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 with traverse of Group I in the reply filed on 05/22/2026 is acknowledged. The traversal is on the ground(s) that groups I and II relate to each other as a product and an embodiment thereof, respectively, and that the group II claims are the same composition as that of group I, and merely reflect a potential embodiment of the first and second labels. Applicant has amended claim 11 to reflect this. Applicant also elects group I without prejudice to group III. Examiner acknowledges that amended claims 11 and 12, contained in group II, are merely alternate embodiments of the invention of claim 1; therefore, Examiner rejoins groups I and II for examination. Group III is withdrawn as per the election of group I.
The requirement is still deemed proper and is therefore made FINAL.
Claims 34-36, 38, 44, 48, 56, and 60 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 05/22/2026.
Status of Claims
Claims 1 and 11 have been amended by the preliminary amendment filed 05/22/2026. Claims 2, 4, 8, 10, 12, 16, 27, 29, 36, 38, 44, 48, 56, 60, 61, and 65 were previously amended and claims 3, 5-7, 9, 13-15, 17-26, 28, 30-33, 37, 39-43, 45-47, 49-55, 57-59, 62-64, 66-72 were previously cancelled, in the amendment filed 04/10/2023. Claims 1-2, 4, 8, 10-12, 16, 27, 29, 34-36, 38, 44, 48, 56, 60-61, and 65 are pending. Claims 34-36, 38, 44, 48, 56, and 60 are withdrawn. Claims 1-2, 4, 8, 10-12, 16, 27, 29, 61, and 65 will be examined on the merits.
Priority
Provisional application 63/090,918 is acknowledged as disclosing the claimed invention and the effective filing date of the invention is 10/13/2020.
Information Disclosure Statement
The Information Disclosure Statements filed on 5/10/2023 and 3/25/2026 have been considered. Signed copies are enclosed.
Claim Objections
Claim 65 is objected to because of the following informalities: claim 65 recites steps (1) generating, (2) measuring, (3) changing, (4) re-measure, and (5) repeat. For consistency i. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 10 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 10 recites "the antibody construct of claim 1, wherein binding of the target analyte to the antibody…increases or decreases the detectable readout." Claim 1 recites that the first and second labels interact to generate a detectable readout that either increases or decreases when the blocking analyte is bound and either decreases or increases when the blocking analyte is not bound. Claim 1 also recites that the blocking analyte competes with the target analyte for binding to the antibody. Therefore, inherently, when the blocking analyte is bound the target analyte is not bound, and when the target analyte is bound the blocking analyte is not bound. Thus, claim 10's recitation of the detectable readout increasing or decreasing upon binding of the target analyte does not further limit claim 1's recitation of the detectable readout increasing or decreasing depending upon if the blocking analyte is bound or not bound. Applicants may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
(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.
Claim(s) 1, 2, 4, 8, 10, 16, 27, 29, 61, and 65 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US 2006/0172318 A1 Medinz et al., published 08/03/2006.
Claim 1 teaches an antibody construct comprising an antibody (or an antigen binding fragment thereof) comprising a first label that is linked, via a linker, to a blocking analyte that competes with the target antigen for binding to the antibody, and a second label. Claim 1 further specifies that the first and second labels interact with each other to generate a detectable readout that increases or decreases when the blocking analyte is bound or not bound. Claim 2 specifies that the second label may be attached to either the blocking analyte or the linker itself. Claim 4 specifies that the first and second labels are fluorophores and quenchers (interchangeably) or donor and acceptor fluorophores (interchangeably). Claim 16 specifies that the linker is a polynucleotide, either double stranded, single stranded, or partially double stranded. Claim 27 recites that the blocking analyte is identical to or a variant of the target analyte, and claim 29 specifies the affinity of the antibody for the target and blocking analytes. Claim 60 recites a method of detecting a target analyte comprising contacting the sample with the antibody construct of claim 1 and measuring binding via the detectable readout, and claim 65 recites a method of adjusting kinetics of an antibody construct comprising measuring the binding of the antibody construct to a target analyte, changing a component of the construct, re-measuring binding, and repeating these steps until the desired kinetics are reached.
Medinz et al. disclose a biosensor comprising a biorecognition element, disclosed in claim 4 as an antibody or antibody fragment, and a flexible arm element, or a linker, which are each labeled with a signaling element (or label), wherein the flexible arm contains an analog of an analyte of interest that binds with the biorecognition element (abstract, claim 1, whole document). Therefore, the biosensor of Medinz et al. comprises the elements of the instant invention: an antibody, a first label, a linker, a second label, and a binding analyte. Paragraph [0028] of Medinz et al. recites that the biosensor can be made by tethering the arm directly to the antibody. Medinz et al. further teach that the arm element is labeled with the second signaling molecule, meeting the limitations of instant claim 2, and claim 3 of Medinz et al. teaches the signaling element is a dye or quencher, thereby teaching instant claim 4. Claim 1 of Medinz et al. teaches that the biosensor comprises a detector for detecting FRET signals, meeting the limitations of instant claim 8. Medinz et al. teach that the flexible arm is comprised of single-stranded DNA, double stranded DNA, or combination thereof, in claim 6, thereby teaching the limitations of instant claim 16. Finally, claim 7 of Medinz et al. teaches that the binding analyte is an antigen or an epitope, or an analog of such, thereby teaching instant claim 27.
As recited in the abstract of Medinz et al., the analog of the analyte, or binding analyte, located on the flexible arm defaults to binding with the antibody, bringing the first label on the antibody and the second label on the arm in close proximity, establishing a baseline fluorescence resonance energy transfer (FRET) signal. When the target analyte, or analyte of interest, is introduced, the target analyte displaces the analyte analog and, with it, the label on the flexible arm, causing a measurable change in the FRET signal. Paragraph [0016] recites that the displacement of the analyte analog by the analyte will cause a change in the FRET signal in a concentration dependent manner. FRET is disclosed in paragraphs [0002], [0011], and [0037] as an optical signal, thereby meeting the limitations of instant claim 8. Additionally, there will be an increase or a decrease in detectable signal upon binding of the target analyte; therefore, Medinz et al. teach instant claim 10. As the analog of the analyte, or the binding analyte, is disclosed as the antigen itself in claim 7, the antibody would necessarily have the same binding affinity (or 100% of the binding affinity) for both the target analyte and the binding analyte, therefore teaching instant claim 29. The description of the invention in paragraph [0016] and [0035]-[0037] and in the examples of Medinz et al. teaches a method of contacting a sample with target analyte with the biosensor of Medinz et al. and measuring binding via the detectable readout, thereby teaching the method of instant claim 60. Additionally, Medinz et al. recite, in claims 12-14, that the binding affinity of the biosensor for the analyte is specific and can be modulated by altering the antibody or the arm of the biosensor, and, in Examples paragraphs [0071]-[0074], demonstrate a method of changing binding kinetics by generating variations of the bioreceptor and repeatedly measuring binding of the target analyte to the bioreceptor. Therefore, Medinz et al. teach the method of instant claim 65. Thus, Medinz et al. anticipate instant claims 1, 2, 4, 8, 10, 16, 27, 29, 60, and 65.
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.
Claim(s) 1-2, 4, 8, 10-12, 16, 27, 29, 61, and 65 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2006/0172318 A1, Medinz et al., in view of Plaxco and Soh, Trends in Biotechnology (2011) 29:1.
Medinz et al. disclose a biosensor comprising a biorecognition element, disclosed in claim 4 as an antibody or antibody fragment, and a flexible arm element, or a linker, which are each labeled with a signaling element (or label), wherein the flexible arm contains an analog of an analyte of interest that binds with the biorecognition element (abstract, claim 1, whole document). Therefore, the biosensor of Medinz et al. comprises the elements of the instant invention: an antibody, a first label, a linker, a second label, and a binding analyte. Paragraph [0028] of Medinz et al. recites that the biosensor can be made by tethering the arm directly to the antibody. Medinz et al. further teach that the arm element is labeled with the second signaling molecule, meeting the limitations of instant claim 2, and claim 3 of Medinz et al. teaches the signaling element is a dye or quencher, thereby teaching instant claim 4. Claim 1 of Medinz et al. teaches that the biosensor comprises a detector for detecting FRET signals, meeting the limitations of instant claim 8. Medinz et al. teach that the flexible arm is comprised of single-stranded DNA, double stranded DNA, or combination thereof, in claim 6, thereby teaching the limitations of instant claim 16. Finally, Medinz et al. teach that the binding analyte is an antigen or an epitope, or an analog of such, thereby teaching instant claim 27.
As recited in the abstract of Medinz et al., the analog of the analyte, or binding analyte, located on the flexible arm defaults to binding with the antibody, bringing the first label on the antibody and the second label on the arm in close proximity, establishing a baseline fluorescence resonance energy transfer (FRET) signal. When the target analyte, or analyte of interest, is introduced, the target analyte displaces the analyte analog and, with it, the label on the flexible arm, causing a measurable change in the FRET signal. Paragraph [0016] recites that the displacement of the analyte analog by the analyte will cause a change in the FRET signal in a concentration dependent manner. FRET is disclosed in paragraphs [0002], [0011], and [0037] as an optical signal, thereby meeting the limitations of instant claim 8. Additionally, there will be an increase or a decrease in detectable signal upon binding of the target analyte; therefore, Medinz et al. teach instant claim 10. As the analog of the analyte, or the binding analyte, is disclosed as the antigen itself in claim 7, the antibody would necessarily have the same binding affinity (or 100% of the binding affinity) for both the target analyte and the binding analyte, therefore teaching instant claim 29. The description of the invention in paragraph [0016] and [0035]-[0037] and in the examples of Medinz et al. teaches a method of contacting a sample with target analyte with the biosensor of Medinz et al. and measuring binding via the detectable readout, thereby teaching the method of instant claim 60. Additionally, Medinz et al. recite, in claims 12-14, that the binding affinity of the biosensor for the analyte is specific and can be modulated by altering the antibody or the arm of the biosensor, and, in Examples paragraphs [0071]-[0074], demonstrate a method of changing binding kinetics by generating variations of the bioreceptor and repeatedly measuring binding of the target analyte to the bioreceptor. Therefore, Medinz et al. teach the method of instant claim 65.
Medinz et al. does not explicitly teach the antibody construct of claim 1 wherein the first label comprises a redox reporter and the second label comprises a sensing electrode. However, Medinz et al. recites, in paragraph [0028] and claim 3, that the signaling molecule can be a dye, a quencher, an electrochemically active group, a quantum dot or an enzyme. Additionally, Medinz et al. recite that, while the examples in Medinz et al. use FRET, or dyes, as the biosensor signal, other read-out modalities are possible, such as electrochemical monitoring (paragraph [0044]). Furthermore, in paragraph [0003], Medinz et al, identify that other sensing modalities that are commonly used in the art as a read-out of the biosensor, including electrochemical modes such as Benson et al. Thus, Medinz et al. define both optical read-outs (such as FRET) and electrochemical read-outs as known equivalents in the art of biosensors. Plaxco and Soh review the state of the art regarding switch-based biosensors. Page 3, left column of Plaxco and Soh recites that optical detection, via fluorescence emission, and electrochemical detection, via electron transfer, are common detectable outputs of switch-based biosensors (seen in Figure 1 as well). Plaxco and Soh describe switch-based electrochemical sensors comprising an electroactive redox reporter such as ferrocene or methylene blue to the biosensor and attaching a sensing electrode in a second, distal position. Plaxco and Soh also state that the electrochemical sensors often perform better than optical or fluorescent counterparts in complex environments, such as in blood and tissues, which provide background fluorescence and limit the utility of these optical techniques for real time monitoring.
In view of Medinz et al. and Plaxco and Soh, it would have been obvious to one of ordinary skill in the art of biosensors to swap the FRET-based signaling method of Medinz et al. with an electrochemical-based signaling method, similar to that disclosed in Plaxco and Soh as routine and well known in the art of biosensors. One would be motivated to do so to in order to avoid contamination by background fluorescence in samples. One would have reasonable expectation of success as Plaxco and Soh disclose that using redox reporters and sensing electrodes are often used with switch-based biosensors. Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that a claim would have been obvious if the substitution of one known element for another yields predictable results to one of ordinary skill in the art. It would be obvious to apply the electrochemical sensors known in the art, such as is disclosed in both Medinz et al. and Plaxco and Soh, for the FRET-based optical sensor of Medinz et al. to be used in the antibody construct of Medinz et al. to yield predictable results; i.e. an electrochemical signal output. Thus, the combination of Medinz et al. and Plaxco and Soh as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary, and claim 11 is considered obvious over the prior art. Medinz et al. disclose, in paragraph [0028], that the signaling molecules, or labels, can be electrochemically active groups and are represented by (60) in the figures. Figures 1, 4, and 5 show that (60) is attached to the same linker as the blocking analyte, as in instant claim 12(a); therefore, Medinz et al. in view of Plaxco and Soh teach instant claim 12.
Taken together, claims 1, 2, 4, 8, 10-12, 16, 27, 29, 60, and 65 are obvious over Medinz et al. in view of Plaxco and Soh.
Conclusion
No claims are allowed.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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