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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e)
or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application claims the benefit of Application Number 62/182,537 filed 2021-04-30. Based on the filing receipt, the effective filing date of this application is April 30, 2021 which is the filing date of Application
Number 63/182,537 from which the benefit of priority is claimed.
Status of Claims
Claims 1-24 are pending.
Applicant’s election without traverse of Group I, claims 1-19, in the reply filed on 09/09/2025 is acknowledged.
Claims 20-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/09/2025.
Therefore, claims 1-19 are examined herein.
Claim Objections
Claims 9 and 17 are objected to because of the following informalities: the claims use the term “LOD” without defining the acronym. For the purpose of applying prior art, LOD will be interpreted as limit of detection based on para. [0011] of the applicant’s specification. Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitations uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitations are:
“the first and second ends are configured to form a coiled-coil structure when the receptor sequence is unbound from the intended target protein; and wherein the first and second ends are configured to form an open-coil structure when the receptor sequence is bound with the intended target protein” in claim 1;
“a receptor sequence capable of binding with the intended target protein” in claim 1;
“the peptide probe is configured to produce at least a detectable fluorescence signal when the peptide probe transitions from the coiled-coil structure to the open-coil structure” in claim 10;
“the peptide probe is configured to have a coiled-coil structure in the absence of the receptor sequence binding with the intended target protein; wherein the peptide probe is configured to have an open-coil structure in the presence of the receptor sequence binding with the intended target protein” in claim 18;
and “a receptor sequence capable of binding with the intended target protein” in claim 18.
Because these claim limitations are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, they are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The “first and second ends are configured to form a coiled-coil structure when the receptor sequence is unbound from the intended target protein; and wherein the first and second ends are configured to form an open-coil structure when the receptor sequence is bound with the intended target protein” in claim 1 is interpreted as the peptide beacon described in FIG. 6A and para. [0086] of the specification and equivalents thereof. “a receptor sequence capable of binding with the intended target protein” in claim 1;
The “receptor sequence capable of binding with the intended target protein” in claim 1 is interpreted as the loop described in FIG. 6A and para. [0086] of the specification and equivalents thereof.
The peptide probe “configured to produce at least a detectable fluorescence signal when the peptide probe transitions from the coiled-coil structure to the open-coil structure; and wherein the peptide probe transitions from the coiled-coil structure to the open-coil structure within a turn-around time of less than 10 minutes” in claim 10 is interpreted as the peptide beacon described in FIGURE 1, FIG. 6A, “Table 1” on p. 10, and para. [0086] of the specification (see, e.g., Sequences in “Table 1”) and equivalents thereof.
The “peptide probe is configured to have a coiled-coil structure in the absence of the receptor sequence binding with the intended target protein; wherein the peptide probe is configured to have an open-coil structure in the presence of the receptor sequence binding with the intended target protein” in claim 18 is interpreted as the peptide beacon described in FIG. 6A and para. [0086] of the specification (see, e.g., “When a target binds to the loop, the coiled-coil stem opens up moving the fluorophore away from the quencher, which increases the fluorescence yield of the system. The increase in the fluorescence yield of the system in response to the target can be exploited as a sensing mechanism”) and equivalents thereof.
The “a receptor sequence capable of binding with the intended target protein” in claim 18 is interpreted the loop described in FIG. 6A and para. [0086] of the specification and equivalents thereof.
Because these claim limitations are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, they are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have these limitations interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitations to avoid them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitations recite sufficient structure to perform the claimed function so as to avoid them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-3, 8-9, and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The terms “low-fluorescence” and “high-fluorescence” in claim 2 are relative terms which renders the claim indefinite. The terms “low-fluorescence” and “high-fluorescence” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For this reason, the claims are indefinite as the metes and bounds of the claims cannot be ascertained in view of this relative term.
The term “about” in claims 3, 9, and 17 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For this reason, the claims are indefinite as the metes and bounds of the claims cannot be ascertained in view of this relative term. For the purpose of applying prior art, the claims will be interpreted to be within a factor of 2 of the Förster distance or the LOD.
Claim 8 recites the limitation "the spike protein receptor binding domain" in the wherein clause of the claim. There is insufficient antecedent basis for this limitation in the claim. For this reason, the claim is indefinite. However, claim 13 recites, “the target protein is a spike protein receptor binding domain”. For the purposes of compact prosecution (consideration of prior art), claim 8 will be interpreted to be referring to “the target protein” of claim 13.
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)(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.
Claims 1-3, 10, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mueller, et al. ("Coiled-Coil Peptide Beacon: A Tunable Conformational Switch for Protein Detection", published 2018-11-09).
With respect to claim 1, Mueller teaches a peptide probe for detection of a target protein, the peptide probe comprising: a stem having a first end and a second end, a fluorophore attached to the first end and a quencher attached to the second end; and a loop proximately located between the first and second ends, the loop comprising a receptor sequence capable of binding with the intended target protein; wherein the first and second ends are configured to form a coiled-coil structure when the receptor sequence is unbound from the intended target protein; and wherein the first and second ends are configured to form an open-coil structure when the receptor sequence is bound with the intended target protein (see, e.g., p. 17080, under “Figure 1.”, and p. 17079, under “Abstract:”).
With respect to claims 2 and 3, Mueller teaches the peptide probe wherein the peptide probe is in a low-fluorescence state in the coiled-coil structure and a high-fluorescence state in the open-coil structure (see, e.g., p. 17080, under “Figure 1.”, and p. 17079, col. 2, para. 3: “To allow a readout of its conformational state, the termini of the coiled-coil hairpin are equipped with a fluorophore/quencher pair (Figure 1)”). Mueller teaches the peptide probe wherein the low-fluorescence state occurs when a distance between the fluorophore and the quencher is about the Förster distance or less, and wherein the high-fluorescence state occurs when a distance between fluorophore and the quencher is greater than the Förster distance (see, e.g., p. 17080, under “Figure 1.”, and p.17080, col. 1, para. 1: “L binds its receptor CBP (R) in a partially α-helical and extended conformation (Figure 1), resulting in a distance between the N- and C-termini of about 30 Å. This is considerably longer than the distance between the N-terminal amino acids in two interacting heptads […] ca. 10 Å”, and p. 17081, col. 1, para. 3: “In the presence of R (c = 25 mm, dark gray; Figure 3a), we observed strong fluorescence increases for f13-L-q21 (2.0-fold) and f17-L-q21(3.0-fold)”). It is understood that based on the data in “Figure 3.”, panel “a” of Mueller, the distance between the fluorophore and the quencher in the bound-state of the peptide probe is greater than the Förster distance because the fluorescence intensity (FI) in the bound-state is more than 2x the unbound-state, and the Förster distance is defined by the distance at which the energy transfer efficiency is 50%.
With respect to claim 10, Mueller teaches a peptide probe, wherein the peptide probe transitions from the coiled-coil structure to the open-coil structure within a turn-around time of less than 10 minutes (see p. 17080, under “Figure 2.”, panels “a)” and “c)”; outlined in red below). Although Mueller does not explicitly teach that the peptide probe transitions from a coiled-coil structure within a turn-around time of less than 10 minutes, in “Figure 2”, panel “a)”, Mueller teaches the same sequence of peptide subunits that form the coils as described in “Table 1” on p. 10 (underlined in red below) of the applicant’s specification. The receptor sequence (shown in “Table 3” on p. 13; portrayed below) does not form the coil. As discussed under the claim interpretation section, claim 10 is interpreted under 35 U.S.C. 112(f). Because the coils of the instant application comprise the same peptide subunit structure as Mueller, the peptide probe of Mueller have the same properties, including turn-around time[AltContent: textbox ([img-media_image1.png][img-media_image2.png])].
[AltContent: textbox ([img-media_image3.png]
[img-media_image4.png]
Mueller – Panels a) and c) of Figure 2.)]With respect to claim 12, Mueller teaches the peptide probe wherein the target protein is a polypeptide (see, e.g., p. 17079, col. 2, para. 3: “To ensure hairpin opening upon target binding, it is crucial to use a peptide ligand (L) which binds its receptor (R) in a conformation that is not compatible with coiled-coil formation. We based our L/R pair on the complex between MLL (mixed-lineage leukemia, aa 2840–2858)[11] and CBP(CREB-binding protein, aa 590–670)”).
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.
Claims 8-9, 13-17, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Mueller, as applied to claims 1-3 and 12 above, and further in view of Pomplun ("De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein", published 2020-12-07) as evidenced by Li (“Structure, Function, and Evolution of Coronavirus Spike Proteins”, published 2016-08-25).
Mueller fails to teach the target protein is a spike protein receptor binding domain associated with a coronavirus, as in claims 8, 13-16, and 18.
Mueller fails to teach the peptide probe is able to detect the spike protein with a limit of detection of about 50-60 pM, as in claims 9 and 17.
Mueller fails to teach the peptide probe is used with a blood sample, as in claim 19.
However, in a journal article on discovery of high-affinity peptide binders for the SARS-CoV-2 spike protein, Pomplun rectifies these deficiencies.
Pomplun teaches peptides receptors for the spike protein receptor binding domain associated with the coronavirus, SARS-CoV-2, as in claims 8, 13-16, and 18 (see p. 156, under “ABSTRACT:”: “We used affinity selection−mass spectrometry for the rapid discovery of synthetic high-affinity peptide binders for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. From library screening with 800 million synthetic peptides, we identified three sequences with nanomolar affinities (dissociation constants Kd = 80−970 nM) for RBD and selectivity over human serum proteins”). It is understood that the spike protein is a part of the viral envelope of a coronavirus as evidenced by Li disclosure: “Associated with the viral envelope are at least three structural proteins: The membrane protein (M) and the envelope protein (E) are involved in virus assembly, whereas the spike protein (S) mediates virus entry into host cells” (see p. 2, para. 2).
Pomplun teaches detection of the SARS-CoV-2 spike protein at about 50-60 pM with the peptide receptors specific for the SARS-CoV-2 spike protein, as in claims 9 and 17 (see, e.g., p. 160, under “Figure 5.”, under panel “C)”).
Pomplun teaches detecting SARS-CoV-2 spike protein in blood, as in claim 19 (see, e.g., p. 160, under “Figure 4.”, panel “C)”
Mueller and Pomplun are analogous to the field of the claimed invention because they are both in the field of affinity assays and both use peptide receptors for their assays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the peptide receptor of Pomplun in the assay of Mueller. Using the receptor of Pomplun would allow the assay of Mueller to detect SARS-CoV-2 spike protein in blood with a limit of detection of about 50-60 pM. An artisan would have been motivated to do so because Pomplun discloses, “Since the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global coronavirus disease 2019 (COVID-19) pandemic. With 30 million cases and over 950 000 deaths (by August 2020), SARS-CoV-2 has spread further than SARS-CoV-1 or middle east respiratory syndrome (MERS-CoV) […] Serologic detection of patient-derived antibodies can be used to track SARS-CoV-2 progression and immunity but has limited early detection ability.6−8 Direct detection of SARS-CoV-2 has been proposed in scalable, rapidly deployed formats but often suffers from low sensitivity that limits effectivity in general population testing.9,10 Thus, the discovery of additional reagents to enable early and rapid SARS-CoV-2 detection and/or neutralization is critical.
Recognition of viral surface proteins by high-affinity reagents represents a promising strategy for virus detection or neutralization.” (see p. 156, col. 1, para. 1-2). Pomplun concludes by disclosing, “From 800 million synthetic peptides screened, we identified three motif-bearing sequences that have nanomolar affinity. These peptides bind SARS-CoV-2-spike-RBD with selectivity over multiple human serum proteins and could detect it at nanomolar to picomolar concentrations” (see p. 161, col. 1, under “CONCLUDING REMARKS”, para. 1). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Mueller and Pomplun, as applied to claims 8-9, 13-17, and 18-19 above, and further in view of Rao (“Point of Care Diagnostic Devices for Rapid Detection of Novel Coronavirus (SARS-nCoV19) Pandemic: A Review”, published 2021-02-02).
Mueller and Pomplun teach as set forth above, but fail to teach the peptide probe is integrated with an on-chip optical sensor to construct a point-of care antigen test, as in claim 11.
However, in a journal article on the state of the art of diagnosis of coronavirus infections, Rao rectifies this deficiency.
When discussing conformational FRET assays, Rao teaches “handheld readers are available to measure the fluorescence”, as in claim 11 (see p. 3, col. 1, para. 1). Rao continues by stating the handheld readers allow FRET assays to be developed into a Point of Care (POC) diagnostic solution (see p.3, col. 1, para. 1).
Mueller, Pomplun, and Rao are analogous to the field of the claimed invention because they are all in the field of diagnostics. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the FRET handheld readers of Rao into the assay of Mueller and Pomplun. An artisan would have been motivated to do so because Rao discloses, “expanding the testing facilities in asymptomatic cases in hotspots require [sic] more Point of Care (PoC) devices. Therefore, fast, inexpensive, and reliable methods of detection of SARS-nCoV-2 virus infection in humans is urgently required. The rapid and easy-to-use devices will facilitate onsite testing” (see p. 1, under abstract). An artisan would have a reasonable expectation of success based on the given disclosures.
Conclusion
Claims 4-7 are free of the prior art. The following is a statement of reasons for the indication of allowable subject matter:
Mueller is the closest prior art. Mueller teaches a peptide probe for detection of a target protein, the peptide probe comprising: a stem having a first end and a second end, a fluorophore attached to the first end and a quencher attached to the second end; and a loop proximately located between the first and second ends, the loop comprising a receptor sequence capable of binding with the intended target protein; wherein the first and second ends are configured to form a coiled-coil structure when the receptor sequence is unbound from the intended target protein; and wherein the first and second ends are configured to form an open-coil structure when the receptor sequence is bound with the intended target protein, as in independent claim 1 (see, e.g., p. 17080, under “Figure 1.”, and p. 17079, under “Abstract:”).
However, Mueller fails to teach the peptide probe comprises a peptide sequence comprising one of SEQ ID Nos. 1-8, as in claims 4-7.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Li discloses: “Associated with the viral envelope are at least three structural proteins: The membrane protein (M) and the envelope protein (E) are involved in virus assembly, whereas the spike protein (S) mediates virus entry into host cells” (see p. 2, para. 2).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL C SVEIVEN whose telephone number is (703)756-4653. The examiner can normally be reached Monday to Friday - 8AM to 5PM PST.
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/MICHAEL CAMERON SVEIVEN/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678