DETAILED ACTION
Disposition of Claims
Claims 1-32 were pending. Claims 2-3, 5, 12-13, 15-16, 18, 22, and 25-32 have been cancelled. New claims 33-35 are acknowledged and entered. Amendments to claims 1, 4, 6-7, 9, 11, 14, 17, 19, 21, and 23-24 are acknowledged and entered. NB: Claim 17 has been amended but the status identifier is listed incorrectly as “previously presented”. Claims 1, 4, 6-11, 14, 17, 19-21, 23-24, and 33-35 will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20230228752A1, Published 07/20/2023. Amendments to the specification presented on 02/27/2026 are acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Optional Authorization to Initiate Electronic Communications
The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization.
Response to Arguments
Applicant's arguments filed 02/27/2026 regarding the previous Office action dated 08/25/2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The English translation of the priority documents is acknowledged and entered.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
It was previously noted that the disclosure of the prior-filed application, Application No. DE10 2020 117 636 A1, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. However, said claims have been cancelled. This notice will remain in the Office action to ensure that any further claim amendments are afforded the correct priority date.
Specification
(Objection withdrawn.) The objection to the abstract of the disclosure is withdrawn in light of the amendments to the abstract.
(Objection withdrawn.) The objection to the disclosure is withdrawn in light of the amendments to the disclosure.
Claim Objections
(Objection withdrawn.) The objection to Claims 2, 14, 15, and 26 is withdrawn in light of the amendments to the claims.
(Objection withdrawn.) The objection to Claim 2 is withdrawn in light of the cancellation of said claim.
(Objection withdrawn.) The objection to Claim 3 is withdrawn in light of the cancellation of said claim.
(Objection withdrawn.) The objection to Claim 7 is withdrawn in light of the amendments to said claim.
Claim Rejections - 35 USC § 112(b); Second Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 1 and 14 and dependent claims 2-13 and 15-24 thereof under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 2, 15, and 26 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of said claims.
(Rejection withdrawn.) The rejection of Claims 5, 18, and 29 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of said claims.
(Rejection withdrawn.) The rejection of Claims 6 and 19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claim 9 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claim.
(Rejection withdrawn.) The rejection of Claims 12, 22, and 32 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of said claims.
(Rejection maintained in part and extended – necessitated by amendment.) Claim 14 and dependent claims 17 and 19-24 thereof 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. Note the rejection is withdrawn with respect to cancelled claims 15-16 and 18. The rationale behind this rejection was presented in a previous Office action and will not be repeated herein.
Response to Arguments
Applicant's arguments filed 02/27/2026 have been fully considered but they are not persuasive.
Applicant argues that a skilled artisan would be apprised to the term “specifically recognizes”. The Office disagrees. MPEP §2173.05(b) notes that terms of degree are acceptable only if the specification provides guidance or a standard for determining the scope. As noted in the rejection, the scope of what is, and what is not, “specifically recognized” is not provided for in the specification, nor is there guidance in the art or the specification as to whether this term is bound to the affinity threshold (e.g. Kd? nM vs uM?), selectivity vs. off-target binding, functional assay (e.g. ELISA or neutralization assay to determine “specificity”), or a competitive binding context. While the claim has been amended to narrow the scope to SARS CoV-2 virus and the use of the binding partner as ACE2, the issue is that SARS CoV also binds to ACE2 as its receptor. Therefore, further questions arise as to how to determine if the binding is “specific” (e.g. is the binding specific if it only binds to SARS CoV-2 S, or is it specific if it binds to both SARS CoV and SARS CoV-2 S?) Applicant is attempting to claim the ACE2 construct by what it does, rather than by what it is, which is functional limitation tied to a protein without measurable scope.
While a skilled artisan may generally understand that “specific binding” differs from “non-specific binding”, the claim fails to provide any objective standard or boundary for determining when binding qualifies as “specific” under the metes and bounds of the claim. The specification does not define the phrase in terms of binding affinity, selectivity, assay conditions, or comparison to non-target interactions. As a result, the scope of the claim depends upon subjective interpretation, and one of skill in the art would not be able to determine, with reasonable certainty, whether a given ACE2 binding agent falls within the scope of the claim.
For at least these reasons, Applicants arguments are not persuasive, and the rejection is maintained.
(Rejection maintained in part and extended – necessitated by amendment.) Claim 24 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.
The term “unique” in claim 24 is a relative term which renders the claim indefinite. The term “unique” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. “Unique” is used in conjunction with an oligonucleotide, but it is not clear how the nucleotide sequence in said oligonucleotide is “unique”, as no basis for comparison has been provided (e.g. it is not clear if the nucleotide is unique relative to other oligonucleotides in the kit, the target viral genome, or any broader set of sequences.) As no degree of measurement has been offered, nor parameter to determine what about the oligonucleotide renders it to be “unique”, a skilled artisan would not be aware if they were infringing upon the metes and bounds of the claim.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 24 remains rejected on the grounds of being indefinite.
Response to Arguments
Applicant's arguments filed 02/27/2026 have been fully considered but they are not persuasive.
While Applicant has removed the term “specific” from the claim, the newly entered term “unique” still creates indefiniteness issues for the reasons noted supra.
For at least these reasons, Applicants arguments are not persuasive, and the rejection is maintained.
(Rejection withdrawn.) The rejection of Claim 25 and dependent claims 26-32 thereof under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of said claims.
(New rejection – necessitated by amendment.) Claims 1 and 4 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.
Claim 4 recites the limitation "the SARS-CoV-2 virus" in line 2. The antecedent basis for this limitation in the claim is unclear, as the method of claim 1 is directed towards detection of SARS-CoV-2, but the actual SARS-CoV-2 is present specifically within a sample (bullet #2 in the method). Furthermore, the method in the preamble and specification appears to be used for the diagnosis of SARS-CoV-2, which does not specifically require that the virus is present; in other words, for detection of a clinical sample, the intent of the method is to determine whether or not said virus is present, meaning said virus is suspected of being in the sample, but does not necessarily have to be present in said sample. To clarify the antecedent basis of claim 4 and the method of claim 1, it is suggested the claims be amended along the lines of:
“1. A method for the detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) comprising:
a) coupling a binding agent selected from the group consisting of an angiotensin-converting enzyme 2 (ACE2), an ACE2 construct, an ACE2 fusion protein, or a modified or mutant ACE2 polypeptide or ACE2 fusion protein that is capable of binding to a virus component of said SARS-CoV-2 to beads;
b) incubating the beads with the thereon coupled binding agent with a sample suspected of comprising SARS-COV-2 under conditions permitting binding of SARS CoV-2 to the binding agent,
c) staining any SARS-CoV-2 immobilized to the beads coupled to the binding agent with a staining agent,
d) detecting stained SARS-CoV-2 particles via a physical, chemical, or biological detection means, wherein detection is performed without nucleic acid amplification.”
“4. The method according to claim 1, wherein the sample suspected of comprising SARS-CoV-2 is obtained from a human or non-human animal.”
For at least these reasons, claim 4 is rejected on the grounds of being indefinite.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1 is drawn to a method for the detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) comprising:
a) coupling a binding agent selected from the group consisting of an angiotensin-converting enzyme 2 (ACE2), an ACE2 construct, an ACE2 fusion protein, or a modified or mutant ACE2 polypeptide or ACE2 fusion protein that is capable of binding to a virus component of said SARS-CoV-2 to beads;
b) incubating the beads with the thereon coupled binding agent with a sample suspected of comprising SARS-COV-2 under conditions permitting binding of SARS CoV-2 to the binding agent,
c) staining any SARS-CoV-2 immobilized to the beads coupled to the binding agent with a staining agent,
d) detecting stained SARS-CoV-2 particles via a physical, chemical, or biological detection means, wherein detection is performed without nucleic acid amplification.
Further limitations on the method according to claim 1 are wherein the sample suspected of comprising SARS-CoV-2 is obtained from a human or non-human animal (claim 4); wherein the staining agent is selected from the group consisting of cyanine fluorescent DNA/RNA dyes, acridine orange (3-N,3-N,6-N,6-N-tetramethylacridine-3,6-diamine), thiazole orange, DAPI (4′,6-diamidino-2-phenylindole), 7-AAD (7-aminoactinomycin D), ethidium bromide, propidium iodide, an enzymatic or fluorescence-coupled staining agent for viral RNA, or a membrane staining agent (claim 6); wherein the physical detection means is a fluorescence activated cell sorting (FACS) analyzer, a microfluidic platform, a microscope, a camera, a confocal laser scanning microscope, and/or a detection means configured to be detected by the human eye (claim 7); wherein the biological detection means is a conjugate- or marker-coupled further secondary binding agent (claim 8); wherein the sample is taken from body secretions (claim 9), wherein the body secretions are selected from the group consisting of saliva, serum, whole blood, sputum, urine, tears, and feces (claim 33); wherein the binding agent is recombinant biotinylated Fc-ACE2 (claim 10), wherein the beads comprise streptavidin-agarose or streptavidin polymethyl methacrylate (PMMA)(claim 11); wherein the sample is taken via a rinse or swab or a gargle sample (claim 34), wherein the rinse or swab is from a mouth, nose, and/or throat (claim 35).
Claim 14 is drawn to a kit for the detection of SARS-CoV-2, comprising:
a) a binding agent selected from the group consisting of an angiotensin-converting enzyme 2 (ACE2), an ACE2 construct, an ACE2 fusion protein, or a modified or mutant ACE2 polypeptide or ACE2 fusion protein that is capable of binding to a virus component of said SARS-CoV-2 to beads;
b) a beads that are coupled to the binding agent, and
c) a staining agent for staining viruses immobilized on the beads.
Further limitations on the kit according to claim 14 are wherein the SARS CoV-2 of the Coronaviridae family is obtained from a human or animal host (claim 17); wherein the staining agent is selected from the group consisting of cyanine fluorescent DNA/RNA dyes, acridine orange (3-N,3-N,6-N,6-N-tetramethylacridine-3,6-diamine), thiazole orange, DAPI (4′,6-diamidino-2-phenylindole), 7-AAD (7-aminoactinomycin D), ethidium bromide, propidium iodide, an enzymatic or fluorescence-coupled staining agent for viral RNA, or a membrane staining agent (claim 19); wherein the binding agent is recombinant biotinylated Fc-ACE2 (claim 20), wherein the beads comprise streptavidin-agarose or streptavidin PMMA (claim 21), wherein a magnifying device is provided for making the staining agent visible to a human eye (claim 23); and wherein the beads are individually labelled with an oligonucleotide comprising a unique nucleotide sequence (claim 24).
Claim Rejections - 35 USC § 112(a); First Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 2, 15, and 26 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in light of the cancellation of said claims.
(Rejection maintained in part and extended – necessitated by amendment.) Claims 1, 4, 6-11, 14, 17, 19-21, and 23-24 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods and kits for detection of binding of SARS-CoV-2 particles to microparticles or beads, wherein said microparticles or beads are bound to biotinylated-Fc-Human ACE2 receptor, wherein said bound viral particles were detected through SYBR™ gold nucleic acid staining or secondary antibody staining, does not reasonably provide enablement for any method to detect only SARS CoV-2 in any sample through the use of any ACE2-related binding agent and any bead-based coupling agent using any detection means. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Note the rejection of claims 2-3, 5, 12-13, 15-16, 18, 22, and 25-32 is withdrawn in light of the cancellation of said claims, and is extended to include new claims 33-35.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to a method for the detection of any severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2) strain, isolate, or mutant, comprising coupling any binding agent to any beads, wherein the binding agent is selected from the group consisting of angiotensin-converting enzyme 2 (ACE2), any ACE2 construct, any ACE2 fusion protein, or any modified or mutant ACE2 polypeptide or fusion protein that is capable of binding to any virus component of said SARS CoV-2, incubating said beads with any sample suspected of containing SARS CoV-2 under any conditions which permit binding of the virus to said binding agent, staining said viruses immobilized on said beads with any staining agent, and detecting said virus particles with any physical, chemical, or biological means for detection.
The breadth of “SARS CoV-2” is drawn to any strain, isolate, or sub-lineage of SARS CoV-2 viruses, which reasonably includes over 30 specific, named, and recognized subvariants/strains actively circulating globally. SARS CoV-2 continues to accumulate significant mutations (e.g., BA.3.2 has over 70 mutations compared to the original strain), and as of August 2021, over 3,400 SARS-CoV-2 genomes had been identified.
The breadth of “ACE2” as the binding agent is a broad genus drawn to any ACE2 protein, chimera, mutant, or fusion protein thereof which may bind to the claimed RNA virus. The breadth of the ACE2 protein is not limited to ACE2 from any singular species, and ACE2 and orthologs thereof are found across many different vertebrate animal species.
The breadth of “staining agent” is drawn to the use of any detection reagent that may be a dye, enzyme, or the like that can be detected, such as colorimetric, fluorometric, or chemiluminescent detection using any means to detect such reactions, such as the naked eye, microscope, or microfluidic platform. The methods are also claiming a broad array of biological samples which may be used in the method, including, but not limited to, saliva, blood, serum, sputum, urine, tears, feces, or gargle samples.
State of the prior art/Predictability of the art. With respect to the ACE2 binding agents and SARS CoV-2, while the art has recognized that human ACE2 binds to the spike (S) protein of SARS CoV-2, there are significant nuances with these limitations in the method of detection as claimed.
First, the binding interaction between ACE2 and S protein is highly structure-dependent, and alterations to ACE2 can unpredictably affect binding capability. The binding of SARS CoV-2 depends upon defined structural contacts, and mutations to ACE2 or non-human versions of ACE2 do not interact with S protein in a manner to facilitate entry (Lan J, et. al. Nature. 2020 May;581(7807):215-220. Epub 2020 Mar 30.) Singular residue changes and interface conformation affect ACE2-binding affinity to SARS CoV-2 S protein (Shang J, et. al. Nature. 2020 May;581(7807):221-224. Epub 2020 Mar 30.) Second, ACE2 is not only utilized by SARS CoV-2 for viral entry; Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and human coronavirus (hCoV)-NL63 all utilize ACE2 as the functional receptor for cell entry, and while some non-human ACE2 bind to one or more of these viruses with high affinity, not all ACE2 bind to SARS CoV-2 spike protein, highlighting that not all ACE2 mutants, variants, or orthologs are equivalent (Lan J, et. al. Structure. 2022 Oct 6;30(10):1432-1442.e4. Epub 2022 Aug 1.; Damas J, et. al. Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22311-22322. Epub 2020 Aug 21.) Thus, the ability of a broadly claimed ACE2 construct, fusion protein, modified ACE2 polypeptide, or mutant ACE2 polypeptide to bind to only SARS CoV-2 sufficiently for SARS CoV-2 detection would depend on the particular structure and sequence of the ACE2 molecule.
Working examples. The working examples were described in the previous Office action, and will not be repeated herein.
Guidance in the specification. The guidance provided for in the specification was described in the previous Office action, and will not be repeated herein
Amount of experimentation necessary. Additional research is required in order to determine how effective the methods and kits, as claimed, would be with respect to the large amount of permutations encompassed by the genera claimed.
In light of the Supreme Court decision in Amgen Inc. et al. v. Sanofi et al., 143 S. Ct. 1243 (2023) (hereafter Amgen), updated guidelines were provided regarding the assessment of enablement (Federal Register, pp. 1563-1566; Pub. Jan. 10, 2024.) In Amgen, the Supreme Court unanimously affirmed that a genus of monoclonal antibodies were not enabled because when a range within a genus is claimed, there must be reasonable enablement of the scope of the range. The Court found in Amgen that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality.
In the instantly claimed invention, as amended, the claims recite a binding agent selected from any angiotensin-converting enzyme 2 (ACE2), ACE2 constructs, ACE2 fusion proteins, and modified or mutant ACE2 polypeptides or fusion proteins. While the specification describes the use of a particular ACE2 construct (e.g. biotinylated Fc-human ACE2) for binding SARS-CoV2 virions/particles, the claim encompasses a broad genus of ACE2 variants, including modified or mutant ACE2 proteins, without providing guidance as to which modification retain the ability to bind only to SARS CoV-2 with sufficient affinity for positive detection. The specification provides no guidance as to how to distinguish the interaction of ACE2 with other known coronaviruses which bind to ACE2. The binding interaction between ACE2 and viral spike protein is highly structure-dependent, and alterations to ACE2 can unpredictably affect binding capability. The specification does not provide representative examples across the full scope of the claimed genus, nor does it disclose structural features, sequence constraints, or screening methods that would enable a person of ordinary skill in the art to identify operative ACE2 variants without undue experimentation.
For the reasons discussed above and in the previous Office action, it would require undue experimentation for one skilled in the art to make and/or use the claimed kits and methods.
Response to Arguments
Applicant's arguments filed 02/27/2026 have been fully considered but they are not persuasive.
Applicant’s assertion that the claim amendments render the claims enabled is not persuasive. Although the claims have been narrowed to incorporate a specific CoV (e.g. SARS CoV-2) and to the use of ACE2-binding agents, the amendments to not address the breadth of the recited genus of ACE2 variants, which still includes modified and mutant ACE2 proteins from different species with unpredictable binding properties. The specification provides only limited examples of specific ACE2 constructs and does not supply guidance sufficient to enable the full scope of the claimed genus without undue experimentation. Further, there is little guidance as to how the method and kits distinguish SARS CoV-2 in a sample from other coronaviruses known to bind to ACE2. Narrowing the target virus fails to resolve the lack of enablement arising from the breadth and unpredictability of the binding agent limitation.
For at least these reasons, the arguments are not persuasive, and the rejection is maintained.
(New rejection – necessitated by amendment.) Claim 24 is 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.
This is a new matter rejection.
The term “unique” as recited in claim 24 is not supported by the original disclosure or claim as filed.
Applicant’s amendment, filed 02/27/2026, fails to provide direction to support this limitation, and fails to assert that no new matter has been added.
The specification as filed does not provide sufficient written description of the above-mentioned limitations. The specification does not provide sufficient support for a “unique” nucleotide sequence. The originally filed specification does not describe oligonucleotides in terms of uniqueness, distinct sequence identity, or any form of sequence-based differentiation. Therefore, the claims represent a departure from the specification and claims as originally filed. Such limitations recited in the present claims, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. §112.
Applicant is required to cancel the new matter in the response to this Office Action. Alternatively, applicant is invited to provide sufficient written support for the “limitations” indicated above. See MPEP §714.02, §2163.05-06 and §2173.05(i).
(New rejection – necessitated by amendment.) Claims 1, 4, 6-11, 14, 17, 19-21, and 23-24 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 following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus 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 Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1, 4, 6-11, 14, 17, 19-21, and 23-24 are rejected as lacking adequate descriptive support for any kit or method of use thereof comprising the testing of any sample using any of the ACE2 proteins as claimed which results in the claimed detection of SARS CoV-2 in said sample.
Claim 1 is directed to detection of SARS CoV-2; however, the specification describes the use of ACE2 as a binding agent for coronavirus spike (S) proteins generally, rather than demonstrating possession of a method that detects SARS CoV-2 as a distinct target. In support of the claimed genus (any ACE2, detection of only SARS CoV-2 S protein from any sample), the application discloses one example in which Fc-human ACE2 is bound to beads and also exhibits the ability to detect SARS CoV-2 virions from a laboratory sample and one patient sample wherein a swab (not clear what type of swab) was immersed in aqueous solution. No ACE2 derivatives, variants, isolates, orthologs, or mutants thereof are disclosed that can achieve this binding to any SARS CoV-2 S or virions. No other clinical samples (e.g. saliva, sputum, nasal swab, blood, etc.) were tested for their ability to work in the claimed method. No other controls, such as SARS CoV or human coronavirus (hCoV)-NL63 which are known to bind to ACE2, were tested to determine if they would result in false-positives. The specification fails to describe how the assay would distinguish between SARS CoV-2 and other coronaviruses which utilize ACE2 as their receptor. Thus, the application fails to provide examples of a sufficient number of species within the claimed genus.
Further, while the claims provide both a structure and a function, the application fails to draw any correlation between the two. In other words, there is no evidence that any ACE2 as claimed can bind to any SARS CoV-2 virion or component thereof, especially in a method to distinguish SARS-CoV-2 in any sample. Moreover, no correlation has been made to which samples can be analyzed in order to achieve the claimed detection, as the art has clearly recognized that not all specimen types are appropriate for all tests, and for diagnostic testing of SARS CoV-2, the most reliable clinical sample is that of an upper respiratory specimen (U.S. Centers for Disease Control and Prevention (CDC). Interim Guidelines for Collecting and Handling of Clinical Specimens for COVID-19 Testing. 10/29/2024. https://www.cdc.gov/covid/hcp/clinical-care/clinical-specimen-guidelines.html). Depending on the stage of infection, the site from where the clinical sample is taken can have great effect on the overall detection of virions using antigen-binding capture based assays (Rubin R.. JAMA. 2023 Feb 7;329(5):357-358.)
Thus, in view of the above, there would have been significant uncertainty that the Applicant was in possession of the full scope of the invention as presently claimed. In view of this uncertainty and the lack of sufficient examples of the claimed genera, the claims are rejected for lack of adequate written description support.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 1-12 and 14-32 under 35 U.S.C. 102(a)(2) as being anticipated by Lapointe et. al. (US20210389308A1, Pub. 12/16/2021, Priority 04/03/2020; hereafter “Lapointe”) is withdrawn in light of the amendments to the claims and Applicant’s arguments regarding the priority date of elements within Lapointe.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claim 13 under 35 U.S.C. 103 as being unpatentable over Lapointe as applied to claims 1-12 and 14-32 above, and further in view of Elliott (Elliott AD. Confocal Microscopy: Principles and Modern Practices. Curr Protoc Cytom. 2020 Mar;92(1):e68.; hereafter “Elliott”) is withdrawn in light of the amendments to the claims and Applicant’s arguments.
(New rejection – necessitated by amendment.) Claims 1, 4, 6-9, 11, 14, 17, 19, 21, 23-24, and 33-35 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et. al. (Huang L, et. al. BioRxiv Preprint 06/12/2020. doi: https://doi.org/10.1101/2020.06.09.142372; hereafter “Huang”) in view of Mehra et. al. (US20130130404A1; Pub. 05/23/2013; hereafter “Mehra”.)
The Prior Art
Huang teaches gold nanoparticles as a solid-phase support wherein ACE2 is bound to the surface, and said nanoparticles are used to immobilize SARS CoV-2 virions for detection on a nanoplasmonic sensor chip (entire document; See Fig. 1). Huang therefore teaches a method in which ACE2 is used as a binding agent, wherein ACE2 is coupled to a particulate carrier and used to bind and detect virus particles.
It was well-known in the art that biomolecules may be immobilized on a variety of particulate solid supports, including beads and nanoparticles, for the purpose of capturing and detecting biological targets. For example, bead-based solid-phase immobilization methods utilize functionalized beads to bind biomolecules from solution and enable their detection or isolation, as taught by Mehra (entire document; see abstract). Mehra teaches that carriers, such as beads and gold nanoparticles, are functional equivalents for immobilizing biomolecules (¶[0056]). Accordingly, it would have been obvious for a person of ordinary skill in the art to substitute the nanoparticle carrier of Huang with the beads of Mehra, as both are known particulate supports used for immobilizing binding agents and capturing biological targets. Such substitution represents a predictable use of prior art elements according to their established functions and would not alter the fundamental operation of the claimed method or kit. Therefore, given the teachings of Huang in view of Mehra, the limitations of instant claims 1, 8, and 14 would be obvious to a skilled artisan.
Further limitations of the instant claims are taught by Huang and Mehra. Huang teaches the use of optical sensing systems to detect the interaction (pp. 3-4, ¶ bridging pages), such as a smartphone app or microplate reader (p. 4, ¶2; instant claims 7, 23). Huang teaches the samples suspected of containing SARS CoV-2 are obtained from human nasopharyngeal swabs or saliva samples (abstract; instant claims 4, 9, 17, 33-35).
Mehra teaches that attachments to ligands, such as biotin, can be useful for associating the detector with ligand receptors, such as avidin, streptavidin, or neutravidin. Avidin, streptavidin, neutravidin, in turn, can be linked to a directly detectable entity, such as colloidal gold (¶[0068]; instant claims 6, 11, 19, 21). Mehra teaches the nanoparticles and beads can be attached to nucleic acids (¶[0072]; instant claim 24).
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Huang in order to substitute the nanoparticle carrier with a bead-based carrier, as both are known particulate supports used for immobilizing binding agents and capturing biological targets. One would have been motivated to do so, given the suggestion by Mehra that such solid supports were known equivalents. There would have been a reasonable expectation of success, given the knowledge that this substitution was a predictable use of prior art elements, as taught by Huang and Mehra, and also given the knowledge that ACE2 could be directly bound to a solid microparticle support and used for the non-PCR related detection of SARS CoV-2 infection. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
(New rejection – necessitated by amendment.) Claims 6, 10, and 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Huang and Mehra as applied to claims 1, 4, 6-9, 11, 14, 17, 19, 21, 23-24, and 33-35 above, and further in view of Reiter et. al. (US20210363512A1; Priority 05/22/2020; hereafter “Reiter”), Messing et. al. (US20210190797A1; Priority 02/19/2020; hereafter “Messing”), and Glasgow et. al. (US20230257726A1; Priority 05/11/2020; hereafter “Glasgow”).
The Prior Art
The teachings of Huang and Mehra have been set forth supra. While Huang teaches that ACE2 can be bound to microparticle carrier supports, Huang teaches the detection method is facilitated by the wavelength shift of the gold nanoparticle supports. Mehra teaches that detection and conjugation methods and tools, such as streptavidin/biotin, are known in the art and can be used with microparticle supports. However, neither Huang or Mehra alone or in combination teach the use of streptavidin-coated beads or Fc-ACE2-biotinylated fusion products. However, the prior art was appraised to these components and methods, as evidenced by Reiter, Glasgow, and Messing.
The prior art, as evidenced by Reiter and Glasgow, teaches fusion proteins comprising ACE2 linked to the Fc portion of immunoglobulin (ACE2-Fc), which were known for binding SARS-CoV-2 S proteins (entire document; see abstract.) Reiter teaches their Fc-ACE2 protein may be used in surface plasmon resonance detection methods for detection of binding between ACE2 and S protein (¶[0056]). It was further well-established in the art that proteins, such as Fc fusion proteins, may be modified for biotinylation to facilitate detection and/or immobilization on solid supports. Glasgow teaches AVITAG™, which is a biotinylated technology known in the art, and teaches that any of the polypeptides or proteins described may comprise such tags and teaches the sequence of said tags (¶[0107]). Glasgow teaches ACE2-Fc fusion proteins (¶[0066][0252][0258-0260]) and teaches that the interaction of dimeric ACE2-Fc constructs with full-length trimeric S protein is stronger than with monomeric RBD of S protein due to avidity effects (¶[0264]). Glasgow teaches that a biotinylated ACE2 variant was tethered to a solid support using biotin-streptavidin interaction (¶[0233]). Glasgow teaches that ACE2 can be bound to beads (¶[0189]).
Messing teaches methods for diagnosis and detection of SARS CoV-2 infection through detection of antibodies to SARS-CoV-2-specific proteins (entire document; see abstract). Messing teaches the SARS CoV-2 proteins can be bound to streptavidin-coated beads (¶[0151-0153]) and that ACE2 can be used as a means for antibody detection through a competitive assay format (¶[0163]) and teaches biotinylated ACE2 (¶[0232]).
Accordingly, it would have been obvious for a person of ordinary skill in the art to incorporate a biotinylation tag, such as AVITAG™, into an ACE2-Fc fusion protein to facilitate its immobilization onto a carrier molecule, such as a streptavidin-coated bead, for use in a viral capture and detection assay. This represents a routine application of established protein engineering and labeling techniques to a known binding construct, and given the teachings of Huang, Mehra, Reiter, Messing, and Glasgow, arriving at the limitations of instant claims 6, 10, and 19-21 would be obvious to a skilled artisan.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Huang and Mehra in order to generate biotinylated Fc-ACE2 constructs, thereby utilizing one predictable and common means of attaching a protein to a carrier for detection. One would have been motivated to do so, given the suggestion by Reiter, Messing, and Glasgow that ACE2 constructs could be used in the art for detection of SARS CoV-2 . There would have been a reasonable expectation of success, given the knowledge that ACE-Fc constructs were known and generated in the art, as taught by Reiter and Glasgow, and also given the knowledge that biotinylated ACE2 was known in the art, as taught by Messing and Glasgow. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
No claims are allowed.
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.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671
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