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 .
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.
Status of the Claims
Claims 1-20 are pending and examined herein.
Priority
This application, 18/681,988, filed 02/07/2024, is a 371 of PCT/US2022/038984 filed on 07/31/2022, and claims benefit of provisional application 63/230,779 filed on 08/08/2021. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 08/08/2021.
Information Disclosure Statement
The Information Disclosure Statements filed on 02/12/2024 are acknowledged and have been considered.
Claim Interpretation
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 also 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 vision system for imaging…” in claims 9, 10, 19 and 20.
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.
The specification does not define corresponding structure, material, or acts and equivalents, for performing the recited function of imaging using a machine vision system. The specification merely repeats the use of a machine vision system without any structure involved in this system to perform the function of imaging, and merely recites the use of a counting program.
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 § 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 1-10 and 16-20 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 9, 10, 19 and 20, the claim limitation “…a machine vision system for imaging…” invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. The specification merely recites the function and does not identify any specific structure that is comprising a machine vision system used for imaging proteins. 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.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Claims 1-10 and 16-20 all recite “A device for the detection of…and an assay to determine the level of…”. The claims are indefinite because they recite both an apparatus and the implied method steps of using the apparatus, which renders it unclear whether infringement occurs when the device is created or the assay is used. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011).
Claims 1-10 and 16-20 also recite “…contained with captured extracellular vesicles”. The claims are indefinite because there are multiple possible conflicting interpretations based on the claim language provided. For example, it is unclear if the claim language is to be interpreted as the assay is being used to determine the level of immune checkpoint proteins/biomarkers contained within captured extracellular vesicles. Or alternatively, whether the claim language is to be interpreted as the assay is being used to determine the level of immune checkpoint proteins/biomarkers contained, in addition to/in parallel with, or in the same sample with captured extracellular vesicles. As there are multiple potential conflicting interpretations of the claim language, these claims are indefinite.
Regarding claims 1 and 16, the recitation of the term “configured” in line 3 also renders the claim indefinite, as it is unclear how the membrane is “configured” or modified to enable the capture of EV. For example, are the EV trapped in the pores of the membrane due to its size or are they captured via binding to capture reagents?
Additionally, claim 2 recites “…assay comprises microscopy”. The recitation that microscopy can be comprised elicits a method step, however, if the claim language was intended as a method, it is unclear what limitations it encompasses as there are no steps involved in the recited method.
Additionally, claim 14 is indefinite because the relationship between EV and immune checkpoint proteins is undefined and unclear. The claim recites that “the antibody-fluorochrome combination is indicative of immune checkpoint proteins”, however, claim 11 from which it depends merely describes that the antibody-fluorochrome combination is added to the EV, and the relationship between EV and immune check point proteins is not clearly defined.
Appropriate correction is required.
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.
(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, 3, 4, 11, 14, 16, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bifeng et al. (CN109884315 A), (herein referred to as Bifeng).
Bifeng teaches an in vitro rapid detection platform and detection method of PD-L1 exosomes, which includes a sample pre-filtration area, a nanofiltration area, a color-developing material pad area, a color-developing area and a water-absorbing pad area (abstract). Bifeng teaches that the detection method is to first filter the sample to be tested through a primary filtration membrane, and then filter it through a nanofiltration membrane to obtain exosomes, where the chromogenic-labeled antibody on the chromogenic pad area is an exosome PD-L1 antibody (abstract)
Regarding claims 1 and 16, Bifeng teaches a device (“detection platform”, claim 1, Figs. 1 and 2) for the detection of immune checkpoint proteins/biomarkers (claim 1, the proteins being PD-L1), the device comprising: a nanoporous membrane ([0013]) comprising a plurality of pores ([0014]); the nanoporous membrane configured to capture extracellular vesicles (“nanofiltration membrane is used for separating the exosomes”, claim 1); and an assay to determine the level of immune checkpoint proteins contained with captured extracellular vesicles (“the content of PD-L1 exosomes is calculated”, [0026]).
Regarding claim 3, Bifeng teaches the device of claim 1, wherein the assay comprises an antibody (“exosomal PD-L1 antibody”, claim 1).
Regarding claims 4 and 17, Bifeng teaches the device of claim 1, wherein the assay comprises an antibody-fluorochrome combination (claims 5 and 8).
Regarding claims 11 and 14, Bifeng teaches a method for the detection of immune checkpoint proteins (claims 5 and 8), the method comprising the steps of: providing a biofluid (“whole blood”, [0023]); passing the biofluid over a nanoporous membrane wherein the nanoporous membrane comprises a plurality of pores (claim 5); capturing with the nanoporous membrane extracellular vesicles contained within the biofluid (claim 5); adding an antibody-fluorochrome combination to the extracellular vesicles (claims 5 and 8); exciting the captured extracellular vesicles with a wavelength of light sufficient to fluoresce the antibody-fluorochrome combination (claims 5 and 8; [0026], to excite a fluorescent dye is implicit to its use as an indicator in order to measure luminescence); and identifying the excited captured extracellular vesicles (“The present invention specifically recognizes exposomes carrying the PD-L1 protein by means of the PD-L1 antibody”, [0025]).
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.
Claims 2, 5-8, 15, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Bifeng et al. (CN109884315 A) as applied to claims 1, 3, 4, 11, 14, 16, and 17 above, and further in view of Zhao et al. (2016). “Flow-through porous silicon membranes for real-time label-free biosensing”. Analytical chemistry, 88(22), 10940-10948, (herein referred to as Zhao).
The teachings of Bifeng are incorporated herein.
Regarding claims 2, 5, 6, 15, and 18 Bifeng recites all of the limitations of claim 1, 11, and 16 of the instant application, as well as that the colour developing object on the colour developing substance markers antibody can be fluorescent nanometer microspheres (claims 5 and 8).
However, Bifeng does not teach wherein the assay comprises microscopy, quantum dots, that the nanoporous membrane is nanoporous silicon nitride, wherein the density of pores of the nanoporous membrane is at least 105 pores per square millimeter, and that the range of pore diameters in the nanoporous membrane is on the average between 20 nanometers and 120 nanometers.
Zhao teaches a flow-through sensing platform based on open-ended porous silicon (PSi) microcavity membranes that are compatible with integration in on chip sensor arrays, that allows for real-time label-free biosensing of small analytes (abstract). Zhao also teaches that the nanoporous silicon membranes were further constructed by placing a 400 nm silicon nitride film on the PSi surface (page 10941, column 2, 3rd full paragraph). Furthermore, Zhao teaches that quantum dots (QD) in DI water were injected into the PSi membrane device (page 10942, column 2, 2nd full paragraph), and QD emission recorded using a fiber coupled Ocean Optics USB400 CCD spectrometer fitted with a microscope objective lens (page 10942, column 2, 3rd full paragraph). Lastly, Zhao teaches that the designed PSi optical microcavity structure increases the sensitivity to the emission of QDs captured within the cavity (page 10946, column 2, 2nd paragraph).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the rapid in vitro exosome measurement device using fluorescent nanometer microspheres with an antibody-fluorochrome combination, as taught by Bifeng, to use quantum dots and microscopy, as disclosed by Zhao, as a matter of using a known technique to improve a similar device in the same way. The fluorescent nanometer microspheres and quantum dots taught by Zhao are both nanoscale particles used for labeling, imaging, and detecting small size analytes. It is known by one of ordinary skill in the art that quantum dots can improve detection sensitivity and allow for detection of analytes that are found in low concentrations. Additionally, Zhao demonstrates that microscopy can be used in combination with spectrophotometry and allows for simultaneous spectra and camera images, and can provide spatial information on the flow of the analyte in relation to the pores as demonstrated by Fig. 3 of Zhao.
It also would have been obvious to modify the nanoporous membrane of Bifeng to be nanoporous silicon nitride because Zhao teaches that such membranes have previously been used for chemical and bioseparations, and represents an improvement on the base device because they can be patterned using photolithographic techniques that enhance the quality and mechanical stability of the membrane, and that the nitride film remaining on PSi ensures that analytes flow only into the membrane regions (page 10941, column 1, 2nd full paragraph; page 10941, column 2, 1st paragraph; page 10942, column 1, first paragraph).
A skilled artisan would have been motivated to make these modifications to the measurement device taught by Bifeng in order to allow for the device/system to operate as a flow-through optical biosensor based on open-ended PSi sensor membranes, which shows a 6-fold improvement in sensor response time when detecting a high molecular weight analyte (streptavidin) versus a standard approach, as taught by Zhao (abstract). A person of ordinary skill would have had a reasonable expectation of success in making these modifications because the art demonstrates that: quantum dots are commercially available, microscopy in the context of nanoporous membranes is a well-understood, routine, and conventional activity, and silicon nitride membranes have been successfully used in devices in the same field of invention to measure analytes.
Regarding claim 7, Zhao teaches wherein the density of pores of the nanoporous membrane is at least 105 pores per square millimeter. Zhao teaches that the silicon sensor device is 1 mm × 1 mm (page 10943, column 1, 2nd full paragraph), and that the number of pores on the sensor is approximately N ≈ 1 × 109 (page 10943, column 2, 2nd full paragraph).
Regarding claim 8, Zhao teaches that the porous silicon membrane has nanopores with pore diameter of ∼25 nm and layer thickness of ∼125 nm in the high porosity layers and pore diameter of ∼20 nm and layer thickness of ∼105 nm in the low porosity layers. (page 10941, column 2, 2nd full paragraph)
Claims 9, 10, 12, 13, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Bifeng et al. (CN109884315 A) as applied to claims 1, 3, 4, 11, 14, 16, and 17 above, and further in view of Dehghani et al. (2019). “Tangential flow microfluidics for the capture and release of nanoparticles and extracellular vesicles on conventional and ultrathin membranes”. Advanced materials technologies, 4(11), 1900539, (herein referred to as Dehghani).
The teachings of Bifeng are incorporated herein.
Regarding claims 9, 10, 12, 13, 19 and 20, Bifeng recites all of the limitations of claim 1, 11, and 16 of the instant application, but does not teach wherein the device further comprises a machine vision system for imaging fluorescing immune checkpoint proteins, that further comprises a counting program for counting the fluorescing immune checkpoint proteins/extracellular vesicles.
Dehghani teaches the use of nanoporous silicon nitride membranes to capture extracellular vesicles (EVs) and similarly sized analytes from undiluted plasma samples in the pores of ultrathin membranes with little evidence of protein fouling (page 2, column 1, 1st paragraph). In addition, Dehghani teaches that the silicon nitride membranes had pore size median of 80 nm median and a pore density of 9.2 × 107 pores per square millimeter (page 5, column 2, 1st paragraph). Dehghani also teaches that their tangential flow for analyte capture method could be used to detect EVs carrying cancer bio-markers among a larger population using the same membrane for capture, labeling, and imaging by fluorescence microscopy. Lastly, Dehghani teaches the use of a machine vision system for imaging fluorescing proteins via MetaMorph software with a Rolera em- camera (page 9, column 2, 1st full paragraph), and a counting program for counting fluorescing proteins (“…measuring and merging channel tool in NIH ImageJ were used for quantifying the average intensity values…”, page 9, column 2, 1st full paragraph).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the rapid in vitro exosome measurement device taught by Bifeng to use a machine vision system for imaging fluorescing proteins and a counting program for counting fluorescing proteins, as disclosed by Dehghani, as a matter of using know technique to improve a similar device in the same way. The devices of Bifeng and Dehghani represent similar devices in that they both comprise a system using nanoporous membranes to capture extracellular vesicles and use a fluorescing agent for detection of biomarkers. One of ordinary skill in the art could have made this modification and the results would have been predictable because Bifeng teaches that the colour developing object can be a fluorescing microsphere (claims 4 and 8), which is the technology used in the method of Dehghani (“polystyrenegreen fluorescent particles”, page 9, column 1, 6th full paragraph
A skilled artisan would have been motivated to make this modification as a matter of convenience and in order to streamline the data acquisition process to save time. A person of ordinary skill would have had a reasonable expectation of success in making these modifications because the art demonstrates that: the fluorescing particles used such nanopore detection device/systems are commercially available, machine vision system for imaging fluorescing and a counting program for counting the fluorescing immune checkpoint proteins have been successfully used.
Conclusion
For all the reasons discussed above, claims 1-20 are rejected and therefore no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER JOSEPH HOFFMAN whose telephone number is (571)272-9080. The examiner can normally be reached 10:00-6:30 M-F.
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/ALEXANDER J. HOFFMAN/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 16, 2026
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