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 .
DETAILED ACTION
Responsive to communication entered 10/17/2025.
Priority
This application, Pub No. US 2025/0341524 A1, published 11/06/2025, is a § 371 National Stage of International Patent Application No. PCT/US21/14142, filed 01/20/2021, Pub. No. WO 2021/150578, published 07/29/2021, and claims benefit of 62/963,298, filed 01/20/2020.
Status of Claims
Claims 1, 3-9, 11-16 and 18-23 are currently pending. Claims 1-24 have been originally filed. Claims 2, 10, 17 and 24 have been cancelled, as set forth in Applicant’s Preliminary amendment filed 07/15/2022. Claims 1, 3-9, 11-16 and 18-23 have been subject to election/restriction requirement mailed 08/27/2025. Claims 9, 11-16 and 18-23 are withdrawn from further consideration. Claims 1 and 3-8 are examined.
Election/Restriction
Applicant's election, with traverse, of Group I, Claims 1 and 3-8, drawn to a method of using time-resolved fluorescence (TR-F) and a fluorescent protein biosensor to quantitate protein binding in solution, and the following species:
Fibrous actin (F-actin) as a first protein;
C0-C2 fragment of cardiac myosin binding protein-C (cMyBP-C) as a second protein; and
5-((((2-Iodoacetyl)amino)ethyl)amino)Naphthalene-1-Sulfonic Acid (IAEDANS) as a fluorescent probe,
in the reply filed on 10/17/2025 is acknowledged.
Applicant identified Claims 1 and 3-8 as encompassing the elected species. Because Applicant did not distinctly and specifically point out the supposed errors in the species election requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant’s traversal of the restriction requirement between Groups I-III is on the ground(s) that:
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This is not found persuasive because, for cases filed under 35 U.S.C. 371 and found to be lacking unity, search burden is not a criterion for the restriction.
The requirement is still deemed proper and is therefore made FINAL.
Claims 9, 11-16 and 18-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Information Disclosure Statement
The information disclosure statement, submitted by Applicant on 09/28/2022, is in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. Accordingly, the information disclosure statement is being considered by the Examiner.
Specification
The use of the terms Alexa Fluor®, HiPrep™ Sephacryl® S-100, SYPRO® Ruby which are a trade name or a mark used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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Claim Objections
Claim 6 is objected to because of the following informalities: use of acronyms. For clarity, it is recommended to introduce an acronym by placing the acronym in parentheses after the first use of the spelled-out term or name, for example, 5-{[2-(2-Iodoacetamido)ethyl]amino}naphthalene-1-sulfonic acid (IAEDANS).
Claims 4 and 5 are objected to because of the following informalities: improper Markush format. Claim 4 recites “wherein the first protein comprises actin, globular actin (G-actin), fibrous-actin (F-actin), actin filament, actin-tropomyosin complex, tropomyosin (Tm), and the regulated thin filament.” Claim 5 recites “wherein the second protein comprises cardiac myosin binding protein-C (cMyBP-C), skeletal MyBP-C, and fragments thereof.” Emphasis added. It is noted that the claim is not indefinite because it is clear what Applicant intends to include in a Markush grouping. However, Applicant is reminded that, according to MPEP § 2173.05(h) Alternative Limitations, when materials recited in a claim are so related as to constitute a proper Markush group, they may be recited in the conventional manner, or alternatively. For example, if "wherein R is a material selected from the group consisting of A, B, C and D" is a proper limitation, then "wherein R is A, B, C or D" shall also be
considered proper.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 112 that form the basis for the rejections under this section made in this Office action.
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 1 and 3-8 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 claims, as recited in independent Claim 1, are drawn to:
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A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, Claim 1 recites the broad recitation(s) ”operably connecting” and “operably connected”, and the claim also recites “labelling” and “labelled”, which is the narrower statement of the range/limitation. Claim 1 recites the broad recitation ”contacting including binding”, “quantitating protein contact including binding”, and the claim also recites “using time-resolved fluorescence (TR-F) and a fluorescent protein biosensor to quantitate protein binding in solution”, which is the narrower statement of the range/limitation. Emphasis added. Claim 1 is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 3-8 are rejected as being dependent upon the rejected claim(s) and fail to cure its indefiniteness.
Regarding Claim 5, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 8 recites the limitation "wherein the method is for screening physiological conditions or compounds that affect the second protein contact including binding to the first protein" in lines 1-3. There is insufficient antecedent basis for this limitation in independent Claim 1, which is drawn to “A method of using time-resolved fluorescence (TR-F) and a fluorescent protein biosensor to quantitate protein binding in solution”. Emphasis added.
Claim 6 contains the trademark/trade name Alexa Fluor®. Where a trademark or
trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe dyes and, accordingly, the identification/description is indefinite.
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, 4 and 6-8 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Papp et al., “Conformational Changes in Actin Filaments Induced by Formin Binding to the Barbed End”, Biophysical J., 2006, vol. 91, No 7, pp. 2564-2572.
Regarding Claims 1, 4, 6 and 7, Papp et al., throughout the publication, teach:
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Emphasis added.
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Page 2565, left column, 2nd and 3rd paragraphs; Emphasis added.
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Page 2565, right column, , 2nd and 3rd paragraphs; Emphasis added.
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Bridging paragraph at pages 2565 2566; Emphasis added.
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Regarding Claim 3, Papp et al., throughout the publication, teach:
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Page 2569, left column, 2nd paragraph; Emphasis added.
Although Papp et al. do not expressly teach the term “time-resolved fluorescence,” one of skill in the art would have known that measuring fluorescence lifetime with an ISS K2 multi-frequency phase fluorometer (ISS Fluorescence Instrumentation, Champaign, IL), taught by Papp et al., is indeed such a technique:
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Regarding Claim 8, recitation " wherein the method is for screening physiological conditions or compounds that affect the second protein contact including binding to the first protein" is considered as “intended use” because this recitation does not require performing an active process step and, accordingly, carries no patentable weight.
As such, Papp et al. teach all limitations of the instant Claims 1, 3, 4 and 6-8 and the elected species (1) and (3).
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 of this title, 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 1 and 3-8 are rejected under 35 U.S.C. 103 as obvious over Colson et al., “Cardiac myosin binding protein-C restricts intrafilament torsional dynamics of actin in a phosphorylation-dependent manner,” Proc. Natl. Acad. Sci., 2012, vol. 109, No 50, pp. 20437-20442, Supporting Information attached to the instant Office Action; in view of Papp et al., “Conformational Changes in Actin Filaments Induced by Formin Binding to the Barbed End”, Biophysical J., 2006, vol. 91, No 7, pp. 2564-2572.
Colson et al., throughout the publication, teach the use of time-resolved phosphorescence anisotropy (TPA) to detect the effects of myosin binding protein-C (MyBP-C) and its domains on the microsecond rotational dynamics of labelled actin:
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Abstract; Emphasis added.
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Emphasis added.
Colson et al. do not teach:
measuring time-resolved fluorescence (TR-F) lifetime as recited in Claim 1; and
5-((((2-Iodoacetyl)amino)ethyl)amino)Naphthalene-1-Sulfonic Acid (IAEDANS) as a fluorescent probe recited in Claim 6.
The teachings of Papp et al., discussed in the 102(a)(1) rejection above, are incorporated herein in its entirety.
It would have been prima facie obvious, before the effective filing date of the claimed invention, for one of ordinary skill in the art to have made and used a time-resolved fluorescence (TR-F) lifetime technique, taught by Papp et al., for measuring binding MyBP-C, taught by Colson et al., with actin, because the use of both fluorescence lifetime and emission anisotropy decay for measuring the interaction of proteins with actin labeled with IAEDANS, was well known in the art, as taught by Papp et al.
As such, combination of Colson et al. and Papp et al. teach all limitations of the instant Claims 1 and 3-8 and the elected species (1) and (3).
Regarding the elected species (1), in Abstract, as indicated above, Papp et al. teach actin filaments (F actin)
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Regarding the elected species (2), it is noted that, although neither Colson et al. nor Papp et al. teach C0-C2 fragment of cardiac myosin binding protein-C (cMyBP-C), this fragment is well known in the art. See, for example, Colson et al., "Site-directed spectroscopy of cardiac myosin-binding protein C reveals effects of phosphorylation on protein structural dynamics," Proc. Natl. Acad. Sci., 2016, vol. 113, No 12, pp. 3233-3238 (IDS submitted on 09/28/2022):
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Page 3233, right column, 2nd paragraph; Emphasis added.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GALINA M YAKOVLEVA whose telephone number is (571)270-3282. The examiner can normally be reached on M-F 8:30 AM-5:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GREGORY S EMCH can be reached on (571)272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GALINA M. YAKOVLEVA/Primary Examiner, Art Unit 1678