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 .
Drawings
The drawings were received on 20 February 2024. These drawings are acceptable.
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.
Standard for Obviousness.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Attention is directed to In re Jung, 98 USPQ2d 1174, 1178 (Fed. Cir. 2011) wherein is stated:
There has never been a requirement for an examiner to make an on-the-record claim construction of every term in every rejected claim and to explain every possible difference between the prior art and the claimed invention in order to make out a prima facie rejection. This court declines to create such a burdensome and unnecessary requirement. “[Section 132] does not mandate that in order to establish prima facie anticipation, the PTO must explicitly preempt every possible response to a section 102 rejection. Section 132 merely ensures that an applicant at least be informed of the broad statutory basis for the rejection of his claims, so that he may determine what the issues are on which he can or should produce evidence.” Chester, 906 F.2d at 1578 (internal citation omitted). As discussed above, all that is required of the office to meet its prima facie burden of production is to set forth the statutory basis of the rejection and the reference or references relied upon in a sufficiently articulate and informative manner as to meet the notice requirement of § 132. As the statute itself instructs, the examiner must “notify the applicant,” “stating the reasons for such rejection,” “together with such information and references as may be useful in judging the propriety of continuing prosecution of his application.” 35 U.S.C. § 132.
Attention is directed to the decision in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007):
When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill in the art has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
It is further noted that prior art is not limited to the four corners of the documentary prior art being applied. Prior art includes both the specialized understanding of one of ordinary skill in the art, and the common understanding of the layman. It includes “background knowledge possessed by a person having ordinary skill in the art. . . [A] court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1396.
Suggestion, teaching or motivation does not have to be explicit and “may be found in any number of sources, including common knowledge, the prior art as a whole or the nature of the problem itself’” Pfizer, Inc. v. Apotex, Inc. 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007) citing Dystar Textilfarben GMBH v. C. H. Patrick Co., 464 F.3d 1356 (Fed. Cir. 2006).
Holding and Rationale
Claim(s) 1-2, 4, 6-8, 10, 15-20, 24-27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Credle et al. (“Multiplexed analysis of fixed tissue RNA using Ligation in situ Hybridization”, Nucleic Acids Research, Vol. 45, No. 14, pages 1-9, 2017) in view of Park et al. (“Detection of Hepatitis C Virus RNA Using Ligation-Dependent Polymerase Chain Reaction in Formalin-Fixed, Paraffin-Embedded Liver Tissues”, American journal of Pathology, Vol. 149, No. 5, pages 1485-1491, November 1996), US 2019/0071661 A1 (Marshall et al.), Wang et al., “Multiplexed PCR-Free Detection of MicroRNAs in Single Cancer Cells Using a DNA-Barcoded Microtrough Array Chip”, Micromachines, 10, pages 1-11, 2019), US 2015/03444942 A1 (Frisen et al.), and Pringle et al. (“In situ hybridization demonstration of poly-adenylated RNA sequences in formalin-fixed paraffin sections using a biotinylated oligonucleotide poly d(T) probe”, Journal of Pathology, Vol. 158, pp. 279-286, 1989).
Credle et al., teach of “Multiplexed analysis of fixed tissue RNA using Ligation in situ Hybridization”. As disclosed therein at page 1, in the abstract:
Clinical tissues are prepared for histological analysis and long-term storage via formalin fixation and paraffin embedding (FFPE). The FFPE process results in fragmentation and chemical modification of RNA, rendering it less suitable for analysis by techniques that rely on reverse transcription (RT) such as RT-qPCR and RNA-Seq. Here we describe
a broadly applicable technique called ‘Ligation in situ Hybridization’ (‘LISH’), which is an alternative methodology for the analysis of FFPE RNA. LISH utilizes the T4 RNA Ligase 2 to efficiently join adjacent chimeric RNA–DNA probe pairs hybridized in situ on fixed RNA target sequences. Subsequent treatment with RNase H releases RNA-templated ligation products into solution for downstream analysis. We demonstrate several unique advantages of LISH-based assays using patient-derived FFPE tissue. These include >100-plex capability, compatibility with common histochemical stains and suitability for analysis of decade-old materials and exceedingly small microdissected tissue fragments. High-throughput DNA sequencing modalities, including single molecule sequencing, can be used to analyze ligation products from complex panels of
LISH probes (‘LISH-seq’), which can be amplified efficiently and with negligible bias. (Emphasis added)
Credle et al., at page 2, left column, last paragraph, ridging to right column, teach:
Tissues were fixed in formalin for at least 48 h prior to dehydration and paraffin wax embedding. 10 µm thick sections were prepared using RNase-free precautions for standard (Plus slides; Thermo Fisher Waltham, MA) and laser capture microdissection (LCM) (Leica PEN-membrane) slides. FFPE blocks and sections were stored in desiccant; blocks were stored at room temperature and sections were stored at −20◦C. (Emphasis added)
The above showing is deemed to fairly suggest limitations of independent claim 1, as well as that of dependent claims 2, 4, 6-8, 10, 15-20, 24-27, and 29.
The aspect of using tissue sections having a thickness of 10 µm is deemed to fairly suggest limitations of claims 1, 6, 11, 12, 13, 16, 19, 20, and 25-27.
Credle et al., at page 2, right column, teaches:
LISH on Plus slides. Sections deposited on Plus slides were baked at 60◦C for 1 h and deparaffinized by incubating 2× for 30 min in 95◦C Trilogy buffer (Cell Marque,
Rocklin, CA, USA). (Emphasis added)
Credle et al., at page 2, right column, last paragraph, teaches that the tissue “sections were incubated with pre-warmed (37◦C) pepsin”. Such is deemed to fairly suggest limitations of claims 2, 6 and 7.
Credle et al., in the caption to Figure 1, teaches:
Workflow of the LISH assay. Step 1. Hybridization of pairs of chimeric 3’-diribonucleotide-containing and 5’-phosphorylated DNA probes on formalin fixed RNA within a tissue section. Step 2. Adjacently annealed probe pairs are then ligated in situ with Rnl2. Step 3. RNase H treatment (i) releases RNA-templated ligation products into solution for downstream analysis and (ii) destroys unwanted DNA-templated ligation products. (Emphasis added)
Park et al., disclose “Detection of Hepatitis C Virus RNA Using Ligation-Dependent Polymerase Chain Reaction in Formalin-Fixed, Paraffin-Embedded Liver Tissues”. (emphasis added)
Park et al., in the abstract, disclose:
[W]e applied the ligation-dependent PCR (LD~PCR) for the detection of HCV RNA in FFPE liver tissue. This method uses two capture probes for RNA isolation and two hemiprobes for the subsequent PCR. Despite cross-links, the capture probes and the hemiprobes a.re able to form hybrids with HCV RNAs released from the FFPE tissue. The hybrids a.re isolated through binding of the capture probes to paramagnetic beads. (emphasis added)
Park et al., at page 1486, in Figure 1, disclose:
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Park et al., at page 1486, right column, last paragraph, teach:
FFPE specimens (approximately 2 to 4 cm2 ) were sectioned on a microtome with a disposable blade to 10 µm in thickness, and each section was placed in a 1.5-ml microcentrifuge tube. To avoid cross-contamination, the blades were changed and the holder was cleaned with a 10% sodium hypochlorite solution between each sample. The sections were deparaffinized by incubating at 60°C for 10 minutes in the presence of 1 ml of xylene (Sigma Chemical Co., St. Louis, MO). (Emphasis added)
Park et al., at page 1490, left column, caption to Figure 3, teach:
Hybridization of hemiprobes and ligation are not interfered with by protein-RNA cross-links.
Park et al., at page 1490, right column, first paragraph, teach:
The target-specific assembly of amplifiable DNA from nonamplifiable probes by ligation significantly increases assay specificity, as the 5' end of one hemiprobe must align perfectly with the 3' end of the other hemiprobe on a target DNA or RNA for ligation to occur. This stringent requirement makes detection of a single nucleotide mutation possible. Thus, the combination of multiplex LD-PCR with target-specific ligation will greatly expand the use of PCR in pathological diagnosis, such as detection of multiple mutations in the p53 gene. Finally, as LDPCR bypasses the primer extension step, it would significantly increase the sensitivity of in situ PCR amplification for which cross-linking is necessary to prevent diffusion of the PCR product. (Emphasis added)
Neither Credle et al., nor Park et al., have been found to teach heating the tissue section for a period recited in claim 4, and which would cause “de-crosslinking one or more formaldehyde crosslinks in the 5-20 µm thick FFPE (claim 1).
Marshall et al., in paragraph [0072], teach:
In some embodiments of aspects provided herein, said sample preparation procedure comprises, prior to said applying of said electric field, removing embedding material by incubating said tissue sample in said fluidic device at a temperature of at least about 37° C. for a duration of at least about 1 minute. In some embodiments of aspects provided herein, said temperature is from about 40° C. to about 80° C. In some embodiments of aspects provided herein, said duration is from about 1 minute to about 120 minutes. (Emphasis added)
It is noted that the temperatures and time spent heating the tissue sample broadly encompass that recited in dependent claim 4, and which are to cause “de-crosslinking one or more formaldehyde crosslinks” (claim 1). While Marshall et al., do not teach that such heating would cause “de-crosslinking one or more formaldehyde crosslinks”, a compound and its properties are inseparable. Given such, the aspect of heating the tissue sample for such a period and at such temperatures would also have the effect of “de-crosslinking one or more formaldehyde crosslinks”.
Wang et al., in the abstract, teach:
Here, we report on an in situ hybridization barcoding workflow implemented in a sub-nanoliter microtrough array chip for high-throughput and multiplexed microRNA detection at the single cell level. The microtroughs are used to encapsulate single cells that are fixed, permeabilized, and pre-incubated with microRNA detection probes, each of which consists of a capture strand complementary to specific microRNA and a unique reporter strand that can be photocleaved in the microtroughs and subsequently detected by an array of DNA barcodes patterned on the bottom of the microtroughs. (Emphasis added)
Wang et al., at page 2, teach use of DNA barcode microarrays. As disclosed therein:
2.1. Fabrication of Flow Patterning Device for Creating DNA Barcode Microarrays
DNA barcode array slides were fabricated in-house using a flow patterning technology we reported previously [21–26].
Wang et al., at page 5, Figure 1, teaches:
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Wang et al., at page 9, teaches:
In summary, we have developed a new biochemical workflow implemented in a microtrough array chip for single-cell multiplexed microRNA measurement. Recent advances [13,14,45] in the field of single-cell microRNA and mRNA sequencing have demonstrated the potential to co-sequence both small and large RNAs in same single cells and to identify novel regulatory mechanisms underlying the development of human cancers. Upon the discovery of the key miRNAs involved in such mechanisms, how to reduce the measurement to a targeted miRNA panel but with high throughput is important for translational development of single-cell miRNA assays for clinical
applications. Our technology bridges the gap with the ability to multiplex to a dozen and potentially tens of miRNA markers and the throughput required to measure ~1000 or more single cells in parallel, providing a new path toward miRNA-based detection and monitoring of complex human diseases. (Emphasis added)
While Wang et al., do teach using an array of probes and that they may comprise a barcode sequence, they have not been found to teach that the probes also comprise a poly-(T) capture sequence.
Frisen et al., at paragraph [0082], teach:
The data from the further analyses may be correlated to images of the tissue sample by, e.g. so-called barcode sequences (or ID tags, defined herein as positional domains) incorporated into the arrayed nucleic acid probes. (Emphasis added)
Frisen et al., at paragraph [0142], teach:
[0142] The capture probe may also be synthesised on the substrate using polymerase extension (similarly to as described above) and a terminal transferase enzyme to add a “tail” which may constitute the capture domain. This is described further in Example 5 below. The use of terminal transferases to add nucleotide sequences to the end of an oligonucleotide is known in the art, e.g. to introduce a homopolymeric tail, e.g. a poly-T tail. Accordingly, in such a synthesis an oligonucleotide that corresponds to the universal domain of the capture probe may be contacted with the substrate and allowed to hybridize to the complementary domain of the surface probes. Excess oligonucleotides may be removed by washing the substrate under standard hybridization conditions. The resultant substrate comprises partially single stranded probes, wherein the 3′ ends of the surface probes are double stranded and the complementary positional domain is single stranded. The substrate may be treated with a polymerase enzyme to extend the 3′ end of the universal domain oligonucleotide, in a template dependent manner, so as to synthesize the positional domain of the capture probe. The capture domain, e.g. comprising a poly-T sequence, may then be introduced using a terminal transferase to add a poly-T tail to the positional domain to generate the capture probe. (Emphasis added)
Frisen et al., at paragraph [0313], teach:
[0313] Thus, in one embodiment the invention provides an object substrate for use in the localised or spatial detection of RNA in a tissue sample, comprising a planar substrate on which one or more species of capture probe, comprising a capture domain, is directly or indirectly immobilized such that each probe is oriented to have a free 3′ end to enable said probe to function as a reverse transcriptase (RT) primer wherein the probes are immobilised on the object substrate with a homogeneous distribution and wherein the capture probe is selected from an oligonucleotide comprising a poly-T, poly-U and/or random oligonucleotide sequence. (Emphasis added)
In view of the teachings of Frisen et al., it would have been obvious to one of ordinary skill in the art at the time of the invention to have modified the array of probes of Wang et al., whereby the barcode, which is used to identify location (applicant’s “spatial” feature) is paired with a poly-(T) sequence, which can serve as a capture probe for the polyA tail of mRNA. As disclosed by Frisen et al., “the probes are capable of hybridizing to (i.e. capturing) all mRNA, i.e. RNA molecules with a polyA tail” (paragraph [073]).
The ordinary artisan would have been motivated to have combined the barcode with the poly-(T) RNA capture sequence for as disclosed by Frisen et al, at paragraph [0082]:
The data from the further analyses may be correlated to images of the tissue sample by, e.g. so-called barcode sequences (or ID tags, defined herein as positional domains) incorporated into the arrayed nucleic acid probes. (Emphasis added)
The above showing is deemed to fairly suggest yet another limitation of independent claim 1.
Pringle et al., in their abstract, teach:
An in situ hybridization technique has been developed for assessing poly(A)+ RNA preservation in routine pathology specimens. The method detects poly-adenylated RNA sequences in tissue sections using a biotinylated polydeoxythymidine (poly d(T)) probe… (Emphasis added)
The results have confirmed that the method is specific for poly(A)+ RNA and shows that poly(A)+ RNA can be demonstrated in routine formalin-fixed sections using non-radioactive techniques with retention of morphology. It also provides a means of optimizing the hybridization conditions for specific mRNA probes and produces a staining pattern demonstrating the relative level of poly(A)+ RNA per cell which may reveal new information about cell activity and tissue function.
Pringle et all, at page 280, left column, teach:
We have developed a method which demonstrates the presence of poly-adenylated sequences in routine paraffin sections using a biotinylated poly d(T) probe, which is detected using a sensitive avidin-biotin (AB) method based upon alkaline phosphatase.
Pringle et al., at page 280, right column, teaches the procedure used. As stated therein:
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It is noted that the aspect of heating the tissue section for 10 minutes at 70°C fairly encompasses an embodiment of dependent claim 4.
Pringle et all, at page 281, left column, teach:
Sections were then digested in nuclease-free proteinase K (Boehringer Mannheim, F.R.G. 161519) solutions in 0·05 M Tris, pH 7 ·65, at concentrations ranging from 0· l to 100 μg/ml either in sterilized Coplin jars or by covering the sections with proteinase K solutions (200 μl) and incubating in a humid chamber. Proteinase K digestions were
incubated at 37°C for 1 h. (Emphasis added)
The aspect of using proteinase K is deemed to fairly suggest limitations of claims 1, 2, 6 and 7.
The aspect of using tissue sections having a thickness of 4-5 µm is deemed to fairly suggest limitations of claims 1, 6, 11, 12, 13, 16, 19, 20, and 25-27.
In view of the well-developed state of the art and the detailed teachings of Credle et al., Park et al., Wang et al., and Pringle et al., it would have been quite obvious to one of ordinary skill in the art to have utilized a step of “de-crosslinking a 5-20 µm thick formalin-fixed paraffin embedded (FFPE) tissue section for determining a location of an RNA in the 5-20 µm thick FFPE tissue section” as the aspect of preparing tissue sections of such thickness and having been de-crosslinked via the use of the enzyme proteinase K, as well as the aspects of using an array on the substrate, were all well-known and well developed. In view of such well-developed status of the art, said ordinary artisan would have had a most reasonable expectation for success.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-2, 4, 6-8, 10, 15-20, 24-27, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Credle et al. (“Multiplexed analysis of fixed tissue RNA using Ligation in situ Hybridization”, Nucleic Acids Research, Vol. 45, No. 14, pages 1-9, 2017) in view of Park et al. (“Detection of Hepatitis C Virus RNA Using Ligation-Dependent Polymerase Chain Reaction in Formalin-Fixed, Paraffin-Embedded Liver Tissues”, American journal of Pathology, Vol. 149, No. 5, pages 1485-1491, November 1996), US 2019/0071661 A1 (Marshall et al.), Wang et al., “Multiplexed PCR-Free Detection of MicroRNAs in Single Cancer Cells Using a DNA-Barcoded Microtrough Array Chip”, Micromachines, 10, pages 1-11, 2019), US 2015/03444942 A1 (Frisen et al.), and Pringle et al. (“In situ hybridization demonstration of poly-adenylated RNA sequences in formalin-fixed paraffin sections using a biotinylated oligonucleotide poly d(T) probe”, Journal of Pathology, Vol. 158, pp. 279-286, 1989).
Claim(s) 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Credle et al. (“Multiplexed analysis of fixed tissue RNA using Ligation in situ Hybridization”, Nucleic Acids Research, Vol. 45, No. 14, pages 1-9, 2017) in view of Park et al. (“Detection of Hepatitis C Virus RNA Using Ligation-Dependent Polymerase Chain Reaction in Formalin-Fixed, Paraffin-Embedded Liver Tissues”, American journal of Pathology, Vol. 149, No. 5, pages 1485-1491, November 1996), US 2019/0071661 A1 (Marshall et al.), Wang et al., “Multiplexed PCR-Free Detection of MicroRNAs in Single Cancer Cells Using a DNA-Barcoded Microtrough Array Chip”, Micromachines, 10, pages 1-11, 2019), US 2015/03444942 A1 (Frisen et al.), and Pringle et al. (“In situ hybridization demonstration of poly-adenylated RNA sequences in formalin-fixed paraffin sections using a biotinylated oligonucleotide poly d(T) probe”, Journal of Pathology, Vol. 158, pp. 279-286, 1989) as applied to claims 1-2, 4, 6-8, 10, 15-20, 24-27, and 29 above, and further in view of Xu et al., “Isothermal amplification detection of miRNA based on the catalysis of nucleases and voltametric characteristics of silver nanoparticles”, Molecular BioSystems, Vol. 12, No. 12, pages 3550-3555, 2016.
See above for the basis of the rejections as it relates to the teachings of teachings of Credle et al., Park et al., Marshall et al., Wang et al., Frisen et al., and Pringle et al.
Neither Credle et al., Park et al., Marshall et al., Wang et al., Frisen et al., nor Pringle et al., have been found to teach the use of an exonuclease, including RecJf exonuclease.
Xu et al., teach of “Isothermal amplification detection of miRNA based on the catalysis of nucleases and voltametric characteristics of silver nanoparticles”. As stated in their abstract:
MiRNAs are a fascinating kind of biomolecule due to their vital functions in gene regulation and potential value as biomarkers for serious diseases including cancers. Exploiting convenient and sensitive methods for miRNA expression assays is imperative. In this study, we employ an exonuclease (RecJf) and a nicking endonuclease (Nt.BbvCI) to catalyse isothermal reactions for the amplified detection of miRNA. (Emphasis added)
Xu et al., at page 3550, right column, last paragraph, teach:
In this work, a simple enzymatic amplification-based sensing strategy is developed for the detection of miRNA.
Xu et al., at page 3551, left column, first paragraph, teach:
RecJf exonuclease and Nt.BbvCI were purchased from New England Biolabs Ltd (Beijing, China).
Xu et al., at page 3551, left column, third paragraph, teach:
RecJf catalysed digestion of DNA1
miRNA standard solutions with a series of concentrations were firstly prepared. The solutions were then blended with DNA1 and RecJf exonuclease (50 mM NaCl, 10 mM Tris–HCl, 10 mM MgCl2, 1 mM DTT, pH 7.9) at 37 1C for 1 h. The concentrations
of DNA1 and RecJf exonuclease were 2 µM and 1 unit µL-1, respectively.
Xu et al., at page 3551, right column, fourth paragraph, teach:
RecJf exonuclease is a single-stranded DNA specific exonuclease that catalyses the removal of deoxynucleotide monophosphates from 5’ to 3’. In the absence of miRNA,
single-stranded DNA1 is digested. However, after the partial hybridization of DNA1 and the target miRNA, the resulting DNA/RNA hybrid resists the exonuclease reaction.
In view of the teachings of Xu et al., it would have been quite obvious to one of ordinary skill in the art to include the use of an exonuclease such as RecJf in the in situ hybridization assay disclosed by Credle et al., Park et al., Wang et al., Frisen et al., and Pringle et al.
As noted above, Xu et al., teaches that the use of such an exonuclease is “simple” and the reagents is also commercially available. Given such, one would have been well motivated to include such a step in their assay and would have also had a most reasonable expectation for success.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Credle et al. (“Multiplexed analysis of fixed tissue RNA using Ligation in situ Hybridization”, Nucleic Acids Research, Vol. 45, No. 14, pages 1-9, 2017) in view of Park et al. (“Detection of Hepatitis C Virus RNA Using Ligation-Dependent Polymerase Chain Reaction in Formalin-Fixed, Paraffin-Embedded Liver Tissues”, American journal of Pathology, Vol. 149, No. 5, pages 1485-1491, November 1996), US 2019/0071661 A1 (Marshall et al.), Wang et al., “Multiplexed PCR-Free Detection of MicroRNAs in Single Cancer Cells Using a DNA-Barcoded Microtrough Array Chip”, Micromachines, 10, pages 1-11, 2019), US 2015/0344942 A1 (Frisen et al.), and Pringle et al. (“In situ hybridization demonstration of poly-adenylated RNA sequences in formalin-fixed paraffin sections using a biotinylated oligonucleotide poly d(T) probe”, Journal of Pathology, Vol. 158, pp. 279-286, 1989) as applied to claims 1-2, 6-8, 10, 15-20, 24-27, and 29-30 above, and further in view of Xu et al., “Isothermal amplification detection of miRNA based on the catalysis of nucleases and voltametric characteristics of silver nanoparticles”, Molecular BioSystems, Vol. 12, No. 12, pages 3550-3555, 2016.
Response to argument
At page 6 of the response of 19 November 2025 applicant’s representative asserts:
Without agreeing with any of the present bases of rejection, Applicant has amended claims 1, 8, 11, 12, 16, and 17 with support found throughout the specification as filed. Claim 30 is cancelled without prejudice or disclaimer.
The amendment to the claims has been considered and an additional piece of prior art has been cited. In view of the above analysis and in the absence of convincing evidence to the contrary, the claims are rejected under 35 USC 103(a).
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM..
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682
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