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 .
Response to Amendment
The Amendment filed 11/04/2025 in which claims 1-3, 8, 9, 13, 18, were amended, claim 7 was canceled, and new claim 37 was added, has been entered. Claims 24-26, 28, 30-31, 33 were previously withdrawn.
Claims 1-3, 5-6, 8-9, 13, 17-18, 34-35, 37 are under examination on the merits.
Drawings
(Previous objection, withdrawn) Applicant’s amendments to the Drawings submitted on 11/04/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 08/08/2025.
Specification
(Previous objection, withdrawn) Applicant’s amendments to the Specification submitted on 11/04/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 08/08/2025.
Nucleotide and/or Amino Acid Sequence Disclosures
(Previous objection, withdrawn) Applicant’s amendments to the Specification concerning nucleotide and/or amino acid sequence disclosures submitted on 11/04/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 08/08/2025.
Claim Objections
(Previous objections, withdrawn as to claims 1, 2, 8, 9 and 13). Applicant’s amendments to the instant claims have overcome previous objections previously set forth in the Non-Final Office Action mailed 06/30/2025.
Claim Rejections - 35 USC § 112
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.
(Previous rejection, withdrawn as to claims 3, 5, 6, and 18) Claims 3, 5, 6, and 18 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite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.
See claims 3, 5, 6, and 18 as submitted on 11/04/2025.
Applicant’s amendments to claims 3 and 18 have overcome previous rejection to claims 3, 5, 6, and 18.
(New rejection, necessitated by amendment as to claim 18) Claim 18 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 18, recites “wherein said peptide probes are selected from SEQ ID NO: 5-213”. It is not clear if Applicant intended to recite “comprising”, “consisting essentially of” or “consisting of” to define the scope of a claim in relation to the sequences in SEQ ID NO: 5-213. See MPEP 2111.03. For purposes of compact prosecution and applying prior art, claim 18 was interpreted herein as reciting the open-ended language of comprising SEQ ID NOs: 5-213.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(Previous rejection, withdrawn as to claims 1-3, 6, 8, 18, 34 and 35) Claims 1-3, 6, 8, 18, 34 and 35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mishra et al. (prior art of record)
See instant claims 1-3, 6, 8, 18, 34 and 35 as submitted on 11/04/2025.
Applicant’s amendments have overcome previous rejection to claims 1-3, 6, 8, 18, 34 and 35.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(Previous rejection, withdrawn as to claim 7, maintained and modified as to as to claims 5, 9, 13 and 17, expanded as to claims 1-3, 6, 8, 34, 35 and 37) Claims 1-3, 5-9, 13, 17, 34, 35, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Mishra et al., in view of Keasey et al. (prior art of record).
See instant claims 1-3, 5-9, 17, 34, 35 and 37 as submitted on 11/04/2025.
The previous rejections of claim 7 is moot in view of Applicant’s cancelation of this claim.
Regarding amended claim 1, the teachings of Mishra et al. were previously explained. In summary, Mishra et al. disclose an array for detection of flaviviruses (Abstract, page 1) comprising a plurality of peptide probes at specific locations on said array (pages 2-3), wherein the peptide probes comprise a probe from multiple flaviviruses, including Zika virus (ZIKV), dengue virus (DENV) 1 to 4, chikungunya virus (CHIKV), West Nile virus (WNV), yellow fever virus (YFV), Ilheus virus (ILHV), and Oropouche virus (OROV) (pages 1-3), wherein said peptide probes are 12 amino acid residues long (page 2). The amendment of claim 1 submitted on 11/04/2025 introduced the following new limitations: wherein the peptide probes are between 10 and 30 amino acids long and wherein the plurality of probes further comprises at least one of
a) an inactivated form of each of said flaviviruses
b) a virus-like particle (VLP) of each of said flaviviruses
c) a lysate from a cell infected by each of said flavivirus and
d) a recombinant protein from each of said flaviviruses
It is noted that Mishra et al. already teach peptide probes 12 amino acid residues long (page 2).
Mishra et al. do not teach a peptide array further comprising one of
a) an inactivated form of each of said flaviviruses
b) a virus-like particle (VLP) of each of said flaviviruses
c) a lysate from a cell infected by each of said flavivirus and
d) a recombinant protein from each of said flaviviruses
However, as previously explained Keasey et al. teach probes comprising recombinant viral proteins from 15 flaviviruses, including ZIKV and TEBV, and whole viruses (Abstract, pages 1, 2). Keasey et al. further teach that such probes exhibit native structural features which reflect the structural heterogeneity from immature to mature forms which may affect the protective potency of antibodies. Further, viral proteins such as the E and M proteins form heterodimers on the surface of the viral particle and undergo extensive conformational changes that facilitate infection of cells, as such these proteins are primary targets for circulating antibodies (page 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated recombinant viral proteins or whole virus probes for each flavivirus as taught by Keasey et al. into the array taught by Mishra et al. for the benefit of including probes that exhibit native structural features of viral proteins and whole virus which are primary targets for circulating antibodies. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the recombinant viral proteins or whole virus probes of Keasey et al. into the array of Mishra et al. given that the methods of formulating arrays with multiple viral probes are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 2, it is noted that all of the amendments were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 08/08/2025. No new limitations were introduced in the amendment filed on 11/04/2025. As previously explained, Mishra et al. disclose the use of thousands of protein probes per flavivirus, for example for ZIKV, 7573 peptide probes were used (page 3, Table 1).
Regarding claims 3 and 6, it is noted that all of the amendments to claim 3 were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 08/08/2025. No new limitations were introduced in the amendment filed on 11/04/2025. As previously explained, Mishra et al. disclose protein probes from multiple flaviviruses in the array, including Zika virus (ZIKV), dengue viruses (DENV) 1 to 4, chikungunya virus (CHIKV), West Nile virus (WNV), yellow fever virus (YFV) (page 2, Table 1).
Regarding claim 5, it is noted that no amendments were introduced in the amendment filed on 11/04/2025. As previously explained, Keasey et al. teach a printed microarray with protein probes for detection of very specific antibody responses to primary infections from 15 species and lineages of flaviviruses, including ZIKV and TBEV (Abstract, page 2, Table 1, Fig. 1).
Regarding amended claim 8, it is noted that all of the amendments were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 08/08/2025. No new limitations were introduced in the amendment filed on 11/04/2025. As previously explained, Mishra et al. disclose protein probes comprising the following:
overlapping 12-mer peptides that tiled the whole proteome of each flavivirus, including the NS1 protein, with 11-aa overlap in a sliding window pattern (pages 2, 10; Fig. 6)
wherein the 12-mer peptides comprise consecutive amino acid residues from a flavivirus protein (pages 2, 10; Fig. 6)
Regarding amended claim 9, Keasey et al. teach probes comprising a viral envelope protein from a flavivirus for example ZIKV and TEBV (Abstract, pages 1, 2). Mishra et al. already teach peptide probes 12 amino acid residues long (page 2). In combination the teachings of Keasey et al. and Mishra et al. meet the limitations of amended claim 9.
Regarding amended claim 13, Keasey et al. teach probes comprising recombinant viral proteins from flaviviruses, for example ZIKV and TEBV, whole viruses (Abstract, pages 1, 2) and lysates from cells infected with a flavivirus (page 10). It would have been prima facie obvious to a person skilled in the art before the effective filing date to have included with reasonable expectation of success all three species of probes in an array comprising peptide probes given that all of these species of probes are taught by Keasey et al. and Mishra et al., and Keasey et al. further teaches the benefit of including probes that exhibit native structural features of viral proteins such as recombinant proteins, whole virus, and lysates from cells infected with a flavivirus to identify circulating antibodies.
Regarding claim 17, it is noted that no amendments were introduced in the amendment filed on 11/04/2025. As previously explained, Keasey et al. teach serial dilutions of a viral probe on the microarray (page 12).
Regarding claims 34 and 35, it is noted that no amendments were introduced in the amendment filed on 11/04/2025. As previously explained, Mishra et al. disclose the array of claim 1 for serodiagnostic use (a kit, as recited in claim 34), wherein the array comprises labeled secondary antibodies which when bound to primary antibodies in the array, can be measured using a detector or sensor, specifically a Roche MS 200 microarray scannerTM (Roche) (a system, as recited in claim 35, see also rejection of claim 35 under 35 USC § 112(b) above) (pages 13, 14, Fig. 6).
Regarding new claim 37, as noted above, Mishra et al. already teach peptide probes 12 amino acid residues long (page 2).
(New rejection necessitated by amendment as to claim 18) Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Mishra et al., and Keasey et al. (prior art of record), as applied to claims 1-3, 5-9, 17, 34 and 35 above, further in view of PGPub US 20200348299 A1 to Khurana S. Effectively filed on 03/26/2019 (See PTO-892: Notice of References Cited.)
Regarding amended claim 18, the teachings of Mishra et al. and Keasey et al. meet the limitations of claim 1.
Neither Mishra et al. and Keasey et al. teach peptide probes comprising SEQ ID NOs: 5-213.
However, Khurana teaches isolated peptide sequences that include antigenic sites of ZIKV and methods for their use to, for example, detect exposure of a subject to a flavivirus (Abstract). Khurana further teach for example three sequences which share 100% identity with instant SEQ ID NOs: 63, 69, and 105. See alignments below.
Alignment 1: Qy is instant SEQ ID NO: 63; Db is Khurana’s SEQ ID NO: 9 E-6
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149
686
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151
698
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Alignment 2: Qy is instant SEQ ID NO: 69; Db is Khurana’s SEQ ID NO: 9 E-6
Alignment 3: Qy is instant SEQ ID NO: 105; Db is Khurana’s SEQ ID NO: 9 NS1-7
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141
702
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It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated peptide sequences of Khurana into the array of Mishra et al. in view of Keasey et al. for the benefit of including known antigenic sites of ZIKV. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the peptide sequences of Khurana into the array of Mishra et al. in view of Keasey et al. given that the methods of formulating arrays with peptide probes are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Response to Arguments
Applicant's arguments filed 11/04/2025 have been fully considered but they are not persuasive.
Applicant contends on page of the Remarks submitted on 11/04/2025:
Antibodies against linear epitopes are generally considered inferior and less likely to be neutralizing. The instant application demonstrates that quite surprisingly it is important to know if a subject's antibody profile is tilted toward linear epitope binding or toward conformational epitope binding. This unexpected finding is clearly shown in Example 4. It was observed that some of the vaccinated subjects only demonstrated cross- reactivity (a sign of ADE) when linear epitopes were examined, while others only demonstrated cross-reactivity when examining conformational epitopes. Further, the comparison of cross-reactivity toward linear and conformational epitopes could be used to determine ADE. It is thus clear that quite surprisingly, in order to get a full picture of ADE in subjects one needs an array such as is described in claim 1 that includes linear epitopes and conformational epitopes. This surprising result could not have been predicted from the cited art.
The cited art all contain either conformational epitopes only as they contain proteins that are properly folded or linear epitopes only as they contain peptide probes. The surprising benefit of combining these two types of probes could not have been predicted from the cited art. There is no indication in any of the art that the combination of longer and shorter probes would be valuable or that the combination of linear and conformational epitopes would be superior to each alone. Certainly the benefits in predicting ADE are in no way suggested.
In response:
Applicant's arguments against the references individually are not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As explained above, Mishra et al. teach linear epitopes comprising peptide probes and Keasey et al. teach conformational epitopes as well as clear teachings and suggestions demonstrating the benefit of including conformational probes that exhibit native structural features into a peptide array to identify circulating antibodies.
Further, as to the alleged surprising results, it is noted that the instant rejection is in view of instant claim language. Although the claims are interpreted in light of the Specification, limitations from the Specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The instant claims do not mention nor require any limitation in regards to cross-reactivity (a sign of ADE) when linear epitopes are examined, nor cross-reactivity when examining conformational epitopes. Further, instant claims do not mention nor require any limitation in regards to comparing cross-reactivity toward linear and conformational epitopes to potentially determine ADE. It is noted that intended use of in a claim, for example, intended use of an array to determine ADE, does not carry patentable weight. Further, such result of obtaining a full picture of the antibody response in a subject when both conformational and linear epitopes are used is not considered surprising, especially when the prior art clearly and abundantly recognizes the advantage of both approaches (see Mishra et al., see Keasey et al., see Slon Campos et al. 2018, see Hertz et al. 2017 cited in Applicant’s IDS submitted on 02/08/2023). In fact, such a result would be considered entirely expected and consistent with the prior art. More importantly, as indicated above, cross-reactivity and predicting ADE are not a limitations of the instant claims and therefore these arguments are of no relevance to the rejections of record.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672