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 .
Status of the Claims
Claim 27 has been cancelled. Claims 17-22 and 24-26 and 28-35 are pending and are examined herein.
Priority
This application, filed 03/06/2022, is a 371 of PCT/GB2020/052144 filed on 09/07/2020, which claims benefit to UNITED KINGDOM 1912866.9 filed on 09/06/2019. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 09/06/2019.
Withdrawn Objections/Rejections
The objection to the Specification has been withdrawn in response to Applicant’s arguments. In particular, the indicated subject matter is disclosed in the published International Application PCT/GB2020/052144, filed 09/07/2020 as WO 2021/044173 A1.
The rejection of claims 27-29 under 35 U.S.C. 112(b) has been withdrawn in response to Applicant’s amendments.
The rejection of claims 19 and 20 under 35 U.S.C. 112(d) has been withdrawn in response to Applicant’s amendments.
The rejection of claims 17-19, 21-22, 26-28, and 30 under 35 U.S.C. 102 has been withdrawn in response to Applicant’s amendments.
The rejection of claim 35 under 35 U.S.C 103 in view of Lee has been withdrawn in response to Applicant’s amendments.
Amended Claim Rejections - 35 USC § 103
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 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.
Claims 17-22, 24-26, 28-30, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over US 7,972,837 “SIGNAL ENHANCEMENT SYSTEM WITH MULTIPLE LABELED-MOIETIES” (patented 07/05/2011, referred to herein as Lee) in view of US 2015/0355187 A1, “MIXED PAYLOAD CONTAINING POLYMERS AND USE THEREOF” (published 12/10/2015, herein referred to as Berniac) and US 2013/0130404 A1, “SIGNAL AMPLIFICATION IN LATERAL FLOW AND RELATED IMMUNOASSAYS” (published 05/23/2013, referred to herein as Mehra).
Regarding claim 17, Lee teaches a lateral flow device (abstract, Figure 2) with a sample loading area (col. 2, lines 13-14, “a contact end”), an area with a labelled protein construct (col. 13, lines 12-14, Figure 2, reference letter D and E), an area with immobilized capture probes (col. 13, lines 19-21, “capture zone”, figure 2, reference letter F), and an absorbent material (col. 13, lines 11-12, “absorbent pad”, Figure 2, reference letter C). Lee teaches a labelled protein construct with a region specific for the target (Figure 5C, reference number 43), a plurality of regions (Figure 5C, reference number 44) specific to detectable nanoparticles (Figure 5C, reference number 47) with two affinity binding sites bound by moieties with separate nanoparticles (Figure 5C, reference numbers 45 and 46).
Regarding claim 18, Lee teaches a lateral flow device with paper and nitrocellulose (col. 2, lines 65-67).
Regarding claim 19, Lee teaches a virus and microorganism target (col. 7, lines 50-58).
Regarding claim 20, Lee teaches that the “methods of the invention may be used to test for any suitable analyte: (col. 7, lines 43-44).
Regarding claims 21 and 22, Lee teaches a method of contacting a urine sample (Col. 13, lines 35-37) with to the device as described above in regards to claim 17. Lee teaches that after contact, the detected amount of the target (“CT-LFS”) is determined by a color change due to the trapped complex of the target and labelled probe captured by the immobilized capture probe (col. 13, lines 51-56).
Regarding claim 24, Lee teaches a construct with a plurality of affinity binding sites, i.e. ligands, such as biotin, fluorescein, and DNP (col. 5, lines 56-59). Lee teaches that although biotin is the preferred embodiment, other ligands could be used (col. 17, line 8).
Regarding claim 25, Lee teaches that the label, i.e. a nanoparticle (col. 6, lines 15-20), is attached to a labelling agent (col. 6, lines 33-35, which are antibodies (col. 6, lines 39-40). Lee teaches that these antibodies are attached to affinity binding sites (Figure 5C, reference number 44) and the protein construct has a plurality of nanoparticles (Figure 5C, reference number 47).
Regarding claim 26, Lee teaches a construct with a region specific for the target (Figure 5C, reference number 43. Col. 20, line 4) with a plurality of affinity binding sites (Figure 5C, reference number 44, col. 20, lines 5-6) that are specific to primary markers (Figure 5C, reference number 45. Col. 20, lines 6-7, “primary moieties”). The primary markers further have affinity binding sites, i.e. the Fc region of the primary marker (Figure 5C), which are bound by a secondary marker (Figure 5C, reference number 46. Col. 20, lines 8-9, “secondary moieties”). Lee teaches that the primary and secondary markers are linked to separate detectable nanoparticles (Figure 5C, reference number 47) in a branched configuration (Figure 5C).
Regarding claim 28, Lee teaches a construct that has “no more than 50 ligands” (col. 5, lines 7-8). Lee also teaches that each ligand can be attached to two detectable nanoparticles (Figure 5C, reference number 47). Therefore, Lee discloses a labelled construct with 100 detectable nanoparticles which is greater than 50 and between 100 and 10,000.
Regarding claim 29, Lee teaches a construct with 100 detectable nanoparticles, as described above regarding claims 28 (col. 5, lines 7-8, Figure 5C). Lee teaches that the optimum number of ligands, and therefore detectable nanoparticles, should be optimized depending on the identity of the targeting agent (col. 5, lines 8-9) and the flow rate of the chromatographic strip (col. 5, lines 14-16).
Regarding claim 30, Lee teaches a construct with gold nanoparticles (col. 6, lines 5-8).
However, Lee does not teach a eukaryotic source target. Lee does not teach a device wherein the affinity binding sites are within the protein sequence of the construct or His, FLAG, E-tag HA, Strept-tag, myc, S-tag, SH3 or G4T as affinity binding sites. Lee does not teach a device with between 500 and 5000 detectable nanoparticles.
Regarding claim 35, Lee teaches a nanoparticle size range of 20-40 nm (col. 6, lines 8-9).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the device as taught by Lee by selecting 20 nm nanoparticles because Lee discloses that nanoparticles may be from a range of 20-40 nm, which overlaps with the claimed range. Lee teaches that the size of the nanoparticles used to labelling an antibody should be optimized to achieve maximum signal (col. 17, lines 4-6).
Berniac’s general disclosure relates to a protein construct for the delivery of detectable nanoparticle payloads to target antigens in immunoassays (Abstract, para. 0002, lines 1-7).
Regarding claims 17 and 24, Berniac teaches the use of biotin, 6x His, and myc as capture tags, i.e. affinity binding sites within the protein sequence to recruit nanoparticles to the construct (para. 0021, lines 1-3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to His or myc affinity binding sites as taught by Berniac for the use and formulation of the method taught by Lee. Based on the teachings of Berniac, an artisan would have reasonably envisioned using a plurality of 6x His or myc tags as disclosed by Berniac as an alternative to biotin, as taught by Lee, as a strategy to bind nanoparticles to a protein construct. Hence, using these affinity tags would have been readily apparent and deemed to be a mere (a) combining of known prior art elements according to known methods to yield predictable results (see MPEP 2141(III): Exemplary Rationales that supports a conclusion of obviousness). The ordinary artisan would have had a reasonable expectation of success because both Lee and Berniac are directed to the detection of analytes using protein constructs in immunoassays, in particular, lateral flow assays.
Regarding claim 20, Berniac teaches a target of a tumor antigen on a tumor cell, which is a mammalian cell (para. 0191, lines 3-5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select a mammalian cell target as taught by Berniac for the use and formulation of the method taught by Lee. The ordinary artisan would have reasonably envisioned targeting a mammalian cell as disclosed by Berniac because these were common methods used in the analyte-detection arts. Hence, targeting a mammalian cell would have been readily apparent and deemed to be a mere (a) combining of known prior art elements according to known methods to yield predictable results (see MPEP 2141(III): Exemplary Rationales that supports a conclusion of obviousness). The ordinary artisan would have had a reasonable expectation of success because both Lee and Berniac are directed to the detection of analytes using methods related to immunoassays, in particular, lateral flow assays.
Regarding claim 29, Berniac teaches the use of nanoparticles as the detectable label (“payload”, para. 0017, lines 1-7) loaded onto a polymer (Figure 5). Berniac teaches an embodiment with 500 total payload molecules (para. 0011, lines 1-7).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device as taught by Lee to include the polymer with detectable nanoparticles as taught by Berniac. Doing so would increase the number of labels attached to the target analyte. The ordinary artisan would have been motivated to do so because, as taught by Lee, more labels results in increased sensitivity of analyte detection (col. 6, lines 9-11). The ordinary artisan would have had a reasonable expectation of success in modifying the prior art references to arrive at the claimed invention because both Lee and Berniac are directed to labelled detection constructs for use in lateral flow devices to detect analytes.
However, Lee in view of Berniac does not teach the construct wherein said affinity binding sites are located within the protein sequence of said labelled protein construct.
Mehra’s general disclosure relates to protein constructs used in immunoassays.
Regarding claims 17 and 21, Mehra teaches the use of affinity binding sites such as biotin or amino acid sequences such as HIS tags with protein constructs for immunoassays (para. 0056, lines 9-16). Mehra teaches the use of these tags as antigens capable of being bound by an antibody (para. 0057, lines 1-7). Mehra teaches that these antigens can be incorporated into protein constructs as “fusion proteins” containing the antigens (para. 0061, lines 1-4). Mehra teaches that the use of fusion proteins can be advantageous in order to “improve purification, improve solubility, enhance expression of the peptide in a hist cell, aid in detection, stabilize the antigenic peptide” (para. 0061, lines 6-10).
It would have been obvious to one of ordinary skill in the art to modify the protein construct containing a plurality of His or myc affinity binding sites, as taught by Lee in view of Berniac, by fusing those affinity binding sites into the protein sequence of the construct as taught by Mehra. An artisan would have been motivated to do so in order to improve purification, improve solubility, enhance expression of the peptide in a hist cell, aid in detection, or stabilize the antigenic peptide as taught by Mehra. An artisan would have had a reasonable expectation of success in doing so because the modification and fusion of protein sequences together into a single sequence is well known in the art of protein engineering and, as taught by Mehra, these fusion proteins can be used in immunoassays for target detection, including lateral flow assays (para. 0054, lines 1-3) as claimed.
Claims 31-34 are rejected under 35 U.S.C. 103 as being unpatentable over Lee in view of Berniac and Mehra, and further in view of US 2016/0178636 A1, “CONJUGATING MOLECULES TO PARTICLES” (published 06/23/2016, referred to herein as Nobuyoshi).
The teachings of Lee in view of Berniac and Mehra discussed above as it pertains to claim 17 are incorporated herein.
Regarding claims 31-34, Lee teaches the use of detectable gold nanoparticles (col. 6, lines 15-20).
However, Lee in view of Berniac and Mehra does not teach the use of carbon, silver-nucleated gold, platinum, or cellulose nanoparticles. Lee does not teach nanoparticles with a size between 5 and 20 nm.
Nobuyoshi’s general disclosure relates to attaching detectable nanoparticles to biomolecules for use in life sciences research (para. 0003, lines 1-5).
Regarding claims 31-35, Nobuyoshi teaches the use of gold, silver, platinum, carbon, and cellulose nanoparticles (para. 0065, lines 1-4, 10, and 14). Nobuyoshi teaches the use of nanoparticles between 5-30 nm (para. 0067, lines 6-7).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the nanoparticles disclosed in Nobuyoshi to modify the device described in Lee. The ordinary artisan would have reasonably envisioned using one of the nanoparticles disclosed by Nobuyoshi because these were common materials used in the analyte-detection arts. Hence, using these nanoparticles would have been readily apparent and deemed to be a mere (a) combining of known prior art elements according to known methods to yield predictable results (see MPEP 2141(III): Exemplary Rationales that supports a conclusion of obviousness). The ordinary artisan would have had a reasonable expectation of success because both Lee and Nobuyoshi are directed towards the use of devices for the detection of analytes using detectable nanoparticles.
Response to Arguments
Applicant's arguments filed 11/07/2025 have been fully considered but they are not persuasive for the following reasons:
Applicant’s arguments, see pages 6 and 7, filed 11/07/2025, with respect to the objection to the Specification have been fully considered and are persuasive. The objection of the Specification has been withdrawn.
Regarding the remarks on the rejection of claims 27-29 under 35 U.S.C. 112(b), the rejection has been withdrawn in response to Applicant’s amendment.
Regarding the remarks on the rejection of claim 19-20 under 35 U.S.C. 112(d), the rejection has been withdrawn in response to Applicant’s amendment.
Regarding the remarks on the rejection of claims 17-19, 21-22, 26-28, and 30 under 35 U.S.C 102, the rejection has been withdrawn in response to Applicant’s amendment.
Regarding the remarks on page 10 and 11 about the rejection under 35 U.S.C. 103 over Lee in view of Berniac, Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on Lee or Berniac applied in the prior rejection of record for any teaching or matter specifically challenged in the argument, i.e. the incorporation of affinity binding sites within the protein sequence of the construct.
Further regarding the remarks on page 11, Applicant argues that the prior art does not teach incorporating binding sites into the protein sequence in order to aid in signal amplification.
This argument is not persuasive. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In this case, as taught by Mehra as described above regarding claim 17, there are numerous potential advantages to fusing antigenic sites into the protein construct sequence and it is not necessary for the prior art to disclose any particular advantage in order to render the claim obvious.
Regarding the remarks on the rejection of claims 31-35 under 35 U.S.C. 103 over Lee in view of Nobuyoshi on pages 11 and 12, Nobuyoshi does not teach the incorporation of the binding sites into the protein construct sequence.
This argument is not persuasive. Nobuyoshi is not relied upon to teach this limitation in the rejection under 35 U.S.C. 103 as detailed above.
Further regarding the remarks on page 12, Applicant argues that Nobuyoshi does not teach the nanoparticles in relation to a device that can create higher levels of signal amplification. This argument is not persuasive. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In this case, the use of alternate nanoparticles is considered to be combining of known prior art elements according to known methods to yield predictable results, as described in the rejection under 35 U.S.C. 103 above.
Regarding the remarks on the rejection of claim 35 under 35 U.S.C 103, the rejection has been withdrawn in response to Applicant’s amendment.
Conclusion
No claims are allowable.
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.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 February 9, 2026