended for the transition ion amino acid sequence requiring 100% identity and the same length to either SEQ ID NO: 142 or 143.
Response to Arguments
Applicant’s arguments, see Response, filed 5/19/26, with respect to 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1, 7-9, 39, and 43 as being unpatentable over Park WO 01/98523 A2 published on December 27, 2001 has been withdrawn.
Applicant’s arguments, see Response, filed 5/19/26, with respect to 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1-3 as being unpatentable over Park WO 01/98523 A2 published on December 27, 2001, 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) has been withdrawn.
New Objections
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 recites, …or an amino acid sequence SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32. It is respectfully requested that claim 1 recites, …or an amino acid sequence SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, or SEQ ID NO: 32, in order to be grammatically correct. Appropriate correction is required.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 7 and 9 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 7 is directed to where the peptide selectively detects or quantitates an eCry3.1Ab protein and consists of an amino acid sequence of SEQ ID NO: 27 or comprises an amino acid sequence selected from SEQ ID NOs: 28-32. However, claim 7 is dependent upon claim 1, which recites where the peptide selectively detects or quantitates a target transgenic protein comprising an eCry3.1Ab protein, and where the surrogate peptide comprising a label and an amino acid sequence consisting of SEQ ID NO: 27 or an amino acid sequence comprising one of SEQ ID NOs: 28-32. As such, claim 1 already is directed to an eCry3.1Ab protein and where the amino acid sequence consists of SEQ ID NO: 27 or comprises one of SEQ ID NOs: 28-32. Thus, the scope of claim 7 does not further limit the scope of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Please note that claim 9 is rejected by virtue of its dependency upon claim 7.
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 1-3, 7-8, 39, and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Hart et al. US 2010/0017914 A1 published on January 21, 2010, in view of Van Emon, JM., J. Agric. Food Chem. 64:36-44 (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).
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claims 1 and 7, with respect to a peptide comprising an amino acid sequence of SEQ ID NO: 31:
Hart et al. teaches engineered hybrid insecticidal proteins (eHIPs) that can be made by fusing unique combinations of variable regions and conserved blocks of at least two different Cry proteins including Cry3A and Cry1Ab (See Hart, [0016], [0041], [0084]). More specifically, Hart et al. teaches that the eHIP comprises an N-terminal peptidyl fragment such as SEQ ID NOs: 126-127 that can confer insecticidal activity upon the eHIP (See Hart, [0083]). When comparing Hart’s SEQ ID NO: 126 (i.e., 35 total amino acids) with instant SEQ ID NO: 31, there is 100% identity with residues 20-30. When comparing Hart’s SEQ ID NO: 127 (i.e., 22 total amino acids) with instant SEQ ID NO: 31, there is 100% identity with residues 7-17. As discussed in the “Sequence Interpretation” section supra, Hart’s SEQ ID NO: 126 and/or 127 are encompassed by the scope of instant claim 1. Therefore, the teachings of Hart et al. satisfy the claim limitation with respect to a peptide comprising instant SEQ ID NO: 31 as recited in instant claims 1 and 7.
For claims 1-3, with respect to where the peptide is a labeled peptide as recited in instant claim 1; 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 arginine as recited in instant claim 3:
As discussed supra, Hart et al. teaches a peptide (i.e., eHIP) comprising instant SEQ ID NO: 31. These eHIPs are engineered to exhibit activity against a spectrum of insects (See Hart, [0016]). Moreover, Hart et al. teaches vectors containing recombinant nucleic acids encoding the eHIP(s), a plant or micro-organism containing the nucleic acid and plants transformed with the nucleic acids such as transgenic corn plants (See Hart, [0017]). Plus, Hart et al. teaches compositions and formulations contains the eHIPs that are capable of inhibiting the ability of insect pests to survive, grow and reproduce, or of limiting insect-related damage or loss to crop plants (See Hart, [0018]). Plant transformation vectors can contain a selective marker, e.g., provide resistance to an antibiotic or a herbicide (See Hart, [0127]).
However, Hart et al. does not expressly teach that the eHIP is labeled by incorporation of a SIL amino acid such as isoleucine or valine.
Van Emon teaches that through the use of genomics, proteomics, transcriptomics, metabolomics (collectively termed “omics”), the consistency and predictability in plant breeding have been improved, reducing the time and expense of producing better quality food crops that are resistant to stress but still exhibit a high nutritional value (See Van Emon, pg. 36, col. 1, 1st paragraph; Fig. 1). Omics has provided insights to the molecular mechanisms of insect resistance to pesticides, and the tolerance of plants to herbicides for better pest management (See Van Emon, pg. 36, col. 1, 1st paragraph). Linking genes to traits provides more scientific certainty leading to improved cultivars and understanding the mechanisms of insect and weed resistance (See Van Emon, pg. 36, col. 1, 1st paragraph). Omics enables a systems biology approach toward understanding the complex interactions between genes, proteins, and metabolites within the resulting phenotype (See Van Emon, pg. 36, col. 1, 1st paragraph). This integrated approach relies heavily on chemical analytical methods, bioinformatics, and computational analysis and many disciplines of biology, leading to crop protection and improvements (See Van Emon, pg. 36, col. 1, 1st paragraph).
Moreover, Van Emon depicts a schematic of the making of a transgenic plant where the plant DNA is mixed with plasmid DNA encoding the desired genomic manipulation that is then grown in culture and transgenic plants are cultivated (See Van Emon, Figure 3). More specifically, Van Emon teaches that the soil bacterium Bacillus thuringiensis (Bt) produces a protein that is toxic to specific insect pests (i.e., corn rootworm, corn earworm, European corn borer, and cotton bollworm) (See Van Emon, pg. 40, col. 1, 5th paragraph). The insertion of this gene (e.g., via the process depicted in Figure 3) into corn and cotton plants provides protection from these pests throughout the plant’s lifespan (See Van Emon, pg. 40, col. 1, 5th paragraph). Two different traits can be combined (i.e., stacked) in the same plant such as herbicide-resistant (HT) with Bt for added benefit (See Van Emon, pg. 40, col. 1, 5th paragraph). The stacked traits of both HT and Bt production accounted for 79% of the cotton grown in the United States in 2014, and 76% of corn was stacked (See Van Emon, pg. 40, col. 1, 5th paragraph).
Furthermore, Van Emon teaches that the field of omics and particularly proteomics has been driven by major improvements in MS instrumentation, advanced data analysis, bioinformatics, and rapid analytical methods (See Van Emon, pg. 39, col. 2, 3rd paragraph). Advances in analytical methods will further advance the applications of omics (See Van Emon, pg. 40, col. 1, 3rd paragraph). Second-generation proteomics employs stable isotope labeling of amino acids in cell culture (SILAC) and other quantitative methods for high-throughput measurement of protein dynamics and interactions rather than just identification by MS (See Van Emon, pg. 40, col. 1, 3rd paragraph). In the SILAC approach either C12- or C13-labeled amino acids are added to the growth media of separately cultured, but identical, cell lines, giving rise to cells containing either light or heavy protein chains (See Van Emon, pg. 40, col. 2, last paragraph). A comparative analysis provides a measurement of protein dynamics and interactions rather than just identification of proteins (See Van Emon, pg. 40, col. 2, last paragraph to pg. 41, col. 1, 1st paragraph). Thus, although not expressly taught, when considering Van Emon’s teachings as a whole, improvements in MS instrumentation such as the use of SILAC allows for high-throughput measurement of protein dynamics and interactions including analysis of genetic manipulation to create transgenic plants such as cotton and corn.
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 arginine (See Pepscan reference, pg. 3, 1st paragraph; Table 2). Given that Hart’s SEQ ID NO: 126, i.e., MASMTGGQQMGRGSTSNGRQCAGIRPYDGRQQHRG, has one isoleucine residue, five arginine residues, two alanine residues, and one proline residue; or Har’s SEQ ID NO: 127, i.e., MTSNGRQCAGIRPYDGRQQHRG, has one isoleucine residue, four arginine residues, one alanine residue, and one proline residue, an ordinary skilled artisan would be motivated to incorporate a SIL amino acid at one of the 9 residues of Hart’s SEQ ID NO: 126 or of the 7 residues of Hart’s SEQ ID NO: 127, and at a minimum, be motivated to try to incorporate a SIL isoleucine or arginine given the finite number of amino acids most commonly incorporated as SIL amino acids. Thus, the combined teachings of Hart, Van Emon, and Pepscan suggest the claim limitation with respect to where the peptide is a labeled peptide where the label is a SIL amino acid where the SIL amino acid is isoleucine or arginine as recited in instant claims 1-3 .
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, Hart et al. teaches engineered hybrid insecticidal proteins (eHIPs) that can be made by fusing unique combinations of variable regions and conserved blocks of at least two different Cry proteins including Cry3A and Cry1Ab (See Hart, [0016], [0041], [0084]). The peptidyl fragment is an amino acid sequence that can be derived from a Bt Cry protein (See Hart, [0035], [0041]) where such fragment confers insecticidal activity or an increase in insecticidal activity against corn rootworms such as Diabrotica sp.) (See Hart, [0016], [0020]). As such, the eHIP of Hart et al. contain amino acid fragments that are derived from a Bt Cry protein. Although Hart et al. does not expressly teach that that eCry3.1Ab is a BT transgenic protein in which peptides are derived from, since Hart et al. teaches two species of peptides that fall with the claimed subgenus of peptides that are derived from eCry3.1Ab (i.e., Hart’s SEQ ID NOs: 126-127), it must follow that Hart’s SEQ ID NO: 126 or 127 constitutes a peptide that is derived from eCry3.1Ab. Thus, the teachings of Hart et al. 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 Hart et al. 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, the labeled peptide functioning as defined renders the suggested labeled peptide of Hart, Van Emon and Pepscan being capable of performing the defined intended use. Thus, the teachings of Hart et al., Van Emon, and Pepscan satisfy the claim limitation with respect to the suggested 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, Hart et al. teaches that the eHIPs contain peptidyl fragments derived from Bt Cry proteins (See Hart, [0035], [0041]) where such fragment confers insecticidal activity or an increase in insecticidal activity against corn rootworms such as Diabrotica sp. (See Hart, [0016], [0020]). However, although Hart et al. does not expressly teach a method of detection such as 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 Hart et al. did not expressly teach the claimed function/intended use, since Hart et al. teaches a peptide as instantly claimed, the intended use of the 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 Hart et al. does not teach where SEQ ID NO: 126 or 127 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 the cited references did not expressly teach the claimed function/intended use, since the combination of refences suggest a labeled surrogate peptide as instantly claimed, the intended use of the labeled peptide is also rendered obvious.
Additionally and/or alternatively, although Hart et al. does not teach where SEQ ID NO: 126 or 127 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:
As discussed supra for claim 1, Hart et al. teaches vectors containing recombinant nucleic acids encoding the eHIP(s), a plant or micro-organism containing the nucleic acid and plants transformed with the nucleic acids such as transgenic corn plants (See Hart, [0017], [0077], [0095]). Hart et al. also teaches that transformed/transgenic/recombinant is defined as where a host organism such as a bacterium or a plant into which a heterologous nucleic acid molecule can be stably integrated into the genome of the host (See Hart, [0075]). Hart et al. also defines plant material as leaves, stems, roots, flowers or flower parts, pollen, egg cells, zygotes, seeds, cuttings, cell or tissue cultures, or any other part or product of a plant (See Hart, [0069]). Expression of the nucleic acids in transgenic plants is driven by promoters that function in plants (See Hart, [0119]). The choice of promoter will vary depending on the temporal and spatial requirements for expression and also depending on the target species (See Hart, [0119]). Thus, expression of the nucleic acids in leaves, in stalks or stems, in ears, in roots and/or seedlings is preferred (See Hart, [0119]). As such, the teachings of Hart et al. satisfy the claim limitation as recited in instant claim 39 where the plant is transformed in its leaf tissue, seed, pollen or root tissue as recited in instant claim 43. However, even if Hart et al. does not expressly teach that the corn transgenic plant or the corn transgenic leaf 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 Hart et al. satisfies the claim limitations as recited in instant claims 39 and 43.
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: 31 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 modify the teachings of Hart et al. and analyze a genetically modified transgenic corn plant transformed by introduction of a nucleic acid encoding an eHIP comprising SEQ ID NO: 126 or 127 derived from a transgenic BT protein by utilizing SILAC such that a C12- or C13-labeled isoleucine or arginine residue is incorporated into eHIP nucleic acid sequence in order to determine whether and to what extent the genetically modified transgenic corn plant will exhibit insecticidal activity against corn rootworms. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the insertion of a Bt gene into corn and cotton plants was known to provide protection against insect pests (i.e., corn rootworm, corn earworm, European corn borer, and cotton bollworm), and because the use of SILAC was known to allow for high-throughput measurement of protein dynamics and interactions including analysis of genetic manipulation to create transgenic plants such as cotton and corn as taught by Van Emon; and because SIL amino acids such as isoleucine and arginine 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 a transgenic corn plant of Hart et al. was known to be genetically modified such that a nucleic acid encoding an eHIP of Hart’s SEQ ID NO: 126 or 127 is introduced into the corn genome in order to provide the corn insecticidal activity against corn rootworms. Therefore, incorporating a C12- or C13-labeled isoleucine or arginine residue into eHIP nucleic acid sequence would support the analysis of the genetically modified transgenic corn plant and determine whether the plant will exhibit insecticidal activity against corn rootworms 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.
Response to Arguments
Applicant’s arguments with respect to claims 1-3, 7-9, 39, and 43 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Examiner Comment
Notwithstanding the 112(d) rejection supra, the scope of claim 9 is free of the prior art when the labeled peptide consists of SEQ ID NO: 27, i.e., 100% identity and the same length. The closest prior art is Park WO 01/98523 A2 published on December 27, 2001. 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 residues 1-11. However, there is no teaching or suggestion to truncate Park’s sequence to the first 11 residues. Therefore, the scope of claim 9 is free of the 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.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654
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