DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1, 5-8, 11-12, 15-17, 21-24, 27-28, and 31-34 are pending and examined on the merits.
Claims 2-4, 9-10, 13-14, 18-20, 25-26, 29-30, and 35-85 are cancelled.
Priority
The instant application is a 371 national stage entry of PCT/US20/45638 having an international filing date of 8/10/2020, and claims the benefit of priority to provisional U.S. Application No. 62/884,974 filed on 8/9/2019. Thus, the effective filing date of the claims is 8/9/2019.
The applicant is reminded that amendments to the claims and specification must comply with 35 U.S.C. § 120 and 37 C.F.R. § 1.121 to maintain priority to an earlier-filed application. Claim amendments may impact the effective filing date if new subject matter is introduced that lacks support in the originally filed disclosure. If an amendment adds limitations that were not adequately described in the parent application, the claim may no longer be entitled to the priority date of the earlier filing.
Information Disclosure Statement
The IDS filed on 2/8/2022 has been entered and considered. A signed copy of the
corresponding 1449 form with any deficiencies noted has been included with this Office action.
The information disclosure statement filed 2/8/2022 fails to comply with 37 CFR 1.98(a)(2),
which requires a legible copy of each cited foreign patent document; each non-patent literature
publication or that portion which caused it to be listed; and all other information or that portion which
caused it to be listed. It has been placed in the application file, but the information referred to therein
has not been considered. Specifically, a copy of the foreign patent document Cite No. 1 is required.
Additionally, the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for
consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the
specification but must be submitted in a separate paper." Therefore, unless the references have been
cited by the examiner on form PTO-892, they have not been considered.
Specification
The abstract of the disclosure is objected to because it contains 207 words, where the requirement is for between 50-150 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
Claim 17 recites "a sequence identification function configured to identify gene targets from one or more genetic databases for a target host". Here the generic placeholder which is used instead of means is “function”. It is noted that claim 1 provides sufficient description of said functions. To further prosecution, the limitations indicated above are interpreted as encompassing the following limitations of claim 1: "generating a genomic library for an organism from known target genes, whole or partial genome assemblies, or biosynthetic gene clusters (BGC’s) derived from microbiome gene analysis; initiating a sequence identification function comprising the steps of: analyzing said genomic library and identifying a plurality of prospective gene targets whose expression may be regulated by a proposed therapeutic oligomer".
Claim 17 also recites "an automated high-throughput therapeutic oligomer production module configured to generate said unique therapeutic oligomers; a testing module configured to evaluate the efficacy and/or toxicity of said unique therapeutic oligomers; and a delivery system configured to deliver said unique therapeutic oligomers to a host cell". It is noted that the specification does contain description of the claimed modules:
The oligomer production module: Page 23 last paragraph "As generally described above the invention may include the design of one or more customized FASTmers that may regulate expression of a target genes in a host organism. As generally referring to figure 21, in one preferred embodiment, the sequences for one or more FASTmers, which may preferably be a PNA or other oligonucleotide sequence such as a dsRNA, or asRNA oligonucleotide may be rapidly produced. In this embodiment, one or more customized FASTmers, which in this embodiment are PNA, may be rapidly generated using solid-phase Fmoc synthesis as generally shown in Figure 9. In one embodiment, an Apex 396 peptide synthesizer (AAPPTec, LLC) may be used to perform solid-state PNA synthesis using Fmoc chemistry on MBHA rink amide resin at a 10pmol scale. Fmoc-PNA monomers were obtained from PolyOrg Inc. A, C, and G monomers are protected at amines with Bhoc groups. As shown in Figure 4, all PNA synthesized for predictive efficacy evaluation may be synthesized with a cell-penetrating peptide, such as (KFF)3K, which has lysine residues protected with Boc groups. PNA products may further be precipitated and purified as trifluoroacetic acid salts.";
The testing module: page 24 "As generally described in Figure 12 and 21, the synthesized FASTmers may be purified and further tested in an in vitro or in vivo environment for specific activity. For example, in some embodiment the FASTmer may be evaluated. As noted above, in some instances the specific activity of a design and built FASTmer may include the up- or down-regulation of the expression of one or more target genes, while in alternative embodiments, the FASTmer may include a specific activity of potentiating known therapeutic compounds. Fr example, as shown in Figure 24, a FASTmer may be used to potentiate activity of traditional small-molecule antibiotics. [] In one preferred embodiment, testing of the PNA candidate efficacy in MDR bacteria occurs over the course of a 16-hour experiment, where inhibition of each antibiotic PNA is measured against that of a scrambled nonsense sequence. As shown in Figure 1, normalized growth data is used to determine the most effective antibiotic PNA, as well as to improve the efficacy predictions of the PNA Finder toolbox. Initial work on efficacy prediction by the inventors has found a moderate correlation between STRING database protein network node degree-a measure of the connectivity of a given gene within bacterial metabolism-and normalized 16- hour growth data of MDR bacteria (R2 = 0.28, Figure 4). Further collection of data, addition of variables, and development of the predictive efficacy framework may improve the predictions of PNA Finder and enhance the overall utility of the novel FAST platform system."; and
The delivery module: page 28 first paragraph "Examples of suitable probiotic microorganisms that may act as a delivery vehicle for one or more PNAs include yeasts such as Saccharomyces, Debaromyces, Candida, Pichia and Torulopsis, molds such as Aspergillus, Rhizopus, Mucor, and Penicillium and Torulopsis and bacteria such as the genera Bifidobacterium, Bacteroides, Clostridium, Fusobacterium, Melissococcus, ropionibacterium, Streptococcus, Enterococcus, Lactococcus, Staphylococcus, Peptostrepococcus, Bacillus, Pediococcus, Micrococcus, Leuconostoc, Weissella, Aerococcus, Oenococcus and Lactobacillus. Specific examples of suitable probiotic microorganisms are: Saccharomyces cereviseae, Bacillus coagulans, Bacillus lichenformis, Bacillus subtilis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Enterococcus faecium, Enterococcus faecalis, Lactobacillus acidophilus, Lactobacillus alimentarius, Lactobacillus casei subsp. casei, Lactobacillus casei Shirota, Lactobacillus curvatus, Lactobacillus delbruckii subsp. lactis, Lactobacillus farciminus, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus (Lactobacillus GG), Lactobacillus sake, Lactococcus lactis, Micrococcus varians, Pediococcus acidilactici, Pediococcus pentosaceus, Pediococcus acidilactici, Pediococcus halophilus, Streptococcus faecalis, Streptococcus thermophilus, Staphylococcus carnosus, and Staphylococcus xylosus", page 32 lines 11-13 “In additional embodiments, a Nanoparticle-based delivery strategy may be utilized. Such a nanotechnology delivery system may provide a delivery vehicle for enhanced PNA transport, lowered toxicity, and increased bioavailability”, page 33 lines 17-19 “Finally, for enhancing intracellular delivery, the present inventors may attach a CPP based on the TAT sequence or quantum dots as described above.”, and Figures 9, 12, and 21 provide graphical representations of the claimed system. To further prosecution, the limitations indicated above for claim 17 are interpreted as they are in Figures 9, 12, and 21, and on pages 23, 24, and 28 of the instant specification, as indicated above.
Claim 33 recites a "sequence identification function comprises a Get Sequence function". Here the generic placeholder which is used instead of means is “function”. It is noted that claim 1 provides sufficient description of said function. To further prosecution, the limitations indicated above are interpreted as encompassing the following limitations of claim 1: "initiating a sequence identification function comprising the steps of: analyzing said genomic library and identifying a plurality of prospective gene targets whose expression may be regulated by a proposed therapeutic oligomer; generating a proposed therapeutic oligomer sequence corresponding to each of said prospective gene targets; outputting a sequence warning for any of said proposed therapeutic oligomer sequences".
Claim 34 recites a "sequence identification function comprises a Get Sequence function". Here the generic placeholder which is used instead of means is “function”. It is noted that claim 1 provides sufficient description of said function. To further prosecution, the limitations indicated above are interpreted as encompassing the following limitations of claim 1: "initiating an off-target sequence function to identify genomic loci that said proposed therapeutic oligomer is predicted to bind comprising the steps of: searching for incidental alignments between said proposed therapeutic oligomer sequence and said genomic library; aligning each of said proposed therapeutic oligomer sequences to its corresponding genome assembly location and applying a user-specified number of allowed mismatches, using the proposed therapeutic oligomer sequence length parameter as the seed length; identifying whether one or more of said proposed therapeutic oligomer sequences overlaps with any genomic features of said genomic library; outputting a file identifying all potentially inhibitory alignments of said proposed therapeutic oligomer sequences; outputting a file identifying all potentially off-target alignments of said proposed therapeutic oligomer sequences".
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 17, 21-24, 27-28, and 31-34 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 17 recites "functions" and "modules" "configured to" perform certain tasks. It is not clear how these tasks are to be performed, or what device(s) are intended to be used to carry them out. To further prosecution, the limitations are interpreted as being performed using the "tools" detailed on pages 28-30 of the instant specification.
Claims 21-24, 27-28, and 31-34 depend from indefinite claim 17, therefore are also rejected as being indefinite.
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 17, 21-24, 27-28, and 31-34 are rejected under 35 U.S.C. 101 because it is directed to non-statutory subject matter (Step 1: No). Claim 17 is rejected because “A system” (consisting of "functions", "modules", and "a delivery system") does not recite any structural component and therefore equates to “software per se.” Claims that equate to “software per se” are not a statutory category of invention (See MPEP § 2106.03.1). However, claim 17 could be amended to be statutory subject matter by adding in structural components such as by replacing “A system” with the phrase “A non-transitory computer-readable medium containing instructions”, as well as the structure of the "tools" detailed on pages 28-30 of the instant specification. Nonetheless, this amendment would still result in a rejection of the claim under 35 U.S.C. 101 for recitation of a judicial exception without significantly more. Therefore, claim 17 has been analyzed below under 35 U.S.C. 101 using the Alice/Mayo test in the interest of compact prosecution. Claims 21-24, 27-28, and 31-34 depend from claim 17, and therefore are also rejected as being directed to non-statutory subject matter.
Claims 1, 5-8, 11-12, 15-17, 21-24, 27-28, and 31-34 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of a mental process, a mathematical concept, organizing human activity, or a law of nature or natural phenomenon without significantly more. In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claims 1 and 17 (based on interpretation above): “analyzing said genomic library and identifying a plurality of prospective gene targets whose expression may be regulated by a proposed therapeutic oligomer” provides an evaluation (analyzing and identifying prospective gene targets) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“identify genomic loci that said proposed therapeutic oligomer is predicted to bind comprising the steps of: searching for incidental alignments between said proposed therapeutic oligomer sequence and said genomic library; aligning each of said proposed therapeutic oligomer sequences to its corresponding genome assembly location and applying a user-specified number of allowed mismatches, using the proposed therapeutic oligomer sequence length parameter as the seed length; identifying whether one or more of said proposed therapeutic oligomer sequences overlaps with any genomic features of said genomic library” provides comparisons and evaluations (identifying genomic loci by aligning and searching sequences, and identifying feature overlap) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“selecting one or more of said proposed therapeutic oligomer sequences wherein said selection is based on at least one of the following criteria” provides an evaluation (making a selection based on criteria) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claim 17: “identify genomic loci that a therapeutic oligomer is predicted to bind” provides an evaluation (identifying genomic loci for binding) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
These recitations are similar to the concepts of collecting information, analyzing it, and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or are mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. Additionally, while claims 17, 21-24, 27-28, and 31-34 recite performing some aspects of the analysis on “A non-transitory computer-readable medium” (as interpreted above), there are no additional limitations that indicate that this requires anything other than carrying out the recited mental processes or mathematical concepts in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then it falls within the “Mental processes” grouping of abstract ideas. As such, claims 1, 5-8, 11-12, 15-17, 21-24, 27-28, and 31-34 recite an abstract idea (Step 2A, Prong 1: YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). The judicial exceptions listed above are not integrated into a practical application because the claims do not recite an additional element or elements that reflects an improvement to technology. Specifically, the claims recite the following additional elements:
Claim 1: “generating a genomic library for an organism from known target genes, whole or partial genome assemblies, or biosynthetic gene clusters (BGC’s) derived from microbiome gene analysis” provides insignificant extra-solution activities (generating a database pre-solution activities involving data gathering steps) that do not serve to integrate the judicial exceptions into a practical application.
“generating a proposed therapeutic oligomer sequence corresponding to each of said prospective gene targets; outputting a sequence warning for any of said proposed therapeutic oligomer sequences” provides insignificant extra-solution activities (processing and outputting data are pre-solution activities involving data gathering steps) that do not serve to integrate the judicial exceptions into a practical application.
“outputting a file identifying all potentially inhibitory alignments of said proposed therapeutic oligomer sequences; outputting a file identifying all potentially off-target alignments of said proposed therapeutic oligomer sequences” provides insignificant extra-solution activities (outputting data are post-solution activities involving data gathering steps) that do not serve to integrate the judicial exceptions into a practical application.
Claims 11 and 27: “PNA is synthesized using solid-state PNA synthesis using Fmoc chemistry” provides insignificant extra-solution activities (synthesizing PNAs is a pre- and post-solution activity involving sample manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
Claims 12 and 28: “high-throughput parallel synthesizing a library of therapeutic oligomer sequences” provides insignificant extra-solution activities (synthesizing PNAs in a high-throughput parallel fashion is a pre- and post-solution activity involving sample manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
Claims 15-16 and 31-32: “testing the efficacy or toxicity of said proposed therapeutic oligomer sequences in an in vitro or in vivo system” and “testing the efficacy or toxicity of said proposed therapeutic oligomer sequence in a macrophage based host-infection model” provides insignificant extra-solution activities (testing efficacy of oligomers is a post-solution activity involving sample manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
Claim 17 (based on interpretation above): “A non-transitory computer-readable medium containing instructions” provides insignificant extra-solution activities (running instructions on generic computer components) that do not serve to integrate the judicial exceptions into a practical application.
“an automated high-throughput therapeutic oligomer production module configured to generate said unique therapeutic oligomers; a testing module configured to evaluate the efficacy and/or toxicity of said unique therapeutic oligomers; and a delivery system configured to deliver said unique therapeutic oligomers to a host cell” provides insignificant extra-solution activities (synthesizing, testing, and delivering oligomers are pre- and post-solution activities involving sample manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
The steps for: generating a database, processing and outputting data; and synthesizing PNAs automatically in a high-throughput fashion, testing efficacy/toxicity, and delivering oligomers are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application because they are pre- and post-solution activities involving data gathering, data manipulation, and sample manipulation steps (see MPEP 2106.04(d)(2)). Furthermore, the limitations regarding implementing program instructions do not indicate that they require anything other than mere instructions to implement the abstract idea in a generic way or in a generic computing environment. As such, this limitation equates to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. Therefore, claims 1, 5-8, 11-12, 15-17, 21-24, 27-28, and 31-34 are directed to an abstract idea (Step 2A, Prong 2: NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application, or equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment.
As discussed above, there are no additional elements to indicate that the claimed “A non-transitory computer-readable medium containing instructions” requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims. Additionally, the limitations for generating a database, processing and outputting data, synthesizing PNAs automatically in a high-throughput fashion, testing efficacy/toxicity, and delivering oligomers are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application. Furthermore, no inventive concept is claimed by these limitations as they are demonstrated to be well-understood, routine, and conventional:
Synthesizing oligomers as evidenced by:
Shakeel et al. (Shakeel et al., "Peptide nucleic acid (PNA)—a review." Journal of Chemical Technology & Biotechnology: International Research in Process, Environmental & Clean Technology 81.6 (2006): 892-899), page 1 col 1 paragraph 1 "Peptide nucleic acid was discovered during the 1990sas a result of the combined efforts of biochemist Peter Nielsen’s and organic chemist Ole Buchardt’s groups. [] So far, almost 1000 articles on PNA have been published in the fields of chemistry, molecular biology, antisense therapy and gene-based diagnostics (see e.g. Refs 1–38)."
Braasch et al. (Braasch, Page 1 paragraph 4 "The automated synthesis of PNAs is illustrated in Figure 4.11.2. Automated synthesis is a convenient strategy for obtaining PNAs, and is performed using the Expedite synthesizer (Applied Biosystems). This instrument has been specially adapted for PNA synthesis, with proprietary software for FMOC chemistry instead of the phosphoramidite chemistry used for typical oligonucleotide synthesis."), Page 1 paragraph 4 "The automated synthesis of PNAs is illustrated in Figure 4.11.2. Automated synthesis is a convenient strategy for obtaining PNAs, and is performed using the Expedite synthesizer (Applied Biosystems). This instrument has been specially adapted for PNA synthesis, with proprietary software for FMOC chemistry instead of the phosphoramidite chemistry used for typical oligonucleotide synthesis."
Testing efficacy and toxicity of oligomers as evidenced by:
Fernandez-Hernando et al. (US-20160138018), para.0086 "Following methodologies which are well-established in the art, effective doses and toxicity of the oligonucleotides and compositions of the present invention, which performed well in in vitro tests, can be determined in studies using small animal models (e.g., mice, rats) in which they have been found to be therapeutically effective and in which these drugs can be administered by the same route proposed for the human trials"
Delivery of oligomers as evidenced by:
Quijano et al. (Quijano et al., "Therapeutic peptide nucleic acids: principles, limitations, and opportunities." The Yale journal of biology and medicine 90.4, 2017: 583), page 1 Abstract "Since their invention in 1991, peptide nucleic acids (PNAs†) have been used in a myriad of chemical and biological assays. More recently, peptide nucleic acids have also been demonstrated to hold great potential as therapeutic agents because of their physiological stability, affinity for target nucleic acids, and versatility. While recent modifications in their design have further improved their potency, their preclinical development has reached new heights due to their combination with recent advancements in drug delivery. This review focuses on recent advances in PNA therapeutic applications, in which chemical modifications are made to improve PNA function and nanoparticles are used to enhance PNA delivery" and page 4 col 2 paragraph 3 "To overcome these limitations in delivery, researchers have explored cell-penetrating peptides (CPPs) to enhance the cellular uptake of PNAs [38-40]. CPPs are short, cationic peptides that vary in length, typically ranging from nine to 30 amino acids [41]. Several CPPs have been investigated for the delivery of PNAs, most notably penetratin, a 16-residue peptide derived from the Drosophila Antennapedia gene [41]."
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1, 5-8, 11-12, 15-17, 21-24, 27-28, and 31-34 are not patent eligible.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1 and 5-8 rejected under 35 U.S.C. 103 as being unpatentable over Malone et al. (US-20160038528) in view of Cradick et al. (US-20170053062).
Regarding independent claim 1, Malone teaches design and production of therapeutic oligomers comprising: generating a genomic library for an organism from known target genes, whole or partial genome assemblies, or biosynthetic gene clusters (BGC’s) derived from microbiome gene analysis (Abstract "The invention relates to rapidly adaptable nanotherapeutics" and para.0027 "The present invention utilizes bioinformatics algorithms for pathogen identification and characterization based on sequence analysis and utilizes existing databases of known pathogen and bacterial strains").
Malone also teaches initiating a sequence identification function comprising the steps of: analyzing said genomic library and identifying a plurality of prospective gene targets whose expression may be regulated by a proposed therapeutic oligomer; generating a proposed therapeutic oligomer sequence corresponding to each of said prospective gene targets; and outputting a sequence warning for any of said proposed therapeutic oligomer sequences (Para.0075 "When a new pathogenic infectious agent is detected in a patient, such as a soldier, its genetic material is first sequenced. Then bioinformatics algorithms are utilized to categorize the pathogen and identify relevant genes for therapeutic knockdown, and to design anti-pathogen nucleic acid-based therapeutics", para.0078 "The sequence information identifies the pathogen as known or unknown. Unknown pathogens are characterized by sequence similarities or other comparisons to known pathogens. From the sequence information of the known or unknown pathogen, a gene or set of genes for expression inhibition are identified and selected. Inhibitors, such as antisense RNA, siRNA, or DNA are then designed by the informatics algorithms.", and para.0087 "After one or more target genes are identified and selected, further informatics software of the invention specifies the nucleotide sequence for the antisense or other inhibitory nucleic acid reagent").
Malone also teaches selecting one or more of said proposed therapeutic oligomer sequences wherein said selection is based on at least regulation of gene expression; stability of said proposed therapeutic oligomer; coding sequence alignments that occur near a start codon of said target gene; and testing one or more of said proposed therapeutic oligomer sequences (para.0092 "the therapeutic RNA may be conjugated to a peptide for bacterial cell permeation and/or for mammalian cell targeting. RNA is a powerful tool for regulatory processes and inhibition of gene expression", para.0098 "Material properties of the therapeutic composition of the invention are demonstrated to form nanoparticle polyplexes capable of transporting nucleic acids with stability in serum", para.0024 "In the present invention, the active ingredient for neutralizing pathogens is designed using genomic sequences and/or expressed sequences. Greater efficacy is achieved from the specificity provided by sequencing pathogens and designing inhibitors to drug-resistant strains and novel pathogens based upon the sequence information", and para.0138 "GAPDH Knockdown Assay: This assay is employed as a way of testing the efficacy of RNAi from platform delivered siRNA").
Malone does not explicitly teach initiating an off-target sequence function to identify genomic loci that said proposed therapeutic oligomer is predicted to bind comprising the steps of: searching for incidental alignments between said proposed therapeutic oligomer sequence and said genomic library; aligning each of said proposed therapeutic oligomer sequences to its corresponding genome assembly location and applying a user-specified number of allowed mismatches, using the proposed therapeutic oligomer sequence length parameter as the seed length; identifying whether one or more of said proposed therapeutic oligomer sequences overlaps with any genomic features of said genomic library; outputting a file identifying all potentially inhibitory alignments of said proposed therapeutic oligomer sequences; nor outputting a file identifying all potentially off-target alignments of said proposed therapeutic oligomer sequences.
However, Cradick teaches an off-target finding method that finds overlaps between sequences, employing sequence alignments using BLAST or FetchGWI against a reference index that allows for search entries such as insertions, deletions, and mismatches (Para.0098 "In preferred embodiments, on-site and off-site targets of the CRISPR guide strands are determined by comparing the query sequence both with and without insertions, deletions, and/or mismatches at one or multiple positions using the FetchGWI search program (Iseli, et al., PLoS ONE, 2(6): e579 (2007). FetchGWI operates on indexed genome sequences that are precompiled and stored (FIGS. 26A-26G). It can identify genomic locations with sequences that match any of the series of search entries. FetchGWI saves run time by searching indexed files that represent the genome sequences, rather than the sequences themselves. There is one index entry for each nucleotide in the genome, which allows a rapid and exhaustive search. In other embodiments, other indexing strategies can be used. Exhaustive, complete searches are a key advantage over BLAST and other programs that scan nonoverlapping words and may miss potential off-target sites"). Either program will output search results to a file. Coupled with the limitations that Malone teaches, the search program is enabled to output a potentially inhibitory alignments of oligomers.
Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to modify the methods of Malone as taught by Cradick in order to determine potential binding of oligomers in the host genome (i.e. patient) and avoid negative impacts of the therapeutic binding to them (Malone, para.0079 "Sequence targets are also filtered against human transcript data to create an orthogonal therapeutic and avoid negative impact on patients." One skilled in the art would have a reasonable expectation of success because both approaches are concerned with targeting genomes or subsequences thereof using oligomers, and both significantly benefit from higher binding specificity (Cradick, para.0310 "Potential off-target cleavage by engineered nucleases poses concerns both for adverse events in therapeutic applications and confounding variables in biological studies").
Regarding claim 5, Malone in view of Cradick teach the methods of Claim 1 on which this claim depends/these claims depend. Malone also teaches said therapeutic oligomer comprises peptide nucleic acid (PNA) (Abstract "The invention relates to rapidly adaptable nanotherapeutics. The therapeutics are nucleic acid molecules, such as, RNA, DNA, or modified-DNA" and para.0066 "Modified nucelic acids are non-natural polymers that hybridize to natural DNA and RNA. Examples of modified nucleic acids are [], peptide nucleic acids (PNAs)").
Regarding claim 6, Malone in view of Cradick teach the methods of Claim 5 on which this claim depends/these claims depend. Malone also teaches said PNA inhibits gene expression in a target host or upregulates gene expression in a target host (Para.0024 "In the present invention, the active ingredient for neutralizing pathogens is designed using genomic sequences and/or expressed sequences. Greater efficacy is achieved from the specificity provided by sequencing pathogens and designing inhibitors to drug-resistant strains and novel pathogens based upon the sequence information" and para.0092 "the therapeutic RNA may be conjugated to a peptide for bacterial cell permeation and/or for mammalian cell targeting. RNA is a powerful tool for regulatory processes and inhibition of gene expression", while not explicitly targeting upregulation of gene expression, it does indicate that it is known that these tools may be used for regulating gene expression (implying both up- and down-regulation).).
Regarding claim 7, Malone in view of Cradick teach the methods of Claim 6 on which this claim depends/these claims depend. Malone also teaches said prospective gene targets comprise essential genes selected from the group consisting of: pathogenicity genes; antibiotic resistance genes; metabolism genes; radiation responsive genes; genes associated with an immune response; genes associated with a disease condition; oncogenes; anti-inflammatory genes, or a combination of the same (Para.0079 "Target genes can include essential genes, housekeeping genes, pathogenicity (invasion) genes, or other genes which have predictive value for organism inhibition" and para.0024 "In the present invention, the active ingredient for neutralizing pathogens is designed using genomic sequences and/or expressed sequences. Greater efficacy is achieved from the specificity provided by sequencing pathogens and designing inhibitors to drug-resistant strains and novel pathogens based upon the sequence information").
Regarding claim 8, Malone in view of Cradick teach the methods of Claim 5 on which this claim depends/these claims depend. Malone also teaches said PNA comprises a 12-mer PNA (Para.0087 "The software scans windows of size 12 bases (as a non-limiting example) including the start codon and ranks self-folding potential by base content").
Claims 11-12, 17, 21-24, 27-28, and 33-34 rejected under 35 U.S.C. 103 as being unpatentable over Malone et al. (US-20160038528) in view of Cradick et al. (US-20170053062) as applied to claims 1 and 5-8 above, and further in view of Braasch et al. (Braasch et al., "Synthesis and purification of peptide nucleic acids." Current Protocols in Nucleic Acid Chemistry 9.1 (2002): 4-11).
Malone et al. in view of Cradick et al. are applied to claims 1 and 5-8.
Regarding claims 11 and 12, Malone in view of Cradick teach the method of Claims 5 and 1 on which this claim depends/these claims depend, respectively.
Malone nor Cradick explicitly teaches said PNA is synthesized using solid-state PNA synthesis using Fmoc chemistry nor said step of synthesizing comprises the step of automated and high-throughput parallel synthesizing a library of therapeutic oligomer sequences.
However, Braasch teaches synthesizing PNAs in an automated and parallel fashion using a synthesizer which employs Fmoc chemistry (Page 1 paragraph 4 "The automated synthesis of PNAs is illustrated in Figure 4.11.2. Automated synthesis is a convenient strategy for obtaining PNAs, and is performed using the Expedite synthesizer (Applied Biosystems). This instrument has been specially adapted for PNA synthesis, with proprietary software for FMOC chemistry instead of the phosphoramidite chemistry used for typical oligonucleotide synthesis").
Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to modify the methods of Malone and Cradick as taught by Braasch in order to conveniently and reliably synthesize PNA molecules (page 1 paragraph 5 "It is probably possible to adapt other synthesizers for PNA synthesis; however, the investigator will need to consider whether the number of PNAs needed justifies the time and expense required to adapt the instrumentation" and page 18 col 1 paragraph 1 "When the Expedite synthesizer is working properly and when all reagents are fresh and dry, an excellent yield of the desired product is almost invariably achieved"). One skilled in the art would have a reasonable expectation of success because both approaches involve synthesizing PNA molecules.
Regarding independent claim 17, Malone teaches a system for the rational design and production of therapeutic oligomers (Para.0031 "An overview of the platform of the invention is illustrated in FIG. 1. Rapidly Adaptable Nano Therapeutic (RANT) platform. The streamlined RANT approach incorporates unified deployment of several step-containing components for rapidly addressing engineered threats, drug resistant threats and orphan threats. These components combine to make a streamlined process and streamlined apparatus that identifies a pathogen, discovers essential orthogonal knockdown sequences for said pathogen, establishes targeted entry into pathogen, synthesizes high fidelity polynucleotides coupled with suitable bacterial entry peptides for blockage and/or knockdown, packages the synthetic polynucleotide with a suitable delivery vehicle, and delivers the synthetic targeted nucleic acid to various tissues within the host. The pretherapeutic steps of this drug development process may take place on dedicated apparatus in a single housing.").
Malone also teaches generating a genomic library for an organism from known target genes, whole or partial genome assemblies, or biosynthetic gene clusters (BGC’s) derived from microbiome gene analysis; initiating a sequence identification function comprising the steps of: analyzing said genomic library and identifying a plurality of prospective gene targets whose expression may be regulated by a proposed therapeutic oligomer (Para.0078 "It is desirable that the whole genome be sequenced; however, the invention encompasses scenarios where incomplete sequence information is available" and para.0075 "When a new pathogenic infectious agent is detected in a patient, such as a soldier, its genetic material is first sequenced. Then bioinformatics algorithms are utilized to categorize the pathogen and identify relevant genes for therapeutic knockdown, and to design anti-pathogen nucleic acid-based therapeutics").
Malone also teaches a therapeutic oligomer identification and generation function comprising a target identification function configured to identify genomic loci that a therapeutic oligomer is predicted to bind, and further configured to design a plurality of unique therapeutic oligomers that exhibit at least one of the following: upregulate or downregulate expression of one or more gene targets in said host (Para.0078 "The sequence information identifies the pathogen as known or unknown. Unknown pathogens are characterized by sequence similarities or other comparisons to known pathogens. From the sequence information of the known or unknown pathogen, a gene or set of genes for expression inhibition are identified and selected. Inhibitors, such as antisense RNA, siRNA, or DNA are then designed by the informatics algorithms.").
Malone also teaches a testing module configured to evaluate the efficacy and/or toxicity of said unique therapeutic oligomers (Para.0122 "To confirm successful antibacterial nucleic acid agent, peptide-RNA agents are tested against bacteria in culture. Agents are optimized to successfully kill bacteria in culture", para.0123 "Two strains of MRSA USA 300 are used", and para.0138 "GAPDH Knockdown Assay: This assay is employed as a way of testing the efficacy of RNAi from platform delivered siRNA").
Malone also teaches a delivery system configured to deliver said unique therapeutic oligomers to a host cell, and as interpreted above (Para.0018 "The invention integrates bioinformatics with rapid synthesis and effective