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 without traverse of Group III, claims 18-29, in the reply filed on 09/16/2025 is acknowledged.
Claims 1-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
New claim 30 is acknowledged.
Claims 1-30 are pending.
Claims 18-30 are under examination on the merits.
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.
Specification
The use of terms which are trade names or marks used in commerce (including TRITON®, Millipore SIGMA® and Cell Signaling Technology® among others), has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term 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.
Claim Interpretation
Claims 18-30 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)
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 18-30 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 limitation “wherein the machine comprises one or more processors configured by machine readable instructions to: (a) facilitate ---; and (b) detect ---" recited in claim 18 has been evaluated under the three-prong test set forth in MPEP § 2181, subsection I, but the result is inconclusive. Thus, it is unclear whether this limitation should be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because it is unclear whether the phrase “machine readable instructions” is intended to be limited to a software program installed in a machine, with a computer being part of the claimed machine, configured in certain way within the claimed machine to perform recited actions/functions (a) and (b), or any forms of instructions that can be read by any machine to perform the functions recited in (a) and (b) of claim 18. The boundaries of this claim limitation are ambiguous; therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
In response to this rejection, applicant must clarify whether this limitation should be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. Mere assertion regarding applicant’s intent to invoke or not invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph is insufficient. Applicant may:
(a) Amend the claim to clearly invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, by reciting “means” or a generic placeholder for means, or by reciting “step.” The “means,” generic placeholder, or “step” must be modified by functional language, and must not be modified by sufficient structure, material, or acts for performing the claimed function;
(b) Present a sufficient showing that 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, should apply because the claim limitation recites a function to be performed and does not recite sufficient structure, material, or acts to perform that function;
(c) Amend the claim to clearly avoid invoking 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, by deleting the function or by reciting sufficient structure, material or acts to perform the recited function; or
(d) Present a sufficient showing that 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, does not apply because the limitation does not recite a function or does recite a function along with sufficient structure, material or acts to perform that function.
Claim 18 is also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. Claim 18 recites the limitation “(b) detect an amount and speed of a cleavage product of the nucleic acid substrate in real time”, which appears to be method steps of using the claimed machine that are not part of machine. If steps of using the claimed machine is intended to be included, the omitted step(s) appear to be: a cleavage step of the nucleic acid substrate. Accordingly, claim 18 should clearly delineate all active steps, in the context of components recited in (a) of claim 18, required for operating the claimed machine.
Claim 18 recites the limitation “detect -- speed of a cleavage product”. It is assumed that the speed of production of a cleavage product is intended to be detected but, as written, it is unclear what element is being detected.
Claims19-30 are similarly indefinite because they directly or indirectly depend from claim 18.
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 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Boles et al. (US PGPub 20140005066).
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).
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 combine solutions in a sample reservoir (para 12); perform multiplex reactions (para 5); and perform incubations (para 5).
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).
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 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Boles et al. (US PGPub 20140005066) in view of Trowell et al. (US PGPub 20150094219).
The teachings of Boles as they relate to claim 18 are stated in the 102 rejection above in this office action.
Regarding claims 21 and 22, Boles does not teach (i) the machine generates target engagement data configured to facilitate the multi-dimensional determination and quantification of engagement between the test compound and the target polypeptide (claim 21) or (ii) the target engagement data is configured to facilitate identification of binding stoichiometry, target occupancy, residence time, KD, K-on, K- off, and EC50 (claim 22).
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 and Trowell to arrive at the instantly claimed invention. The modification would have entailed adding the system of Trowell to the device of Boles. Boles used a system that incorporated microfluidics (para 50) and it would have been routine to ass additional microfluidic elements. 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 claim 23, Boles teaches a device that is programmable (para 122 and 123), and the device may combine solutions in a sample reservoir (para 12); perform multiplex reactions (para 5); and perform incubations (para 5).
Claims 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Boles et al. (US PGPub 20140005066) in view of Knight et al. (US PGPub 20120052560).
Regarding claim 28, Boles does not teach the container is a tube or multi-well plate compatible with real-time fluorescence measuring (claim 28) or the multi-well plate comprises a microfluidic chip enabling reaction multiplexing (claim 29).
Knight teaches systems for the rapid serial processing of multiple nucleic acid assays (Abstract). Knight teaches a system comprising a microfluidic cartridge and a fluorescence imaging system (Abstract). Knight further teaches illumination of a microfluidic chip (cartridge) for real time fluorescence detection (para 222), satisfying the requirements of claims 28 and 29.
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 and Wang to arrive at the instantly claimed invention. The modification would have entailed using the microfluidic chip of Knight as the detection device of Boles. One would have been motivated to use the microfluidic chip of Knight for the added benefit of control of reagents and increased multiplexing while retaining real-time fluorescence detection. 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.
Claims 24 and 30 are rejected 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).
Regarding claims 24 and 30, Boles does not teach the fusion protein comprises the target polypeptide and an S-tag acceptor peptide (claim 24) or the nuclease donor is an RNase S protein, and wherein the fusion protein comprises the target polypeptide and an S-tag acceptor peptide (claim 30).
Horecka teaches determining the state of a protein using a fusion protein comprising a member of an enzyme fragment complementation complex and a target protein (Abstract). Horecka teaches an enzyme donor such as the S-peptide from RNase (para 26).
Horecka does not explicitly teach the S-tag acceptor peptide. However, Horecka teaches any enzyme donor may be used that will allow for detection with an enzyme acceptor, so the use of an S-tag acceptor would have been understood.
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 and Horecka to arrive at the instantly claimed invention. The modification would have entailed using the reagents of Horecka in the device of Boles. One would have been motivated to use the reagents in order to interrogate proteins with high sensitivity in a programmable device. 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
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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