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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The earliest potential effective filing date of the claimed inventions is 06-04-2020 based on the filing date of foreign application ATA 50486/2020.
Status of Claims
Claims 1-20 are pending and examined on their merits.
Information Disclosure Statement
The Information Disclosure Statement filed 12-01-2022 is acknowledged and has been considered.
Claim Objections
Claim 20 is objected to because it attempts to recite a Markush group using the phrase “being one of”. Please amend the claim to read “a solid phase selected from the group consisting of a plate, beads, a graphene surface, and a semiconducting surface” or similar wording as applicant sees fit to put the claim in proper Markush group form.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4, 10, 17-18, and 20 are 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.
The phrases "such as" and “preferably” render claims 4, 18, and 20 indefinite because it is unclear whether the limitations following the phrases are part of the claimed inventions. See MPEP § 2173.05(d).
Regarding “such as” limitations, the examiner has interpreted the claims to be drawn to the broadest claimed category. Regarding claim 4, claim 4 recites “a body fluid such as blood, serum, plasma, or urine”; the examiner has interpreted claim 4 to be limited to any body fluid. Regarding claim 18, claim 18 recites “a plate such as a 96-well plate, beads such as agarose or magnetic beads”; the examiner has interpreted claim 18 to be limited to any plate or any type of bead. Regarding claim 20, claim 20 recites “beads such as agarose beads”; the examiner has interpreted claim 20 to be limited to any type of bead.
Claim 20 additionally recites “A kit for detecting virus particles in a sample, preferably for use in the method of claim 14”. The phrase “for use in the method of claim 14” denotes an intended use of the kit. MPEP 2111.02(II) states “statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference between the claimed invention and the prior art”. In this case, the intended use in the method of claim 14 does not impart a structural difference on the kit of claim 20. Thus, the limitation “preferably for the use in the method of claim 14” does not hold patentable weight, and the examiner has interpreted claim 20 to be drawn a kit for detecting virus particles in a sample (i.e., not preferably for use in the method of claim 14).
Claim 10 recites the limitation “the sample is a native or inactivated virus”. “Native virus” is not a common term in the field, and the specification does not define the term. Thus, the metes and bounds of the limitation “native virus” are indefinite. For the purposes of compact prosecution and applying prior art, the examiner has interpreted “native virus” to be drawn to a naturally occurring/wildtype virus within an infected subject.
Claim 17 recites the limitation “the soluble virus entry receptor”. There is no antecedent basis for this limitation in the claim because claim 1 does not establish a soluble virus entry receptor.
It is noted that any interpretation of the claims set forth above does not relieve applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different from that posited by the examiner, additional rejections and art may be readily applied in a subsequent office action.
Claim Rejections - 35 USC § 102
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.
Claims 1, 4-6, 10-13, 18, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carter et al (ACS Central Science April 2020- included on IDS).
Claim 1 is drawn to a method for detecting virus particles in a sample, comprising: (a) incubating the sample with at least one virus-binding molecule bound to a solid phase; and (b) detecting binding of virus particles to the at least one virus-binding molecule bound to the solid phase.
Claim 18 is drawn to the method of claim 1 wherein the solid phase is a plate, beads, a graphene surface, or a semiconducting surface.
Regarding claim 1 and 18, Carter et al discloses ELISA detection methods for SARS-CoV-2 wherein a microwell plate (i.e., a solid phase) is coated with SARS-CoV-2 antigens or antibodies (i.e., virus-binding molecules), incubated with patient samples, and binding of viral antigens (which are within full viral particles) to the virus-binding molecule is detected (section 3.1 and Figure 5).
Claim 4 is drawn to the method of claim 1 wherein the samples is a clinical sample comprising BAL fluid, sputum, tracheal aspirate, epithelial cells obtained by a swab, or a body fluid.
Carter et al discloses various commercially-available SARS-CoV-2 test kits and the clinical sample sources used in the viral detection method of the kits including serum, nasal swabs, and blood (Table 2).
Claim 5 is drawn to the method of claim 1 wherein the binding of virus particles is detected directly or indirectly.
Claim 6 is drawn to the method of claim 1 wherein the binding of virus particles is detected by one or more labeled antibodies.
Carter et al discloses indirect detection of viral particle binding in an ELISA wherein the virus binding is detected via enzyme-labeled antibodies binding to the viral particles followed by enzymatic-conversion of substrate to generate a measurable color change (Figure 5B).
Claim 10 is drawn to the method of claim 1 wherein the sample is a native or inactivated virus or pseudo virus preparation. As discussed above, the examiner has interpreted the limitation “native virus” to be drawn to a wildtype/naturally occurring virus within an infected subject.
Carter et al discloses an ELISA that detects SARS-CoV-2 viral particles from a biological sample from an infected subject (Figure 5B).
Claim 11 is drawn to the method of claim 1 wherein the sample is incubated in the presence of body fluids.
Carter et al discloses an ELISA that detects SARS-CoV-2 viral particles from a biological sample from an infected subject (Figure 5B) and that ELISA assays use body fluids such as blood, serum, and plasma (Table 2).
Claim 12 is drawn to the method of claim 1 wherein the sample is incubated in the presence of neutralizing antibodies.
Carter et al discloses an ELISA to detect SARS-CoV-2 wherein the sample is detected by incubation with antibodies that bind to (i.e., neutralize) the virus (Figure 5B).
Claim 13 is drawn to the method of claim 1 wherein the virus particles are infectious viral particles.
Carter et al discloses methods to detect SARS-CoV-2 in an actively infected subject (i.e., detection of infectious viral particles) (background paragraph 4).
Claim 19 is drawn to a kit for performing the method of claim 1, comprising a manual, one or more solvents, one or more buffers, and/or one or more solid phases, enzymes, antibodies, primers, enzyme substrates, and/or inactivated virus or pseudo virus preparations.
The examiner notes that claim 19 recites an intended use limitation. The claim does not provide any additional limitations on how the kit is used in the method of claim 1. Additionally, MPEP 2112.01(II) states that nonfunctional matter (i.e., a manual) does not distinguish a claimed product from an otherwise identical prior art product. Thus, the broadest reasonable interpretation is that any kit comprising one or more solvents, buffers, and/or solid phases enzymes, antibodies, primers, enzyme substrates, and/or inactivated virus or pseudo virus preparations is capable of performing the intended use of the method of claim 1.
Carter et al discloses numerous serological and immunological test kits to detect SARS-CoV-2 (Table 2).
Thus, Carter et al anticipates claims 1, 4-6, 10-13, 18, and 19.
Claim Rejections - 35 USC § 103
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 2-3, 7, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Carter et al as applied to claims 1, 4-6, 10-13, 18, and 19 above and further in view of Monteil et al (Cell May 2020- see attached form 892).
Claim 2 is drawn to the method of claim 1 wherein the virus-binding molecules comprise a virus entry receptor.
Claim 3 is drawn to the method of claim 1 wherein the at least one virus-binding molecule comprises native, recombinant, or modified recombinant human ACE2 and wherein the virus particles are SARS-CoV-1, SARS-CoV-2, or HCoV-NL63.
Claim 7 is drawn to the method of claim 1 wherein binding is detected by one or more soluble recombinant virus entry receptors.
Claim 15 is drawn to the method of claim 1 further comprising the steps of incubating with a washing solution, incubating with a soluble virus entry receptor, and incubating with a washing solution.
Claim 16 is drawn to the method of claim 1 wherein the detecting step comprises detecting soluble virus entry receptor bound to the virus particles which are bound to the virus-binding molecule on the solid phase.
As discussed above, claims 1, 4-6, 10-13, 18, and 19 were anticipated by Carter et al. This reference does not teach that a method of detecting virus particles in a sample using a virus-binding molecule comprising a virus entry receptor or using soluble virus entry receptor.
However, Monteil et al teaches that ACE2 is the SARS-CoV-2 receptor and is normally expressed on a cell membrane (abstract and graphical abstract). Monteil et al also teaches human recombinant soluble ACE2 (hrsACE2), which is a version of ACE2 not bound to the cell membrane that retains binding to SARS-CoV-2 (i.e., is a soluble virus entry receptor; graphical abstract).
It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Carter et al and Monteil et al to arrive at a method of detecting SARS-CoV-2 using a virus entry receptor (i.e., ACE2) bound to a solid phase and a soluble virus entry receptor (i.e., hrsACE2) in an ELISA to detect SARS-CoV-2. One would have been motivated to do so for the advantage of eliminating the need for SARS-CoV-2-specific antibodies for capture and detection in the ELISA method taught by Carter at (Figure 5B). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Thus, the inventions of claims 2-3, 7, and 15-16 as a whole were prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention, especially in the absence of evidence to the contrary.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Carter et al as applied to claims 1, 4-6, 10-13, 18, and 19 above and further in view of Nasheri et al (Journal of Food Protection March 2020- see attached form 892).
Claim 8 is drawn to the method of claim 1 wherein virus binding is detected by PCR.
As discussed above, claims 1, 4-6, 10-13, 18, and 19 were anticipated by Carter et al. This reference does not teach detection of virus binding to a solid phase using PCR.
However, Nasheri et al teaches antibodies coupled to beads (i.e., a virus-binding molecule bound to a solid phase) which are used to recover/bind virus present in food samples (HAV-antibody coupling to epoxy Dynabeads and virus recovery using anti-HAV antibody-conjugated beads). After virus binding to the beads, virus is detected using ddRT-PCR (ddRT-PCR).
It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Carter et al and Nasheri et al to arrive at a virus detection method comprising virus binding to a solid phase followed by PCR. One would have been motivated to do so for the advantage of specifically capturing intact/infectious viruses of interest in a sample before detection as taught by Nasheri et al (introduction paragraph 7). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Thus, the invention of claim 8 as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention, especially in the absence of evidence to the contrary.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Carter et al as applied to claims 1, 4-6, 10-13, 18, and 19 above and further in view of Liu et al (Nature April 2020- included on IDS).
Claim 9 is drawn to the method of claim 1 wherein the sample is an aerosol.
As discussed above, claims 1, 4-6, 10-13, 18, and 19 were anticipated by Carter et al. This reference does not teach aerosol samples.
However, Liu et al teaches collection of aerosol samples and detection of SARS-CoV-2 in the aerosolized samples (abstract and sample collection).
It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Carter et al and Liu et al to arrive at the ELISA-based SARS-CoV-2 detection method taught by Carter et al in the aerosol samples taught by Liu et al. One would have been motivated to do so for the advantage of detecting SARS-CoV-2 in settings with high aerosol transmission, such as crowded hospitals, as taught by Liu et al (abstract). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Thus, the invention of claim 9 as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention, especially in the absence of evidence to the contrary.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Carter et al as applied to claims 1, 4-6, 10-13, 18, and 19 above and further in view of Gheblawi et al (Circulation Research April 2020- see attached form 892).
Claim 14 is drawn to the method of claim 1 wherein the at least one virus-binding molecule bound to the solid phase comprises an enzymatically inactive virus entry receptor.
As discussed above, claims 1, 4-6, 10-13, 18, and 19 were anticipated by Carter et al. This reference does not teach that the virus-binding molecule bound to the solid phase comprises an enzymatically inactive virus entry receptor.
However, Gheblawi et al teaches that ACE2 is the SARS-CoV-2 entry receptor (abstract) and that ACE2 has an enzymatically-active protease domain comprising the site that the SARS-CoV-2 RBD binds (Figure 2B).
It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Carter et al and Gheblawi et al to arrive at a method of detecting SARS-CoV-2 using an enzymatically inactive ACE2 as the virus-binding molecule on the solid phase. One would have been motivated to do so for the advantage of eliminating ACE2 protease activity that could disrupt the detection assay while still retaining binding to SARS-CoV-2. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Thus, the invention of claim 14 as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention, especially in the absence of evidence to the contrary.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Carter et al as applied to claims 1, 4-6, 10-13, 18, and 19 above and further in view of Monteil et al and Gheblawi et al.
Claim 17 is drawn to the method of claim 1 wherein the virus entry receptor bound to the solid phase is enzymatically inactive ACE2, a soluble virus entry receptor is soluble enzymatically active ACE2, and the virus particles are SARS-CoV-1, SARS-CoV-2 or HCoV-NL63.
As discussed above, claims 1, 4-6, 10-13, 18, and 19 were anticipated by Carter et al. This reference does not teach that the virus-binding molecule bound to the solid phase comprises an enzymatically inactive virus entry receptor or soluble enzymatically active ACE2.
However, Gheblawi et al teaches that ACE2 is the SARS-CoV-2 entry receptor (abstract) and that ACE2 has an enzymatically-active protease domain comprising the site that the SARS-CoV-2 RBD binds (Figure 2B). Monteil et al teaches human recombinant soluble ACE2 (hrsACE2), which is a version of ACE2 not bound to the cell membrane that retains its catalytic ectodomain and binding to SARS-CoV-2 (i.e., is an enzymatically active soluble virus entry receptor; graphical abstract).
It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Carter et al, Monteil et al , and Gheblawi et al to arrive at a method of detecting SARS-CoV-2 using an enzymatically inactive ACE2 as the virus-binding molecule on the solid phase and a soluble recombinant enzymatically active ACE2. One would have been motivated to do so for the advantage of eliminating ACE2 protease activity that could disrupt the detection assay while still retaining binding to SARS-CoV-2 and for the advantage of eliminating the need for SARS-CoV-2-specific antibodies for capture and detection in the ELISA method taught by Carter at (Figure 5B). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Thus, the invention of claim 17 as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention, especially in the absence of evidence to the contrary.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Carter et al and further in view of Monteil et al and Gheblawi et al.
Claim 20 is drawn to a kit for detecting virus particles in a sample comprising:
a solid phase selected from the group consisting of a plate, beads, a graphene surface, and a semiconducting surface
a virus entry receptor for the virus particles bound to the solid phase
a soluble virus entry receptor for the virus particle
at least one substrate for the enzymatic activity of the soluble entry receptor
at least one washing solution, and
at least one inactivated virus or pseudovirus preparation
wherein: the virus entry receptor bound to the solid phase is enzymatically inactive ACE2, the soluble virus entry receptor is soluble enzymatically active ACE2, and the virus particles ae SARS-CoV, SARS-CoV-2, or HCoV-NL63.
MPEP 2112.01(II) states that nonfunctional matter does not distinguish a claimed product from an otherwise identical prior art product. The broadest reasonable interpretation of “a kit” includes a box comprising instructions and the additional claimed components recited above. A box and instructions are nonfunctional matter. Thus, art disclosing the claimed components recited above is not patentably distinct from a kit comprising said components. Additionally, as discussed in the 35 USC 112(b) rejection above, the examiner has interpreted that the limitation “preferably for use in the method of claim 14” does not hold patentable weight.
Carter et al teaches ELISA detection methods for SARS-CoV-2 wherein a microwell plate (i.e., a solid phase) is coated with SARS-CoV-2 antigens (i.e., virus-binding molecules), incubated with patient samples, and binding of viral antigens (which are within full viral particles) to the virus-binding molecule is detected (section 3.1 and Figure 5). Carter et al also teaches numerous serological and immunological test kits to detect SARS-CoV-2 (Table 2). Carter et al does not teach that the virus-binding molecule bound to the solid phase comprises an enzymatically inactive virus entry receptor or soluble enzymatically active ACE2.
However, Gheblawi et al teaches that ACE2 is the SARS-CoV-2 entry receptor (abstract) and that ACE2 has an enzymatically-active protease domain comprising the site that the SARS-CoV-2 RBD binds (Figure 2B). Gheblawi et al also teaches that Ang I and II are substrates for ACE2 (introduction paragraph 1). Monteil et al teaches human recombinant soluble ACE2 (hrsACE2), which is a version of ACE2 not bound to the cell membrane that retains its catalytic ectodomain and binding to SARS-CoV-2 (i.e., is an enzymatically active soluble virus entry receptor; graphical abstract).
It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Carter et al, Monteil et al , and Gheblawi et al to arrive at a kit for detecting SARS-CoV-2 using an enzymatically inactive ACE2 as the virus-binding molecule on the solid phase and a soluble recombinant enzymatically active ACE2. One would have been motivated to do so for the advantage of eliminating ACE2 protease activity that could disrupt the detection assay while still retaining binding to SARS-CoV-2 and for the advantage of eliminating the need for SARS-CoV-2-specific antibodies for capture and detection in the ELISA method taught by Carter at (Figure 5B). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Thus, the invention of claim 20 as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE A WILLARD whose telephone number is (571)272-0153. The examiner can normally be reached M-F 8-4 ET.
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/KATHERINE ARCENEAUX WILLARD/Examiner, Art Unit 1671
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1671