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
Claims 1-8 are pending and are examined herein.
Priority
This application, filed 09/28/2022, claims benefit of 63/249,417, filed 09/28/2021. This benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 09/28/2021.
Withdrawn Rejections/Objections
The objection to claim 3 is withdrawn in response to Applicant’s amendment.
The rejection of claim 8 is withdrawn in response to Applicant’s amendment.
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.
Claim 8 is 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. This is a new matter rejection.
Claim 8 recites “establishing interference based on said comparing” which is directed toward “determining an amount of free target from said signal by comparing the signal to a standard…”; however, in the instant specification, interference is only described in methods directed toward determining the total target or total drug (see, for example, para. 0066, and Example 1 “Use of Mild Acidic Assay pH to Mitigate Target Interference in the Total Drug Assay” and Example 2 “Capture and Detection Antibody Selection and Use of Mild Acidic Assay pH to Mitigate Drug Interference in the Total Target Assay” and para. 0109, lines 3-9). As a whole, including the working examples and drawings, the newly added claim limitation of establishing interference in an assay directed toward only measuring the free target using a capture agent with less affinity and a slower association rate for the target compared to the drug is not supported by the specification.
Claim Rejections - 35 USC § 102/103
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 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.
(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 1-8 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Liu et al., “Development of a Meso Scale Discovery ligand-binding assay for measurement of free (drug-unbound) target in nonhuman primate serum” Bioanalysis (IDS filed 02/15/2023, published 03/22/2021, referred to herein as Liu), as evidenced by “MSD SECTOR and QUICKPLEX Plates” published by Meso Scale Discovery in July 2014 (herein referred to as Meso).
Regarding claim 1, Liu teaches a method for determining concentration of free target in a sample (p. 580, para. 2). Liu teaches that the method comprises adding a sample having a target bound to a drug and free target to a solid support coated with a capture agent (p. 580, para. 2, lines 1-7). Liu teaches adding a detection agent that has a detectable label (p. 580, para. 1, lines 3-5). Liu teaches measuring the signal from the detectable label to determine the concentration of free target, whereby the signal is proportional to the concentration (p. 580, para. 2, lines 7-13). Liu teaches that the antibody used as the capture agent, “Ab2” (p. 580, para. 1, lines 2-3), has lower affinity for the target compared to the drug which reduces target-drug complex dissociation (p. 580, para. 1, lines 5-8). Further, Liu teaches that the assay results in a stable target-drug complex (p. 580, para. 2, lines 13-16). As disclosed in the instant specification, a capture antibody with lower affinity and slower association rate results in a stable target-drug complex, whereas an antibody with only a lower affinity for the target does not (instant specification para. 0105, lines 3-12, Figure 4). Therefore, because Liu teaches the use of a capture antibody with lower affinity for the target (p. 580, para. 1, lines 5-8) that results in a stable target-drug complex in the assay (p. 580, para. 2, lines 13-16), the capture antibody is also considered to have a slower association rate.
In the alternative interpretation where the capture antibody taught by Liu is not considered to have a slower association rate for the target compared to the drug, it would have been obvious for one of ordinary skill before the effective filing date of the claimed invention to modify the method taught by Liu by selecting a capture antibody with a slower association rate. An artisan would have been motivated and had a reasonable expectation of success in making this change in order to further stabilize the target-drug complex in the assay which is important to prevent over-estimation of the amount of free target in the assay, as taught by Liu (p. 580, para. 1, lines 5-8).
Regarding claim 2, Liu teaches that the solid support is streptavidin coated (p. 576, para. 4, line 1).
Regarding claim 3, Liu teaches that the capture agent is biotinylated (p. 576, para. 4, lines 1-2).
Regarding claim 4, Liu teaches incubating the sample for 30 or 60 minutes (p. 580, para. 2, lines 5-7, which is considered about 15 or 45 minutes.
In the alternative interpretation where 30 or 60 minutes is not considered to be about 15 or 45 minutes, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to perform routine optimization of the timing in the claimed invention to make and use the claimed invention. As noted in In re Aller, 105 USPQ 233 at 235, more particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Routine optimization is not considered inventive and no evidence has been presented that arriving at the claimed incubation time was anything other than routine, that the properties of the incubation from the optimization has any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Optimization of parameters is a routine practice that would be obvious for the artisan to employ. See MPEP § 2144.05. The artisan would have had a reasonable expectation of success based on the cumulative disclosure of Liu, which teaches that incubation from 30-60 minutes, which contains the claimed about 45-minute incubation time, can be used for the claimed immunoassay.
Regarding claim 5, Liu teaches that the detectable label is a sulfo-tag (Figure 1, p. 580, para. 1, line 5). As evidenced by Meso, the sulfo-tag is a ruthenium label (Meso Figure 2, “Ru(bpy)32+”).
Regarding claim 6, Liu teaches that the sulfo-tag label is an electrochemiluminescent substrate (p. 577, para. 1, line 10).
Regarding claim 7, Liu teaches detecting the sulfo-tag signal with the Meso Sector S600 (p. 576, para. 4, lines 10-12). As evidenced by Meso, the Sector imager applies a voltage to the plates (Meso p. 5, para. 2, lines 7-9) to produce a signal from a sulfo-tag label.
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.
Claim(s) 8 is rejected under 35 U.S.C. 103 as being unpatentable over Liu in view of Chen et al., “Overcoming multimeric target interference in a bridging immunogenicity assay with soluble target receptor, target immunodepletion and mild acidic assay pH” Bioanalysis (published 07/31/2020, IDS dated 02/15/2023, referred to herein as Chen).
Regarding claim 8, Liu teaches determining the amount of free target by comparing to a standard calibration curve (p. 576, para. 4, lines 3-7) wherein the curve was produced with at least three standard solutions, i.e. recombinant AA reference standard (p. 576, para. 4, lines 3-7. Figure 5, Right panel).
However, Liu does not teach establishing target interference and minimizing target interference by acidification.
Chen teaches identifying interference based on target levels, i.e. “target-mediated signal”, and reducing the interference by acidification (p. 1075, para. 3, lines 1-8).
It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to include the steps of interference identification and acidification taught by Chen to the free target assay taught by Liu. An artisan would have been motivated to add these steps in order to reduce the interference signal in the assay which would make the assay more accurate. An artisan would have had a reasonable expectation of success in making this change as the steps taught by Chen are intended to be used in target:drug interaction based assays, such as the assay taught by Liu.
Response to Arguments
Applicant's arguments filed 05/26/2026 have been fully considered but they are not persuasive for the following reasons:
The objection to claim 3 is withdrawn in response to Applicant’s amendment.
The rejection of claim 8 under 35 U.S.C. 101 is withdrawn in response to Applicant’s amendment.
Regarding the remarks on pages 7 and 8 regarding the rejection of claims 1-8 under 35 U.S.C. 102/103, Applicant argues that the rejection is improper because the conclusion that the antibody of the prior art has a slower association rate is reached from the teachings of the instant specification.
This argument is not persuasive. The discovery of a property of a product in the prior art does not render something patentable (see MPEP 2112(I)). In this case, the discovery that a capture antibody with lower affinity and slower association rate results in a stable target-drug complex, whereas an antibody with only a lower affinity for the target does not (instant specification para. 0105, lines 3-12, Figure 4), describes an inherent property of antibodies. This discovery of how inherent characteristics of some antibodies affects assay results can be applied to antibodies in the prior art to determine whether the inherent property, i.e. whether the antibody has a slower association rate, is present. Importantly, the instant specification is not used as prior art in the rejection; rather, it is used to provide the rationale for why the antibody of the prior art is considered to have the claimed inherent property.
Further regarding the remarks on page 8, Applicant argues that the inherent feature is not necessarily present in the cited art and that the examiner must provide a basis or technical reasoning to support the determination that the inherent feature is present.
This argument is not persuasive. The technical reasoning used to determine that the inherent feature was present in the prior art is described in the rejection under 35 U.S.C. 102/103. Restated, Liu teaches a method for determining concentration of free target in a sample using a capture agent, “Ab2” (p. 580, para. 1, lines 2-3), that has lower affinity for the target compared to the drug which reduces target-drug complex dissociation (p. 580, para. 1, lines 5-8). Two possibilities exist for the association rate of Ab2, 1) it has a slower association rate for the target compared to the drug, or 2) it does not. The instant specification teaches that, regarding the association rate for the target compared to the drug, if the antibody has a slower association rate for the target compared to the drug, then the antibody will form a stable target-drug complex. Because Liu teaches that the antibody, Ab2, has a lower affinity for the target compared to the drug and forms a stable target-drug complex, the inherent property of a slower association rate for the target compared to the drug must be present. This inherent property of Ab2 is considered to be present in the assay of the prior art regardless of whether this property was actually recognized in the prior art (See MPEP 2112(II) and (III)).
Conclusion
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 June 25, 2026
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