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 .
Election/Restrictions
Applicant’s election without traverse of Group I and the species of i) the nanostructured metal comprises a plurality of metal particles, ii) the virus is a coronavirus, and iii) the first portion of the target virus is a surface protein in the reply filed on 7/6/2026 is acknowledged.
Claim Objections
Claim 21 is objected to because of the following informalities: Claim 21 should recite “adjacent to the capture portion”. Appropriate correction is required.
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.
Claim 1 is 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 1 recites “wherein the surface of the nanostructured metal is configured to enhance a Raman signal of at least a second portion of the target virus bound to the capture portion of one or more of the first plurality of peptides”.
It is not clear what is meant by “configured to enhance a Raman signal of at least a second portion of the target virus”. How is the surface configured such that a Raman signal of at least a second portion of the target virus bound to the capture portion is enhanced? The specification does not describe such a configuration or process to configure the surface of the nanostructured metal to enhance a Raman signal.
Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
This rejection also affects all claims depending from claim 1.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 6, 9, 12, 19-21, 30-31, 38-39 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (U.S. Patent Application No. 2006/0252065; published 11/9/2006; cited by applicant), and further in view of Tadepalli et al. (Scientific Reports, 2015, 5:16206).
The instant claims are directed to an assay for detection of a target virus via Surface Enhanced Raman Spectroscopy (SERS), the assay comprising:
a peptide-modified nanostructured metal comprising a nanostructured metal having a first plurality of peptides attached to a surface thereof,
wherein each of the first plurality of peptides comprises a capture portion configured to capture and selectively bind with at least a first portion of the target virus,
wherein the capture portion of each of the first plurality of peptides has an average length of from 3 to 60 amino acids, and
wherein the surface of the nanostructured metal is configured to enhance a Raman signal of at least a second portion of the target virus bound to the capture portion of one or more of the first plurality of peptides.
In view of the 112(b) rejection above and for purposes of examination, the limitation “wherein the surface of the nanostructured metal is configured to enhance a Raman signal of at least a second portion of the target virus bound to the capture portion of one or more of the first plurality of peptides” is interpreted as meaning that there is a change in Raman signal when the analyte is bound by the peptide conjugated nanorod.
Zhao et al. teaches an assay for detection of a target virus via Surface Enhanced Raman Spectroscopy (SERS). The assay comprises a peptide-modified nanostructured metal comprising a nanostructured metal having a first plurality of peptides attached to a surface thereof. Paragraph [0008] teaches a SERS system comprising an array of nanostructures (e.g., nanorods) with one or more binding agents disposed on one or more of the nanorods, where the binding agent has an affinity for an analyte of interest.
Zhao et al. teaches that the binding agent is “generally a biomolecule (as defined above), such as, a polynucleotide, polypeptide, carbohydrate, lipid, or the like” (see paragraph [0069]). Zhao et al. defines a biomolecule as deoxyribonucleic acid (DNA), ribonucleic acid (RNA), nucleotides, oligonucleotides, nucleosides, proteins, peptides, polypeptides, selenoproteins, antibodies, protein complexes, combinations thereof, and the like (see paragraph [0033]). The nanostructure, which can be a nanorod, can be made of metal such as silver, nickel, aluminum, silicon, gold, platinum, palladium, titanium, copper, cobalt, zinc, other transition metals (see paragraph [0043]). The analyte of interest is a biomolecule such as a virus, bacterium, or other pathogen (see paragraph [0008]).
Zhao et al. also teaches that the surface of the nanostructured metal is configured to enhance a Raman signal of at least a second portion of the target virus bound to the capture portion of one or more of the first plurality of peptides (Figure 12, see item "RSV+antibody", change in signal is reasonably understood as an enhanced signal to detect binding).
Lastly, Zhao et al. teaches a method of detecting an analyte of interest (e.g., a biomolecule) in a sample, includes attaching at least one first biomolecule to an array of nanorods on a substrate, measuring a SERS spectrum, exposing the substrate including the first biomolecule to the sample containing the analyte of interest (e.g., a second biomolecule), and measuring a second SERS spectrum. Association of the first biomolecule with the second biomolecule can be detected because the SERS spectrum of the array of nanorods and first biomolecule is detectably different than the SERS spectrum of the array of nanorods, first biomolecule, and the second biomolecule (see paragraph [0009]).
While Zhao et al. teaches that peptides, which bind the analyte of interest, can be immobilized on the nanostructure, Zhao et al. does not teach that the binding portion of the peptides is from 3 to 60 amino acids in length.
Tadepalli et al. teaches the use of metal nanorods (e.g. gold nanorods) conjugated with the human troponin I (TnI) binding peptide FYSHSFHENWPS to detect cardiac biomarker troponin I (cTnI). Tadepalli et al. teaches that short peptides as biorecognition elements (BRE) compared to larger antibodies as target capture agents offer several advantages. The smaller sized peptide provides higher sensitivity and a lower detection limit. Furthermore, the excellent shelf-life and thermal stability of peptide-based localized surface plasmon resonance (LSPR) sensors, which precludes the need for special storage conditions, makes it ideal for use in resource-limited settings (see, for example, the abstract and page 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use short peptides (e.g., 12 amino acids in length as taught by Tadepalli et al.) as the analyte-binding peptide that can be conjugated to the nanorod of Zhao et al. for detecting a virus. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Zhao et al. [peptides can be used] and given the teachings and findings of Tadepalli et al. [smaller sized peptide provides higher sensitivity and a lower detection limit].
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
For claims 3 and 6, Zhao et al. teaches that the nanostructure, which can be a nanorod, can be made of metal such as silver, nickel, aluminum, silicon, gold, platinum, palladium, titanium, copper, cobalt, zinc, other transition metals (see paragraph [0043]).
For claim 9, Zhao et al. teaches a method of making a SERS sensor comprising providing a substrate (e.g., a planar or a non-planar substrate), rotating the substrate in a polar direction relative to a vapor arrival line of a vapor flux of a material to achieve a desired incident angle between the vapor arrival line and the substrate, optionally rotating the substrate azimuthally, and exposing at least a portion of a surface of the substrate to the vapor flux of a material at the desired incident angle to form an array of nanostructures (e.g., nanorods) on the surface of the substrate. Then, one or more binding agents (e.g., first biomolecules) having an affinity for an analyte of interest (e.g., a second biomolecule) are disposed on the surface of one or more of the nanostructures (see paragraphs [0010] and [0045]).
For claim 12, Zhao et al. teaches that one or more binding agents having an affinity for an analyte of interest are disposed on the surface of one or more of the nanostructures (see paragraphs [0008] and [0010]). Thus, the binding agent can be, for example, two different peptides (e.g., ligands) attached to the nanorod.
For claims 19 and 20, Zhao et al. teaches that in a preferred aspect, the biomolecule is a virus, including, but not limited to, RNA and DNA viruses. In addition, the biomolecule may include additional viruses including, but not limited to, an astrovirideae, a calivirideae, a herpes virus, a picomaviridea, a poxuvirideae, a reovirideae, a togavirideae, an avian influenza virus, a polyomavirus, an adenovirus, a rhinovirus, a Bunyavirus, a Lassa fever virus, an Ebola virus, a coronavirus, an arenavirus, a Filovirus, a rhabdovirus, an alphavirus, a flavivirus, Epstein-Barr Virus (EBV), and viruses of agricultural relevance such as the Tomato Spotted Wilt Virus (see paragraph [0034]).
For claim 21, Zhao et al. teaches that the nanorods can be functionalized by immobilizing the binding agent on the nanorod surface by annealing to the metal (e.g., Ag or Au) surface of the nanorod via a linking agent (see paragraph [0069]).
For claims 30 and 31, Zhao et al. teaches the detection of RSV using Ag nanorod-based SERS that bind to the RSV glycoprotein. Zhao et al. also teaches that the biomolecule can be, inter alia, a glycoprotein (see paragraphs [0112] and [0115] and see claims 6 and 24). Based on the teachings of Zhao et al., it would obvious for one of ordinary skill in the art to detect viral surface proteins, e.g., glycoproteins, in the assay of Zhao et al.
For claim 38, Zhao et al. teaches that “peptides” in general can be used as the binding agent. Zhao et al. teaches that the phrase "peptides", "polypeptide", or "protein" is intended to encompass a protein, a glycoprotein, a polypeptide, a peptide, fragments thereof and the like, whether isolated from nature, of viral, bacterial, plant, or animal (e.g., mammalian, such as human) origin, or synthetic, and fragments thereof. Biomimetic peptides are synthetic peptides that mimic/imitate a natural peptide. Thus, Zhao et al.’s definition of “peptides” reads on biomimetic (synthetic) peptides as well.
For claim 39, Zhao et al. teaches that the binding agent can be attached/coupled to a surface of the nanostructure using conventional linking chemistry (e.g., biologically (e.g., hybridization) and/or chemically (e.g., ionically or covalently)) (see paragraph [0069]).
For claim 44, Zhao et al. teaches one or more binding agents having an affinity for an analyte of interest are disposed on the surface of one or more of the nanostructures. The term “surface” is interpreted to mean the entire surface as there is no teaching otherwise. Accordingly, it is obvious and well within the purview of one of ordinary skill in the art to coat the entire surface (substantially homogenous) or a portion of the surface with the binding agent depending on the desired outcome.
Claims 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (U.S. Patent Application No. 2006/0252065; published 11/9/2006) and Tadepalli et al. (Scientific Reports, 2015, 5:16206) as applied to claims 1, 3, 6, 9, 12, 19-21, 30-31, 38-39 and 44 above, and further in view of Kannan et al. (WO 2016/205515; published 12/22/2016).
The teachings of Zhao et al. and Tadepalli et al. are outlined above and incorporated herein. While Zhao et al. teaches that the nanorods can be functionalized by immobilizing the binding agent on the nanorod surface by annealing to the metal (e.g., Ag or Au) surface of the nanorod via a linking agent, Zhao et al. does not teach the limitations of claim 22-24. However, Kannan et al. teaches the use of a gold nanorod conjugated with a peptide which selectively binds c-MET (HGF) receptor for detecting cMET receptors on cells expressing the receptor (see paragraphs [0009] to [0013] and [0018]). The peptide is linked to the nanorod via a linker comprising thioctic acid-disulate attached to polylysine comprising several lysine residues or a linker comprising a thiol group and ethylene glycol. Various ethylene glycols are suitable, including monoethylene glycol, diethylene glycol, and polyethylene glycol (see paragraphs [0031] to [0035]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use known linkers, such as the linkers taught by Kannan et al. as the linking agent of Zhao et al. and the result would be predictable [linking the peptide to the nanorod such that the capture portion of the peptide is away from the surface of the nanorod].
As for claim 24, the linkers taught by Kannan et al. were sufficient to space the capture portion of the peptide away from the surface of the nanorod. Thus, determining other linker lengths is routine experimentation. Furthermore, according to section 2144.05 of the MPEP, “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“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.”) Lastly, applicant has not demonstrated unexpected or superior results using a spacer/linker with an average length of 1 nm to 10 nm.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
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/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
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