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
Claims 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected apparatus and system, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 15 JULY 2026.
Applicant’s election without traverse of Group I: Claims 1-13 in the reply filed on 15 JULY 2026 is acknowledged.
Status of Claims
Applicant has elected Group I: Claims 1-13 for examination. In the claim set, Claims 1-13 are ‘Previously Presented’ or ‘Original’; Claims 14-20 are ‘Withdrawn’.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03 OCTOBER 2023 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
On page 8 line 12, the instance of ‘0,1’ should be consistent with the English notation for decimals and should read ‘0.1’.
Appropriate correction is required.
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 1-13 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.
Regarding claims 1, 3 and 8, the phrase "in particular" 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).
Regarding claims 4, 5, 7 and 9 includes a phrase off set in parenthesis. It is unclear if the portion of the part off set by parenthesis is part of the claimed invention. The portion off set by the parenthesis is not a reference character or an abbreviation.
Claims 6 and 7 recites the limitation "the at least one time cross-correlation function" . There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the corrected intensity cross-correlation function" . There is insufficient antecedent basis for this limitation in the claim.
Dependent claims follow the same reasoning.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The claim(s) recite(s) a method for characterizing transient interactions between biomolecules comprising following steps:- providing a plurality of plasmonic nanoparticles which are configured to allow first biomolecules to adhere thereto,- providing a mixture comprising the nanoparticles, first biomolecules and second biomolecules to allow the first biomolecules to adhere to the nanoparticles and to allow the second biomolecules to, in particular transiently, interact with the first biomolecules adherent to the nanoparticles,- irradiating the mixture with first electromagnetic radiation, in particular broadband electromagnetic radiation,- detecting second electromagnetic radiation, which is scattered by the mixture while irradiating the mixture with the first electromagnetic radiation, in a time-resolved and spectrally-resolved manner so as to obtain intensity signals representing changes in the spectrum of the detected second electromagnetic radiation, and- determining at least one interaction parameter characterizing transient interactions of the second biomolecules with the first biomolecules based on the intensity signals.
The claim recites steps of ‘determining’ which is considered to be an abstract idea which can be done with or performed with the human mind and or pen and paper or considered to be math.
The steps prior to the ‘determining’ step are all considered to be extra pre-solution activities.
This judicial exception is not integrated into a practical application because after the determining step; nothing else is done. The method does not include any additional steps that transforms the claim into something that integrates the abstract idea into a practical application of the abstract idea.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps in Claim 1 are well understood routine and conventional. The reference to PRINS anticipates the claim.
Additional Claims 2-12 do not include any limitations which integrates the abstract idea into a practical application of the abstract idea and many of dependent claims include steps which just further manipulate / process the data by a math equations or mathematical concepts of a cross-correlation function, which is considered to be an abstract idea. MPEP 2106.04 (a). Claim 13 only further defines the contents of the mixture, which does integrate the abstract idea into a practical application nor is the mixture and its content significantly more than the abstract idea.
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 1, 11, 12 and 13 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by PRINS, WO 2016/075229 A1, submitted on the Information Disclosure Statement on 03 OCTOBER 2023; Foreign Patent Document, Cite No. 2.
Applicant’s invention is directed towards a method.
Regarding Claim 1, the reference PRINS method for characterizing transient interactions between biomolecules, page 8 line 5-6, dynamic binding and unbinding event that are detected at the single molecule level, page 14 line 31-32, comprising following steps:
- providing a plurality of plasmonic nanoparticles which are configured to allow first biomolecules to adhere thereto, page 5 line 25-27, page 6 line 18-19, probe, page 22 line 15-17, bipyriamids, Figure 2A;
- providing a mixture comprising the nanoparticles, page 6 line 25-28, page 22 line 15-17, first biomolecules and second biomolecules to allow the first biomolecules to adhere to the nanoparticles and to allow the second biomolecules to, in particular transiently, interact with the first biomolecules adherent to the nanoparticles, Figure 2B, 2C,page 5 line 29-page 6 line 2, page 8 line 18-23,
- irradiating the mixture with first electromagnetic radiation, in particular broadband electromagnetic radiation, Figure 5, 6A, 6B, page 15 line 26-30,
- detecting second electromagnetic radiation, which is scattered by the mixture while irradiating the mixture with the first electromagnetic radiation, in a time-resolved and spectrally-resolved manner so as to obtain intensity signals representing changes in the spectrum of the detected second electromagnetic radiation, Figure 5, 6A, 6B, page 20 line 4-21, and
- determining at least one interaction parameter characterizing transient interactions of the second biomolecules with the first biomolecules based on the intensity signals, page 18 line 28-page 19 line 3.
Additional Disclosures Included are: Claim 11: wherein the method according to claim 1, wherein determining the at least one interaction parameter includes determining at least one parameter characterizing reversible interactions between the first and second biomolecules, Figure 5, page 15 line 13-page 16 line 14, see bound and unbound configurations (reversible interactions). ; Claim 12: wherein the method according to claim 1, wherein determining the at least one interaction parameter includes determining at least one of the following: - a first transition rate characterizing a time rate at which transitions occur between an unbound state, in which the second biomolecules are not bound to and/or do not interact with first biomolecules, to a bound state, in which the second biomolecules are bound to and/or interact with the first biomolecules, and/or - a second transition rate characterizing a time rate at which transitions occur between a bound state, in which the second biomolecules are bound to and/or interact with the first biomolecules, to an unbound state, in which the second biomolecules are not bound to and/or do not interact with the first biomolecules, and/or - a dissociation constant characterizing a tendency of the first and second biomolecules to reversibly dissociate between a bound state, in which the second biomolecules are bound to and/or interact with the first biomolecules, and an unbound state, in which the second biomolecules are not bound to and/or do not interact with the first biomolecules, page 8 line 17 page 9 line 20.; and Claim 13: wherein the method according to claim 1, wherein the mixture comprising the nanoparticles, first biomolecules and second biomolecules is a solution and/or dispersion, wherein the nanoparticles, first biomolecules and second biomolecules are dissolved in a solvent or dispersed in a dispersion agent, respectively, page 5 line 29- page 6 line 16, 25-28, Figure 2A-2C.
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.
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.
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over PRINS, WO 2016/075229 A1, submitted on the Information Disclosure Statement on 03 OCTOBER 2023; Foreign Patent Document, Cite No. 2, and further in view of BROKMANN, submitted on the Information Disclosure Statement on 03 OCTOBER 2023; Non-Patent Literature Cite No. 2.
Regarding Claim 2, the PRINS reference discloses the claimed invention, but is silent in regards to wherein the step of detecting the second magnetic radiation comprises - splitting the second electromagnetic radiation into a first partial beam and a second partial beam,- providing one or more different path length differences between the first partial beam and the second partial beam,- superimposing the first partial beam and the second partial beam for each of the path length differences so as to obtain a first interference beam and a second interference beam for each of the path length differences, and - separately detecting the first interference beam and the second interference beam by means of two separate detectors at different times and for each of the path length differences so as to obtain two series of intensity signals representing intensities of the first interference beam and second interference beam, respectively, at the different times and for the different path length differences.
BROKMANN discloses a method to probe the spectral fluctuations of a transition over broad ranges of frequencies and timescales with the high spectral resolution of Fourier spectroscopy, abstract. The reference further teaches setup is investigated theoretically, simulated numerically, and compared to standard spectroscopy experiments, page 2, Figure 1.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the invention of PRINS so that the step of detecting the second electromagnetic radiation comprises - applying the second electromagnetic radiation to at least one spectral splitting element, in particular a dichroic optical element, so as to obtain at least one first partial beam of electromagnetic radiation having a first spectrum and at least one second partial beam of electromagnetic radiation having a second spectrum which is different from the first spectrum, and- separately detecting the first partial beam and the second partial beam by means of two separate detectors at different times so as to obtain two series of intensity signals representing intensities of the first partial beam and second partial beam, respectively, at the different times and for the first and second spectrum to determine spectral dynamics of the detector at high temporal and high spectral resolutions.
Regarding Claim 3, the PRINS reference discloses the claimed invention, but is silent in regards to wherein the step of detecting the second magnetic radiation particulars.
BROKMANN discloses a method to probe the spectral fluctuations of a transition over broad ranges of frequencies and timescales with the high spectral resolution of Fourier spectroscopy, abstract. The reference further teaches setup is investigated theoretically, simulated numerically, and compared to standard spectroscopy experiments, including wherein the step of detecting the electromagnetic radiation comprises - applying the electromagnetic radiation to at least one spectral splitting element, in particular a dichroic optical element, so as to obtain at least one first partial beam of electromagnetic radiation having a first spectrum and at least one second partial beam of electromagnetic radiation having a second spectrum which is different from the first spectrum, and- separately detecting the first partial beam and the second partial beam by means of two separate detectors at different times so as to obtain two series of intensity signals representing intensities of the first partial beam and second partial beam, respectively, at the different times and for the first and second spectrum, page 2, Figure 1.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the invention of PRINS so that the step of detecting the second electromagnetic radiation comprises - applying the second electromagnetic radiation to at least one spectral splitting element, in particular a dichroic optical element, so as to obtain at least one first partial beam of electromagnetic radiation having a first spectrum and at least one second partial beam of electromagnetic radiation having a second spectrum which is different from the first spectrum, and- separately detecting the first partial beam and the second partial beam by means of two separate detectors at different times so as to obtain two series of intensity signals representing intensities of the first partial beam and second partial beam, respectively, at the different times and for the first and second spectrum to determine spectral dynamics of the detector at high temporal and high spectral resolutions.
Claims 4-10 are rejected under 35 U.S.C. 103 as being unpatentable over PRINS, WO 2016/075229 A1, submitted on the Information Disclosure Statement on 03 OCTOBER 2023; Foreign Patent Document, Cite No. 2, and further in view of BEYLER, submitted on the Information Disclosure Statement on 03 OCTOBER 2023; Non-Patent Literature Cite No. 1.
Regarding Claim 4, the PRINS reference discloses the claimed invention, but is silent in regards to determining at least one time auto-correlation function (intensity-time auto-correlation function).
BEYLER discloses a method for characterizing interactions between molecules, abstract, which include a step of determining at least one time auto-correlation function (intensity-time auto-correlation function), page 112-113.
While BEYLER discloses a known characterization step of a time autocorrelation function including obtaining information about the intensity fluctuations, it is silent in regards to characterizing a time auto-correlation of a combination of the two series of intensity signals, wherein at least one diffusion parameter characterizing a diffusion of the nanoparticles in the mixture is determined based on the at least one time auto-correlation function.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the PRINS reference with determining step of at least one time auto-correlation function (intensity-time auto-correlation function) to determine the spectral information, but also information about the intensity fluctuations of the emitter, which can be isolated by calculating the ratio of the intensity cross-correlation to the autocorrelation of the sum signal of the two outputs, page 113.
Regarding Claim 5, the PRINS reference discloses the claimed invention, but is silent in regards to determining at least one time auto-correlation function (intensity-time auto-correlation function).
BEYLER discloses a method for characterizing interactions between molecules, abstract, which include a step of determining at least one time auto-correlation function (intensity-time auto-correlation function), page 112-113.
While BEYLER discloses a known characterization step of a time autocorrelation function, it is silent in regards to characterizing a time cross-correlation between the two series of intensity signals, wherein the at least one interaction parameter is determined based on the at least one time cross-correlation function and optionally also on the at least one time auto-correlation function.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the PRINS reference with determining step of at least one time auto-correlation function (intensity-time auto-correlation function) to determine the spectral information, but also information about the intensity fluctuations of the emitter, which can be isolated by calculating the ratio of the intensity cross-correlation to the autocorrelation of the sum signal of the two outputs, page 113.
Regarding Claims 6 - 8, the PRINS reference discloses the claimed invention, but is silent in regards to determining at least one time auto-correlation function (intensity-time auto-correlation function) and the different parameters characterizing the interactions.
BEYLER discloses a method for characterizing interactions between molecules, abstract, which include a step of determining at least one time auto-correlation function (intensity-time auto-correlation function), page 112-113.
BEYLER teaches the interferometer has varying path lengths and takes into account the varying path length difference during analysis, it would be obvious to one having ordinary skill in the art before the effective filing date to modify the method so that at least one time auto-correlation function and/or the at least one time cross-correlation function is determined for the different path length differences between the first partial beam and the second partial beam or for the first and second spectrum, respectively; and to remove effects of nanoparticle diffusion on the time cross-correlation function to determine if changes in the spectral coherence or whether they are caused by intensity fluctuations like fluorescence intermittancy or microscope drift, page 112.
Regarding Claim 9, the references PRINS and BEYLER suggests the claimed invention. BEYLER further discloses comprising Fourier transforming the time cross-correlation functions, which are determined for the different path length differences, with respect to the dimension of the path length differences so as to obtain spectral correlation functions (spectral-time correlation function) at different times and for different wavelength changes, wherein the at least one interaction parameter is determined based on the spectral correlation functions, page 111-113.
It would be obvious to one having ordinary skill to modify the method of PRINS to explore the relation between lineshape broadening and decoherence in molecules and semiconductor quantum dots, as well as the dynamical interactions of these systems with optical fields and their nanoscale environment. Implemented in a fluorescence correlation spectroscopy (FCS) experiment, PCFS might also provide some insight into the spectral dynamics of nanoscale emitters under the influence of chemical reactions, conformational changes or intermolecular interactions in liquid environments, Conclusion.
Additional Disclosure Included is: Claim 10: wherein the method according to claim 9 further comprising determining a temporal behavior of the spectral correlation functions, wherein the at least one interaction parameter is determined based on the temporal behavior of the spectral correlation functions and/or intensity correlation functions, page 86 Section 2.3.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINE T MUI whose telephone number is (571)270-3243. The examiner can normally be reached M-Th 5:30 -15:30 EST.
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CTM
/CHRISTINE T MUI/Primary Examiner, Art Unit 1797
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