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
Summary
This is the Non-Final Office Action based on application 17/635632 filed 02/15/2022.
Claims 1-8 & 16-25 have been elected, examined and fully considered.
Election/Restrictions
Applicant’s election without traverse of Claims 1- 8 & 16-25 in the reply filed on 05/06/2025 is acknowledged.
Claims 9-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 05/06/2025.
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 1-8 & 16-25 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.
With respect to Claim 1, in step c) “precise,” is a relative term which renders the claim indefinite. The term “precise” 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. Further every person reading the claim could have a slightly different idea of what they consider precise and what they think is not considered precise. Correction is required.
With respect to Claims 3 & 22, “local,” is a relative term which renders the claim indefinite. The term “local” 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. Further every person reading the claim could have a slightly different idea of what they consider local and what they think is not considered local.
With respect to Claim 5, what “protein gray intensity,” is unclear. Does applicant mean that they are measuring gray intensity of an image? No imaging is claimed prior to this so it is confusing. It is also unclear what the “intensity,” is of. Is it of an image, or of an acoustic wave?
With respect to Claim 16, in step d) what “gray intensity,” is unclear. Does applicant mean that they are measuring gray intensity of an image? No imaging is claimed prior to this so it is confusing. It is also unclear what the “intensity,” is of. Is it of an image, or of an acoustic wave?
Further for Claim 16, “conventional,” is a relative term that is not defined by the claim and therefore is unclear.
Claims 2, 4, 6-8, 17-21, & 23-25 are rejected by virtue of being dependent on claims which are found to be unclear.
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.
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 non-obviousness.
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 1-4, & 7-8 are rejected under 35 U.S.C. 103 as being obvious over WILSON in US 20130330247 in view of HUFF in US 20180104694.
With respect to Claim 1, WILSON teaches of a method, comprising:
a) providing:
i) an acousto-thermal device comprising a surface acoustic wave source and at least one microfluidic channel or chamber (abstract, “A fluidics apparatus for manipulation of at least one fluid sample is disclosed. A manipulation surface locates the fluid sample. A surface acoustic wave (SAW) generation material layer is provided,” paragraph 0105, “The fluid sample pinning zone can also be formed by physical structures, for example the pinning zone may be formed as a well in the manipulation surface”), and further that micro particles may be focused in a microfluidic channel (paragraph 0078) and
ii) a sample comprising at least one protein (abstract, “A fluidics apparatus for manipulation of at least one fluid sample is disclosed. A manipulation surface locates the fluid sample,” paragraph 0109, “The fluid sample may consist of or comprise a biological sample such as blood, saliva or urine. For example, the fluid sample may be whole blood,” paragraph 0025, “Notably, for a biological sample containing cells the molecule of interest may be an intracellular molecule,” paragraph 0130, “The term intracellular molecule, or intracellular molecule of interest includes macromolecules (protein, DNA, lipid, polysaccharide)”;
b) introducing said sample into said at least one microfluidic channel or chamber (abstract, “A fluidics apparatus for manipulation of at least one fluid sample is disclosed. A manipulation surface locates the fluid sample. A surface acoustic wave (SAW) generation material layer is provided,” paragraph 0105, “The fluid sample pinning zone can also be formed by physical structures, for example the pinning zone may be formed as a well in the manipulation surface.”);
c) controlling the temperature of the said sample with said surface acoustic wave source to a plurality of precise temperatures within said at least one microfluidic channel or chamber (paragraph 0302).
WILSON further teaches of aggregating the particles which are subjected to the SAW, and the aggregation occurs in concentric rings (in a pattern) (paragraph 0154, & Figure 53).
WILSON further teaches of the surface having a piezoelectric material to form a SAW layer (paragraph 0053-0060) and of parallel transducers (paragraph 0007, 0009, 0021, 0114, 0116, 0208).
WILSON further teaches of separating out particles in the fluid phase to concentrate a specified in the droplet that the particles are essentially centrifuged (though not true centrifugation) (paragraph 0079).
WILSON does not teach in the specific term “precipitating,” the proteins and aggregating specifically precipitated proteins with SAW.
HUFF is used to remedy this. HUFF teaches of an integrated devices that include a sample preparation component integrated with a detection component are disclosed. The sample preparation component may be a digital microfluidics module or a surface acoustic wave module which modules are used for combing a sample droplet with a reagent droplet and for performing additional sample preparation step leading to a droplet that contains beads/particles/labels that indicate presence or absence of an analyte of interest in the sample (abstract). The device of HUFF further uses SAW (as is also done in WILSON) for analyte detection (paragraph 0028, 0037, 0048). HUFF further teaches that the fluid can be concentrated by precipitation (paragraph 0187, 0217). It would have been obvious to one of ordinary skill in the art to use precipitation as is done in HUFF in the method of WILSON due to the known advantages this offers for concentration of protein and other additional functionality (HUFF, paragraph 0187).
With respect to Claim 2, WILSON further teaches of aggregating the particles which are subjected to the SAW, and the aggregation occurs in concentric rings (concentric rings can be considered, parallel lines through broadest reasonable interpretation since all circles are a continuous line and concentric means that the circles are around each other so the lines are parallel to each other) (paragraph 0154, & Figure 53).
With respect to Claim 3, WILSON teaches of the claim as shown above for Claim 1. WILSON does not teach of precipitation. HUFF is used to remedy this and teaches of concentration by precipitation. It would have been obvious to precipitate as is done in HUFF in the method of WILSON due to the advantage this offers for concentration and therefore detection of the sample (paragraph 0187).
With respect to Claim 4, WILSON further teaches of aggregating the particles which are subjected to the SAW, and the aggregation occurs in concentric rings (in a pattern) (paragraph 0154, & Figure 53). WILSON further teaches of separating out particles in the fluid phase to concentrate a specified in the droplet that the particles are essentially centrifuged (though not true centrifugation) (paragraph 0079).
WILSON teaches that the aggregating occurs while SAW occurs (paragraph 0154). WILSON also teach particles are concentrated and separated by SAW (which does the aggregating) (so they occur at the same time.
WILSON does not teach in the specific term “precipitating”. Please see above for claim 1 how HUFF remedies this and teaches of precipitating.
With respect to Claim 7, WILSON teaches that the sample may consist of or comprise a biological sample such as blood, saliva or urine. For example, the fluid sample may be whole blood,” paragraph 0025, “Notably, for a biological sample containing cells the molecule of interest may be an intracellular molecule,” paragraph 0130, “The term intracellular molecule, or intracellular molecule of interest includes macromolecules (protein, DNA, lipid, polysaccharide).”
With respect to Claim 8, WILSON teaches of using SAW to perform lysis (paragraph 0099).
Claims 16-25 & 5-6 are rejected under 35 U.S.C. 103 as being obvious over WILSON in US 20130330247 in view of HUFF in US 20180104694 and further in view of RAMOS in Induced clustering of Escherichia coli by acoustic fields and further in view of HUYNH in Current Protocols in Protein Science: Analysis of protein stability and ligand interactions by thermal shift assay.
With respect to Claims 16 & 6 WILSON teaches of a method, comprising:
a) providing:
i) an acousto-thermal device comprising a surface acoustic wave source and at least one microfluidic channel or chamber (abstract, “A fluidics apparatus for manipulation of at least one fluid sample is disclosed. A manipulation surface locates the fluid sample. A surface acoustic wave (SAW) generation material layer is provided,” paragraph 0105, “The fluid sample pinning zone can also be formed by physical structures, for example the pinning zone may be formed as a well in the manipulation surface,” “in the form of the arrangement of the SAW scattering elements, the SAW actuator usually an interdigitated transducer, IDT, and the fluidics either as channels (so there is more than 1 channel) (paragraph 0253), and further that micro particles may be focused in a microfluidic channel (paragraph 0078) and
ii) a sample comprising at least one protein (abstract, “A fluidics apparatus for manipulation of at least one fluid sample is disclosed. A manipulation surface locates the fluid sample,” paragraph 0109, “The fluid sample may consist of or comprise a biological sample such as blood, saliva or urine. For example, the fluid sample may be whole blood,” paragraph 0025, “Notably, for a biological sample containing cells the molecule of interest may be an intracellular molecule,” paragraph 0130, “The term intracellular molecule, or intracellular molecule of interest includes macromolecules (protein, DNA, lipid, polysaccharide)”;
b) introducing said sample into said at least one microfluidic channel or chamber (abstract, “A fluidics apparatus for manipulation of at least one fluid sample is disclosed. A manipulation surface locates the fluid sample. A surface acoustic wave (SAW) generation material layer is provided,” paragraph 0105, “The fluid sample pinning zone can also be formed by physical structures, for example the pinning zone may be formed as a well in the manipulation surface.”);
c) controlling the temperature of the said sample with said surface acoustic wave source to a plurality of precise temperatures within said at least one microfluidic channel or chamber (paragraph 0302).
WILSON further teaches of aggregating the particles which are subjected to the SAW, and the aggregation occurs in concentric rings (in a pattern) (paragraph 0154, & Figure 53).
WILSON further teaches of the surface having a piezoelectric material to form a SAW layer (paragraph 0053-0060) and of parallel transducers (paragraph 0007, 0009, 0021, 0114, 0116, 0208).
WILSON further teaches of separating out particles in the fluid phase to concentrate a specified in the droplet that the particles are essentially centrifuged (though not true centrifugation) (paragraph 0079).
WILSON does not teach in the specific term “precipitating,” the proteins and aggregating specifically precipitated proteins with SAW. Though WILSON teaches of the device used having multiple channels, it does not teach of the channels having separate different proteins and repeating the analysis.
HUFF is used to remedy this. HUFF teaches of an integrated devices that include a sample preparation component integrated with a detection component are disclosed. The sample preparation component may be a digital microfluidics module or a surface acoustic wave module which modules are used for combing a sample droplet with a reagent droplet and for performing additional sample preparation step leading to a droplet that contains beads/particles/labels that indicate presence or absence of an analyte of interest in the sample (abstract). The device of HUFF further uses SAW (as is also done in WILSON) for analyte detection (paragraph 0028, 0037, 0048). HUFF further teaches that the fluid can be concentrated by precipitation (paragraph 0187, 0217).
HUFF further teaches of the method being capable of simultaneous analysis of a plurality of different analyte samples (paragraph 0165-0166, 0207) and that there are an array of wells (multiple microfluidic chambers) for this purposes (paragraph 0396 & 0399, 0402-0403).
It would have been obvious to one of ordinary skill in the art to use precipitation as is done in HUFF in the method of WILSON due to the known advantages this covers for concentration of protein and other additional functionality (HUFF, paragraph 0187). It also would have been obvious to one of ordinary skill to perform the simultaneous analysis as is done in HUFF in the method of WILSON due to the advantage this offers in increasing throughput and in analysis of multiple samples at a time (paragraph 0165-0166). From combining the references--- it would be obvious a second pattern would be present if using two samples/proteins from the teaching of the formulation of a pattern in WILSON.
WILSON and HUFF do not teach of measuring gray intensity, determining a first or second melting temperature of calculating the difference between a first and second melting temperature.
RAMOS is used to remedy this. RAMOS teaches of a method of measuring E. coli by acoustic fields (Abstract, Figure 1). RAMOS teaches that the acoustic field causes the bacteria to cluster(aggregate) and then the bacteria concentration is estimated in terms of the intensity of the grey scale image from multiple cluster rings (Figure 5 description). It would have been obvious to one of ordinary scale in the art to use grayscale image analysis as is done in RAMOS in the methods of WILSON And HUFF due to the advantage it offers in providing an improved image and as it is a more simple and clearly contrasting image analysis compared to colored images(Page 7, paragraphs 3-4).
WILSON, HUFF and RAMOS do not teach of calculating a first and second melting temperature.
HUYNH is used to remedy this teaches of a method of using a thermal device comprising at least one microfluidic channel or chamber (pg 2 para 2 .. The basic scheme of a thermal shift assay (Figure 1) involves incubation of natively folded proteins with SYPRO Orange dye in a 96-well PCR plate. Through a systematic increase in temperature and concomitant monitoring of SYPRO Orange fluorescence emission, it is possible to monitor thermal denaturation of the protein in many conditions simultaneously.) ii) a sample comprising at least one protein; b) introducing said sample into said at least one microfluidic channel or chamber c) controlling the temperature of the said sample to a plurality of precise temperatures within said at least one microfluidic channel or chamber under conditions that create a denatured protein; (pg 2 para 2 .. The basic scheme of a thermal shift assay (Figure 1) involves incubation of natively folded proteins with SYPRO Orange dye in a 96-well PCR plate. Through a systematic increase in temperature and concomitant monitoring of SYPRO Orange fluorescence emission, it is possible to monitor thermal denaturation of the protein in many conditions simultaneously..).
Specifically, HUYNH teaches of determining the melting points of multiple proteins (Page 2, paragraph 3, line 3) and of forming a MELT curve (Page 4, 1., bullet point 2), and then calculating the different between the temperatures- which can be done by site on a melting point curve/curves (Page 3, Set up 96-well plate, 1. Paragraph 2).
It would have been obvious to one of ordinary skill to determine and derive the differences in melting temperatures for different proteins as is done in HUYNH in the methods of WILSON, HUFF, and RAMOS as it offers advantages in making determinations of protein stability and the thermal shift techniques provides a rapid and inexpensive way to improve recombinant proteins for in vitro study ( Page 11, paragraph 2). Further—the prior art does not teach of the instantly specifically claimed 3-45 fold increased sensitivity, however this is a material property of the method, and therefore as the method is made obvious, so is its result.
With respect to Claim 17, WILSON, HUFF, and RAMOS teach of the invention as shown above, but do not teach of protein bound to a ligand. HUYNH is used to remedy this and teaches of studying and discovering protein-ligand interactions. It would have been obvious to detection protein ligand interactions as they capitalized on increases in protein stability upon binding to a ligand (HUYNH, abstract).
With respect to Claim 18, WILSON, HUFF, and RAMOS teach of the invention as shown above, but do not teach of protein bound to a ligand. HUYNH is used to remedy this and teaches of studying and discovering protein-ligand interactions. HUYNH also teaches of using small molecule ligands (Page 2, paragraph 2, line 7). It would have been obvious to detection protein ligand interactions as they capitalized on increases in protein stability upon binding to a ligand (HUYNH, abstract).
With respect to Claim 19, RAMOS teaches of having a wild type sequence (Page 7, lines 1-3).
With respect to Claim 20, WILSON teaches of diagnosing diseases (paragraph 0298). Through BRI all diseases can be considered genetic diseases.
With respect to Claim 21, WILSON further teaches of aggregating the particles which are subjected to the SAW, and the aggregation occurs in concentric rings (concentric rings can be considered, parallel lines through broadest reasonable interpretation since all circles are a continuous line and concentric means that the circles are around each other so the lines are parallel to each other) (paragraph 0154, & Figure 53).
With respect to Claim 22, WILSON teaches of the claim as shown above for Claim 1. WILSON does not teach of precipitation. HUFF is used to remedy this and teaches of concentration by precipitation. It would have been obvious to precipitate as is done in HUFF in the method of WILSON due to the advantage this offers for concentration and therefore detection of the sample (paragraph 0187).
With respect to Claim 23, WILSON further teaches of aggregating the particles which are subjected to the SAW, and the aggregation occurs in concentric rings (in a pattern) (paragraph 0154, & Figure 53). WILSON further teaches of separating out particles in the fluid phase to concentrate a specified in the droplet that the particles are essentially centrifuged (though not true centrifugation) (paragraph 0079).
WILSON teaches that the aggregating occurs while SAW occurs (paragraph 0154). WILSON also teach particles are concentrated and separated by SAW (which does the aggregating) (so they occur at the same time.
WILSON does not teach in the specific term “precipitating”. Please see above for claim 1 how HUFF remedies this and teaches of precipitating.
With respect to Claim 24, WILSON teaches that the sample may consist of or comprise a biological sample such as blood, saliva or urine. For example, the fluid sample may be whole blood,” paragraph 0025, “Notably, for a biological sample containing cells the molecule of interest may be an intracellular molecule,” paragraph 0130, “The term intracellular molecule, or intracellular molecule of interest includes macromolecules (protein, DNA, lipid, polysaccharide).”
With respect to Claim 25, WILSON teaches of using SAW to perform lysis (paragraph 0099).
With respect to Claim 5, WILSON teaches of measuring acoustic field intensity (paragraph 0201, 0208, 0213, 0182). HUFF teaches of the claims as shown above. They do not teach of using a gray intensity. RAMOS is used to remedy this. RAMOS teaches of a method of measuring E. coli by acoustic fields (Abstract, Figure 1). RAMOS teaches that the acoustic field causes the bacteria to cluster(aggregate) and then the bacteria concentration is estimated in terms of the intensity of the grey scale image from multiple cluster rings (Figure 5 description). It would have been obvious to one of ordinary scale in the art to use grayscale image analysis as is done in RAMOS in the methods of WILSON And HUFF due to the advantage it offers in providing an improved image and as it is a more simple and clearly contrasting image analysis compared to colored images (Page 7, paragraphs 3-4).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758