DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of invention I in the reply filed on 9/29/25 is acknowledged.
Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/29/25.
Claims 1-16 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/9/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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. Presently, page 2-line 28 possesses a hyperlink.
Allowable Subject Matter
SEQ ID NO:s 4-6 are free of the prior art of record.
Claim Interpretation
Claims 2, 13 and 16 recite, “at least 90% sequence similarity…”. The specification on page 10, lines 22-23 states: ‘polypeptide "having at least 90% sequence similarity" refers to a polypeptide having 90%, 91%, 92%, 93%, 94%, 95%, 96,%, 97%, 98%, 99% or 100% similarity to the reference polypeptide.’ Therefore, the claim limitation of “at least 90% sequence similarity” will be interpreted to include polypeptides that are homologous to the claimed polypeptide, but not possessing an amino acid sequence with at least 90% sequence identity to that claimed polypeptide.
Claim Rejections - 35 USC § 112
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 1-16 are 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 detecting antibodies reactive to CMV UL144 when using the UL144 proteins of SEQ ID NO:s 4, 5 and/or 6, does not reasonably provide enablement for selectively detecting CMVs by using a fragment of a UL144 or a polypeptide having at least 90% similarity with a UL144 from serotypes A, B and C or at least 90% similarity to SEQ ID NO:s 4, 5 or 6. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Nature of the invention/Breadth of the claims. The claims are drawn to an immunoassay kit for selectively detecting cytomegalovirus in a biological sample, the kit comprising:
A capture reagent comprising a fragment of UL144 protein, and
A detection reagent.
The capture reagent comprises a UL144 protein selected from one of SEQ ID NOs:4-6 or a sequence having about at least 90% sequence similarity to one of SEQ ID NOs: 4-6.
The immunoassay is also a multiplex assay capable of detecting two or more CMV serotypes in a sample, the immunoassay comprising:a) a first capture reagent to a first serotype and a second capture reagent to a second serotype, wherein the two capture reagents are in different detection zones in the assay; and
b) the detection reagent, wherein the two different detection zones are able to detect the two or more CMV serotypes in the sample.
The first, second and third capture reagents are elected from:
UL144A protein of serotype A of SEQ ID NO:4 or a polypeptide having about at least 90% sequence similarity to UL144A serotype A;
UL144A protein of serotype B of SEQ ID NO:5 or a polypeptide having about at least 90% sequence similarity to UL144A serotype B; and
UL144A protein of serotype C of SEQ ID NO:6 or a polypeptide having about at least 90% sequence similarity to UL144A serotype C.
As shown in the following sequence alignments, SEQ ID NO:s 4, 5 and 6 share considerable amino acid sequence identity.
SEQ ID NO: 4 aligned with SEQ ID NO: 5
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SEQ ID NO: 4 aligned with SEQ ID NO: 6
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SEQ ID NO: 5 aligned with SEQ ID NO: 6
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State of the prior art/Predictability of the art. Miller et al. (infra) teach using CMV UL144 fragments, which are the same as SEQ ID NO:s 4, 5 and 6 of the instant invention, can detect antibodies present in serum collected from humans. However, Miller et al. also teach that using these UL144 fragments (Assay UL144A, Assay UL144B and Assay UL144C) did not reliably detect CMV in a selective manner. Miller et al. summarized that serum samples and their ability to bind to the UL144 proteins. For example, Miller et al, states “Thirty-nine samples showed reactivity to more than one UL144 antigen, likely due to antibody recognition of shared epitopes, infection with a recombinant UL144 strain, or infection with more than one UL144 subtype. Twelve (16%) were reactive to UL144 A and B, seven (9.3%) to UL144 B and C, four to UL144 A and C (5.3%), and 16 (21.3%) to A, B, and C. [see first paragraph on page 4]
Guidance in the specification. The specification provides guidance towards using fragments of UL144 to selectively detect different serotypes of CMV.
Amount of experimentation necessary. Additional research is required in order to determine how effective a fragment of UL144, as presently claimed, would be capable of selectively detecting CMV in a biological sample.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed methods.
Claims 1-16 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 BU 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 1-16 are rejected as lacking adequate descriptive support for a possession of an
CMV immunoassay kit comprising:
(a)A capture reagent comprising a fragment of UL144 protein, and
(b)A detection reagent.
The detection reagent is a detectable antibody, such as a monoclonal antibody.
The claimed monoclonal antibody is not defined by any structure, such as the 6 CDRs of the variable domains. For the purposes of this rejection, the monoclonal antibody is capable of detecting a substance that binds to the UL144 fragment.
In support of the claimed genus of an “the monoclonal antibody is a detection reagent” The specification discloses anti-Human IgG antibody (109-065-088, Jackson Immunoresearch, West Grove, PA). No derivatives or variants or mutants thereof are disclosed that can function as detection reagent which would bind to a substance that binds to the UL144 fragment. Thus, the application fails to provide a representative number of examples of an monoclonal antibody that can function as a detection reagent.
Moreover, the decision arrived at in Amgen Inc. v. Sanofi, 598 U.S. (2023) supports expanded analysis of whether a claim drawn to an antibody being specific for an epitope, even a specific epitope, permits an applicant to pursue all possible antibodies that are capable of being produced against such an epitope. Presently, the claimed monoclonal antibody detection reagent is only defined by functional properties but no specific structure is recited by the claims. In view of the fact patterns detailed in Amgen v. Sanofi, applicants are in possession of the detection reagent of a monoclonal antibody of anti-Human IgG antibody (109-065-088, Jackson Immunoresearch, West Grove, PA).
In view of this uncertainty and the lack of a representative number of examples of the claimed genus, the claims are rejected for lack of adequate written description support.
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 1-16 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 1 recites, “An immunoassay kit for selectively detecting cytomegalovirus in a biological sample, the kit comprising a capture reagent comprising a fragment of UL144…”; and
claim 11 recites, “…a multiplex assay capable of detecting two or more CMV serotypes in a sample…wherein the two different detection zones are able to detect the two or more serotypes in the sample.”
However, the kit uses a fragment of UL144, which will capture and bind to any antibodies present in the biological sample. Therefore, the kit detects CMV UL144 specific antibodies but not CMV or serotypes of CMV. More specifically, the presence of the antibodies would be indicative of prior exposure to CMV, but the virus itself is not being detected by this kit. Therefore, the intended use and goal of detecting two serotypes of CMV of claims 1 and 11 are unclear since the kit as described would not achieve these limitations.
Claims 2-10 and 12-16 are also rejected because they depend from claim 1 or 11 but do not remedy this deficiency.
Claims 2 recites “wherein the capture reagent comprises a UL144 protein selected from one of SEQ ID NO:s 4-6…”;
claim 13 recites, “i) UL144A protein of serotype A or a polypeptide having about at least 90% sequence similarity to UL144A serotype A;
UL144A protein of serotype B or a polypeptide having about at least 90% sequence similarity to UL144A serotype B; and
UL144A protein of serotype C or a polypeptide having about at least 90% sequence similarity to UL144A serotype C” and
claim 16 recites, “i) UL144A protein of serotype A of SEQ ID NO:4 or a polypeptide having about at least 90% sequence similarity to UL144A serotype A;
UL144A protein of serotype B of SEQ ID NO:5 or a polypeptide having about at least 90% sequence similarity to UL144A serotype B; and
UL144A protein of serotype C of SEQ ID NO:6 or a polypeptide having about at least 90% sequence similarity to UL144A serotype C.”
However, claim 1, which these claims depend from, states that a fragment of UL144 is the capture reagent, but claims 2, 13 and 16 require that UL144 (UL144A, UL144B and UL144C) is the capture reagent, which reads on full-length UL144 proteins. Therefore, it is unclear if full-length UL144 is permitted to be part of this kit or only fragments thereof.
Claim 8 recites, “The immunoassay kit of claim 1, wherein the detection reagent is biotinylated and the kit further comprises avidin or streptavidin-peroxidase and 3,3',5,5'- tetramethyl benzidine.” However, it is unclear if the kit further comprises avidin; streptavidin-peroxidase and 3,3',5,5'- tetramethyl benzidine; or avidin and 3,3',5,5'- tetramethyl benzidine.
Claim 13 recites, “i) UL144A protein of serotype A or a polypeptide having about at least 90% sequence similarity to UL144A serotype A;
ii)UL144A protein of serotype B or a polypeptide having about at least 90% sequence similarity to UL144A serotype B; and
iii)UL144A protein of serotype C or a polypeptide having about at least 90% sequence similarity to UL144A serotype C”
and
claim 16 recites,
“i) UL144A protein of serotype A of SEQ ID NO:4 or a polypeptide having about at least 90% sequence similarity to UL144A serotype A;
UL144A protein of serotype B of SEQ ID NO:5 or a polypeptide having about at least 90% sequence similarity to UL144A serotype B; and
UL144A protein of serotype C of SEQ ID NO:6 or a polypeptide having about at least 90% sequence similarity to UL144A serotype C.”
However, for serotypes B and C in claims 13 and 16, it is unclear if UL144A should be the protein required or UL144B and UL144C, respectively.
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.
Claim(s) 1-14 and 16 are rejected under 35 U.S.C. 102a1 as being anticipated by Miller et al. (Journal of Clinical Microbiology, 2021, Vol. 59, Issue 8, pages 1-8, published 7/19/2021).
The claimed invention is drawn to an immunoassay kit for selectively detecting cytomegalovirus in a biological sample, the kit comprising:
A capture reagent comprising a fragment of UL144 protein, and
A detection reagent.
The capture reagent is attached to a solid or semi-solid support or coated on a microtiter plate and the capture reagent comprises a UL144 protein selected from one of SEQ ID NOs:4-6 or a sequence having about at least 90% sequence similarity to one of SEQ ID NOs: 4-6.
The detection reagent is a detectable antibody, such as a monoclonal antibody.
The detection reagent is biotinylated and the kit further comprises avidin or streptavidin-peroxidase and 3,3’5,5’-tetramethyl benzidine.
The kit further comprises reagents for colorimetric detection and a fluorometric reagent that amplifies the signal of the detection reagent in a detection buffer.
The immunoassay is a multiplex assay capable of detecting two or more CMV serotypes in a sample, the immunoassay comprising:a) a first capture reagent to a first serotype and a second capture reagent to a second serotype, wherein the two capture reagents are in different detection zones in the assay; and
b) the detection reagent, wherein the two different detection zones are able to detect the two or more CMV serotypes in the sample.
The detection zones are either separate wells on a microtiter plate or are separate channels in a lateral flow device.
The first, second and third capture reagents are elected from:
i)UL144A protein of serotype A of SEQ ID NO:4 or a polypeptide having about at least 90% sequence similarity to UL144A serotype A;
ii)UL144A protein of serotype B of SEQ ID NO:5 or a polypeptide having about at least 90% sequence similarity to UL144A serotype B; and
iii) UL144A protein of serotype C of SEQ ID NO:6 or a polypeptide having about at least 90% sequence similarity to UL144A serotype C.
Miller et al. teach a immunoassay for detecting different serotypes of cytomegalovirus (CMV). In order to achieve this, Miller et al. utilize 3 different recombinant fragments of UL144 that possess a heterologous linker, truncated C-terminal end and an attached histidine tag at the truncated C-terminal end. The resulting fragments are labeled Assay UL144A, Assay Ul144B and Assay UL144C. [see supplemental figure 1 below]
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The Assay UL144A, Assay UL144B and Assay UL144C proteins are identical to SEQ ID NO: 4, 5 and 6, respectively. Miller et al. also teach that these proteins are attached to separate wells in a 96 well microtiter plate, which is a solid support. [see page 2, 6th paragraph] Serum was collected from patients and applied to the microtiter plate in order for antibodies specific for CMV to be detected by using a secondary antibody (detection reagent). The secondary antibody is a monoclonal anti-human IgG antibody that has biotin conjugated to it. Any bound secondary antibody was detected by using Streptavidin-horse radish perioxidase and 3,3’,5,5’ tetramethyl bensizidine to yield a colored signal. [see page 3, first paragraph] Based on these teachings of Miller et al., the fluorometric reagent includes horseradish peroxidase. [see page 9, lines 21-25 of specification] Miller et al. also teach a multiplex assay that can detect antibodies present in a biological sample that are specific for UL144 of CMV. [see figure 2 and first paragraph of page 4]
Therefore, Miller et al. anticipates the instant invention.
Claim(s) 1, 2, 9 and 10 are rejected under 35 U.S.C. 102a1 as being anticipated by Cheung et al. (US PGPub 2009/0311280).
The claimed invention is drawn to an immunoassay kit for selectively detecting cytomegalovirus in a biological sample, the kit comprising:
A capture reagent comprising a fragment of UL144 protein, and
A detection reagent.
The capture reagent comprises a UL144 protein selected from one of SEQ ID NOs:4-6 or a sequence having about at least 90% sequence similarity to one of SEQ ID NOs: 4-6.
The kit further comprises reagents for colorimetric detection and a fluorometric reagent that amplifies the signal of the detection reagent in a detection buffer.
Cheung et al. teach the human CMV (hCMV) UL144 [see paragraph 99] binds to B and T lymphocyte attenuator (BTLA). [see abstract] In Examples 6 and 7 of Cheung et al., hCMV UL144 from 5 different serotypes of hCMV are expressed in transfected HEK 293T cells. Each of these UL144 expressing cells were separately incubated with BTLA-Fc proteins and any binding by the BTLA-Fc confirmed expression of the UL144 protein. [see figure 8A and paragraph 237] In order to detect binding of UL144 by BTLA-Fc, Cheung et al. used a stain and analyzed any binding with flow cytometry. [see paragraph 237] In addition, the hCMV UL144 employed [see paragraph 99] shares sequence similarity to SEQ ID NO: 4 of the instant invention. [see alignment below between the UL144 of Cheung and SEQ ID NO: 4]
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While Cheung et al. do not state they are detecting CMV in a sample, the claim recites an intended use of the claimed kit.
MPEP § 2111.02 (II) recites, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the pre-amble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limita-tions, then the preamble is not considered a limitation and is of no significance to claim construction.” Therefore, the intended use of “for selectively detecting cytomegalovirus in a biological sample” is not considered a limitation to be considered in this prior art rejection.
Therefore, since Cheung et al. teach a capture reagent (UL144), a detection reagent (BTLA-Fc) and reagents for colorimetric detection and a fluorometric reagent that amplifies the signal of the detection reagent in a detection buffer (stain suitable for flow cytometry and conducting flow cytometry), the claimed product is anticipated.
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.
Claim(s) 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US PGPub 20190127422), La Caze (WO/2019/232453) and Cheung et al. (supra).
The claimed invention is drawn to an immunoassay kit for selectively detecting cytomegalovirus in a biological sample, the kit comprising:
(a)A capture reagent comprising a fragment of UL144 protein, and
(b)A detection reagent.
The capture reagent is attached to a solid or semi-solid support or coated on a microtiter plate and the capture reagent comprises a UL144 protein selected from one of SEQ ID NOs:4-6 or a sequence having about at least 90% sequence similarity to one of SEQ ID NOs: 4-6.
The detection reagent is a detectable antibody, such as a monoclonal antibody.
The detection reagent is biotinylated and the kit further comprises avidin or streptavidin-peroxidase and 3,3’5,5’-tetramethyl benzidine.
The kit further comprises reagents for colorimetric detection and a fluorometric reagent that amplifies the signal of the detection reagent in a detection buffer.
The immunoassay is a multiplex assay capable of detecting two or more CMV serotypes in a sample, the immunoassay comprising:a) a first capture reagent to a first serotype and a second capture reagent to a second serotype, wherein the two capture reagents are in different detection zones in the assay; and
b) the detection reagent, wherein the two different detection zones are able to detect the two or more CMV serotypes in the sample.
The detection zones are either separate wells on a microtiter plate or are separate channels in a lateral flow device.
The first, second and third capture reagents are elected from:
i)UL144A protein of serotype A of SEQ ID NO:4 or a polypeptide having about at least 90% sequence similarity to UL144A serotype A;
ii)UL144A protein of serotype B of SEQ ID NO:5 or a polypeptide having about at least 90% sequence similarity to UL144A serotype B; and
iii) UL144A protein of serotype C of SEQ ID NO:6 or a polypeptide having about at least 90% sequence similarity to UL144A serotype C.
*For the purpose of this rejection, the claimed invention will be interpreted to require a full-length UL144 protein or a fragment of UL144 with amino acid sequence identity to SEQ ID NO: 4, which meets the claimed requirement and the intend of the kit is to detect anti-CMV antibodies.
Yang et al., at paragraph 171, teach recombinant polypeptides which react immunologically with serum containing CMV antibodies. For example, the immunoassay may utilize the polypeptide having the sequence set forth in SEQ ID NO: 2. Alternatively, the immunoassay may use a combination of viral antigens derived from the gB polypeptides described herein. It may use, for example, a monoclonal antibody directed towards one modified gB polypeptides described herein, a combination of monoclonal antibodies directed towards the modified gB polypeptides described herein, monoclonal antibodies directed towards different viral antigens, polyclonal antibodies directed towards the modified gB polypeptides described herein, or polyclonal antibodies directed towards different viral antigens. Protocols may also, for example, use solid supports. Assays involve the use of labeled antibody or polypeptide; the labels may be, for example, fluorescent, chemiluminescent, radioactive, or dye molecules. Assays which amplify the signals from the probe are also known; examples of which are assays which utilize biotin and avidin, and enzyme-labeled and mediated immunoassays, such as ELISA assays. [see paragraph 171] Yang et al. also teach kits suitable for immunodiagnosis and containing the appropriate labeled reagents are constructed by packaging the appropriate materials, including the recombinant polypeptides of the invention containing CMV epitopes or antibodies directed against epitopes in suitable containers, along with the remaining reagents and materials required for the conduct of the assay, as well as a suitable set of assay instructions.
Yang et al. provide an example of an immunoassay in which monoclonal antibodies were tested for binding to hcmv gB. Cell culture supernatants from gB705 transfected Expi293F cells were added on a pre-blocked HISGRAB™ Nickel Coated plate and incubated for 1 hour at room temperature. After wash, serial diluted antibody solutions were added to the plate and incubated for 1 hour at room temperature, followed by addition of HRP-conjugated anti-human IgG secondary antibody. After 1 hour incubation, the plate was washed and the peroxidase substrate TMB was added to be read by a plate reader when the color was developed. The results showed all five human anti-gB mAbs bound efficiently to gB705 (FIG. 4A). [see paragraph 199] The use of the HRP conjugated IgG and TMB substrate meet the requirements of reagents for colorimetric detection and a fluorometric reagent that amplifies the signal of the detection reagent in a detection buffer.
However, Yang et al. do not teach the use of fragments of UL144 or a UL144 with at least 90% sequence similarity to SEQ ID NO:s 4-6; the use of a lateral flow device with UL144 fragments in different detection zones or a multi-well plate.
La Caze teach immunoassay kits for detecting anti-CMV IgG and/or IgM monoclonal antibodies. La Case teach a capture molecule of interest, such as a CMV antigen can be immobilized on a solid phase, such as the surface of a multi-well plate. [see paragraphs 33 and 86] If anti-CMV IgG and/or IgM antibodies are present in a sample, these antibodies would bind to the immobilized CMV antigen and their binding can be directly identified (with an attached detectable moiety) or indirectly identified by using a monoclonal antibody having a detectable moiety that is specific for the IgG or IgM Fc region. [see paragraph 33] La Caze teach detectable moieties of “fluorophores, quantum dots, enzymes, substrates, metal particles, radiolabels, dyes and the like.” [see paragraph 33] It is also taught that immunoassays can be ELISAs, lateral flow systems or no-wash assays. [see paragraphs 34 and 86 and Example 3]
Cheung et al. teach the human CMV (hCMV) UL144 [see paragraph 99] binds to B and T lymphocyte attenuator (BTLA). [see abstract] In Examples 6 and 7 of Cheung et al., hCMV UL144 from 5 different serotypes of hCMV are expressed in transfected HEK 293T cells. Each of these UL144 expressing cells were separately incubated with BTLA-Fc proteins and any binding by the BTLA-Fc confirmed expression of the UL144 protein. [see figure 8A and paragraph 237] In order to detect binding of UL144 by BTLA-Fc, Cheung et al. used a stain and analyzed any binding with flow cytometry. [see paragraph 237] In addition, the hCMV UL144 employed [see paragraph 99] shares significant sequence identity to SEQ ID NO: 4 of the instant invention. [see alignment below between the UL144 of Cheung and SEQ ID NO: 4] Cheung et al. also teach additional UL144 proteins from different serotypes of CMV that share significant sequence identity with SEQ ID NO:s 5 and 6.
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SEQ ID NO: 5 aligned with AF179198 from Cheung et al.
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SEQ ID NO: 6 aligned with AF179199 of Cheung et al.
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While Cheung et al. do not state they are detecting CMV in a sample, the claim recites an intended use of the claimed kit.
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Yang et al. in order to utilize UL144; the use of a lateral flow device with UL144 fragments in different detection zones or a multi-well plate in order to detect antibodies specific for cmv. One would have been motivated to do so, given the suggestion by Yang et al. teach the detection of cmv specific antibodies by using cmv proteins as part of an immunoassay, which include immobilizing a cmv protein to a plate/solid support. There would have been a reasonable expectation of success, given the knowledge that cmv specific antibodies, such as IgG and IgM, can be detected by immobilizing cmv proteins on multi-well plates or lateral flow devides as part of an immunoassay, as taught by La Caze, and also given the knowledge that hCMV UL144 from serotypes A, B and C of hCMV, with significant sequence identity to SEQ ID NO:s 4-6, can be used to test for binding of ligands and detection reagents, as taught by Cheung et al. 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
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671