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 Group I, claims 1, 4-14 and 18-21 in the reply filed on December 1, 2025 is acknowledged. Claims 28-29, and 33-50 are withdrawn as being drawn to non-elected invention. Claims 1, 4-14 and 18-21 are under examination in this Office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 29, 2023, March 27, 2025 and July 22, 2025 has been considered by the examiner.
Claim Objection
Claim 21 is objected to for minor informalities. The claim recites a typographical error 100 fM. It should be 100 µM.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 7, 11 and 20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Gehrke et al. (US Patent Application Publication US 2018/0372755).
Gehrke et al. discloses a method of detecting Ebola virus in a sample, comprising: contacting the sample with gold nanoparticles (AuNPs) conjugated with an antibody that binds to an epitope of a secreted glycoprotein (sGP) from the Ebola virus under conditions sufficient for the one or more antibodies, or the antigen binding portions thereof, to bind to the epitope of the sGP from the Ebola virus in the sample to produce bound sGP; and, detecting the sGP from the Ebola virus when one or more aggregations of the bound sGP form with one another, thereby detecting the Ebola virus in the sample (see claims 1-24, Figure 14, 17A, and 21B, Example 1, paragraphs [0120], [0137], [0162], [0169-0173]).
Regarding claim 7. Gehrke et al. disclose quantifying the amount sGP in the sample (see paragraph [0170]).
Regarding claim 11. Gehrke et al. disclose obtaining a sample from a subject (see paragraph [0111].
Regarding claim 20, Gehrke et al. teach detecting the colorimetric change using a spectrometer (see paragraph [0108-0109], [0116]).
Thus, by this disclosure Gehrke et al. anticipate the present claims.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 4-14 and 18-21 are rejected under 35 U.S.C. 103 as being unpatentable over Gehrke et al. (US Patent Application Publication Us 2018/0372755) as applied to claim 1 and further in view of Liu et al 2017 (Microb Cell Fact (2017) 16:223 in IDS on March 27, 2025).
Gehrke et al. teaches a method of detecting Ebola virus in a sample, comprising: contacting the sample with gold nanoparticles (AuNPs) conjugated with an antibody that binds to an epitope of a secreted glycoprotein (sGP) from the Ebola virus under conditions sufficient for the one or more antibodies, or the antigen binding portions thereof, to bind to the epitope of the sGP from the Ebola virus in the sample to produce bound sGP; and, detecting the sGP from the Ebola virus when one or more aggregations of the bound sGP form with one another, thereby detecting the Ebola virus in the sample (see claims 1-24, Figures 1, 14, 17A, and 21B, Example 1, paragraphs [0120], [0137], [0169-0173]).
Regarding claim 4. Gehrke et al. teaches determining the equilibrium dissociation constant (KD) (see paragraph [0145]) but does not provide a number of about 1nM to 100 nM. It would have been within the skill of the ordinary artisan to optimize the equilibrium dissociation constant (KD) in a colorimetric detection method.
Regarding claim 5. Gehrke et al. does not teach a nanobody that bind to an Ebola virus secreted glycoprotein (sGP) conjugated to AuNPs.
Liu et al. teaches camelid (llama) nanobodies that specifically bind to an Ebola virus glycoprotein, disclosing characterization of initially selected 10 sdAbs 10 (See, page 3, column 1 for section on characterization of initially selected sdAbs) table 1 listing binding affinity of sdAs nanobodies EBOV-GP-G6, EBOV-GP-H7, EBOV-GP-A8, EBOV-GP-B11, EBOV-GP-G3, EBOV-GP-C11, EBOV-GP-G3, EBOV-GP-B5, and EBOV-GP-D1 bind to epitopes on Ebola virus GP (Table 1, Table 3); and detection of Ebolavirus glycoprotein using the nanobodies.
It would have been prima facie obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art teachings of Gherke on the method of detection of Ebola virus sGP1 glycoprotein and to incorporate the teachings of Liu et and to use a AuNP bound nanobody specific for Ebola virus glycoprotein. The skilled artisan would have been motivated to exploit the properties of nanobodies (SdAbs) in a method of Gherke because Lie teaches that the nanobodies have superior thermal stability, ability to recognize hidden epitopes combined with specificity and binding affinity comparable to conventional antibodies (See, Liu et al, page 1, introduction, para 1).
Regarding claim 6. Gehrke et al. teaches determining the change in absorbance at a resonance wavelength (see paragraph [0135] A solution is to exploit the properties of the nanoparticles (NPs) responsible for the test line signal. Gold NPs absorb strongly in the visible and their color can be tuned by changing their size, producing different test line colors).
Regarding claim 8-10 and 12-14. Gehrke et al. teaches detecting Ebola virus in a sample, they do not teach detecting the virus within 20 minutes. It would have been within the skill of the ordinary artisan to perform the detection method within a reasonable time to obtain the test results.
Regarding claims 18-19. Gherke et al. teaches detecting Ebola virus in a sample, they don’t teach visually detecting the colorimetric change when aggregations are formed of the bound sGP. It would have been within the skill of the ordinary artisan to perform the detection method by visually detecting the colorimetric change.
Regarding claim 20. Gehrke et al. teaches detecting Ebola virus in a sample using a spectrometer (see paragraph [0170]).
Regarding claim 21. Gehrke et al. teaches detecting Ebola virus in a sample, however they do not teach the concentration of the sGP in a sample. It would have been within the skill of the ordinary artisan to optimize the concentration of sGP in a sample.
Thus, the present invention would have been prima facie obvious at the time the invention was made.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1, 4-14 and 18-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5-20 of copending Application No. 17/489,273. Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are drawn to method of detecting Ebola virus in a sample, comprising: contacting the sample with gold nanoparticles (AuNPs) conjugated with an antibody that binds to an epitope of a secreted glycoprotein (sGP) from the Ebola virus under conditions sufficient for the one or more antibodies, or the antigen binding portions thereof, to bind to the epitope of the sGP from the Ebola virus in the sample to produce bound sGP; and, detecting the sGP from the Ebola virus when one or more aggregations of the bound sGP form with one another, thereby detecting the Ebola virus in the sample.
The claims of the copending application are drawn to A method of detecting Ebola virus in a sample, the method comprising: contacting the sample with a plurality of gold nanoparticles (AuNPs) and/or other plasmonic metal nanoparticles (MNPs) that are conjugated with at least two sets of nanobodies that each comprise a universal scaffold and three variable complementarity-determining regions, wherein at least a first set of nanobodies each comprise a mono-binder sGP49 nanobody having a kD of about 4.6 nM that binds to a first epitope of a secreted glycoprotein (sGP) from the Ebola virus, wherein complementarity-determining regions (CDRs) of the sGP49 nanobody comprise the amino acid sequences of SEQ ID NOs:4-6, and wherein at least a second set of nanobodies each comprise a mono-binder sGP7 nanobody having a kD of about 199 nM that binds to a second epitope of the sGP from the Ebola virus, wherein CDRs of the sGP7 nanobody comprise the amino acid sequences of SEQ ID NOs:1-3, under conditions sufficient for the first and second sets of nanobodies to bind to the first or second epitopes of the sGP from the Ebola virus in the sample to produce bound sGPs; or contacting the sample with a plurality of gold nanoparticles (AuNPs) and/or other plasmonic metal nanoparticles (MNPs) that are conjugated with a single set of nanobodies that each comprise a universal scaffold and three variable complementarity-determining regions that bind to an identical epitope from different monomers of a dimerized secreted glycoprotein (sGP) from the Ebola virus under conditions sufficient for the nanobodies to bind to the identical epitope from the different monomers of the dimerized sGP from the Ebola virus in the sample to produce bound sGPs, wherein the single set of nanobodies each comprise a mono-binder sGP49 nanobody having a kD of about 4.6 nM, wherein complementarity-determining regions (CDRs) of the sGP49 nanobody comprise the amino acid sequences of SEQ ID NOs:4-6, or a mono-binder sGP7 nanobody having a kD of about 199 nM, wherein CDRs of the sGP7 nanobody comprise the amino acid sequences of SEQ ID NOs:1-3; and, detecting the sGPs from the Ebola virus when one or more aggregations of the bound sGPs form with one another, thereby detecting the Ebola virus in the sample.
The present claims are obvious over the claims of the copending application because they are drawn to a method of detecting Ebola virus with gold nanoparticles (AuNPs) and antibodies. The only difference between the present claims and the claims of the copending application is that the claims of the copending application are limited the specific nanobodies.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM.
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/AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648