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 .
Status of the Claims
Claims 1-20 are pending in the application.
Claims 1-8 and 19-20 are withdrawn.
Claims 9-18 are the subject of this office action.
Election/Restrictions
Applicant's election with traverse of Group II, claims 9-18 in the reply filed on 30 March 2026 is acknowledged. The traversal is on the ground(s) that Applicant disputes the assertion that the groups involve separate and distinct inventions and that the subject matter of the groups is linked by a common inventive concept, and that as a result there is no burden in collectively examining the claim groups. This argument is not persuasive. The restriction requirement acknowledges that there are shared technical features between the group, but cites prior art which indicates that this shared technical feature does not make a contribution over the prior art, and that therefore, the restricted claim groups lack unity of invention. Applicant has not provided specific argument to overcome this art and reasoning.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-8 and 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 30 March 2026.
Priority
The instant application is a 371 National Stage of PCT/US21/59934, filed 18 November 2021, which claims benefit of provisional application 63/236,006, filed 23 August 2021 and provisional application 63/115,164, filed 18 November 2020.
However, it is noted that the provisional application 63/115,164 fails to provide support for the full scope of instant claims 9-18, at least because claims 9-18 encompass antibody N11 and antibodies that bind to epitopes on the SARS-CoV-2 that are bound by the N11 antibody, while provisional application 63/115,164 does contain any disclosure or recitation of antibody N11 or antibodies that bind to epitopes on the SARS-CoV-2 that are bound by N11 antibody.
As such, instant claims 9-18 are granted the priority date of provisional application 63/236,006, 23 August 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11 May 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 9-18 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 claims encompass genera of antibodies that are defined by their binding function: “the capture and the detection antibody are selected from the antibodies that bind to epitopes on the SARS-CoV-2 that are bound by N6 antibody, N7 antibody, N11 antibody or N5 antibody” or which are defined by a generic lab name (i.e. N5, N6, N7, N11). However, the disclosure fails to demonstrate possession of all antibodies having the claimed function or defined by the claimed lab name and thus all antibodies encompassed by the claimed genera.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) actual reduction to practice (2) disclosure of drawings or structural chemical formulas (3) sufficient relevant identifying characteristics (such as: i. complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. See MPEP 2163.
The claimed invention is directed to a system for detecting the presence of SARS-CoV-2 in a fluid sample, the system comprising capture and detection antibodies selected from the antibodies that bind to epitopes on the SARS-CoV-2 that are bound by N6 antibody, N7 antibody, N11 or N5 antibody.
As discussed in more detail in the 112(b) section below, the breadth of the claims is unclear because of indefiniteness produced by claiming antibodies by their laboratory names and because the disclosure does not define what epitopes on the SARS-CoV-2 peptide are bound by each antibody. Thus, the claim encompasses genera of antibodies which are defined by their binding function, but the precise nature of that binding function is unclear.
Regarding the functional limitation that the capture and detection antibodies are antibodies that bind to epitopes on the SARS-CoV-2 that are bound by N6 antibody, N7 antibody, N11 or N5 antibody, the disclosure does not provide description of a particular structural features that imparts the claimed antibodies with their particular claimed binding function. Further, the specification does not explicitly or clearly describe the structure of the epitope to which the claimed antibodies are required to bind. Thus, the physical structure associated with the claimed function that defines the genera of antibodies is unclear.
Although the specification provides examples of four commercially available antibodies within the claimed genera (N6C, N7C, N5D, and N11D, as listed in Table 1), the specification does not identify any partial structure or other identifying characteristics that are responsible for imparting the claimed binding function. The specification fails to disclose, for example, what particular amino acid residues of the antibodies are responsible for conferring the desired functional property of binding to particular SARS-CoV-2 epitopes. Indefinite description of an epitope to which an antibody binds is insufficient to describe the antibodies themselves, since there is no structure-function correlation either disclosed or known in the art (as discussed below, antibody sequence does not correlate to binding in a predictable fashion). Accordingly, the disclosure of four species is not sufficient to reflect the breadth and variation within the genus. A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that would exhibit the claimed functional property of binding to epitopes of SARS-CoV-2 which are bound by N5, N6, N7 or N11 antibodies. The structural features common to the members of the genus are unknown.
Additionally, without a specific definition of what amino acid sequence or epitope comprises the epitope to which the claimed genera of antibodies bind, it is impossible to determine whether or not a particular antibody binds to the same epitope as antibodies N5, N6, N7, or N11.
There is a general lack of structure-function correlation for the claimed antibodies and the level of predictability in the art between the structure of an antibody and the epitope to which is binds is low. The general structure of antibodies was known in the art before the effective filing date. It was known that the CDRs of antibodies generally control antigen binding, but while CDRs are necessary for binding, they are highly diverse in structure, and their sequences do not correlate to binding in a predictable fashion. See for instance:
Goel et al. (“Plasticity within the Antigen Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response,” The Journal of Immunology (2004), 173(12):7358-7367), who made three antibodies that bind to the same 12-mer but have very different CDRs.
Lloyd et al. (“Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens,” Protein Engineering, Design & Selection (2009), 22(3):159-168) found that on average, about 120 different antibodies in a library can bind to a given antigen.
Edwards et al. (“The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BlyS,” Journal of Molecular Biology (2003), 334:103-118) found that a library contained over 1000 antibodies that bound to a single 51 kDa protein, including 1098 unique VH and 705 VL sequences. There were 568 different CDR3 regions, indicative of high diversity.
Furthermore, the level of predictability in the art is low, and more evidence would be necessary to support the scope of the claims. For example, given the unpredictability of antibody to epitope binding, the limitation that an antibody binds to a particular epitope is even broader in a case where the specific amino acid sequence of the epitope is not defined. The level of predictability in the art is low because even minor changes in antigen structure can profoundly affect antibody-antigen interaction. For example:
Harlow et al (Harlow, E. and Lane, D., Antibodies: A Laboratory Manual (1988) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pages 23-26), teach that the loss of a single hydrogen bond can dramatically affect the ability of an antibody to recognize a cognate antigen (Pg. 26, first full par.);
Lederman et al (“A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody OKT4” Mol Immunol. 1991 Nov; 28(11):1171-81) found that a single amino acid substitution on the antigen CD4 ablated binding of a monoclonal antibody (Abstract);
Colman et al (Research in Immunology, 1994; 145(1):33-36) teach that amino acid changes in an antigen can effectively abolish antibody antigen binding entirely (Pg. 33-34).
Regarding claim 10, the disclosure also does not define particular structural features that define the genus of antibodies represented by each given laboratory name, and does not clarify whether or not the laboratory names encompass more than one species of antibody. Although the specification provides examples of four commercially available antibodies within the claimed genera (N6C, N7C, N5D, and N11D, as listed in Table 1), the specification does not identify any partial structure or other identifying characteristics which define, for example, an N5 antibody or an N6 antibody. Additionally, the naming of specific commercially available antibodies which have names that are more particular than the lab names recited in the claims (e.g. N6 vs N6C or N11 vs N11D) indicates the possibility that what is claimed is broader than what is represented by the particularly recited species of commercially available antibodies. A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that fall within the claimed lab-named antibodies. The structural features common to the members of each genus are unknown. No prior art was found which discusses the structural features or requirements of each recited genus of lab-named antibodies, thus the predictability of the art in determining and envisioning the possible species of antibodies that fall within each genus is low.
Claims 17-18 further recite limitations regarding detection thresholds of the claimed system. This is understood to be a functional output which is due, at least in part, to the binding function and binding properties of the particular capture and detection antibodies used in the system. However, the particular structural features that are required of or common to the genus of antibodies that would fulfill this functional limitation are not defined in the instant disclosure. As such, one of ordinary skill in the art visualize or recognize the identity of the members of the genus of antibodies represented by these functional limitations.
Given the breadth of the claims, the lack of either a disclosed or art-recognized correlation between structure and function for the claimed genera of antibodies binding the claimed genera of epitopes, and the unpredictability associated with making changes to either antibody or antigen structure while preserving antibody binding function, one or ordinary skill in the art would not have envisioned possession of the claimed genera of antibodies having the claimed binding function.
Dependent claims 10-18 are rejected because they depend from a rejected claim and fail to remedy its deficiencies of written description.
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 9-18 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.
Claims 9-10 are rejected as indefinite over the recitation of antibodies by their lab names (i.e. N5, N6, N7, N11). The use of the laboratory name as the means for identifying claimed antibodies is indefinite because it presents confusion. Some laboratories may use the same laboratory designations to define completely distinct antibodies and/or hybridomas, such that the metes and bounds of an antibody or genus of antibody claimed by a lab name are unclear. Similarly, a catalog number as a sole means of identification would similarly render the claim indefinite because a catalog number is merely a commercial designation and does not clearly define a product. Further, the material sold under a given catalog number is subject to change.
This confusion is further compounded by the context of the instant specification, which lists slightly different names for each antibody. For example, Table 1 lists antibodies N6C, N7C, N5D, N11D and their catalog numbers as exemplary N5, N6, N7, and N11 antibodies, wherein it is unclear whether or how these differ in scope (i.e. is there a difference in scope between an N5 antibody and an N5D antibody? if so, what other species does the genus N5 encompass and how is this defined?). The metes and bounds of these terms are unclear.
Further, claim 9 encompasses “antibodies that bind to epitopes on the SARS-CoV-2 that are bound by N6 antibody, N7 antibody, N11 or N5 antibody”. This is indefinite because the epitopes bound by N5, N6, N7, or N11 antibodies are not explicitly or clearly defined in the instant disclosure, such that the scope of antibodies encompassed by this recitation or what binding function they need to have is unclear.
Claim 11 is vague regarding “the method”. There is no previous introduction of a method in claim 11 or any of the claims from which it depends, therefore there is insufficient antecedent basis for this limitation in the claim. Additionally there is a lack of connection between the claimed system and the method “performed in an assay device” because no assay device is recited in the system. Clarification is required
The recitation of “inactivating reagents” in claim 16 is unclear and indefinite. The metes and bounds of the term are unclear because it defines a reagent by a function, wherein the function itself is also unclear. What is being inactivated by an “inactivating reagent” and in what way? It is unclear what reagents do or do not fall within the scope of the term. Clarification is required.
Dependent claims 10-18 are rejected as indefinite because they depend from an indefinite claim and fail to remedy its deficiencies.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 11-13 and 16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 11 depends from the system of claim 9, however, the only limitations recited in the claim are relevant to a method performed in an assay device, wherein there is no recited link between “the method” or “an assay device” and the claimed system. Therefore, limitations regarding a method and an assay device recited in claims 11-12 do not further limit the system of claim 9.
Claims 13 and 16 depend from the system of claim 9, however only recite limitations regarding method steps in a process of using the system. A system claim is defined by what the system is (i.e. it’s physical properties and structures) and not by what it does (i.e. its intended use). As such, recitations regarding the intended use of the system fail to further limit the claimed system itself. See MPEP 2114 and 2115
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 9-10, 13, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Ogata et al (“Serial Profiling of SARS-CoV-2 antigens and antibodies in COVID-19 patient plasma,” MedRxiv, 26 July 2020, Pgs. 1-50; IDS entered) in view of R&D Systems (“SARS-CoV-2 nucleocapsid antibody”, 30 September 2020, Pgs. 1-2.; IDS entered).
Regarding claims 9-10, 13, 16-18, Ogata teaches a system for detecting the presence of SARS-CoV-2 in a fluid sample (Abstract), the system comprising:
a detection antibody that binds to a SARS-CoV-2 peptide, wherein the detection antibody is coupled to a detectable label (Pg. 20, Par. 2-3: Simoa assay comprising detector antibodies which are detected via an enzyme label);
A capture antibody that binds to a SARS-CoV-2 polypeptide, wherein the capture antibody is coupled to a matrix (Pg. 20, Par. 2-3: antibody conjugate capture beads; Pg. 22, Table S2 indicates capture antibodies that bind to a SARS-CoV-2 polypeptide).
Wherein the detection antibody is selected from the antibodies that bind to epitopes on the SARS-CoV-2 that are bound by N6 antibody, N7 antibody, N11 antibody, or N5 antibody (Pg. 22, Table S2 of Ogata includes detection antibody for SARS-CoV-2 nucleocapsid, Sino biological, 40143-R040 (i.e. antibody N5D according to instant specification Pg. 19, Table 1).
Ogata differs from the instant claim in that it does not explicitly teach the system wherein the capture antibody is selected from the antibodies that bind to epitopes on the SARS-CoV-2 that are bound by N6 antibody, N7 antibody , N11 antibody, or N5 antibody. However, as detailed in the 112(b) rejection above, the metes and bounds of the genus of antibodies that bind to epitopes on the SARS-CoV-2 that are bound by N6 antibody, N7 antibody , N11 antibody, or N5 antibody, such that it is not clear whether or not the capture antibody taught by Ogata, which specifically binds to an epitope of the SARS-CoV-2 nucleocapsid protein reads on this limitation of the claim.
R&D Systems discloses antibodies which bind specifically to epitopes of SARS-CoV-2. Specifically, R&D Systems discloses N6 antibody (as best interpreted in light of the 112(b) issues discussed above) (Pg. 1, SARS-CoV-2 Nucleocapsid antibody monoclonal mouse IgG2B clone#1035111, Catalog Number: MAB10474; see instant specification Pg. 19, Table 1 which indicates that this is antibody N6C).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Ogata such that the capture antibody comprises the N6 antibody taught by R&D system. Substitution of the anti-SARS-CoV-2 nucleocapsid capture antibody taught by Ogata for the anti-SARS-CoV-2 nucleocapsid N6 antibody taught by R&D systems amounts to simple substitution of known elements to achieve predictable results with a reasonable expectation of success because both the capture antibody taught by Ogata and the N6 antibody taught by R&D systems are antibodies which bind to epitopes of the nucleocapsid protein of SARS-CoV-2.
Regarding the additional limitations of claims 13 and 16, these are noted as recitations of intended use or limitations on the method of using the claimed system, as the limitations are directed to the method of using the claimed system but do not provide additional limitations on the physical features or structure of the claimed system itself. A recitation of intended use or method of using of a claimed product must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. In the instant case, Ogata in view of R&D systems teaches all structural and physical features of the claimed system, and therefore is understood to be sufficient to read on claims 13 and 16, regardless of whether the art explicitly teaches the same method of using the claimed system. See MPEP 2114 and 2115.
Regarding the additional limitations of claims 17-18, these are noted to be functional limitations of the claimed system which are understood to be an output which results from the recited structure of the claimed system, such that prior art which teaches all structural features of the claimed system is understood to meet the claim and is assumed to inherently be capable of the same functional output and same limits of detection, since there is no discernible difference between the system as claimed and the system of the prior art, and as no particular features of the claimed invention which are distinct from the prior art are identified as being responsible for producing the recited limits of detection. See MPEP 2112, 2114 and 2115.
Claims 9-18 are rejected under 35 U.S.C. 103 as being unpatentable over ProteinSimple (“Ella. You immunoassay Problem Solver”. Protein Simple a Biotechne Brand. Pgs. 1-8. 2017), hereinafter Ella, in view of Aldo et al (Simple Plex™: a novel multi-analyte, automated microfluidic immunoassay platform for the detection of human and mouse cytokines and chemokines. Am J Reprod Immunol2016; 75: 678–693), ProteinSimple (“SimplePlex: 48-Digoxigenin Cartridge Quick Start Guide”. ProteinSimple a Biotechne Brand. Pgs. 1-4. 2019), hereinafter SimplePlex, Ulrich et al (US 2024/0302369 A1) and R&D Systems (“SARS-CoV-2 nucleocapsid antibody”, 30 September 2020, Pgs. 1-2.; IDS entered).
It is noted that the instant specification specifically recites a known and commercially available immunoassay system and does not recite production or use of any other immunoassay system. Thus, the physical features of the system in the recited claim (with the exception of the particular combination of capture and detection antibodies used in the system) are acknowledged by the instant disclosure to have been known in the art and available before the effective filing date of the claimed invention. (see instant Specification Pg. 5, Ln. 24; Pg. 6, Ln. 23; Pg. 9, Ln. 9; Pg. 12, Ln. 15-18; Pg. 16, Ln. 3-10: embodiments of the invention include optimized and validated ELISA-based point-of-care antigen test for SARS-CoV-2 using an existing research use only platform named Ella ProteinSimple. Ella is a rapid, fully automated immunoassay platform that can run up to 72 samples loaded on a single cartridge in 80 mins with no additional labor required. The technology uses pneumatic pistons and valves to direct the sample through microfluidic channel and three GNRs where three sandwich ELISAs are captured per sample; Pg. 16, Ln. 11-12: Using Ella ProteinSimple’s 48-sample “open cartridge” platform which allows for the use of any combination of sample, capture and detection antibodies).
It is also noted that the instant specification specifically indicates that species of the instantly claimed capture and detection antibodies were known and commercially available prior to the effective filing date of the claimed invention (see instant specification, Pg. 17, Ln. 10-17).
These limitations are additionally addressed herein by the cited prior art which describes the same known and available immunoassay system and the same known and available antibodies.
Ella, Aldo, and SimplePlex all describe the features and use of the same commercially available immunoassay system (i.e. the Ella ProteinSimple SimplePlex immunoassay system). As such, features of the system disclosed in the different references are understood to be inherent features of the SimplePlex immunoassay system which was known and commercially available before the effective filing date of the claimed invention.
Regarding claims 9, 13, 16-18, Ella teaches a system for detection of a protein analyte in a fluid sample (Pg. 3, Par. 2: immunoassay for detecting a protein of interest), the system comprising:
a detection antibody that binds to the protein analyte, wherein the detection antibody is coupled to a detectable label (Figure 1: detection antibody coupled to a fluorescent tag binds the protein of interest); and
a capture antibody that binds to the protein analyte, wherein the capture antibody is coupled to a matrix (Pg. 3, Par. 2: microfluidic channels coated with a capture antibody that binds the protein of interest; Figure 1).
SimplePlex discloses the details and intended use of a particular cartridge which may be used in the immunoassay system described in Ella and which may be modified for use with any desired species of capture and detection antibody for the detection of a protein of interest (see Pgs. 1-4) (see also, instant specification Pg. 16, Ln. 11-12 which describes the same cartridge used in the same immunoassay system).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the particular 48-Digoxigenin Cartridge described in SimplePlex in the immunoassay system disclosed in Ella. One would be motivated to use the 48-Digoxigenin Cartridge because it may be modified for the use of any desired species of capture and detection antibodies for the detection of a protein of interest. One of ordinary skill in the art would have a reasonable expectation of success in using this cartridge in the immunoassay system because the 48-Digoxigenin Cartridge is explicitly disclosed as a cartridge intended to be used within the Ella ProteinSimple SimplePlex immunoassay system described in both Ella and SimplePlex.
The cited references which describe the Ella ProteinSimple SimplePlex immunoassay do not explicitly teach the system comprising N5, N6, N7, or N11 antibodies (or antibodies which bind to the same epitopes). Rather, the references describe an immunoassay system which can be modified for use with any desired species of capture and detection antibodies for a sandwich immunoassay to detect a protein of interest.
Ulrich discloses immunoassay systems and methods for the detection of peptides from coronavirus, including detection of SARS-CoV-2 nucleocapsid protein by a sandwich immunoassay comprising an immobilized capture antibody that specifically binds to the target protein and a labeled detection antibody that specifically binds to the target protein (Abstract; Par. 112: an immobilized capture antibody and a labeled detection antibody which bind to the protein of interest may be used to detect SARS-CoV-2; Par. 19, 24: protein of interest may be SARS-CoV-2 nucleocapsid protein). Ulrich teaches that a wide variety of anti-SARS-CoV-2 antibodies can be used as the capture and detection antibodies, including antibodies which bind to the nucleocapsid protein, such as N5 antibody (as best interpreted in light of the 112(b) issues identified above) (Table 1: anti-nucleocapsid antibody 40143-R040 from Sino Biological).
R&D Systems discloses antibodies which bind specifically to epitopes of SARS-CoV-2. Specifically, R&D Systems discloses N6 antibody (as best interpreted in light of the 112(b) issues discussed above) (Pg. 1, SARS-CoV-2 Nucleocapsid antibody monoclonal mouse IgG2B clone#1035111, Catalog Number: MAB10474; see instant specification Pg. 19, Table 1 which indicates that this is antibody N6C).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the Ella ProteinSimple SimplePlex immunoassay system such that N5 and N6 are the capture and/or detection antibodies used for detection of SARS-CoV-2 nucleocapsid protein, as taught by Ulrich and R&D Systems. One would be motivated to modify the system for the detection of SARS-CoV-2 nucleocapsid protein because Ulrich teaches that detection of SARS-CoV-2 nucleocapsid protein is important and useful for detecting presence of SARS-CoV-2 virus and infection (Abstract; Par. 6). One would be motivated to use the N5 antibody (40143-R040) taught by Ulrich and the N6 antibody (SARS-CoV-2 Nucleocapsid antibody monoclonal mouse IgG2B clone#1035111, Catalog Number: MAB10474) taught by R&D systems because Ulrich and R&D systems teach that these antibodies specifically bind to SARS-CoV-2 nucleocapsid protein, and thus are appropriate for use as capture and detection antibodies in a sandwich immunoassay for detecting SARS-CoV-2 nucleocapsid protein. Additionally, one would be motivated to try different combinations of capture and detection antibodies in order to find combinations which might improve assay sensitivity and specificity for detection of the protein of interest. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because the references teach that the Ella ProteinSimple SimplePlex immunoassay system can be used with different capture and detection antibodies to perform a sandwich immunoassay for the detection of a protein analyte; Ulrich teaches that a sandwich immunoassay comprising capture and detection antibodies which specifically bind to SARS-CoV-2 nucleocapsid protein can be used to detect the nucleocapsid protein; and Ulrich and R&D systems teach particular species of antibodies which specifically bind to SARS-CoV-2 nucleocapsid protein.
Regarding the additional limitations of claims 13 and 16, these are noted as recitations of intended use or limitations on the method of using the claimed system, as the limitations are directed to the method of using the claimed system but do not provide additional limitations on the physical features or structure of the claimed system itself. A recitation of intended use or method of using of a claimed product must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. In the instant case, the cited prior art teaches all structural and physical features of the claimed system, and therefore is understood to be sufficient to read on claims 13 and 16, regardless of whether the art explicitly teaches the same method of using the claimed system. See MPEP 2114 and 2115.
Regarding the additional limitations of claims 17-18, these are noted to be functional limitations of the claimed system which are understood to be an output which results from the recited structure of the claimed system, such that prior art which teaches all structural features of the claimed system is understood to meet the claim and is assumed to inherently be capable of the same functional output and same limits of detection, since there is no discernible difference between the system as claimed and the system of the prior art, and as no particular features of the claimed invention which are distinct from the prior art are identified as being responsible for producing the recited limits of detection. This is especially true in the instant case wherein the instant disclosure explicitly recites use of the same commercially available immunoassay system and antibodies disclosed in the prior art. See MPEP 2112, 2114 and 2115.
Regarding claim 11, Ella further teaches the system comprising an assay device comprising microfluidic channels wherein capture and detection antibody are coupled to one or more regions within the microfluidic channels (Figure 1: shows capture and detection antibodies coupled to one or more regions within the microfluidic channels; Pg. 3, Par. 2: each microfluidic channel is coated with a capture antibody).
Regarding claim 12, Ella further teaches the detection antibody coupled to a fluorescent label (Figure 1). Ella further teaches a system comprising means for moving fluid sample into a region where the capture antibody is coupled to a matrix (Pg. 3, Par. 2; Figure 1), but does not explicitly teach the means comprising pneumatic pistons and valves which may move the fluid sample into a region where the capture antibody is coupled to a matrix.
Aldo is a reference which describes the use of the Ella ProteinSimple SimplePlex immunoassay system for the measurement of proteins in a fluid sample (i.e. Aldo describes the same commercially available system described in Ella) (Pg. 678, Par. 2: cytokine and chemokine expression levels in serum determined using SimplePlex cartridges from ProteinSimple). Aldo further teaches that the SimplePlex immunoassay system (i.e. the same system described in Ella) comprises pneumatic pistons and valves which move fluid sample into a region where the capture antibody is coupled to a matrix (Pg. 682, Col. 1, last Par.-Col. 2, first Par.: each test sample is actively drawn and split into discrete parallel channels by a combination of micropumps and valves) (see also, instant specification Pg. 16, Ln. 5-7).
Thus, the teachings of both Ella and Aldo, which describe the same immunoassay system which was known and available before the effective filing date of the claimed invention are understood to read on instant claim 12.
As discussed above, claim 12 contains multiple recitations of intended use. A recitation of intended use or method of using of a claimed product must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. In the instant case, the cited prior art teaches all structural and physical features of the claimed system, and therefore is understood to be sufficient to read on claim 12, regardless of whether the art explicitly teaches the same method of using the claimed system. See MPEP 2114 and 2115.
Regarding claims 14-15, SimplePlex teaches the capture and detection antibodies are each present in concentrations of about 1-10ug/ml (Pg. 4, Pipette Cartridge, Step 2: start with 3.5 ug/mL for both the capture and detection reagents).
As such, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have capture and detection antibodies each present in concentration of about 1-10ug/ml. One would be motivated to provide antibodies in this concentration because one would be motivated to use reagents in the proper concentration for the cartridge used with the system. One of ordinary skill in the art would have a reasonable expectation of success in using these concentrations because they are explicitly recommended by the instructions for use of the immunoassay system and cartridge.
Conclusion
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677
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