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
This application 18/056,440 filed on 11/17/2022 claims the benefit of provisional U.S. Patent Application No. 63/280,287, filed on 11/17/2021.
The priority date of claim 18 and its dependent claims is determined to be 11/17/2021, the filing date of provisional U.S. Patent Application No. 63/280,287.
Status of Claims
Applicant’s amendments to claims filed 02/04/2026 in response to the Non-Final Rejection mailed 11/05/2025 are acknowledged.
Claim 18 is amended.
Claims 24 and 30 have been canceled.
Claims 1-23 and 25-29 are pending and claims 18-23 and 25-29 are under examination.
Response to Remarks filed 02/04/2026
The amendments and arguments presented in the papers filed 02/04/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 11/05/2025 listed below have been reconsidered as indicated.
a) The objections to the specification regarding the use of trade names or marks are withdrawn in view of the amendments to the specification.
b) The 35 USC 112(b) indefiniteness rejections of claim 18 have been withdrawn in view of amendments to claim.
c) The rejection of claims 18 and 21-23 under 35 U.S.C. 103 as being unpatentable over Boles et al. (US PGPub 2014/0005066) in view of Trowell et al. (US PGPub 2015/0094219) is withdrawn in view of amendments to claim.
d) The rejection of claims 28 and 29 under 35 U.S.C. 103 as being unpatentable over Boles et al. (US PGPub 2014/0005066) in view of Knight et al. (US PGPub 20120052560) is withdrawn in view of amendments to claim.
e) The rejection of claims 24 and 30 under 35 U.S.C. 103 as being unpatentable over Boles et al. (US PGPub 20140005066) in view of Horecka, et al. (US PGPub 20060019285) is withdrawn in view of the cancellation of the claims.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Claim Interpretation
Claims 18-23 and 25-29 are drawn to a “machine.” The specification recites a “machine” wherein the “machine” is defined in terms of structural limitations. In addition, the claims recite structural limitations of the “machine.” Thus, the “machine” is interpreted to encompass any collection of reagents and parts used together that are not necessarily part of a completely integrated single unitary device. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation on the claimed subject matter.
Claim Rejections - 35 USC § 112(b) - Indefiniteness - New
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 18-23 and 25-29 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.
Claim 18 recites the limitation “facilitate preparation of a reaction solution and contact of a fusion protein comprising the target polypeptide and an S-tag acceptor peptide with the reaction solution, the reaction solution comprising:--“. The limitation is references “preparation of a reaction solution—" and “contact of a fusion protein— with the reaction solution". The relationship between preparation of a reaction solution and contact of a fusion protein is unclear and it is not clear if “facilitate preparation of a reaction solution” is intended to incorporate “contact of a fusion protein”.
Claims 19-23 and 25-29 are similarly indefinite because they directly or indirectly depend from claim 18.
Claim Interpretation- 35 USC § 112 (f) - New
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.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
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 limitation(s) 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 limitation(s) is/are: “A machine configured to determine if a test compound can interact with a target polypeptide, wherein the machine comprises one or more processors and a non- transitory computer-readable storage medium storing machine-readable instructions that, when executed by the one or more processors, cause the machine to: (a) facilitate ---; and (b) determine ---" recited in claim 18.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/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 this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/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 limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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.
Claims 18-20 and 25-27 remain/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Boles et al. (US PGPub 20140005066).
This maintained rejection has been modified to address claim amendments filed on 02/04/2026.
Regarding claim 18, Boles teaches a system for performing multiplexed real-time amplification and detection (para 10) that comprises a processor for executing code (para 10) and computer readable medium storing processor-executable instructions for performing a method (para 11). Boles teaches the machine detects fluorescence signals (para 5).
Regarding claim 19, Boles teaches a device that performs real-time PCR (qPCR) (para 12).
Regarding claim 20, Boles teaches a device that is programmable (para 122 and 123), and the device may load a reaction mixture (para 11), which reads on part (a) mixing reaction solution in batch wherein all ingredients are added from start of mixing; perform multiplex reactions (para 5), which reads on part (c); and perform incubations (para 5), which reads on part (e).
Regarding claim 25, Boles teaches preparing a reaction on the bench (para 6).
Regarding claim 26, Boles teaches device communication with a computer connected by coaxial cable (local) or the internet (remote) (para 119 and 120).
Regarding claim 27, Boles teaches the device can perform real-time analysis of fluorescence and detect signal while a reaction is in progress (para 47) and the solution is held in a detection system (container compatible with real-time fluorescence) (Fig. 9).
Response to Arguments against Claim Rejection - 35 U.S. C § 102
The response asserts that as amended, claim 18 requires, inter alia,(i) a fusion protein comprising the target polypeptide and an S-tag acceptor peptide, (ii) an RNase S protein donor that associates with the S-tag acceptor peptide to form a functional RNase complex, and (iii) denaturant-gated RNase assembly such that cleavage of the nucleic acid substrate in real time occurs only when a test compound interacts with and stabilizes the target polypeptide. The response further asserts that Boles describes a real-time PCR fluorescence system relying on probe hydrolysis during amplification and is silent regarding RNase S/S-tag complementation and denaturant gating to report drug-target engagement and therefore cannot anticipate independent claim 18 or dependent claims 19, 20, and 25-27 (p. 10).
Applicant's arguments have been fully considered but are not persuasive.
Firstly, a fusion protein, RNase S protein donor and denaturant denaturant-gated RNase assembly are not part of the machine. Further, the machine does not require detecting fluorescence from RNase S/S-tag complementation and denaturant gating to report drug-target engagement.
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.
Claims 18, 21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Boles et al. (US PGPub 20140005066) in view of Kopito et al. (US20070270486A1, on IDS dated 09/01/2023) and Treiber et al. (US20180275133).
These are new rejections necessitated by claim amendments filed on 02/04/2026.
The teachings of Boles as they relate to claim 18 are stated in the 102 rejection above in this office action.
Regarding claim 18, Kopito teaches assays for screening biologically active agents (test compounds) that alter the conformation of conformationally defective proteins (i.e. interact with polypeptides). The assays comprise engineering a protein of interest to comprise one or more S-tag sequence; and contacting the engineered protein (fused protein) with RNase S and a substrate for detection (para 10). A substrate can be a cleavable ribonucleic acid molecule (para 33). Kopito teaches activity is detected by cleavage of the substrate when the S-tagged protein is complemented with the RNase S in the presence of agents or conditions that are sufficient to stabilize the S-tagged protein (para 10). Kopito teaches monitoring for a change in fluorescence resulting from cleavage (para 33), and that a number of different machines, including sophisticated detection systems and data-management software, can be used to monitor and screen results (para 95).
Neither Boles nor Kopito teach a denaturant that inhibits the association of the S-tag acceptor peptide with the RNase S protein donor.
Treiber teaches methods for detecting and quantitatively measuring a binding property of a compound to a target macromolecule. Treiber teaches a fusion protein and labeling peptide (S-tag acceptor peptide) that is heated (treated with a denaturant), making the labeling peptide inaccessible for complementation (paras 28- 29 and Figs. 1 and 2). Treiber teaches the enzyme complementation comprises a labeling peptide enzyme fragment which combines with a complementary enzyme fragment to create an active enzyme (para 19). Treiber further teaches test compounds that binds to the tagged native macromolecule, enabling detection of the binding with an enzyme complementation assay (para 28, Fig 1). Treiber states that the assay provides sensitive and precise detection of ligand protein interaction (para 8).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Boles with Kopito and Treiber to arrive at the instantly claimed invention. The modification would have entailed using the assay of Kopito in the machine of Boles. The modification would have further entailed using the S-tag and RNase S donor pair of Kopito together with the target engagement assay of Treiber. One would have been motivated by the advantages provided by the sensitivity (high signal-to noise and low background) of the reporter assay of Kopito (para 25) with the screening method of Treiber. The method of Kopito relied on conformationally defective proteins, while Treiber used a denaturant to cause disruption to a native protein structure and test for compound interactions. And both methods used a split-enzyme activity measure for stability provided by a test compound. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 21, Treiber teaches quantitatively measuring a binding property of a compound to a target macromolecule (abstract) and using the methods for detection of protein engagement by drugs (i.e. target engagement) (para 75). Treiber further teaches measuring temperatures (Fig. 4), Kd dissociation constants (Fig. 7), and dose-responses (Fig. 7). Thus, Treiber teaches elements that reads on generating target engagement data configured to facilitate the multi-dimensional determination and quantification of engagement between the test compound and the target polypeptide.
Regarding claim 23, Boles teaches a device that is programmable (para 122 and 123), and the device may load a reaction mixture (para 11), which reads on part (a) mixing reaction solution in batch wherein all ingredients are added from start of mixing; perform multiplex reactions (para 5), which reads on part (c); and perform incubations (para 5), which reads on part (e).
Claims 22, 28, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Boles et al. (US PGPub 20140005066) in view of Kopito et al. (US20070270486A1, on IDS dated 09/01/2023) and Treiber et al. (US20180275133) as applied to claims 18, 21, and 23 above, and further in view of Trowell et al. (US PGPub 20150094219).
These are new rejections necessitated by claim amendments filed on 02/04/2026.
Regarding claim 22, neither Boles nor Kopito teach target engagement data is configured to facilitate identification of binding stoichiometry, target occupancy, residence time, KD, K-on, K- off, and EC50.
Treiber teaches measuring target engagement data including Kd dissociation constants (Fig. 7) and EC50 (Fig. 11), but does not teach binding stoichiometry, target occupancy, residence time, K-on or K- off.
Trowell teaches systems for detecting analytes in real time using microfluidics, a system comprising (i) detecting binding (i.e. target engagement data) of an analyte (target polypeptide) to a sensor molecule (compound) (para 84).
Trowell also teaches (ii) EC50 (Fig. 30), residence times (which incorporate K-off) (Fig. 51) using BRET (para 198). BRET is a variant of FRET, which enables one with skill in the art to calculate binding parameters such as occupancy, affinity and kinetics, including association (k-on) and dissociation (k-off) rates.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Boles, Kopito, and Treiber with Trowell to arrive at the instantly claimed invention. The modification would have entailed adding the measurements of Trowell to the measurements of Treiber for target engagement. Boles used a system that incorporated microfluidics (para 50) and it would have been routine to assay additional microfluidic elements. Similarly, it would have been routine for one of skill in the art performing the method of Treiber to assay additional multiple measures of target engagement. One would have been motivated to make the combination in order to assay additional data types including binding kinetics. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claims 28 and 29, Boles teaches real-time fluorescent monitoring but does not teach the container is a tube or multi-well plate compatible with real-time fluorescence measuring. Boles teaches a microfluidic system with multiplexing (paras 8, 9, 50), but does not teach a multi-well plate comprising a microfluidic chip.
Kopito teaches the use of a tubes or a multiwell plate that are transparent to light and flat (para 94) and the use of sophisticated detection systems (para 95), but does not specifically state the use of a tube or a multi-well plate compatible with real-time fluorescence measuring. Kopito further teaches the use of fluid-control channels (i.e. microfluidics) (para 94), but does not teach a multi-well plate comprising a microfluidic chip.
Treiber teaches use of a multi-well plate (para 158) but does not specifically state the use of a tube or a multi-well plate compatible with real-time fluorescence measuring and on-chip real-time measurements (para 498), but not a multi-well plate comprising a microfluidic chip.
Trowell teaches real-time measurements using a microplate assay and microfluidic chips (Figs. 7, 30, 31), which reads on use of multi-well plates compatible with real-time fluorescence measuring (claim 28) and microfluidic chips enabling reaction multiplexing.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Boles, Kopito and Treiber with Trowell to arrive at the instantly claimed invention. The modification would have entailed using the plate or chip of Trowell in the machine of Boles for the method of Kopito and Treiber. One of skill in the art would have known to use plates that were compatible with real-time fluorescence measuring for a machine and method that make real-time measurements. One of skill in the art would further have been motivated to use the chip of Trowell to implement the fluid channels and regions of Kopito to ensure a working system for reaction multiplexing. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA GRAY whose telephone number is (571)272-0116. The examiner can normally be reached Monday-Friday 8-5 with second Fridays off.
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, WINSTON SHEN can be reached at (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
Prosecution Insights