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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114.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 September 10, 2024 has been entered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Status of Claims
Claims 48, 52, 53, 61, 63-66, 68, 72-75, 78 and 79 are currently pending. Claims 48, 52, 53, 68, 72, 73 and 78 have been amended by Applicants’ amendment filed 09-10-2024. Claims 50, 51, 58, 60, 67, 70, 71, 76, 77 and 80 have been canceled by Applicants’ amendment filed 09-10-2024. No claims have been added by Applicants’ amendment filed 09-10-2024.
Applicant elected without traverse of Group I, claims 48-61 directed to a label-free method of detecting one or more unlabeled analytes in a first sample on a first detectable array in the reply filed March 8, 2023.
Applicant subsequently elected with traverse of Group I, claims 48-53, 58, 60, 61 and 63-67, directed to a label-free method of detecting one or more unlabeled analytes in a first sample on a first detectable array; and the election of Species with traverse including:
Species (A): wherein the substrate comprises at least two chemically distinct macromolecules affixed to different surfaces (instant claim 52); and
Species (B)/(C): wherein each surface further comprises a photoinitiator (instant claim 76), in the reply filed on August 25, 2023 was previously acknowledged.
Please Note: it is noted that amended claims 68, 72-75, 78 and 79 correspond to original non-elected Group II, and are directed to a label-free method of detecting an unlabeled analyte associated with a subject on a detectable array. Amended claim 68 recites that the method comprises (in part) “comparing the identified unlabeled analytes with a database of known analytes”. Originally elected Group I, claims 48-53, 58, 60, 61 and 63-67 was directed to a method of detecting one or more unlabeled analytes in a first sample on a first detectable array. In the claims filed August 25, 2023, elected claim 48 recites (in part) “comparing one or more first images, or representations thereof, to one or more second images of one or more second detectable arrays, or representations thereof, each of the second images being associated with a second sample”. Thus, amended claims 68, 72-75, 78 and 79 recite an invention that is different from originally elected Group I (claims 48-53, 58, 60, 61 and 63-67), such that the non-elected invention encompassed by claims 68, 72-75, 78 and 79 creates a serious search and examination burden on the Examiner. Non-elected Group II will not be examined on the merits because it is not commensurate in scope with the originally elected invention.
Claims 50, 51, 70 and 71 were previously withdrawn and claims 68, 72-75, 78 and 79 are newly withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on August 25, 2023.
The restriction requirement was deemed proper and was made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 48, 52, 53, 61 and 63-66 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed September 10, 2021 is a DIV of US Patent Application 15/023,321, filed March 18, 2016 (now abandoned), which is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2014/056822, filed on September 22, 2014, which claims the benefit of US Provisional Patent Application No. 61/881,754, filed September 24, 2013.
Interview Summary
Applicant contacted the Examiner to set up an interview, where such telephonic interview was conducted between the Examiner and Applicant’s representative Aeraj Haque on September 5, 2024. Applicant and the Examiner discussed the rejections of record; as well as, proposed amendments to the claims that might assist in moving prosecution forward including amending the claims to reflect the reaction temperatures taught in the as-filed Specification.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 10, 2024 has been considered. An initialed copy of the IDS accompanies this Office Action.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed September 10, 2024 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or
objection not specifically addressed below are herein withdrawn.
Claim Rejections - 35 USC § 103
The rejection of claims 68 and 72-80 is withdrawn under 35 U.S.C. 103 as being unpatentable over Charych et al. (US Patent No. 6306598, issued October 23, 2001) in view of Haynes et al. (US Patent No. 5089278, issued February 18, 1992) as evidenced by Bowman et al. (US Patent No. 7498394, issued March 3, 2009); and Science of Cooking (Science of Cooking, 2023, 1-5).
Instant claims 68, 72-75, 78 and 79 have been withdrawn.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Maintained Objections/Rejections
Claim Interpretation: the term “representations thereof” such as recited in claim 48 is interpreted to refer to any type of representation of the one or more first images and/or one or more predetermined second images such as, for example, mathematical representations, digital representations, visual representations, optical representations, graphical representations, color representations, textural representations, vocal representations, false color images, etc. (e.g., algorithms, video, audio, photographs, texture, absorption, fluorescence, digital images or formats, charts, color values, color grids, binary patterns, paintings, impressions, a memory of the image, etc.).
The term “caramelization” such as recited in claim 48 is interpreted to refer to any process undergone by any component of a detectable array (to any degree) including one or more of the unlabeled or labeled analytes, macromolecules, coatings substrate surfaces, silane, siloxane, functional groups, polymers, monomers, etc. including: (1) turning brown (or any other color in a false color image); (2) the oxidation of sugar molecules at high temperatures; (3) solvent-mediated browning; and (4) the development of a rich, sweet, nutty and/or buttery flavor, etc.
The term “receiving a result” such as recited in claim 48 is interpreted to refer to a result that is determined, provided, calculated, received, and/or transmitted by any method such as, for example, via computer, computer program, algorithm, mathematical equations, visual assessment, human brain interpretation, comparisons, measurements, statistical analysis, telephone, etc.
The term “chemically distinct macromolecules” such as recited in claim 52 and 53 is interpreted to refer to macromolecules that are: (a) structurally different; (b) functionally different; and/or (c) reside in a different chemical environment as compared to one or more of a plurality of macromolecules.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 48, 52, 53, 61 and 63-66 is maintained under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards
as the invention.
Claim 48 is indefinite for the recitation of the terms “one or more analytes”; “a plurality of analytes”; and “at least one of the analyte” such as recited in claim 48, lines 3, 11 and 33 because claim 48, line 1 recites the term “one or more unlabeled analytes”. Moreover, it is unclear whether the first detectable array binds only unlabeled analytes, if it binds both labeled and unlabeled analytes, or whether it binds only labeled analytes and, thus, the metes and bounds of the claim cannot be determined. The Examiner suggests that Applicant amend claim 48 to recite, for example, “for binding one or more unlabeled analytes”.
Claim 48 is indefinite for the recitation of the term “the one or more substrates” in claim 48, lines 10-11. There is insufficient antecedent basis for the term “the one or more substrates” in the claim because claim 48, line 3 recites the term “a substrate”. Moreover, it is unclear whether the term “the one or more substrates” is meant to refer to “one or more substrate coatings” and, thus, the metes and bounds of the claim cannot be determined.
Claim 48 is indefinite for the recitation of the term “a plurality of binding sites” in claim 48, line 11 because it is unclear what component of the array comprises the “plurality binding sites”. It is unclear whether the substrate coatings comprise the “plurality binding sites”; whether the one or more substrates comprises the “plurality binding sites”; whether the plurality of macromolecules comprises the “plurality binding sites”; and/or whether each of the plurality of macromolecules comprise a “plurality binding sites” and, thus, the metes and bounds of the claim cannot be determined.
Claim 48 is indefinite for the recitation of the term “to cause a color change” in claim 48, line 33 because it is unclear what component of the first detectable array undergoes a color change; and whether it is the unlabeled analytes, labeled analytes, macromolecules, macromolecule bound to an analyte, coatings, surfaces, and/or something else that undergoes a color change when heated and, thus, the metes and bounds of the claim cannot be determined.
Claim 48 is indefinite for the recitation of the term “a representation thereof including a false color image thereof” in claim 48, lines 41-42 because a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989). In the instant case, the claim recites a broad limitation of representations of one or more images; as well as, a narrow limitation of a “false color image” (perhaps, a preferred image representation thereof?). Thus, the metes and bounds of the claim are unclear.
Claim 48 is indefinite for the recitation of the term “the one or more second images” such as recited in claim 48, lines 46-47. There is insufficient antecedent basis for the term “the one or more second images” in the claim because claim 48, line 45 recites the term “one or more predetermined second images”.
Claim 48 is indefinite for the recitation of the term “estimation of a likelihood” in claim 48, line 49 encompasses both a broad range or limitation, and a narrow range or limitation in the same claim. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language; as well as, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949). The term “estimation of a likelihood” recites two different possibilities and/or probabilities including a rough calculation of a value, or a judgement (estimation); and a chance or probability of something happening and/or determining the best data distribution (likelihood).
Claim 48 is indefinite for the recitation of the term “a subject associated with the first sample” in claim 48, lines 49-50 because claim 48 does not recite: the presence of a subject; that a subject is “associated” in any way with a first sample; and/or any specific first samples (e.g., a sample obtained from a subject such as a blood, urine, plasma, saliva, etc.). Thus, the “first sample” can comprise any labeled or unlabeled analytes, any ‘subject’, and/or any first sample (e.g., dirt, metal oxides, lake water, agricultural plants, air, fungi, bacteria, blood, etc.). The origin of the “subject” and the identity of the ‘first sample’ such as recited in lines 49-50 is completely unclear and, thus, the metes and bounds of the claim cannot be determined.
Claim 48 is indefinite for the recitation of the term “susceptible” in claim 48, line 50 because the term “susceptible” is a relative term that renders the claim indefinite. The term “susceptible” is not defined by the claim, and the as-filed Specification does not provide a request standard for ascertaining an amount or degree of ‘susceptibility’ that is indicates that a subject is ‘susceptible’ to one or more unidentified disease or disorders, and/or how the disease, disorder, and/or amount of susceptibility is determined or measured, such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention.
Claim 52 is indefinite for the recitation of the term “the two chemically distinct macromolecules” in claim 52, line 4. There is insufficient antecedent basis for the term “the two chemically distinct macromolecules” in the claim because claim 52, line 3 recites the term “at least two chemically distinct macromolecules”.
Claim 52 is indefinite for the recitation of the term “affixed to a different surface” in claim 52, line 4 because claim 52 depends from claim 48, such that it is unclear what structures the chemically distinct macromolecules are actually affixed to. For example, instant claim 48, lines 12-13 recite that the plurality of macromolecules is “affixed to the one or more substrate coatings by polymerizing”, while claim 52 recites that the macromolecules are “affixed to a different surface of the plurality of surfaces of the substrate” (e.g., the macromolecules are not affixed to a coating). Thus, claim 52 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends; and, thus, the metes and bounds of the claim cannot be determined.
Claim 52 is indefinite for the recitation of the term “composites” in claim 52, line 6 because it is unclear what “composites” are encompassed by the term. It is unclear whether the term refers to any composite material (e.g., metal matrix composites, fiberglass, Kevlar, etc.); whether the term refers to composites of the materials recited in claim 52 (e.g., composites of glass and metal, plastic and glass; different glasses, different plastics, different polymers, etc.); or whether the term refers to substrates comprising some other composite materials and, thus, the metes and bounds of the claim cannot be determined.
Claim 61 is indefinite for the recitation of the term “the assessing” in claim 61, line 2. There is insufficient antecedent basis for the term “the assessing” in the claim because claim 48, lines 39-40 recites the term “assessing a color of each of the plurality of surfaces of the substrate by colorimetric analytical technique”. The Examiner suggests that Applicant amend claim 61 to recite, for example, “determining the identity of one or more analytes based on the color change of at least one analyte caused by heating the first detectable array”.
Claim 61 is indefinite for the recitation of the term “the unlabeled analyte” in claim 61, line 2. There is insufficient antecedent basis for the term “the unlabeled analyte” in the claim because claim 48, line 1 recites the term “one or more unlabeled analytes”.
Claim 63 is indefinite for the recitation of the term “each of the one or more second images” such as recited in claim 63, lines 1-2. There is insufficient antecedent basis for the term “each of the one or more second images” in the claim because claim 48, line 45 recites the term “one or more predetermined second images”.
Claim 63 is indefinite for the recitation of the term “have been obtained after contacting a second detectable array of the one or more second detectable arrays with one or more second analytes present in the second sample, heating the second detectable array, and then making the one or more second images” in claim 63, lines 2-5 because claim 63 depends from claim 48, wherein claim 48 recites that the one or more second images are stored in a database; and that the second images are associated with a second sample. However, instant claim 48 does not recite the presence of a plurality of detectable arrays, the presence of one or more second detectable arrays; contacting, capturing, heating and/or detecting second analytes; and/or making additional images. Thus, claim 63 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends; and, thus, the metes and bounds of the claim cannot be determined.
Claim 63 is indefinite for the recitation of the term “the one or more second detectable arrays” such as recited in claim 63, line 3. There is insufficient antecedent basis for the term “the one or more second detectable arrays” in the claim.
Claims 64 and 65 are indefinite for the recitation of the term “first environmental sample” such as recited in claim 64, line 5 because the term “subject” is defined in the instant as-filed Specification as including any plant or animal including mammals, and humans (See; paragraph [0022]). The term “subject” is not defined to include all types of environmental samples (e.g., dirt, rocks, fungi, prokaryotes, salts, metals, mineral deposits, etc.), wherein not all environmental samples are associated with a diseases and/or disorders that can be found on an unidentified list and, thus, the metes and bounds of the claim cannot be determined.
Claim 65 is indefinite for the recitation of the term “obtaining the one or more unlabeled analytes, the one or more unlabeled analytes being associated with the subject, or the first environmental sample” in lines 1-3 because claim 65 depends from claims 48 and 64, wherein claim 48 recites that the first sample is associated with a subject, and that the first sample is associated with a disease or disorder. Moreover, the term “subject” is defined in the instant as-filed Specification as including any plant or animal including mammals, and humans (See; paragraph [0022]). Therefore, the one or more unlabeled analytes cannot be obtained from all types of environmental samples because the term “subject” is not defined to include all environmental samples (e.g., dirt, rocks, fungi, prokaryotes, microorganisms, etc.). Additionally, the step “further comprising obtaining one or more unlabeled analytes” is not commensurate with the scope of the claims. Thus, claim 65 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends; and, thus, the metes and bounds of the claim cannot be determined.
Claim 66 is indefinite for the recitation of the term “wherein the one or more first images of the first detectable array or representation thereof represents one or more of fluorescence, phosphorescence, texture or color, or lack of one of the foregoing of the plurality of surfaces of the substrate” in claim 66, lines 1-4 because the claim language is unclear. It is unclear whether the claim is intended to recite that the first image or a representation thereof is a fluorescent image, a texture image, and/or a color image. Moreover, it is unclear how the one or more first images or representations thereof can be a lack of one or more of fluorescence, phosphorescence, texture or color, given that instant claim 48 clearly recites that the one or more unlabeled analytes undergoes a color change and that the color of each of the surfaces is assessed by a colorimetric analytical technique. Additionally, it is unclear how fluorescence and/or phosphorescence can be detected if the analytes of the invention are unlabeled. Thus, claim 66 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends; and, thus, the metes and bounds of the claim cannot be determined.
Claim 53 is indefinite insofar as it ultimately depends from instant claim 48.
Claim Rejections - 35 USC § 103
Please Note: the references have been modified slightly in view of Applicant’s amendments and arguments filed, September 10, 2024.
The rejection of claims 48, 52, 53, 58, 60, 61 and 63-66 is maintained under 35 U.S.C. 103 as being unpatentable over Hubbard et al. (hereinafter “Hubbard”) (US Patent Application Publication 20050042612, published February 24, 2005; of record) further in view of Kennedy et al. (hereinafter “Kennedy”) (US Patent Application Publication 20120083465, published April 5, 2012; of record) as evidenced by Tamanna et al. (hereinafter “Tamanna”) (International Journal of Food Science, 2015, 526762, 1-6).
Regarding claims 48 (in part), 52, 53, 58, 60, 61 and 63-66, Hubbard teaches that an important development in medicine has been the ability to quickly and reliably screen individuals for diseases and more recently genetic markers which can pre-dispose individuals to develop illnesses during their lifetime; and the generation of animal models to study human disease and many other genomic and proteomic approaches being applied to decipher the molecular pathogenesis of disease over the last decade (paragraph [0002]). Hubbard teaches that highly specific probes generated to query a large number of molecules (e.g. antigens or nucleic acid sequences) are attached to the surface of a sample slide and exposed to target molecules generated from a wide variety of biological materials, such that if target molecules are present in the hybridization cocktail, they will bind with high affinity and specificity to substrate-bound probe molecules immobilized on the slide, wherein the slide is processed and imaged in a way that only areas containing bound target/probe substrate are detectable and fully quantifiable through radiolabeling, enzymatic colorimetry, fluorescence spectroscopy, mass spectroscopy or other techniques known to those skilled in the art (interpreting biological materials to encompass biological fluids, etc.; determining the identity of the unlabeled analyte; and interpreted to encompass colorimetry; images or representations thereof; comparing a first image and a second image; and a colorimetric analytical technique, claims 48 and 64) (paragraph [0003]). Hubbard teaches that the method involves providing a pool of target nucleic acids comprising RNA transcripts of one or more target genes, or nucleic acids derived from the RNA transcripts, hybridizing said pool of nucleic acids to an array of oligonucleotide probes immobilized on the surface, where the array comprises more than 100 different oligonucleotides and each different oligonucleotide is localized in a predetermined region of the surface (interpreting 100 different oligonucleotides as one or more macromolecules; at least 12 chemically distinct macromolecules; and array, claims 48, 52, 53, 68 and 72) (paragraph [0012]). Hubbard teaches that Turner et al. disclose in U.S. Pat. No. 5,948,62 a stamp for transferring molecules and molecular patterns to a substrate face which includes a backing and a polymeric gel bound to the backing and loaded with the molecular species, where the molecule to be patterned is a biomolecule, such as a protein or nucleic acid, the polymeric gel is typically a hydrogel, such as sugar-based polyacrylates and polyacrylamides, such that the process includes preparation of silanized glass plates and formation thereon of hydrogel layers via polymerization of 6-acryloyl-B-O-methylgalactoside (2% crosslinking) and N,N'-methylenebisacrylamide, such that a relief image-wise pattern is created on the hydrogel surface, which is used to transfer monoclonal antibodies or other biomolecules onto a substrate, wherein this process uses a crosslinked hydrogel like a relief printing plate (interpreted as identity or pattern; identity and pattern; crosslinker; acrylamide functional group; and methylenebisacrylamide, claims 48 and 60) (paragraph [0016]). Hubbard teaches that one common microarray surface structure comprises a linker molecule connecting the surface of the substrate (typically glass) with one end of the probe molecule, wherein typical linker molecules for DNA microarrays are amino-terminated silanes, which covalently to the glass surface through the silane end and are photo-crosslinked through the amine end to a DNA probe; and that initiator contained in the aqueous copolymer medium can lead to non-grafted polymer and block copolymer, which requires crosslinking to be permanently retained in the layer (interpreted as a crosslinker, claims 52 and 60) (paragraphs [0005]; and [0008]). Hubbard teaches a method for applying a three-dimensional, non-crosslinked, linear or branched graft polymer matrix with controlled graft polymer chain density to an uncoated glass surface, the method comprising; (a) applying to a glass surface a solution comprising (i) an organic solvent or mixture of organic solvents, (ii) a silane monomer or mixture of silane monomers and unreactive silanes; (b) removing the solvents to leave a coating of silane attached monomers and silane attached unreactive groups (interpreted as one or more silane substrate coating); (c) exposing said silane coated surface to an initiator; (d) immersing the silane-coated surface in a medium having one or more monomers in solution that are capable of reacting with the reactive sites created by surface bound initiator to form a polymer chain grafted onto said surface; (e) initiating a graft polymerization reaction on said silane-coated surface; and (f) graft polymerizing onto the silane-coated surface the reactive monomers from the medium by forming covalent bonds between the monomer molecules and the surface at reactive radical sites on the silane-coated surface (interpreted as a substrate with a plurality of surfaces; glass surface; silane substrate coating; on-substrate polymerization; glass; and macromolecules comprising a polymer of monomers, claims 48 and 52) (paragraphs [0067]-[0075]). Hubbard teaches that the invention provides for an article having at its surface a permanently attached three-dimensional, non-crosslinked graft polymer matrix containing probe molecules, said probe molecules having inherent specificity for binding to target chemical or biochemical species for which information on its presence or concentration in a sample is of interest, wherein probes can be attached as side-chains to the backbone of the graft polymer (interpreted as sample, claims 48 and 68) (paragraph [0027]). Hubbard teaches that a target is a chemical or biochemical species that is the subject of an assay experiment including viruses, bacteria, DNA, RNA, proteins, lipids, toxins, or other chemical or bioactive agents for which information on their presence or concentration in a sample is of interest (interpreted as unlabeled analytes; an interpreting toxins and bacteria as environmental samples; and obtaining unlabeled analytes, claims 48, 61 and 65) (paragraph [0114]). Hubbard teaches that the graft polymer matrices of the invention can be constructed and used so as to provide an increased capacity and efficiency for a single type of reactive group, or can be constructed and used for mixtures of multiple layers of probes/functional groups in a single location (interpreted as a plurality of surfaces; and graft polymer matrices as macromolecules, claims 48 and 68) (paragraph [0088]). Hubbard teaches that in a particularly preferred embodiment of the invention, the graft matrix is applied to the article surface in a pattern, which facilitates the placement of different types of reactive probes, and the reading of results once the matrix has been allowed to react with a test sample (interpreted as a pattern; and for binding one or more analytes, claims 48 and 68) (paragraph [0087]). Hubbard teaches in Examples 1-3, preparation of a graft polymer layer containing acrylamide, aminopropyl-acrylamide and PEG-methacrylate with an initiator incorporated into the primer, wherein a reactive monomer solution was prepared by dissolving acrylamide, polyethylene glycol methacrylate, and 3-aminopropylmethacrylamide hydrochloride, and five coated glass microscope slides were placed in the reactor vessel with the monomer solution such that slides were prepared having a graft polymer comprising poly(ethyleneglycol) spacer arms and alkylamine active groups attached to the graft polymer backbone (interpreted as one or more monomers including acrylamide and methacrylates, claim 1) (paragraphs [0156]-[0167]). Hubbard teaches in Table 2, the different mole percent of the respective monomers that were in the reactive monomer salt solutions including different mole percent of N,N,-dimethyl acrylamide (interpreted as identity is different; and N,N’-dimethyl acrylamide, claim 1) (paragraph [0248], lines 1-2 and Table 2). Hubbard teaches that the silane monomer solution was prepared by mixing together ethanol and methacryloxypropyl trimethoxy-silane, wherein examples of silanes with attached reactive monomers are (3-acryloxypropyl)trimethoxy-silane and methacryloxypropyl-trimethoxy-silane (corresponding to methacryloxypropyl trimethoxy-silane, claim 2) (paragraph [0261], Example 16). Hubbard teaches that the term “non-crosslinked” is intended to refer to a polymer matrix in which the benefits of a porous, coherent material are achieved with individual polymer chains bound to the substrate without the requirement of extensive crosslinking, wherein a limited amount of crosslinking is contemplated within the scope of the invention so long as the polymer chains are directly bound to the surface, and the crosslinking does not interfere with the functionality of the matrix (interpreted as encompassing at least one crosslink, claim 10) (paragraphs [0023], lines 10-14; and [0025], lines 27-30). Hubbard teaches that probe reactive groups (active chemical moieties) can be incorporated into the graft polymer matrix that bind to either DNA or protein based on the probes (corresponding to a protein bound to a macromolecule, claim 20) (paragraph [0023], lines 6-9). Hubbard teaches that photo-initiators/photo-sensitizers include, but are not limited to, organic peroxide and azo initiators, benzophenone, benzophenone derivatives (interpreted as encompassing DMPA), camphorquinone-N,N-dimethylaminoethyl-methacrylate (interpreted as encompassing DMPA, claim 48) (paragraph [0128], lines 30-35). Hubbard teaches that a second method to apply the unreactive surface primer layer which can be exposed to a medium containing initiator molecules is to apply to the unreactive surface, an initiator/primer layers, and then applying a coating to the surface to be graft polymerized; and a third method is to attach an initiator to a glass surface using a silane group attached to the initiator, wherein suitable initiators can be found in US6358557 including photoinitiators (interpreted as photoinitiators, claims 52 and 76) (paragraph [0126]-[0127], lines 1-3). Hubbard teaches that photoinitiators/photosensitizers include, but are not limited to, organic peroxide and azo initiators, benzophenone, benzophenone derivatives, camphorquinone-N,N dimethyl-amino-ethyl-methacrylate, and others (interpreted as encompassing DMPA, claims 58 and 77) (paragraph [0128], last five lines). Hubbard teaches that the graft polymer layer is typically a linear or branched polymer comprising one or more distinct monomer units, wherein monomers include 2,3-hydroxypropyl acrylates, 2-hydroxypropyl acrylate, 2- and 3-hydroxypropyl acrylate, poly(ethylene glycol) acrylates, poly(ethylene glycol) methacrylates, acrylic acid, methacrylic acid, acrylamide, etc. (interpreted as macromolecules having a polymer of monomers, claims 48 and 68) (paragraph [0133]). Hubbard teaches that samples (N=9 per dilution) were printed in a staggered pattern using a Virtek Chipwriter, such that after washing, the slides were scanned with a Virtek chip reader; and FIG. 4C is a composite of images from each sample, wherein a false color spectrum gradient was applied to each image; wherein Figure 4C is a composite fluorescent image of FITC binding to amnio groups in graft coat on glass slides and includes a false color scale spectrum indicating degree of binding (red indicating high fluorescence) (interpreted as comparing a first detectable array and a second detectable array or representations thereof; color change; assessing color; and a false color images, claims 48 and 63) (paragraphs [0097; and [0226]; and Figures 4A and 4C). Hubbard teaches that graft polymer matrices of the present invention can be constructed and used so as to provide an increased capacity and efficiency for a single type of reactive group or probe, or can be constructed and used for mixtures of or multiple layers of probes/functional groups in a single location (paragraph [0088]). Hubbard teaches that the functional utility is an enhanced ability to be imaged by an imaging method selected from the group consisting of magnetic resonance imaging, computer tomography, x-ray radiology, fluorescence, and ultrasouography; as well as, an enhanced resistance to infection and thrombosis (interpreted as making a first image and a second image or a representation thereof; and associated with a disease or disorder, claim 48) (paragraph [0031]). Hubbard teaches in Figures 3A and 3B, an increase in color density corresponding to an increase in printed biocytin concentration across the graft polymer surface, wherein Figure 3A shows an amount of biocytin printed, and Figure 3B shows images after development (interpreted as comparing a first image and a second image, claim 48) (paragraphs [0093]; and Figures 3A and 3B). Hubbard teaches that Figure 4C illustrates a composite fluorescent image of FTIC binding to amino groups in graft coat on glass slides with either a low or high concentration of initiator in primer, wherein a false color scale spectrum indicates degree of binding with red the highest (interpreted as a false color image; comparing a first and second image; associated with disease or disorders such as having, not having, or is susceptible to each of the disease or disorders; glass substrate; and fluorescence, claims 48, 52 and 66) (paragraph [0097]; and Figure 4C).
Hubbard does not specifically exemplify at least one of a Maillard reaction or caramelization, claim 48).
Regarding claims 48 (in part), Kennedy teaches that one type of ligands known to bind to RAGE are advanced glycation end-products (AGEs), which are the chemical products of nonenzymatic attachment of sugars to proteins and lipids, wherein AGEs accumulate in a plethora of biologic settings and have now been demonstrated to play important roles in the pathogenesis of a diverse array of diseases, including diabetes, inflammation, renal failure, aging, systemic amyloidosis, Alzheimer's dementia, inflammatory arthritis, atherosclerosis and colitis, to name but a few (interpreted as making a first image and a second image or a representation thereof; and associated with a disease or disorder, claim 48) (paragraph [0004], lines 1-9). Kennedy teaches that in diabetes patients, AGEs form as a direct consequence of chronically elevated glucose, which proceeds through the polyol pathway to be reduced to sorbitol by the enzyme aldose reductase, where sorbitol is in tum converted to fructose, then fructose-3-phosphate, and then to 3-deoxyglucose, a reducing sugar whose aldehyde carbonyl can react in the Maillard reaction with the amino group of a target molecule such as an amino acid to form a Schiff base, such that the Schiff base can then undergo an intramolecular rearrangement to form Amadori products, which can further rearrange and condense to form fluorescent, yellow brown products that represent AGEs (interpreted as a Maillard reaction, with heating from 120-300C, claims 48 and 68) (paragraph [0004], lines 10-22), wherein it is known that the typical roasting temperature range is from 180-250oC, and roasting time varies between 2 and 25 minutes depending on the process employed, such that when an internal temperature exceeds 180oC, a Maillard reaction, carbohydrate caramelization, and pyrolysis of organic compounds results as evidenced by Tamanna (pg. 3, col 2, first full paragraph).
“It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, " ... a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S._,_, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson's-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303,306 (1950)". Therefore, in view of the benefits of detecting the presence of advanced glycan end-produces (AGEs) as exemplified by Kennedy, it would have been prima facie obvious before the effective filing date of the claimed invention to modify the arrays of highly specific probes that bind targets including DNA, RNA, proteins, carbohydrates, and lipids in graft polymer matrixes as disclosed by Hubbard to include ligands that bind to AGEs as taught by Kennedy with a reasonable expectation of success in using the Maillard reaction to colorimetrically signify the presence of AGEs bound to arrays comprising highly specific probes; and/or in using the fluorescent yellow-brown of the Maillard reaction to detect target AGEs in a sample applied to an array, where specific color changes can signify the degree of binding and/or suggest the presence of a pathogenic disease in a subject including diabetes, inflammation, renal failure, Alzheimer’s dementia, etc.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
Response to Arguments
Applicant’s arguments filed September 10, 2024 have been fully considered but they are not persuasive. Applicants essentially asserts: (a) Applicant has amended claim 48 to recite at least one of a Maillard reaction or a caramelization, and wherein heating comprises heating at a temperature from about 200°C to about 400°C for about 1 min to about 5 min for the Maillard reaction, or at a temperature from about 100°C to about 210°C for about 1 minute to about 5 minutes for the caramelization; and assessing a color…to each of the diseases or disorders on the list” as recited in claim 48, lines 32-51 such that none of the references teach the combination of elements of instant claim 48 (Applicant Remarks, pg. 11, first full paragraph).
Regarding (a), it is noted that none of the references has to teach each and every claim limitation. If they did, this would have been anticipation and not an obviousness-type rejection. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Moreover, although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993). As noted in 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).
Applicant’s assertion that amended claim 48 to recite at least one of a Maillard reaction or a caramelization, and wherein heating comprises heating at a temperature from about 200°C to about 400°C for about 1 min to about 5 min for the Maillard reaction, or at a temperature from about 100°C to about 210°C for about 1 minute to about 5 minutes for the caramelization; and assessing a color…to each of the diseases or disorders on the list” as recited in claim 48, lines 32-51 such that none of the references teach the combination of elements of instant claim 48, is not found persuasive. Applicant essentially included a recitation of half of claim 48, such that Applicant did not distinctly and specifically point out the supposed errors in the Examiner’s action as required by 37 CFR 1.111(b). Thus, the claims remain rejected for the reasons already of record.
Additionally, the Examiner respectfully points out that Hubbard teaches:
That a target is a chemical or biochemical species that is the subject of an assay experiment including viruses, bacteria, DNA, RNA, proteins, lipids, toxins, or other chemical or bioactive agents for which information on their presence or concentration in a sample is of interest (interpreted as unlabeled analytes; an interpreting toxins and bacteria as environmental samples; and obtaining unlabeled analytes).
Highly specific probes generated to query a large number of molecules (e.g. antigens or nucleic acid sequences) are attached to the surface of a sample slide and exposed to target molecules generated from a wide variety of biological materials, such that if target molecules are present in the hybridization cocktail, they will bind with high affinity and specificity to substrate-bound probe molecules immobilized on the slide, wherein the probe or target can be a toxin, and
wherein the slide is processed and imaged in a way that only areas containing bound target/probe substrate are detectable and fully quantifiable through radiolabeling, enzymatic colorimetry, fluorescence spectroscopy, mass spectroscopy or other techniques known to those skilled in the art.
(interpreting biological materials to encompass biological fluids, etc.; determining the identity of the unlabeled analyte; an antigen and toxin are interpreted to be associated with a disease or disorder; interpreting slide imaging as images or representations thereof; comparing a first image and a second image; and via a colorimetric analytical technique).
That the functional utility is an enhanced ability to be imaged by an imaging method selected from the group consisting of magnetic resonance imaging, computer tomography, x-ray radiology, fluorescence, and ultrasouography; as well as, an enhanced resistance to infection and thrombosis (interpreted as making a first image and a second image or a representation thereof; and associated with a disease or disorder).
Figure 3A shows an amount of biocytin printed, and Figure 3B shows images after development (interpreted as comparing a first image and a second image).
Figure 4C illustrates a composite fluorescent image of FTIC binding to amino groups in graft coat on glass slides with either a low or high concentration of initiator in primer, wherein a false color scale spectrum indicates degree of binding with red the highest (interpreting a graft coat as a surface coating; a false color image; comparing a first and second image; associated with disease or disorders such as having, not having, or is susceptible to each of the disease or disorders; glass substrate; and fluorescence, claims 48, 52 and 66)
Kennedy teaches:
That one type of ligands known to bind to RAGE are advanced glycation end-products (AGEs), which are the chemical products of nonenzymatic attachment of sugars to proteins and lipids, wherein AGEs accumulate in a plethora of biologic settings and have now been demonstrated to play important roles in the pathogenesis of a diverse array of diseases, including diabetes, inflammation, renal failure, aging, systemic amyloidosis, Alzheimer's dementia, inflammatory arthritis, atherosclerosis and colitis, to name but a few (interpreted as a list associated with a disease and/or disorder).
That in diabetes patients, AGEs form as a direct consequence of chronically elevated glucose, which proceeds through the polyol pathway to be reduced to sorbitol by the enzyme aldose reductase, where sorbitol is in turn converted to fructose, then fructose-3-phosphate, and then to 3-deoxyglucose, a reducing sugar whose aldehyde carbonyl can react in the Maillard reaction with the amino group of a target molecule such as an amino acid to form a Schiff base, such that the Schiff base can then undergo an intramolecular rearrangement to form Amadori products, which can further rearrange and condense to form fluorescent, yellow brown products that represent AGEs, wherein it is known that the typical roasting temperature range is from 180-250oC, and roasting time varies between 2 and 25 minutes depending on the process employed, such that when an internal temperature exceeds 180oC, a Maillard reaction, carbohydrate caramelization, and pyrolysis of organic compounds results as evidenced by Tamanna (interpreted as a Maillard reaction or a browning; and encompassing heating from 100-210C and/or 200-300C).
Moreover, Applicant is reminded that MPEP 2144.05(II)(A) states that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).”
Thus, the claims remain rejected for the reasons of record.
New Objections/Rejections
Claim Objection
Claim 64 is objected to because of the following informalities: Claim 64 recites “interstitial fluid, gastric juice, tears, or milk of the subject; or a first environmental sample” in lines 2-4, wherein the term “wherein the first sample is a biological sample or an environmental sample, wherein the biological sample is selected from the group consisting of a selected blood, serum, plasma…gastric juice, tears, and breast milk obtained from the subject” might be more appropriate.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(d)
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 52, 63, 65 and 66 are rejected under 35 U.S.C. 112(d) 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 52 recites (in part): “wherein the plurality of macromolecules comprises: at least two chemically distinct macromolecules, and wherein each chemically distinct macromolecule of the two chemically distinct macromolecules is affixed to a different surface of the plurality of surfaces of the substrate; and the substrate comprises one or more of glass, plastic, metal, composites, acrylics or wood” in claim 52, lines 1-7 because claim 52 depends from claim 48, wherein claim 48, lines 12-13 recite that the plurality of macromolecules is “affixed to the one or more substrate coatings by polymerizing”, while claim 52 recites that the macromolecules are “affixed to a different surface of the plurality of surfaces of the substrate” (e.g., the macromolecules are not affixed to a coating). Thus, claim 52 is an improper dependent claims 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 63 recites (in part): “have been obtained after contacting a second detectable array of the one or more second detectable arrays with one or more second analytes present in the second sample, heating the second detectable array, and then making the one or more second images” in claim 63, lines 2-5 because claim 63 depends from claim 48, wherein claim 48 recites that the one or more second images are stored in a database; and that the second images are associated with a second sample. However, instant claim 48 does not recite the presence of a plurality of detectable arrays, the presence of one or more second detectable arrays; that the steps recited in claim 48 comprise contacting a plurality of detectable arrays with one or more second unlabeled analytes, heating additional arrays; and/or making additional images. Thus, claim 63 is an improper dependent claims 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 65 recites (in part): “further comprising obtaining the one or more unlabeled analytes, the one or more unlabeled analytes being associated with the subject, or the first environmental sample” in claim 65, lines 1-3 because claim 65 depends from claims 48 and 64, wherein claim 48 recites that the first sample is associated with a subject, and that the first sample is associated with a disease or disorder. Moreover, the term “subject” is defined in the instant as-filed Specification as including any plant or animal including mammals, and humans (See; paragraph [0022]). Therefore, the one or more unlabeled analytes cannot be obtained from all types of environmental samples because the term “subject” is not defined to include all environmental samples (e.g., dirt, rocks, fungi, prokaryotes, microorganisms, amoeba, etc.), such that the step “further comprising obtaining one or more unlabeled analytes” is not commensurate with the scope of the claims. Thus, claim 65 is an improper dependent claims 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 66 recites (in part): “wherein the one or more first images of the first detectable array or representation thereof represents one or more of fluorescence, phosphorescence, texture, or color, or lack of one or more of the foregoing, of the plurality of surfaces of the substrate” in claim 66, lines 1-4 because instant claim 48 clearly recites that the one or more unlabeled analytes undergoes a color change and that the color of each of the surfaces is assessed by a colorimetric analytical technique. Moreover, it is unclear how fluorescence and/or phosphorescence can be detected if the analytes of the invention are unlabeled. There cannot be a lack of color in the one or more images when the step of assessing depends upon a color and/or a change in color using a colorimetric technique. Thus, claim 66 is an improper dependent claims 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.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 48, 52, 53, 61 and 63-66 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. An analysis with respect to the claims as a whole reveals that they do not include additional elements that are sufficient to amount to significantly more than the judicial exception. See; Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 110 U.S.P.Q.2d 1976 (2014); Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2116, 106 U.S.P.Q.2d 1972 (2013); Mayo Collaborative Svcs. v. Prometheus Laboratories, Inc., 132 S. Ct. 1289, 101 U.S.P.Q.2d 1961 (2012). See also 2014 Interim Guidance on Patent Subject Matter Eligibility, available at http://www.gpo.gov/fdsys/pkg/FR-2014-12-16/pdf/2014-29414.pdf (“2014 Interim Guidance”), and the Office’s examples to be considered in conjunction with the 2014 Interim Guidance in examination of nature-based products, available online at: http://www.uspto.gov/patents/law/exam/mdc_examples_ nature-based_products.pdf (“Nature-Based Products Examples”). This rejection is proper.
Analysis of subject-matter eligibility under 35 U.S.C. § 101 requires consideration of three issues: (1) whether the claim is directed to one of the four categories recited in §101; (2) whether the claim recites or involves a judicial exception (i.e., a law of nature, natural phenomenon, or natural product); and (3) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. In the instant case, the claims are directed to a natural phenomenon, which is the natural presence of analytes in a first sample including a biological sample from a subject and an estimation of a likelihood that a subject associated with the first sample has, does not have, or is susceptible to a disease or disorder. Therefore, each claim must be considered to determine whether, given their broadest reasonable interpretation, they amount to significantly more than the judicial exception.
The claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claims as a whole, claims 48, 52, 53, 61 and 63-66 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
In the instant case, claim 48 is broadly directed to a label-free method of detecting one or more unlabeled analytes in a first sample on a first detectable array, the first detectable array comprising: a substrate with a plurality of surfaces for binding one or more analytes, each surface of the plurality of surfaces independently comprising: one or more substrate coatings on the surf ace for fixing one or more a plurality of macromolecules to the surface of the substrate, said one or more substrate coatings comprising at least one silane or at least one siloxane; and the plurality of macromolecules affixed to at least a portion of the one or more substrate coatings, the such that the one more substrates comprise a plurality of binding sites for binding a plurality of analytes; wherein each macromolecule of the plurality of macromolecules has been affixed to the one or more substrate coatings by polymerizing a functional group of the silane or siloxane into a backbone of the macromolecule; wherein each macromolecule of the one or more plurality of macromolecules comprises a polymer of monomers selected from a group consisting of: acrylamide; 2-carboxyethyl acrylate; acrylic acid; N-[tris(hydroxymethyl)methyl] acrylamide; hydroxypropyl acrylates; 4-hydroxybutyl acrylate; N-hydroxyethyl acrylamide; N,N-dimethylacryl-amide; N-(1,1-dimethyl-3-oxobutyl) acrylamide; N-iso-propylacrylamide; (meth)acrylates; 2-cyanoethyl acrylate; ethylene glycol phenyl ether acrylate; N-tert-octylacrylamide; 1-(acryloyloxy)-3 (methacryloyloxy)-2-propanol; bis-acrylamide; trimethylolpropane triacrylate; and combinations thereof; and wherein the identity, pattern, or both identity and pattern of the one or more plurality of macromolecules on the one or more substrate coatings of each of the plurality of surfaces is no identical to the identity, pattern, or both identity and pattern of the plurality of macromolecules on any other substrate coating of any other of the plurality of surfaces; the label-free method comprising: contacting the first sample including the one or more unlabeled analytes with the first detectable array to affix at least a portion of the one or more unlabeled analytes to the first detectable array; and heating the first detectable array with the one or more unlabeled analytes affixed thereto to cause a color change of at least one of the analyte and the first detectable array, wherein the heating induces a non-enzymatic browning reaction that includes at least one of a Maillard reaction or a caramelization, and wherein the heating comprises heating at a temperature from about 200°C to about 400°C for about 1 min to about 5 min for the Maillard reaction, or at a temperature from about 100°C to about 210°C for about 1 minute to about 5 minutes for the caramelization; and assessing a color of each of the plurality of surf aces of the substrate by colorimetric analytical technique, the assessing including: making one or more first images of the first detectable array, or a representation including a false color image thereof, after the detecting the one or more unlabeled analyte; comparing the one or more first images, or the representation thereof, to one or more predetermined second images of one or more second detectable arrays stored in a database, or representations thereof, each of the one or more second images being associated with a second sample; and receiving a result of the comparison in the form of a list of diseases or disorders and an estimation of a likelihood that a subject associated with the first sample has, does not have, or is susceptible to each of the diseases or disorders on the list.
Beginning with Step I of the analysis, which asks whether the claimed invention falls within a statutory category, such that the instant claims are directed to a process, thus, the instant claims are directed to a statutory category. Step I [YES].
Proceeding to Step IIA – Prong One of the analysis, which asks if the claimed invention is directed to a judicial exception, such that claims 48, 52, 53, 61 and 63-66 are drawn to a natural phenomenon, and an abstract idea including: a natural phenomenon in the form of a natural correlation between the unlabeled analytes in a sample assessed a color change by a colorimetric technique, wherein the first images and second images are compared, and results are generated in the form of a list of diseases or disorders and an estimation of a likelihood that a subject associated with the first sample has, does not have, or is susceptible to each of the diseases or disorder on the list; and to an abstract idea in the form of accessing the color and/or a color change of each of the plurality of surfaces of the substrate by a colorimetric analytical technique; making one or more images of the color and/or a color change of at least one unlabeled analyte; and/or comparing the one or more first images with one or more second images, wherein the color and/or color change is induced by heating the first detectable array (e.g., encompassing mathematical concepts; mathematical relationships, formulas or equations; calculations; as well as, mental process performed in the human mind including concepts such as observation, evaluation, judgement, and/or opinion in the form of detecting, determining, comparing, assessing, identifying, etc.).
Thus, the claims recite a natural phenomenon, and an abstract idea, which falls within the groupings of abstract ideas enumerated in the 2019 PEG including encompassing mathematical concepts, equations, and calculations that can be carried out in the human mind, and/or by using a general computer that performs routine and conventional functions, as well as, mental process performed in the human mind including concepts such as observation, evaluation, judgement, and/or opinion. Thus, under the revised Step IIA analysis, the claims are directed to a natural phenomenon, and to an abstract idea. Step IIA – Prong One [YES].
Step IIA - Prong Two asks whether the claim recites additional elements that integrate the exception into a practical application of the exception. In the instant case, the claims are directed to a judicial exception in the form of a natural phenomenon and an abstract idea. Claim 48 recites: “a label-free method of detecting one or more unlabeled analytes in a first sample on a first detectable array, the first detectable array comprising: a substrate with a plurality of surfaces for binding one or more analyte” in lines 1-3; “wherein the identity, pattern, or both identity and pattern of the one or more plurality of macromolecules on the one or more substrate coatings of each of the plurality of surfaces is not identical to the identity, pattern, or both identity and pattern of the plurality of macromolecules on any other substrate coating of any other of the plurality of surfaces” in lines 23-27; “wherein the heating induces a non-enzymatic browning reaction that includes at least one of a Maillard reaction or a caramelization, and wherein the heating comprises heating at a temperature from about 200°C to about 400°C for about 1 min to about 5 min for the Maillard reaction, or at a temperature from about 100°C to about 210°C for about 1 minute to about 5 minutes for the caramelization; and assessing a color of each of the plurality of surf aces of the substrate by colorimetric analytical technique, the assessing including: making one or more first images of the first detectable array, or a representation including a false color image thereof” in lines 32-42; and “after the detecting the one or more unlabeled analyte; comparing the one or more first images, or the representation thereof, to one or more predetermined second images of one or more second detectable arrays stored in a database, or representations thereof, each of the one or more second images being associated with a second sample; and receiving a result of the comparison in the form of a list of diseases or disorders and an estimation of a likelihood that a subject associated with the first sample has, does not have, or is susceptible to each of the diseases or disorders on the list” in lines 42-51. These limitations simply describe a process of collecting and analyzing information, which is analogous to “obtaining and comparing intangible data” (i.e. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 99 U.S.P.Q.2d 1690 (Fed. Cir. 2011)); as well as, “collecting information, analyzing it, and displaying certain results of the collection analysis” (i.e. Electric Power Group, LLC, v. Alstom, 830 F.3d 1350, 119 U.S.P.Q.2d 1739 (Fed. Cir. 2016)). Moreover, many of Applicant’s process steps can be practiced as a mental process performed in the human mind, by pen and paper, or through the use of a generic computer, for example, “comparing information regarding a sample or test subject to a control or target data” (i.e. Univ. of Utah Research Found. v. Ambry Genetics Corp. (Also known as In re BRCA1– and BRCA2–Based Hereditary Cancer Test Patent Litigation), 774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) or Association for Molecular Pathology v. USPTO (Also known as Myriad CAFC), 689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)). Hence, these limitations are akin to an “abstract idea itself” which was at issue in Alice Corp. and has been identified among non-limiting examples to be an abstract idea. Additionally, the dependent limitations of claims 52, 53, 61 and 63-66 also suffer from the same issue. In other words, the dependent limitations do not rectify the rejection of the independent claim. By way of example, the limitations of claim 61 recites, “further comprising determining an identity of the unlabeled analyte based on the assessing”; and claim 66 recites “wherein the one or more first images of the first detectable array or representation thereof represents one or more of fluorescence, phosphorescence, texture, or color, or lack of one or more of the foregoing, of the plurality of surfaces of the substrate”, which clearly resembles “organizing information through mathematical correlations” (i.e. Digitech Image Techs., LLC v Electronics for Imaging, Inc., 758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)); and is analogous to “obtaining and comparing intangible data” (i.e. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 99 U.S.P.Q.2d 1690 (Fed. Cir. 2011)); “collecting information, analyzing it, and displaying certain results of the collection analysis” (i.e. Electric Power Group, LLC, v. Alstom, 830 F.3d 1350, 119 U.S.P.Q.2d 1739 (Fed. Cir. 2016)); and “comparing information regarding a sample or test subject to a control or target data” (i.e. Univ. of Utah Research Found. v. Ambry Genetics Corp. (Also known as In re BRCA1– and BRCA2–Based Hereditary Cancer Test Patent Litigation), 774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) or Association for Molecular Pathology v. USPTO (Also known as Myriad CAFC), 689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)). Thus, the claims do not integrate the judicial exceptions into a practical application of the exceptions. Step IIA – Prong Two [NO].
Proceeding to Step IIB of the analysis: the question then becomes what element or what combination of elements is sufficient to amount to significantly more than the abstract idea?
The instant independent claim is recited at a high level of generality, such that substantially all practical applications of the judicial exception are covered. For instance, claim 48 is recited without any specificity as to the identity of the substrate; the identity of the one or more surfaces; the identity of the unlabeled analytes; the substrate coatings; the identity of the plurality of macromolecules, and/or combinations thereof; the pattern of the macromolecule arrangement; the method of contacting the first detectable array; the identity of the first detectable array and/or subsequent arrays; the method of heating; the specific non-enzymatic browning reaction; the level of browning; the colors changes; the level and specific colors; what unlabeled analytes are detected by a color change; the method of assessing a color; the colorimetric analytical technique; the method of comparing images; the samples (e.g., biological, environmental, biological fluids, tissue samples, etc.); the subject (e.g., microorganisms, prokaryotes, dirt, metal, plants, mammals, humans, etc.); the databases; the representations of images; the list of diseases and/or disorders; how the results associate the subject with an estimation of a likelihood of the subject having, not having, or being susceptible to any of the disease and/or disorders (or combinations thereof), etc. The claims amount to nothing more than assessing changes and/or levels of color determined by a colorimetric analytical technique when unlabeled analytes bind to macromolecules bound to a coating on the surface of a substrate are heated; such that comparing a first image with a second image determines an estimation of the likelihood that a subject associated with a first sample has, does not have, or is susceptible to a disease or disorder, wherein the steps of the method are well-known in the art.
For example, methods and compositions for the direct detection of analytes using color changes that occur in biopolymeric material in response to the selective binding of analytes including biopolymeric material comprising a plurality of polymerized self-assembling monomers and one or more nucleic acid ligands, wherein said polymeric material change color in the presence of an analyte; the steps of: (i) providing biopolymeric materials comprising a plurality of polymerized lipid monomers and one or more ligands wherein the biopolymeric materials change color in the presence of analyte, and a sample suspected of containing an analyte; (ii) contacting the biopolymeric materials with the sample; and detecting a color change in the biopolymeric materials, wherein the biopolymeric material comprises self-assembling monomers such as lipids are known in the art; and that the biopolymeric materials contain nucleic acids as ligands that have affinity for an analyte including nucleic acid molecules, enzymes, pathogens, drugs receptor ligands, antigens, ions, proteins, hormones, blood components, antibodies and lectins from any organism including pathogens and microorganisms such as bacteria, fungi, viruses, parasites, etc.; that self-assembling monomers are selected from the group consisting of acetylenes, alkenes, thiophenes, polythiophenes, imides, acrylamides, methacrylates, vinylether, malic anhydride, urethanes, allylamines, siloxanes anilines, pyrroles, vinylpyridinium, and combinations thereof; and that direct colorimetric detection" refers to the detection of color changes without the aid of an intervening processing step (e.g. conversion of a color change into an electronic signal that is processed by an interpreting device), wherein the term encompasses visual observing (e.g., observing with the human eye) as well as detection by simple spectrometry, wherein lipid monomers can be made with silane or thiol anchoring groups, which allows dipping of solid supports into the solution to form a coated solid support including wherein diacetylene monomers are anchored by the silane and thiol groups and are then polymerized as evidenced by Charych et al. (US6306598; col 2, lines 48-58 and 67; col 3, lines 1-8; 28-35 and 59-64; col 4, lines 51-60; col 11, lines 27-34; and col 22, lines 42-47); and that heat- or microwave-activated browning composition prepared for coating a food product to produce surface browning on exposure to heat or microwave energy is known in the art, including the steps of coating a food product with a microwaveable browning composition and subjecting the coated product to heat or microwave energy, wherein the browning composition includes at least one liposome-encapsulated Maillard browning reagent; and the invention provides a system to easily attach protein molecules including antibodies to the surface of polydiacetylene thin films and liposomes to provide protein ligands, as well as, peptides, lipoproteins, glycoproteins, enzymes, receptors, channels, etc. such that upon binding an analyte (e.g., an enzyme substrate, receptor ligand, antigen, and other protein), a disruption of the polymer backbone of the biopolymeric material can occur, resulting in a detectable color change; and that as a general procedure for hybridization, the two complementary DNA stands are mixed, heated for ~3 minutes in boiling water and slowly cooled. Moreover, the invention is directed to a stable composition that does not undergo premature browning during storage and that is readily activated by microwave energy to produce a golden brown color on the surface of a food, wherein a water-soluble Maillard browning reagents can alternatively be sequestered inside the liposomes including glucose; while the amino acids or proteins can be part of the external aqueous environment, as well as, encapsulating a base or other pH adjusting agent in an amount sufficient to adjust the pH of the browning composition to a point such that the Maillard browning reaction occurs as evidenced by Haynes et al. (US5089278; Abstract, lines 1-10; col 4, lines 11-15 and 37-46; col 32, lines 26-36; and col 76, lines 30-34). Additionally, highly specific probes generated to query a large number of molecules (e.g. antigens or nucleic acid sequences) are attached to the surface of a sample slide and exposed to target molecules generated from a wide variety of biological materials, such that if target molecules are present in the hybridization cocktail, they will bind with high affinity and specificity to substrate-bound probe molecules immobilized on the slide, wherein the slide is processed and imaged in a way that only areas containing bound target/probe substrate are detectable and fully quantifiable through radiolabeling, enzymatic colorimetry, fluorescence spectroscopy, mass spectroscopy or other techniques known to those skilled in the art; and that the method comprising; (a) applying to a glass surface a solution comprising (i) an organic solvent or mixture of organic solvents, (ii) a silane monomer or mixture of silane monomers and unreactive silanes; (b) removing the solvents to leave a coating of silane attached monomers and silane attached unreactive groups (interpreted as one or more silane substrate coating); (c) exposing said silane coated surface to an initiator; (d) immersing the silane-coated surface in a medium having one or more monomers in solution that are capable of reacting with the reactive sites created by surface bound initiator to form a polymer chain grafted onto said surface; (e) initiating a graft polymerization reaction on said silane-coated surface; and (f) graft polymerizing onto the silane-coated surface the reactive monomers from the medium by forming covalent bonds between the monomer molecules and the surface at reactive radical sites on the silane-coated surface; wherein the silane monomer solution was prepared by mixing together ethanol and methacryloxypropyl trimethoxy-silane, wherein examples of silanes with attached reactive monomers are (3-acryloxypropyl)trimethoxy-silane and methacryloxypropyl-trimethoxy-silane; and wherein the graft matrix is applied to the article surface in a pattern, which facilitates the placement of different types of reactive probes, and the reading of results once the matrix has been allowed to react with a test sample as evidenced by Hubbard (US Patent Application Publication 20050042612, published February 24, 2005; paragraphs [0003]; [0027]; [0067]-[0075]; [0087]; and [0261]); and it was known in the art that hat in diabetes patients, AGEs form as a direct consequence of chronically elevated glucose, which proceeds through the polyol pathway to be reduced to sorbitol by the enzyme aldose reductase, where sorbitol is in turn converted to fructose, then fructose-3-phosphate, and then to 3-deoxyglucose, a reducing sugar whose aldehyde carbonyl can react in the Maillard reaction with the amino group of a target molecule such as an amino acid to form a Schiff base, such that the Schiff base can then undergo an intramolecular rearrangement to form Amadori products, which can further rearrange and condense to form fluorescent, yellow brown products that represent AGEs as evidenced by Kennedy (US Patent Application Publication 20120083465, published April 5, 2012; paragraph [0004], lines 10-22). Furthermore, chemical sensor arrays based upon cross-reactive colorimetric response are known in the art, wherein each of many sensor elements in an array is a mixture of dyes or other compounds that changes color upon exposure to an analyte, such that these arrays typically use strong, poorly-reversible chemical reactions involving a diverse set of color-changing dyes or chromogens; such colorimetric sensor arrays have evolved to be fast, sensitive, portable, and inexpensive. Importantly, the analyte scope of the developed arrays has been shown to be capable of tailoring based on their intended applications, and can be made to be either broad or narrow as desired: in previous works, they have proven to be capable of discriminating among a broad range of analytes including both gaseous and aqueous analytes involving many different types of chemical reactivity, including Lewis and Brønsted acidity/basicity, molecular polarity, redox properties, and chelation; and that colorimetric sensor arrays are monitored by optical transduction, development of portable scanners involves investigating inexpensive, compact, low-noise optical imagers. Moreover, the mechanism of transduction in thermometric sensors relies on the measurement of the local heat change from specific chemical reactions or adsorption events involving the analyte, wherein thermometric sensors are constructed by coating a catalytic sensor layer on the surface of a thermometer; and that the interaction of a target analyte with a chemical sensor can generate or consume heat that is then measured by sensitive thermistor (i.e., semiconductors with strongly temperature-dependent conductivity), wherein thermometric sensors most commonly utilize enzymatic reactions with high enthalpy changes, such that due to the simplicity of the thermal biosensing approach (e.g., there is no need for labeling reactants), such that this method can be considered as a suitable replacement for other signal transduction methods that require a sophisticated cascades of reaction steps; and that the sensor spots can turn yellow-brown as evidenced by Askim (Dissertation, 2015, pg. ii, second full paragraph; pg. iii, last full paragraph; pg. 4, last partial paragraph; pg. 5, first partial paragraph; and pg. 172, first and second paragraphs). Thus, the claims as a whole simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality to the judicial exception, wherein the steps are well-understood, routine and conventional activities previously known to the industry, as discussed in Alice Corp., 134 S. Ct. at 2359-60, 110 USPQ2d at 1984 (see MPEP § 2106.05(d)). Step IIA [YES].
In sum, when the relevant factors are analyzed, the claims as a whole do NOT recite additional elements that amount to significantly more than the judicial exception itself. Accordingly, claim 47 DOES NOT qualify as eligible subject matter.
Dependent claims 52, 53, 61 and 63-66 when analyzed as a whole are held to be patent ineligible under 35 U.S.C. 101 because they do not add anything that makes the natural phenomenon in claim 1, significantly different. For example, claim 53 encompasses the method of claim 48, wherein the plurality of macromolecules comprise: at least 12 chemically distinct macromolecules, but it does not add anything that makes the natural phenomenon and abstract idea in claim 48 significantly different.
In light of the above consideration and the new guidance, claims 48, 52, 53, 61 and 63-66 are non-statutory. This rejection is newly recited as necessitated by the new Guidance set forth in the Memorandum of July 30, 2015 updating the June 25, 2014 guidance (see June 25, 2014 memorandum from Deputy Commissioner for Patent Examination Policy Andrew Hirshfeld titled Preliminary Examination Instructions in view of the Supreme Court Decision in Alice Corporation Pty. Ltd. v. CLS Bank International, et al. (Alice Corp. Preliminary Examination Instructions) and the Revised Patent Subject Matter Eligibility Guidance (See, Federal Register, vol. 84, No. 4, January 7, 2019).
The Examiner suggests that Applicant amend instant claim 48 to recite: (1) specific coatings, macromolecules, subjects, analytes, and samples (e.g., cellulose coating, sugar coating; plants; mammals; humans; biological fluids; antibodies, nucleic acids, etc.); (2) identify what component of the array undergoes a color change and/or a non-enzymatic reaction upon heating; (3) clarify what the unlabeled analytes bind to (e.g., macromolecules, substrate, surface coatings, fluorescently labeled probes or primers comprising a capture sequence, a silane functional group, etc.); (4) indicate how the comparison between the images provides results for a subject with regard to an estimate a likelihood of a specific disease or disorder; (5) amend the term an “estimate a likelihood” and (6) clarify the origin of the list and how a disease or disorder from the list is indicative of results obtained from the image.
Conclusion
Claims 48, 52, 53, 61 and 63-66 are rejected.
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/AMY M BUNKER/
Primary Examiner, Art Unit 1684
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