Notice of Pre-AIA or AIA Status
1. 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
Status of Claims
2. Applicant's preliminary amendment of the instant application, which was originally submitted on 08/25/2023 and later amended on the same day, is acknowledged by the Examiner. The cancellation of claims 2, 5, 10, 12, and 13 pursuant to the amendment on 08/25/2023 is acknowledged. Claims 1, 3, 4, 6 – 9, 11, and 14 – 21 are pending and under review.
Priority
3. The instant application is a National Stage Entry of International Patent Application No. PCT/JP2022/007766 filed on 02/25/2022, and also claims priority to Japanese Patent Application No. 2021-177927 filed on 10/29/2021; Japanese Patent Application No. 2021-072243 filed on 04/22/2021; and Japanese Patent Application No. 2021-029807 filed on 02/26/2021.
It is noted, however, that Applicant has not filed a certified copy of these applications that complies with 37 CFR 1.55. An English language translation of a non-English language foreign application is required (i) when the application is involved in an interference or derivation proceeding; (ii) when necessary to overcome the date of a reference relied upon by the examiner; or (iii) when specifically required by the examiner. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
4. The information disclosure statements (IDS) submitted on 08/25/2023, 09/22/2023, and 02/13/2025 have been considered by the Examiner. Notably, 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.
Additionally, there are numerous documents in the European search report (Cited in Applicant’s IDS on 02/13/2025) that have not been submitted by Applicant on an IDS. Applicant is reminded of the duty to disclose information to the Office which is material to patentability as defined in 37 CFR 1.56. This includes a list of all patents, publications, or other information that should be considered by the Office pursuant to 37 CFR 1.98(b). See MPEP § 609.
Specification
5. The use of the terms FG beads™ on page 4; Tween™ on page 17; Triton X-100™ on page 17; NucleoSpin™ on page 18; Dynabeads™ on page 21; KOD One™ on page 22; QuantiTect™ on page 22; QIAamp™ on page 22; iScript™ on pages 22, 43, and 45; BIOTAQ™ on page 22; PAC 700A™ on page 24; PAC 300A on page 24™; TaqMan™ on page 45, and possibly others in the specification, which are trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, ℠, or ® following the terms. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Applicant is required to properly annotate all trade names and/or marks that are present in the specification.
6. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pages 34 and 37. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http://, www., or other browser-executable code. See MPEP § 608.01.
7. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Drawings
8. The drawings are objected to because there are missing y-axis labels in Figures 2 – 4.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
9. Claims 9 and 21 are objected to because of the following informalities:
In claim 9, line 1, the acronym “SARS-CoV-2” is recited, but not defined in the claim. An acronym should be defined the first time it appears in an independent claim or in the group of claims under an independent claim. For the purposes of examination, “SARS-CoV-2” is interpreted to mean “severe acute respiratory syndrome coronavirus 2”, as defined in the specifications;
Claim 20, line 2 recites the phrase “a protocol described ”. This is grammatically incorrect. It is recommended that the phrase read “a protocol ”.
Claim 21, line 2 recites the phrase “a protocol described the method.” This is grammatically incorrect. It is recommended that the phrase read “a protocol describing the method”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
35 USC § 112(b)
10. 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.
11. Claims 6 – 9, and 14 – 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the requisite amplification step of (C).
Claim 1 is drawn to a method for quantitatively detecting RNA and/or DNA derived from a virus or bacterium in an environmental or fecal sample, but only optionally requires amplification of nucleic acids in step (C). The instant disclosure is replete with requirements of nucleic acid amplification. For example, figure 1 and working examples 1 – 8 in paragraphs 0094 – 0139, chiefly working example 1 in paragraphs 0094 – 0100, all require amplification, which is recited as an “optional” step in (C). There is no teaching in the instant disclosure for quantitatively detecting RNA and/or DNA from a virus or bacterium in a sample without amplification, a requisite oligonucleotide, and other ingredients necessary for amplification (paragraphs 0007, 0050, 0062, 0095 – 0102, 0105, 0123, 0134, and 0137). Thus, the step of amplification is essential, not optional, as stated in claim 1. This rejection includes all dependent claims that do not recite further limitations. Claims 4 and 11 require amplification and are not included in this rejection.
35 USC § 112(a) – Written Description
12. Claims 6 – 9, 11, and 14 – 21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
"The purpose of [the written description requirement] is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification"); LizardTech Inc. v. Earth Resource Mapping Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005). This requirement is separate and distinct from the enablement requirement. To satisfy the written description requirement for a claimed genus, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing. See In re Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345, 54 USPQ2d 1915, 1917 (Fed. Cir. 2000). “Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement.” See In re Enzo Biochem, Inc. v. Gen–Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002). See also MPEP § 2163.
The written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See In re University of California v. Eli Lilly & Co., 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997); and Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, the applicant must describe a sufficient variety of species to reflect the variation within the genus. See In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See In re Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." See In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. This is because functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.” The description needed to satisfy the written description varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. See In re University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014); In re Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 94 USPQ2d 1161 (Fed. Cir. 2010); and In re Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.
Claims 6 – 9, 11, and 14 – 17 are drawn to a method for quantitatively detecting RNA and/or DNA derived from a virus or bacterium in an environmental or fecal sample, but only optionally requires amplification of nucleic acids in step (C). The instant disclosure is replete with requirements of nucleic acid amplification. For example, figure 1 and working examples 1 – 8 in paragraphs 0094 – 0139, chiefly working example 1 in paragraphs 0094 – 0100, all require amplification, which is recited as an “optional” step in (C). There is no teaching in the instant disclosure for quantitatively detecting RNA and/or DNA from a virus or bacterium in a sample without amplification, requisite primers, and other ingredients necessary for amplification (paragraphs 0007, 0050, 0062, 0095 – 0102, 0105, 0123, 0134, and 0137). Thus, the step of amplification is essential, not optional, as stated in claim 1.
Since amplification is an essential component of the invention, there must be oligonucleotides, i.e., primers, drawn to any virus or bacterium that can be found in an environmental or fecal sample. However, no such primers are taught by the claims, leading one to turn to the instant disclosure. Paragraph 0007 of the instant disclosure teaches that the primer has a base sequence specific to a nucleic acid sequence of a specific virus or bacterium to be detected. In general, this creates an enormous breadth of potential primer sequences for a single virus or bacterium that becomes innumerable when coupled with the massive genera of sequences per virus or bacterium in existence.
When there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The claims are drawn to several genera, i.e., virus or a bacterium, which are each comprised of innumerable sequences, yet, the specification has only adequately described, and successfully reduced to practice, a specific primer set to SARS-CoV-2 (page 37, paragraph 0105; SEQ ID NOs: 1 and 2) and associated probe (SEQ ID NO: 3) and another specific primer set to pepper mild mottle virus (PMMoV; page 43, paragraph 0123; SEQ ID NOs: 4 and 5) and associated probe (SEQ ID NO: 6). This is not representative of the extremely large genus of sequences claimed. One of ordinary skill in the art cannot conclude that Applicant was in possession of the innumerable sequences encompassed by the disclosed genera. Absent the disclosed sequences, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, each individual sequence utilized. Thus, it is clear that the breadth of the recited genera in the claims far overreaches the Applicant’s contribution.
In the absence of a representative number of examples, the specification must at least describe the structural features that are required for the claim function. In the instant case, the specification should explain the tolerated mismatches in the primers that would still allow amplification of the target nucleic acid. However, the specification fails to describe any substantive structural limitations as to establish the criteria necessary to design a primer to a given viral or bacterial sequence. At best, the specification contemplates the use of BLAST to identify functional homologs based on sequence homology. This is even suggested as the method to determine primers in the instant disclosure (page 19, paragraph 0050). However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Therefore, one having ordinary skill in the art would readily appreciate that relying on a non–patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
The art teaches that nucleic-acid based assays rely heavily on efficient hybridization of nucleotides to the target sequence, wherein mismatches between the nucleotides and target sequence hinder the system. For example, Christopherson, C., et. al., (The Effects of Internal Primer-Template Mismatches on RT-PCR: HIV-1 Model Studies, Nucleic Acids Research, (25)3, 654–658; Published 02/01/1997), hereby Christopherson, teaches that internal primer-template mismatches have reduced amplification efficiency in RT-PCR experiments (page 654, left column). It is further taught that while two to four mismatches in the primer-template duplex can be tolerated without significant effects on RT-PCR, the presence of five or six mismatches within 28 and 30 base primers significantly reduced the PCR product yield by 22- and 100-fold, respectively, relative to the template (page 654, abstract). Furthermore, Stadhouders, R., et. al., (The effect of primer-template mismatches on the detection and quantification of nucleic acids using the 5' nuclease assay. The Journal of molecular diagnostics: JMD, 12(1), 109–117; Published 01/2010), hereby Stadhouders, teaches that a single mismatch in the primer-template can have severe impacts on PCR amplification (page 109, left column). Green, S. J., et. al., (Deconstructing the Polymerase Chain Reaction: Understanding and Correcting Bias Associated with Primer Degeneracies and Primer Template Mismatches. PLoS ONE 10(5): e0128122; Published 05/21/2015), hereby Green, teaches that, ideally, the primers should match the target sequence, wherein a single mismatch results in poor amplification (page 2). When taken with the teachings of Christopherson, Stadhouders, and Green, one having ordinary skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function, especially towards mismatched primers during PCR.
In summary, these examples teach that the function of nucleic acid-based assays is heavily dependent on the hybridization of the primers, wherein mismatches are not well tolerated and greatly reduce the efficiency. Thus, while Applicant has described a species within the genus recited, and the art may provide more, each genus is very large and would encompass primer structures that cannot be visualized from the prior art or instant disclosure. One having ordinary skill in the art cannot determine the structures encompassed by the claimed genera. The described species cannot be considered representative of the entire recited genus.
Overall, the claims as currently written are not adequately described and one of ordinary skill in that art would readily appreciate that Applicant was not in possession of the claimed genera at the time of filing.
35 USC § 112(a) – Enablement
13. Claims 6 – 9, 11, and 14 – 21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The disclosure does not enable one of ordinary skill in the art to practice the invention without specific oligonucleotides, i.e., primers, for amplification, which are critical or essential to the practice of the invention, but not included in the claims. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit has developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors, to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." The factors considered include, but are not limited to: (A) the breadth of the claims; (B) the nature of the invention; (C) the state of the prior art; (D) the level of one of ordinary skill in the art; (E) the level of predictability in the art; (F) the amount of direction provided by the inventor; (G) the existence of working examples; and (H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims and nature of the invention: Claim 1 is drawn to a method for quantitatively detecting RNA and/or DNA derived from a virus or bacterium in an environmental or fecal sample, but only optionally requires amplification of nucleic acids in step (C). The instant disclosure is replete with requirements of nucleic acid amplification. For example, figure 1 and working examples 1 – 8 in paragraphs 0094 – 0139, chiefly working example 1 in paragraphs 0094 – 0100, all require amplification, which is recited as an “optional” step in (C). There is no teaching in the instant disclosure for quantitatively detecting RNA and/or DNA from a virus or bacterium in a sample without amplification, requisite primers, and other ingredients necessary for amplification (paragraphs 0007, 0050, 0062, 0095 – 0102, 0105, 0123, 0134, and 0137). Thus, the step of amplification is essential, not optional, as stated in claim 1. Further limitations include the type of sample, number of amplification cycles, and employment of PCR.
At a minimum, the claims encompass the amplification of any virus or bacterium that can be found in an environmental sample or a fecal sample. Therefore, since amplification is an essential component of the invention, there must be oligonucleotides, i.e., primers, drawn to any virus or bacterium that can be found in an environmental or fecal sample. However, the specification only provides sufficient disclosure for two primer sets and their associated proves: one directed to SARS-CoV-2 (page 37, paragraph 0105; SEQ ID NOs: 1 – 3) and another directed to PMMoV (page 43, paragraph 0123; SEQ ID NOs: 4 – 6).
Those with relevant skill in the art: The level of skill in the art is that of Ph.D.–level scientists and
medical doctors (D.O. and/or M.D.).
Amount of direction and existence of working examples: The instant application teaches eight working examples (examples 1 – 8 in paragraphs 0094 – 0139), which do not represent an example for the innumerable potential primer sequences per virus or bacterium in existence.
Paragraph 0007 of the instant disclosure teaches that the primer has a base sequence specific to a nucleic acid sequence of a specific virus or bacterium to be detected. Paragraph 0050 describes examples of the primers as including “an oligonucleotide having an oligo (dT) sequence, an oligonucleotide having a base sequence specific to a viral nucleic acid to be detected, and the like. For example, when RNA derived from a virus (for example, coronavirus) or a bacterium having a poly (A) tail is extracted, an oligo (dT) primer can be used). No universal primer that universally detects any and all possible viruses and bacterium in existence is described. The specification has only adequately described, and successfully reduced to practice, a specific primer set to SARS-CoV-2 (page 37, paragraph 0105; SEQ ID NOs: 1 and 2) and associated probe (SEQ ID NO: 3) and another specific primer set to PMMoV (page 43, paragraph 0123; SEQ ID NOs: 4 and 5) and associated probe (SEQ ID NO: 6). Thus, the instant application offers no reasonable guidance or direction to use the claimed method to quantitatively detect any viral or bacterium RNA and/or DNA in a sample.
State of the prior art and unpredictability in the art: It is taught by Rasooly, A. and Herold, K. E. (Food microbial pathogen detection and analysis using DNA microarray technologies. Foodborne pathogens and disease, 5(4), 531–550; Published 08/2008), hereby Rasooly, that bacterial mRNA lacks poly(A) tails (page 534, left column, first paragraph). It is further taught random priming is an inefficient method to yield cDNA from bacterial mRNA, whereas specific oligo(dT) priming is more efficient, yielding more cDNA, and employed with eukaryotic mRNA (page 532, left column, first paragraph). Rasooly goes on to teach that universal PCR primers can be employed to amplify the variable region of the bacterial 16S rRNA gene, but requires subsequent hybridization of the products to species-specific oligonucleotides to differentiate the pathogens (page 543, multi-pathogen microarrays). It is also taught that when doing a microarray to detect bacteria and viruses in a single sample, the oligoprobes must be directed to unique diagnostic regions (page 543, left column, third paragraph). Green, S. J., et. al., (Deconstructing the Polymerase Chain Reaction: Understanding and Correcting Bias Associated with Primer Degeneracies and Primer Template Mismatches. PLoS ONE 10(5): e0128122; Published 05/21/2015), hereby Green, teaches that, ideally, the primers should match the target sequence, wherein a single mismatch results in poor amplification (page 2).
Quantity of experimentation needed: At a minimum, the art teaches that there must be specificity in the probes when detecting a virus or bacteria in a sample. The skilled artisan would not recognize an oligonucleotide that universally binds to any possible virus and/or bacteria that may be present in a sample. In the instantly claimed invention, there would be undue experimentation to individually analyze every possible primer sequence to every virus or bacterium that can be found in a sample. Thus, one of skill in the art would neither expect nor predict the appropriate function of any primer sequence of the instant claims for any virus or bacterium as broadly as claimed.
Any and all enablement of the claimed agents must therefore come from the instant disclosure. However, the instant disclosure only teaches a set of primers and their associated probes for SARS-CoV-2 and PMMoV, i.e., two distinct primer sets. The claims are clearly not enabled to their full scope. Moreover, claims not containing elements critical or essential to the practice of the invention, such as sequence fragments not having the specific sequence of the defined primers, are not enabled by the disclosure.
For the reasons discussed above, undue experimentation would be required to practice
the claimed invention commensurate with the scope of the claims. Reasonable correlation must exist between the scope of the claims and scope of enablement set forth. It would take undue trials and errors to practice the claimed invention in view of the quantity of experimentation necessary, the limited working examples, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims.
Claim Rejections - 35 USC § 102
14. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
15. Claims 18, 20, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fan, J., et. al., (CN 110902933 A; Published 03/24/2020), hereby Fan.
Claim 18 is drawn to a kit comprised of polyaluminum chloride (PAC) and a solid carrier and its intended use of quantitatively detecting RNA and/or DNA from a virus or bacterium in a sample. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999); Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81; and MPEP § 2111.02.
The preamble purpose of quantitatively detecting RNA and/or DNA is not supported by any structure or material in the kit. Therefore, a prior art reference that teaches PAC and a solid carrier together would anticipate the claim. Fan teaches a wastewater processing method that uses magnetic beads to bind contaminants and PAC as a coagulant (claims 1, 3, and 4), as required in instant claim 18.
It is noted that instant claim 20 and 21 require “a protocol” in the kit. “Instructions”, “manual”, “protocol”, and other forms of printed matter are a physical component of the claimed kit. To be given patentable weight, the printed matter and associated product must be in a functional relationship. A functional relationship can be found where the printed matter performs some function with respect to the product to which it is associated. Where a product merely serves as a support for printed matter, no functional relationship exists. See In re Gulack, 703 F.2d 1381, 1385, 217 USPQ 401, 403-04 (Fed. Cir. 1983) and MPEP § 2111.05. For example, in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864. In light of this case law, the printed matter, i.e., the protocol, as defined in instant claims 20 and 21, is not functionally related to the detection method or kit and, thus, has no patentable weight over the kit taught by Fan. The protocol describing directions to have a final concentration, as defined in instant claim 20, and describing the method according to claim 1, as required in instant claim 21, is printed matter that is not patentable because there is no functional relationship and, therefore, the content is only protect by copyright law. Thus, claims 20 and 21 are also anticipated by Fan.
Claim Rejections - 35 USC § 103
16. 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.
17. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
18. Claims 1, 3, 4, 6, 11, and 14 – 17 are rejected under 35 U.S.C. 103 as being unpatentable over Callahan, H., et. al., (WO 2019/209597 A1; Published 10/31/2019; See European search report dated 01/15/2025), hereby Callahan, in view of Pratt, W. E. and Stevens, J. J. (US 20070187256 A1; Published 08/16/2007), hereby Pratt.
Callahan teaches methods, compositions, and kits for isolating nucleic acids, i.e., any DNA or RNA, from a water, air, soil, or stool sample to detect bacterial or viral infectious agents, (abstract; page 2, lines 4 – 27; page 7, lines 17 – 27; page 31, lines 17 – 20; claims 6 and 46), as disclosed in instant claims 1 and 3. The sample is lysed in a reagent in the range of pH 6 to 12 and simultaneously subjected to aluminum chlorohydrate to release the biomolecules (page 8, lines 21 and 22; page 15, lines 2 – 4; page 19, lines 1 – 11; page 23, lines 17 – 20; claims 52 and 62), as recited in instant claims 1 and 16. The lysate may be directly used or further separated/concentrated using filtration, sedimentation, or centrifugation (page 25, lines 23 – 29; page 29, lines 27 – 30), as required in instant claim 1. It is further taught that proteases can be included in the lysis step (page 17, lines 1 – 3 and 9 – 14), as defined in instant claim 17. Callahan goes on to teach that the treated lysate is in a liquid phase and subsequently used for isolating the nucleic acids, wherein a nucleic acid-binding solid support, including magnetic beads, is employed (page 16, lines 6 – 17; page 31, lines 15 – 26), as disclosed in instant claims 1 and 6. It is further taught that the isolated DNA can be analyzed using PCR, qPCR, and RT-PCR, whereas the isolated RNA can be converted to cDNA using cDNA synthesis or analyzed with RT-PCR (page 35, lines 1 – 8), as required in instant claims 1 and 11.
In essence, Callahan teaches the order of (1) collect sample; (2) lyse with aluminum chlorohydrate and protease present; (3) separate and/or concentrate via filtration; (4) isolate with magnetic beads in a liquid phase; and (5) quantitate with PCR or cDNA synthesis (pages 31 – 35; nucleic acid isolation). However, the order taught by the instant claims is (1) collect sample; (2) concentrate via filtration in the presence of PAC; (3) lyse at a pH of 7 to 8 with a protease present; (4) isolate with magnetic beads in a liquid phase; and (5) quantitate with PCR or cDNA synthesis, then PCR. Callahan and the instant claims only differ in that steps (2) and (3) are switched. The selection of any order of mixing ingredients is prima facie obvious. See Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959); In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); and MPEP § 2144.04.
Callahan does not teach the explicit usage of PAC, as required in instant claims 1, 14, and 15; and the basicity of PAC, as disclosed in instant claim 15.
However, Callahan does teach the usage of aluminum chlorohydrate, as discussed above. It is taught by Pratt that water treatment favors the usage of PAC with a basicity from 50% to 83%, wherein aluminum chlorohydrate is PAC of the highest basicity (page 1, paragraphs 0008 and 0009), as disclosed in instant claims 1, 14, and 15. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). See also In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960) and In re Ryco, Inc. v. Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988). Moreover, it would have been prima facie obvious to a person having ordinary skill in the art to substitute aluminum chlorohydrate for PAC as they are equivalents known for the same purpose. In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958). See also Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980). An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). In light of these case laws, it would have been obvious to a person having ordinary skill in that art to select PAC for its intended purpose, i.e., the treatment of water, as disclosed in instant claims 1 and 14. Also, it would have been obvious to use PAC instead of aluminum chlorohydrate to achieve the basicity of 50 – 70%, as required in instant claim 15.
Callahan and Pratt do not teach the number of PCR cycles, as disclosed in instant claim 4; and the final concentration of the PAC in the sample, as required in instant claim 14. However, the number of PCR cycles and final concentration of PAC is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the number of PCR cycles and final concentration of PAC, needed to achieve the desired results. The principle of law states from MPEP §§ 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). 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," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). In light of this case law, Callahan teaches that the total final concentration of the mixture of a sample and lytic reagent, which can include aluminum chlorohydrate, wherein PAC is an obvious substitution, as outlined above, may be 0.005% to 12% (page 13, lines 20 – 23), as defined in instant claim 14. Also, Callahan teaches that the PCR cycling was performed with 5 cycles and 45 cycles (page 54, lines 2 and 3; page 56, lines 6 and 7), as disclosed in instant claim 4.
Callahan and Pratt are considered to be analogous to the claimed invention because both are drawn to sample treatment with aluminum chlorohydrate. Based on the prior art teachings, it would have been obvious to a person having ordinary skill in the art to use the PAC taught by Pratt for its obvious purpose and as an obvious substitute in a method and/or kit for isolating nucleic acids, i.e., any DNA or RNA, from a water, air, soil, or stool sample to detect bacterial or viral infectious agents, as taught by Callahan. Therefore, it would have been obvious to a person having ordinary skill in the art to have combined the teachings of Callahan and Pratt before the effective filing date of the claimed invention with a reasonable expectation of success to more efficiently treat water (Pratt; page 1, paragraph 0009) and isolate nucleic acids from a complex sample (Callahan; page 1, lines 5 – 7). All the claimed elements were known in the prior art. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415–421, 82 USPQ2d 1385, 1395–97 (2007) and MPEP §§ 2143B and 2143.02.
19. Claims 7 – 9 are rejected under 35 U.S.C. 103 as being unpatentable over Callahan and Pratt, as applied to claims 1, 3, 4, 6, 11, and 14 – 17 above, and further in view of Kitajima, M., et. al., (SARS-CoV-2 in wastewater: State of the knowledge and research needs. The Science of the total environment, 739, 139076; Published 04/30/2020; Cited in Applicant’s IDS on 08/25/2023 as Non-Patent Literature (NPL) Document Cite No. 8), hereby Kitajima.
Callahan and Pratt do not teach that the virus in the sample is an RNA virus, as recited in instant claim 7; a coronavirus, an influenza virus, a norovirus, a sapovirus, an Aichi virus, an adenovirus, an orthopneumovirus, or a polyomavirus, as defined in instant claim 8; and that the coronavirus is SARS-CoV-2, as disclosed in instant claim 9.
However, Kitajima teaches that SARS-CoV-2 belongs to the coronavirus family, which are a group of enveloped viruses with a single-stranded, positive sense RNA genome (page 2, left column, first paragraph), as defined in instant claims 7 – 9. It is further taught that viable SARS-CoV-2 and viral RNA are shed in bodily excrement, including saliva, sputum, and feces, and subsequently disposed of in wastewater (page 2, right column, second paragraph). Kitajima goes on to teach that wastewater can be used as a potential source of epidemiological data (page 2, right column, second paragraph).
Callahan, Pratt, and Kitajima are considered to be analogous to the claimed invention because all are drawn to water treatment, wherein Callahan and Kitajima are specifically drawn to isolating viral genetic material. Based on the prior art teachings, it would have been obvious to a person having ordinary skill in the art to use the PAC taught by Pratt for its obvious purpose and as an obvious substitute in a method and/or kit for isolating nucleic acids, i.e., any DNA or RNA, from a water, air, soil, or stool sample to detect bacterial or viral infectious agents, as taught by Callahan, to isolated SARS-CoV-2 RNA from a water sample, as taught by Kitajima. Therefore, it would have been obvious to a person having ordinary skill in the art to have combined the teachings of Callahan, Pratt, and Kitajima before the effective filing date of the claimed invention with a reasonable expectation of success to strengthen our understanding on the occurrence, persistence, and potential public health risks associated with SARS-CoV-2 in wastewater (Kitajima; page 2, right column, second paragraph). All the claimed elements were known in the prior art. Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415–421, 82 USPQ2d 1385, 1395–97 (2007) and MPEP §§ 2143F and 2143.02.
20. Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Fan, as applied to claims 18, 20, and 21 above, and further in view of Hawkins, T., (US 5705628; Published 01/06/1998), hereby Hawkins.
Fan does not teach that the solid carrier is carboxyl-group modified paramagnetic beads, as required in instant claim 19.
However, Hawkins teaches a method of separating nucleic acids from a solution by binding them to a solid surface, wherein the surface is a magnetic microparticle coated with a functional group, including a carboxyl-group coated magnetic bead (column 1, lines 24 – 29; column 2, lines 61 – 64; column 3, lines 28 – 43), as disclosed in instant claim 19. It would have been prima facie obvious to a person having ordinary skill in the art to substitute the solid carrier taught by Fan with the carboxyl-group coated magnetic beads of Hawkins as they are equivalents known for the same purpose. In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958). See also Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980). An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
Fan and Hawkins are considered to be analogous to the claimed invention because both are drawn magnetic bead separation of samples. Based on the prior art teachings, it would have been obvious to a person having ordinary skill in the art to use the carboxyl-modified magnetic beads taught by Hawkins as an obvious substitute for the magnetic bead taught by Fan. Therefore, it would have been obvious to a person having ordinary skill in the art to have combined the teachings of Fan and Hawkins before the effective filing date of the claimed invention with a reasonable expectation of success to allow for rapid throughput in isolating nucleic acids that is low cost, simple to perform, and produces high yields (Hawkins; column 2, lines 6 – 10). All the claimed elements were known in the prior art. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415–421, 82 USPQ2d 1385, 1395–97 (2007) and MPEP §§ 2143B and 2143.02.
Conclusion
21. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Shirasaki, N., et. al., (Improved virus removal by high-basicity polyaluminum coagulants compared to commercially available aluminum-based coagulants. Water research, 48, 375–386; Published 10/09/2013; Cited in Applicant’s IDS on 08/25/2023 as NPL Document Cite No. 12) teaches that an increase in PAC basicity improves virus removal efficiency from river water samples.
22. Claims 1, 3, 4, 6 – 9, 11, and 14 – 21 are rejected. No claims are allowed.
23. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Hallie N. Pennington, Ph.D. whose telephone number is (571)272-6781. The examiner can normally be reached M-Th 7:30-5:30 ET.
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/HALLIE N. PENNINGTON, PH.D./Examiner, Art Unit 1671
/Shanon A. Foley/Primary Examiner, Art Unit 1671