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 .
Change of Examiner
The examiner of your application in the USPTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Art Unit 1671, Examiner Nianxiang (Nick) Zou.
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on May 7, 2026. Claims 1, 2, 4, 6-13, 15-16, 22-25, 33-35, 38-40, 52, 53, 60 and 61 are pending. Claims 7-12, 24-25, 33-35, 38-40 and 52-53 are withdrawn. Claims 1, 2, 4, 6, 13, 15-16, 22-23, and 60-61 are currently examined.
Previous Objections and Rejections not included in the current Office action are withdrawn. Applicant’s arguments to the withdrawn Objections/Rejections are moot.
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.
(Previous Rejection – Maintained) Claims 1, 2, 13, 16, 22, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Tyan, D. B. and Chen, G. (US 2011/0281757, Published 11/17/2011; U.S. National Stage Entry of WO 2010/065425 A1 as Cited in Applicant’s IDS on 04/06/2023 as Foreign Patent Document Cite No. 2), hereby Tyan, and in further view of Mehlhop, E., et. al., (Cell host & microbe, 2(6), 417–426; Published 12/13/2007), hereby Mehlhop. This rejection is extended to new claims 60-61.
(Previous Rejection – Maintained) Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Tyan and Mehlhop, and further in view of Sakamoto, S., et. al., (Enzyme-linked immunosorbent assay for the quantitative/qualitative analysis of plant secondary metabolites. Journal of natural medicines, 72(1), 32–42; Published 11/21/2017), hereby Sakamoto.
(Previous Rejection – Maintained) Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Tyan and Mehlhop as applied to claims 1, 2, 5, 13 – 16, 22, and 23 above, and further in view of Dianova, (Fluorescent Dyes for Secondary Antibodies; Accessed 10/21/2019), hereby Dianova.
(Previous Rejection – Maintained) Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Tyan and Mehlhop, and further in view of Schreiber, M. and Franzke, K (EP 2980099 A1; Published 03/02/2016), hereby Schreiber as evidenced by Dasso, J., et. al., (A comparison of ELISA and flow microsphere-based assays for quantification of immunoglobulins. Journal of immunological methods, 263(1-2), 23–33; Published 05/01/2002), hereby Dasso.
Applicant argues that pending claim 1 differs from Tyan in that the latter does not disclose that the antigen being coupled to a microsphere is a flavivirus virus-like particle (VLP), and the complement-fixing antibody is a flavivirus-reactive antibody. Applicant argues that Tyan describes that the antigen of interest may be a virus antigen, which does not suggest a particular type of virus, and that Tyan does not teach or suggest that the antigen may be a VLP. Applicant argues that the other documents referred to by the Examiner with respect to claim 15 do not remedy this deficiency.
Applicant argues that Mehlhop relates to C1q inhibition of antibody-dependent enhancement of flavivirus infection, that the document does not describe any microsphere-based experiments, and that, in particular, it does not teach or suggest coupling of a flavivirus VLP to a microsphere. Applicant argues that Schreiber relates to flavivirus envelope protein (E protein), especially to the flavivirus E protein domain III which may be coupled to bead surfaces but does not teach or suggest coupling of a flavivirus VLP to a microsphere. Applicant argues that Dasso relates to a comparison of ELISA and flow microsphere-based assays for quantification of immunoglobulins or albumin, and that the document does not suggest coupling of a flavivirus VLP to a microsphere. Applicant argues that none of the cited references teach or suggest to a person of ordinary skill in the art that the HLA antigens coupled to microspheres in Tyan do not allow any extrapolation to flavivirus VLPs, and that, rather, a person of skill in the art would assume that the direct coupling of VLPs to microspheres may have a negative impact on the three-dimensional structure of the epitopes displayed on the surface of flavivirus VLPs, which then would compromise the suitability of the assay for complement-fixing antibodies being specific for conformational epitopes.
Applicant’s arguments above are not persuasive. Tyan teaches a method that is indistinguishable to the one as claimed except for the antigen attached to the microspheres, which is required by the instant claims to be VLPs of a flavivirus. On the other hand, Tyan teaches that the antigens of the invention can be virus antigens. Mehlhop teaches the application of virus-like particles (VLPs), including West Nile virus and dengue virus VLPs (WNV and DENV RVPs), as antigens for interaction with C1q and immune IgG. See page 419, left column and Figures 1-3. Viral VLPs (here, WNV and DENV RVPs) contain all of the viral proteins resembling the natural state of the virus particles. One of skill in the art would have been motivated to use viral VLPs as test antigens when there is a need to test overall immune response to virus infection. In this way, host antibodies to both linear and conformational epitopes of viral proteins can be tested.
As to Applicant’s argument that a person of skill in the art would assume that the direct coupling of VLPs to microspheres may have a negative impact on the three-dimensional structure of the epitopes displayed on the surface of flavivirus VLPs. It is noted that direct coupling of any antigens with a three-dimensional structure to the surface of a substrate may have a negative impact on three-dimensional structure of the epitopes displayed on the surface of the antigens. However, such a concern has not prevented one of skill in the art from doing so. E.g., Tyan teaches coupling HLA molecules to microsphere, and the assumed “negative impact” does not appear to abolish the interaction between the HLA antigens and antibodies in the test samples.
Conclusion
No claims are allowed.
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 extension fee 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 NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/ Primary Examiner, Art Unit 1671
