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Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 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Specification Objection-Withdrawn in view of amendment
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 1, 11, 12 and 13 recite, “at least 95% sequence similarity…”. The specification on page 10, lines 22-23 states: ‘polypeptide "at least 95% 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 95% 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 95% sequence identity to that claimed polypeptide.
Response to Amendment
The declaration under 37 CFR 1.130 filed 6/29/26 is sufficient to overcome the rejection of claims 1-14 and 16 based upon 35 USC 102a1 based on Miller et al. (Journal of Clinical Microbiology, 2021, Vol. 59, Issue 9, pages 1-8).
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.
(Prior rejection withdrawn in view of amendments) 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 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.
(Prior rejection maintained) 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
The claimed invention is drawn to an immunoassay kit comprising:
a capture reagent comprising one of SEQ ID NO:s 4-6 or a sequence having about at least 95% sequence similarity to one of SEQ ID NO:s 4-6, and
a detection reagent, wherein the detection reagent is an anti-human immunoglobulin antibody.
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 detection reagent is a monoclonal antibody capable of detecting a human antibody. However, the human antibody to be detected by the detection reagent is not identified by what it may bind.
In support of the claimed genus of an “the anti-human immunoglobulin antibody is also interpreted as a monoclonal antibody”. 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 human immunoglobulin. Thus, the application fails to provide a representative number of examples of an monoclonal antibody that can function as a detection reagent of a human immunoglobulin.
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.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
Applicants argue that anti-human immunoglobulin antibodies are well known and characterized reagents in the field and therefore the person of ordinary skill in the art would understand that the inventor was in possession of the claimed invention at the time of filing.
In response, the Examiner acknowledges that anti-human antibodies are available and commonly used in immune assays. Applicants have used such an antibody in their specification, i.e., anti-Human IgG antibody (109-065-088, Jackson Immunoresearch, West Grove, PA). However, these antibodies are specific for a target epitope and are defined by a unique combination of 6 CDRs that interact with the epitope. Applicants are claiming an anti-human immunoglobulin antibody, which would be capable of binding the any human Ig. Furthermore, the claims do not require that the human immunoglobulin to be bound is specific for SEQ ID NO:s 4, 5 or 6. From applicant’s specification and claims, little is known about the claimed detection reagent, other than it is an antibody that can bind to a human antibody and the detection reagent might be a monoclonal antibody. 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.
(Prior rejections withdrawn in view of amendments) 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.
(New rejection necessitated by amendment) Claim 16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 recites the limitation "multiplex" in line 1. There is insufficient antecedent basis for this limitation in the claim.
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.
(Rejection withdrawn in view of declaration) 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).
(Rejection withdrawn in view of amendments) Claim(s) 1, 9 and 10 are rejected under 35 U.S.C. 102a1 as being anticipated by Cheung et al. (US PGPub 2009/0311280).
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.
(Prior rejection maintained and extended to new limitations) Claim(s) 1 and 3-15 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. (US PGPub 2009/0311280).
The claimed invention is drawn to an immunoassay kit comprising:
a capture reagent comprising one of SEQ ID NO:s 4-6 or a sequence having about at least 95% sequence similarity to one of SEQ ID NO:s 4-6, and
a detection reagent, wherein the detection reagent is an anti-human immunoglobulin antibody.
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 95% 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) a polypeptide having about at least 95% sequence similarity to SEQ ID NO: 4
ii) a polypeptide having about at least 95% sequence similarity to SEQ ID NO: 5 and
iii) a polypeptide having about at least 95% sequence similarity to SEQ ID NO: 6.
*For the purpose of this rejection, the claimed invention will be interpreted to require a full-length UL144 protein or a UL144 with amino acid sequence similarity to SEQ ID NO:s 4-6, which meets the claimed requirement of sequences having at least 95% sequence similarity to SEQ ID NO:s 4-6 as discussed above.
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 CMV UL144 with at least 95% 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 use of human CMV (hCMV) UL144 to screen for binding to B and T lymphocyte attenuator (BTLA) or test agents (antibodies) that will interfere with binding to BTLA. [see abstract and paragraph 99] 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.
SEQ ID NO: 4 aligned with AF179198 from Cheung et al.
PNG
media_image1.png
257
518
media_image1.png
Greyscale
SEQ ID NO: 5 aligned with AF179198 from Cheung et al.
PNG
media_image2.png
310
535
media_image2.png
Greyscale
SEQ ID NO: 6 aligned with AF179199 of Cheung et al.
PNG
media_image3.png
294
528
media_image3.png
Greyscale
Therefore, these sequence similarities with SEQ ID NO:s 4-6 meet the claimed requirements of at least 95% sequence similarity to SEQ ID NO:s 4, 5 and 6 (see Claim Interpretation section above and page 10 of the instant specification).
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 devices as part of an immunoassay, as taught by La Caze, and also given the knowledge that hCMV UL144, with significant sequence similarity 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.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
Applicants state that by amending the claims to require at least 95 % similarity to SEQ ID NO: 4-6, the rejection is overcome.
As stated in the previous Office action and repeated above, claims 1, 11, 12 and 13 recite, “at least 95% sequence similarity…”. The specification on page 10, lines 22-23 states: ‘polypeptide "at least 95% 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 95% 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 95% sequence identity to that claimed polypeptide. More specifically, “sequence similarity” as defined by applicants, is not the same as “sequence identity”. Therefore, the teaching of Yang et al., La Caze and Cheung et al. render prima facie obvious the claimed invention.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
Prosecution Insights