DETAILED ACTION
This Office action is responsive to communications filed on 06/13/2025. Claims 29-36, and 38-46 have been amended. Claims 1-28 previously canceled. Presently, Claims 29-48 remain pending and are hereinafter examined on the merits.
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 .
Response to Arguments
Previous Drawing objection is withdrawn in view of the Replacement Drawings filed on 06/13/2025.
Previous rejections under 35 USC § 112(a) of claims 29, 39 are withdrawn in view of the amendments filed on 06/13/2025.
Previous rejections under 35 USC § 112(b) for claims 36, 46 are withdrawn in view of the amendments filed on 06/13/2025.
The Applicants argue claim interpretations under 35 USC 112(f). The Applicant argues the term “processing arrangement” recited in claim 1 under 35 USC 112(f) for the reasons stated previously, the MPEP 2181 states, “ a claim limitation that does not use the phrase “means for” or “step for” will trigger a…112(f)” and does not apply to the term invoking 35 U.S.C. 112f. In that the 35 USC 112(f) is an error.
The Examiner disagrees, as recited in the previous 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. In other words, the term “processing arrangement” invokes 35 U.S.C. 112(f) because it is used in a functional manner without providing sufficient structure. The interpretation under 35 U.S.C. 112(f) is not an error. In other words, “a processing arrangement”, specially – arrangement -- is not a structural term. “a processing arrangement” is a functional phrase and functional by definition because it tells what it does, not what it is. In addition, the claim does not recite any structural limitations for the processing arrangement. The phrase is interpreted as a generic processor. As stated in the Non-Final filed on 03/13/2025, “The Examiner suggest amending the recitation of “a processing arrangement” to “a processor”.” Accordingly, the interpretation is maintained.
Previous rejections under 35 USC § 112(a) of claims 36 & 46 are maintained:
The Applicant’s argue: those skilled in the art fully understand how to perform the recited steps in view of the disclosure and that not further teaching is required to enable one skilled in the art to use the invention as claimed.
The Examiner disagrees, these arguments are unpersuasive. The Applicant argues “those skilled in the art fully understand how to perform the recited steps in view of the disclosure and that not further teaching is required”. However, this argument is conclusory and unsupported by any citation to specific portions of the specification that would demonstrate how the claim function “remove[ing] contributions to the signal data from static tissue including fat within the portion of tissue” is actually carried out. Applicant has not pointed to any algorithm, mathematical expression, processing technique, or series of steps in the specification that would inform one of ordinary skilled in the art how the claimed function is achieved in the processing arrangement.
In addition, the Applicant’s reliance on what “those skilled in the art” might know or be able to implement is insufficient. It is not whether a skilled artisan could device a way to perform the function, but whether the inventor has conveyed with sufficient specificity how they purport to perform it, which is the Applicant specification fails to disclose nay computational logic, filtering methodology, or a step-by-step process the computer implemented method performs to accomplish the claimed function. Accordingly, the 35 USC § 112(a0 is therefore maintained.
Previous rejections under 35 USC § 112(b) of claims 38 & 48 are maintained:
The Applicant argue: the rejection of claims 38 and 48 referring to calibration parameters, it is submitted that those skilled in the art understand fully how to determine calibration parameters, e.g., by testing a device according to the invention against a known test to see what calibration parameters are required to reconcile the results of the new device to the results from the known test and that therefore this rejection should be withdrawn. Thus, withdrawal of the rejection under §112 is respectfully requested.
The Examiner respectfully maintains the rejection of claims 38 & 48 under 35 USC § 112(b). The Applicant contexts that one skilled in the art would understand how to determine calibration parameters such a parameters a and b in the formula CGlu= a* ( AGlu / Aw )+b, by comparing the device’s results to those of a known test. However, the claims recite that “quantitative value is calculate […] based on a pre-set calibration parameters” without further quantification or explanation. The term “pre-set” suggest that the parameters are determined prior to use, yet the claim and specification fail to provide any disclosure regarding how these values are derived, whether they are user-defined, empirically derived, or universal.
While one of ordinary skill in the art may be familiar with linear calibration in general, the absence of any description or definition in the specification regarding the deviation, meaning, or constraints of “a” and “b” leaves the scope of the claim indefinite. The formula, standing alone, does not impart sufficient clarity as to what the calibrations parameters refer to in the context of the claim. Accordingly, the 35 USC § 112(b) is therefore maintained.
Applicant’s arguments with respect to the rejections to the claim(s) under 35 U.S.C. 103 have been considered but are moot because the new ground of rejection does not rely on Shames et al (US 2015/0018638 A1) in view of Iannello (US 2016/0011290 A1) in view of Den Boef (US 4,890,061) applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. The new grounds of rejection now relied upon Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061).
Examiner Notes
In an interview on 07/29/2025, the Applicant’s representative confirmed claim 38 which currently depends from claim 29 should depend from claim 37. In accordance with the Applicant’s representative confirmation, claim 38 is interpreted to depend from claim 29.
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 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 processing arrangement” in claim 29, Claim 35, Claim 36, and Claim 37 configured to receive signal data corresponding to the detected RF signal from the sensor, further configured to demodulate the signal data and apply a Fast Fourier Transform (FFT) to the signal data to extract a magnetic resonance (MR) spectrum corresponding to a component of the signal data contributed solely by blood circulating through the blood vessels within the portion of tissue, further configured to remove contributions to the signal data from static tissue and fat within the portion of tissue, & wherein the processing arrangement is further configured to determine an area, AGlu, under the MR spectrum corresponding to glucose and an area, Aw, under the MR spectrum corresponding to water, respectively invokes 35 U.S.C. 112(f). The term “arrangement” is a non-structural generic placeholder configured to select the spectroscopic data target data that does not include any specific structure for performing the accompany functions. See MPEP 2181.I.A: The following is a list of non-structural generic placeholders that may invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, paragraph 6: "mechanism for," "module for," "device for," "unit for," "component for," "element for," "member for," "apparatus for," "machine for," or "system for." Welker Bearing Co., v. PHD, Inc., 550 F.3d 1090, 1096, 89 USPQ2d 1289, 1293-94 (Fed. Cir. 2008); Massachusetts Inst. of Tech. v. Abacus Software, 462 F.3d 1344, 1354, 80 USPQ2d 1225, 1228 (Fed. Cir. 2006); Personalized Media, 161 F.3d at 704, 48 USPQ2d at 1886–87; Mas-Hamilton Group v. LaGard, Inc., 156 F.3d 1206, 1214-1215, 48 USPQ2d 1010, 1017 (Fed. Cir. 1998).
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.
A review of the specification shows that the following appears to be the corresponding structure described in the specification for the 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph limitation:
“a processing arrangement” configured to receive signal data invokes 35 USC 112(f), and the specification recites in paragraph [0041], ‘The device 100 further comprises a processing arrangement is configured to execute instructions stored on a computer accessible medium (e.g., memory storage device). The computer-accessible medium may, for example, be a non-transitory computer-accessible medium containing executable instructions therein.’
Therefore, the phrase “a processing arrangement” refers to generic computer accessible medium such as a generic processor. The Examiner suggest amending the phrase to recite “a processor”.
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 the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 36-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 36 & Claim 46 recite: “the processing arrangement is further configured to remove contributions to the signal data from static tissue including fat within the portion of tissue”; and “further comprising: removing contributions to the signal data from static tissue including fat within the portion of tissue.”, respectively.
An algorithm is defined, for example, as "a finite sequence of steps for solving a logical or mathematical problem or performing a task." Microsoft Computer Dictionary (5th ed., 2002). Applicant may "express that algorithm in any understandable terms including as a mathematical formula, in prose, or as a flow chart, or in any other manner that provides sufficient structure." Finisar Corp. v. DirecTV Grp., Inc., 523 F.3d 1323, 1340 (Fed. Cir. 2008) (internal citation omitted). This can occur when the algorithm or steps/procedure for performing the computer function are not explained at all or are not explained in sufficient detail (simply restating the function recited in the claim is not necessarily sufficient). In other words, the algorithm or steps/procedure taken to perform the function must be described with sufficient detail so that one of ordinary skill in the art would understand how the inventor intended the function to be performed. It is not enough that one skilled in the art could write a program to achieve the claimed function because the specification must explain how the inventor intends to achieve the claimed function to satisfy the written description requirement. See, e.g., Vasudevan Software, Inc. v. MicroStrategy, Inc., 782 F.3d 671, 681-683, 114 USPQ2d 1349, 1356, 1357 (Fed. Cir. 2015), see MPEP § 2161(I).
Indeed the specification recites describes at ¶0058 contributions from surrounding tissues are removed & the application acknowledges that fat signals overlap with glucose at 3.4-3.5 ppm, but does not provided proper written descriptions how the computer implemented step differentiates and removes signals from tissue versus those from glucose in the blood (i.e, removing contributions). Furthermore, the specification does not provide the following: Any specific algorithm for removing contributions, filter technique for removing contributions, and/or a signal processing method for removing contributions. In addition, Fig. 13 does not provide a sufficient algorithm for removing contributions to obviate the proper written description requirement. Consequently, one of ordinary skill in the art would not deem the instant specification having sufficient detail so that they could understand how the inventor intended to achieve said removal of contributions. Since the instant specification fails to provide a finite sequence of steps for performing the ”remove contributions” in claim 36 and “removing contributions” in claim 46 the aforementioned claims fails to meet the written description requirement under 35 U.S.C. 112(a).
The dependent claims of the above rejected claims are rejected due to their dependency.
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 29-48 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 29: line 18, it is unclear if a locally uniform static magnetic field refers to or is separate from the static magnetic field recited in line 3. Consistent claim language is required when referring to the same term. The phrase is interpreted as a locally uniform static magnetic field. Appropriate correction is required.
Claim 43: line 2-3, “the RF frequency”. There is insufficient antecedent basis for this limitation in the claim, as required by MPEP 2173.05(e). Consistent claim language is required when referring to the same term. The phrase is interpreted as the RF frequency. Appropriate correction is required.
Claim 38 & Claim 48, the phrase “wherein the quantitative value is calculated as an absolute glucose concentration in blood plasma, CGlu, based on pre-set calibration parameters a and b according to CGlu= a* ( AGlu / Aw )+b.” render the claim indefinite. First, it is unclear what the calibration parameters refer to. The specification does not provide a numerical value or physical basis for the pre-set calibration parameters. The pre-set calibration parameters are interpreted as a standard linear calibration technique. Appropriate correction is required.
Claim 39: line 18, it is unclear if a locally uniform static magnetic field refers to or is separate from the static magnetic field recited in line 3. Consistent claim language is required when referring to the same term. The phrase is interpreted as a locally uniform static magnetic field. Appropriate correction is required.
The dependent claims of the above rejected claims are rejected due to their dependency.
Claim Objections
The following claims are objected to because of the following informalities and should recite:
Claim 29, 30, 35-36, 39, 40, 45-46: after the first recitation of “a portion of tissue” in claim 29 and claim 39, each similar phrase thereafter should recite “the portion of the tissue”. Consistent claim language is required when referring to the same term. Appropriate correction is required.
Claim 29: line 7, “the skin[[,]]”. Appropriate correction is required.
line 16, “the received signal data”. Appropriate correction is required.
Claim 42: line 1, “the stati[[s]]c magnetic field”. Appropriate correction is required.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 29, 31, & 39 are rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061).
Claim 29: Shames discloses, A device for monitoring a blood glucose level in a patient, comprising: ([0001]: “The present invention is generally in the field of medical applications and relates to an apparatus and method for non-invasive assessment of living blood parameters, … using pulsed nuclear magnetic resonance (NMR) relaxometry techniques.”)
a magnet (FIG. 1, permanent magnet assembly 1 indicated by N-pole) configured to generate a static magnetic field ([0054]: “the permanent magnet assembly 1 is configured to apply a magnetostatic field 1 f”) in a portion of tissue under a skin of the patient; (FIG. 1 shows the tissue under the skin of the finger 9 being the portion of tissue, [0049]: “For example, in some embodiments an in vivo blood test is carried out by placing a finger phalange in the test volume of the probehead (i.e., where the magnetostatic field is generated), applying electromagnetic energy pulses (also referred to herein as excitation signals) by a coil of the probehead to excite nuclear spin echoes from protons (or other nuclei) in the living liquids, tissues and bones of the finger, and using the probehead coil to acquire electromagnetic relaxation signals from the finger phalange in response to the applied excitation signals. The acquired relaxation signals are then analyzed and processed to obtain NMR signals (e.g., spin-lattice and/or spin-spin relaxation signals) of the excited nuclei, and the blood parameters of the examined organ are determined based on the NMR signals obtained.”; [0054]: “… FIG. 1 the finger 9 is introduced into the test volume 2 v such that the magnetic field 1 f from the magnet assembly 1 is applied over a portion of the finger 9 placed between the “N” and “S” poles of the magnet assembly 1…the permanent magnet assembly 1 is configured to apply a magnetostatic field 1 f being substantially perpendicular to the length of the finger 9 and the coil 2 c is adapted to apply the electromagnetic excitation signals 1 e substantially along the length of the examined finger, such that the direction of the magnetic field 1 f is substantially perpendicular to the direction of the excitation signals 1 e.”)
a transmitter (FIG. 1, RF transmitter 3 includes inductive coil 2c, [0062]: “…a pulsed RF transmitter 3 electrically connected to the probehead 2 and configured and operable to apply radio frequency excitation signals through the inductive coil 2 c of the probehead.”) configured to deliver radiofrequency (RF) energy to the portion of tissue to excite proton nuclear spins in the portion of tissue (FIG. 1; [0014]: “… Blood parameters of the examined subject are determined using nuclear spin echo signals received from the test organ in response to specific (e.g., short hard off-resonance) electromagnetic pulse sequences having relatively low radiofrequencies (RF). …”; [0049]: “applying electromagnetic energy pulses (also referred to herein as excitation signals) by a coil of the probehead to excite nuclear spin echoes from protons (or other nuclei) in the living liquids, tissues and bones of the finger,”), wherein at least a portion of the transmitter (inductive coil 2c of RF transmitter 3) is positioned between the magnet and the skin,; (skin of finger 9: FIG. 1; [0062]; “a pulsed RF transmitter 3 electrically connected to the probehead 2 and configured and operable to apply radio frequency excitation signals through the inductive coil 2 c of the probehead.”)
a sensor (FIG. 4, RF receiver 4) configured to detect an RF signal from the excited proton nuclear spins in the portion of tissue; and (FIG. 1; [0001], ‘The present invention is generally in the field of medical applications and relates to an apparatus and method for non-invasive assessment of living blood parameters, such as, for example, blood glucose content, blood viscosity, haematocrit, oxygen saturation and pH, using pulsed nuclear magnetic resonance (NMR) relaxometry techniques.’; [Claim 19], ‘The method according to claim 14 wherein the blood related parameters comprise one or more of the following: blood glucose content, blood viscosity, blood haematocrit, blood oxygen saturation, and blood pH.’; [0062]: “The probehead 2 is further connected to an RF receiver 4 configured and operable to receive through the coil 2 c radio frequency electromagnetic relaxation signals from the examined finger 9 responsive to the radio frequency excitation signals applied by the RF transmitter 3.”; [0049]: “applying electromagnetic energy pulses (also referred to herein as excitation signals) by a coil of the probehead to excite nuclear spin echoes from protons (or other nuclei) in the living liquids, tissues and bones of the finger, and using the probehead coil to acquire electromagnetic relaxation signals from the finger phalange in response to the applied excitation signals.”; [0073], ‘The copper coil in this example is part of a tuned tank circuit (i.e., resonant circuit e.g., LC circuit), placed between the poles of an electromagnet of a commercial Varian E-12 EPR spectrometer. In vivo measurements were carried out in a fixed magnetic field B0=0.273 Tesla at radiofrequency ƒ0=11.62 MHz.’; [0082], ‘1H spin-lattice relaxation times measurements were carried out in vivo on a series of living forefinger phalanges of individuals having different blood glucose levels using the instrumental setup used in Example 1 (ƒo=11.62 MHz) and saturation comb sequence combined with phase cycled spin-echo detection as used in Example 2 (see FIG. 4). Thermal stabilization of the examined finger phalanges was maintained by internal body temperature at normal physiological conditions (36.6±0.5° C.). All individuals under the tests did not suffer from diseases affecting blood viscosity (like polycythemia, hydraemia etc.). Parallel assessment of the blood glucose level was done using a commercial Abbot FreeStyle Lite invasive strip-type glucose meter. Results of the series of tests are shown in FIG. 6, showing dependence of the 1H spin-lattice relaxation time T11 measured on the series of forefinger phalanges as a function of the blood glucose content.’; [0083], ‘FIG. 6 demonstrates clear dependence of the 1H spin-lattice relaxation time T11 on the blood glucose content. Within the normal physiological range of blood glucose levels, and above the normal level the relaxation time T11 shows a tendency to increase.’)
a processing arrangement (FIG. 1, control unit 7, [0062]: “As exemplified in FIG. 1, the control unit 7 may be configured and operable to provide the demodulator unit 5 control signal for adjusting the gain of the IF receiver. For example, when operating with different materials (changing the nuclei under examination e.g., from 1H to 19F) unit 5 adjusts the frequency of signals generated by its local oscillator 5 a, to obtain the same intermediate frequency (IF), and also adjusts the gain of the IF receiver.”) configured to receive signal data corresponding to the detected RF signal from the sensor, (FIG. 1, RF receiver 4, [0016]: “The receiver may further comprise a demodulator configured and operable to extract the nuclear spin echo signals from the signals received from the probehead unit. The nuclear spin echo signals are then processed by a processor to determine one or more blood parameters of the tested subject.”; [0049]: “The acquired relaxation signals are then analyzed and processed to obtain NMR signals (e.g., spin-lattice and/or spin-spin relaxation signals) of the excited nuclei, and the blood parameters of the examined organ are determined based on the NMR signals obtained.”) and to generate a quantitative value corresponding to a level of blood glucose in the patient based on the signal data, ([0049]: “The acquired relaxation signals are then analyzed and processed to obtain NMR signals (e.g., spin-lattice and/or spin-spin relaxation signals) of the excited nuclei, and the blood parameters of the examined organ are determined based on the NMR signals obtained.”, FIG. 6; [0082], ‘1H spin-lattice relaxation times measurements were carried out in vivo on a series of living forefinger phalanges of individuals having different blood glucose levels using the instrumental setup used in Example 1 (ƒo=11.62 MHz) and saturation comb sequence combined with phase cycled spin-echo detection as used in Example 2 (see FIG. 4). Thermal stabilization of the examined finger phalanges was maintained by internal body temperature at normal physiological conditions (36.6±0.5° C.). All individuals under the tests did not suffer from diseases affecting blood viscosity (like polycythemia, hydraemia etc.). Parallel assessment of the blood glucose level was done using a commercial Abbot FreeStyle Lite invasive strip-type glucose meter. Results of the series of tests are shown in FIG. 6, showing dependence of the 1H spin-lattice relaxation time T11 measured on the series of forefinger phalanges as a function of the blood glucose content.’; [0083], ‘FIG. 6 demonstrates clear dependence of the 1H spin-lattice relaxation time T11 on the blood glucose content. Within the normal physiological range of blood glucose levels, and above the normal level the relaxation time T11 shows a tendency to increase.’)
Shames fails to disclose:
wherein the processing arrangement controls operating parameters of the transmitter including an average RF frequency and bandwidth to select in the portion of tissue,
wherein the operating parameters of the transmitter are selected to define a depth and thickness of the portion of tissue ensuring that the portion of tissue includes blood vessels and tissue surrounding the blood vessels.
However, Blank in the context of magnetic and coil configurations for MRI probes discloses: wherein the processing arrangement controls operating parameters of the transmitter including an average RF frequency and bandwidth to select in the portion of tissue a static magnetic field
-The controller 122 controls operating parameters of the transmitter including an RF frequency and bandwidth to select in the portion of tissue a locally uniform static magnetic field.
-The controller (e.g., a PC), ¶0190 overseas an RF power supply, which dictates the transmission of RF power in the form of pulse sequences, ¶0190-0191. The system of Blank features a tuning mechanism, such a variable capacitor, which allows for the adjustment of the RF circuit to a “desired range of frequencies” by applying a DC voltage, ¶0194-0195, ¶0236. Hence the controller has direct control over the RF power supply and tuning mechanisms means for the controller to actively set the RF frequency. The “field of view”, the region from which substantial NMR signals are received, is defined as the region where static magnetic field process magnetic frequency within the bandwidth of the transmitted RF frequency, ¶0185. This establishes that the RF frequency acts as a center point, and the bandwidth defines the ranges of frequencies (and thus magnetic field strengths) over which signals are collected, thereby spatially selecting the region of interest, ¶0185, ¶0196.
Note; based on the Applicants specification at ¶0056, the average RF frequency, f0 is used to adjust a depth (d) of the target area. In the Application’s specification the phrase “average RF frequency (f0)” is described as adjusting the depth and “span of the bandwidth range” is described as adjusting the thickness implies that the (f0) function as the center frequency. Hence, under the broadest reasonably interpretation, the average RF frequency constitutes the center frequency. Further note, the Applicant’s specification does not provide any further detail regarding the average RF frequency other than ¶0056.
-Accordingly, in further detail the RF frequency is used to provide a radial resolution by sequentially exciting different radial regions, ¶0196, by a method which is analogous to “slice selection” in conventional MRI, ¶0196. By changing the RF frequency, the system of Blank can selectively excite nuclei shown in the wall of blood vessel 136 at different magnetic field strengths, which correspond to different radial distances (depths) from the probe, ¶0196, ¶0225-0226. Hence, the RF frequency is indeed used to adjust the depth of the tissue being imaged. To select a specific depth, the system of Blank adjust the transmitted RF frequency, ¶0185, ¶0196. This adjusted RF frequency acts as the center frequency for the excitation of nuclei at that particular depth, where the magnetic field strength matches that frequency, ¶0185, ¶0225-0226. Hence, in view of the broadest reasonable interpretation, when the system of Blank adjust the RF frequency to change depth, its is performing a adjustment of the RF center frequency (f0) to target specific spatial locations.
-The Field of View is defined as the area where the static magnetic field produces the NMR Frequency within the bandwidth of the transmitted RF frequency, ¶0185. This principle ties the RF parameters directly the magnetic field strength in the tissue.
wherein the operating parameters of the transmitter are selected to define a depth and thickness of the portion of tissue ensuring that the portion of tissue includes blood vessels and tissue surrounding the blood vessels.
-Blank indicates that the RF frequency and bandwidth are selected and controlled to define the depth and thickness of the portion of tissue from which NMR signals are acquires, ¶0185, ¶0196, ¶0198. This spatial selection is a fundamental aspect of how MRI probes operate.
-RF frequency is used to provide a radial resolution by sequentially exciting different radial regions, ¶0196, by a method which is analogous to “slice selection” in conventional MRI, ¶0196. By changing the RF frequency, the system of Blank can selectively excite nuclei shown in the wall of blood vessel 136 at different magnetic field strengths, which correspond to different radial distances (depths) from the probe, ¶0196, ¶0225-0226.
-The RF bandwidth directly determines the radial thickness of the “slice” or portion of tissue being excited, ¶0198. For example, a 1 MHz bandwidth corresponding to a magnetic field range of 0.024 tesla.
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the control of the processing arrangement of Shames to includes controlling operating parameters operating parameters of the transmitter including an average RF frequency and bandwidth to select in the portion of tissue a locally uniform static magnetic field, wherein the operating parameters of the transmitter are selected to define a depth and thickness of the portion of tissue ensuring that the portion of tissue includes blood vessels and tissue surrounding the blood vessels as taught by Blank. The motivation to do this yields predictable results such as “improved properties compared to the prior art. Improved properties may include one or more of: higher static magnetic field in the imaging region for a given strength magnet; greater radial penetration of the static magnetic field and the RF field into the region surrounding the probe; a field of view with greater axial extent; and the ability to image regions in more than one azimuthal direction, and/or at one more than one axial position, simultaneously, without any need to rotate the probe or to move the probe axially.”, as suggested by Blank, ¶0014.
Shames in view of Blank fail to disclose: a locally unfirm static magnetic field.
However, Den Boef in the context of magnetic resonance imaging discloses, a locally uniform static magnetic field; (Col. 1 lines 60-64, ‘An RF coil generates a locally homogeneous RF magnetic field in the examination area, the frequency of this field corresponding to the Larmor frequency of the precissional motion of the nuclear spins about the z-axis in the examination area.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify radiofrequency coil of modified Shames to provide a locally uniform RF field to the portion of tissue as taught by Den Boef. The motivation to do this yields predictable results such as improve locally the homogeneity of a special region of interest within the examination zone, Col 4 of Den Boef.
Claim 31: Shames as modified discloses all the elements above in claim 29, Shames discloses: wherein the transmitter delivers the RF energy in a frequency bandwidth ranging from 1 to 20 MHz. (¶0012, ‘and electromagnetic excitation signals of relatively low radiofrequencies, i.e., in the range of 1 to 20 MHz.’)
In regards to the claimed feature of frequency bandwidth ranging from 2.1 megahertz (MHz) to 4.2 MHz, though the above noted modified references do no explicitly teach such range, such ranges are considered a design choice based on the following consideration:
The device of modified Shames discloses wherein the transmitter delivers the RF field within a bandwidth ranging from 1 to 20 MHz. (¶0012, ‘and electromagnetic excitation signals of relatively low radiofrequencies, i.e., in the range of 1 to 20 MHz.’). It appears the device of modified Shame would operate equally well such that wherein the transmitter delivers the RF field within a bandwidth ranging from 2.1 megahertz (MHz) to 4.2 MHz. Further the Applicant has not disclosed that the claim bandwidth respect to the claimed range solves any stated problem or is for any particular purpose. That is, other than stating “the RF transmitting component is configured to generate a dynamic magnetic field having a radiofrequency range within a focused, narrow bandwidth ranging from 2.1 MHz to 4.2 MHz.”, ¶0038. It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the bandwidth modified Shame to range from 2.1 MHz to 4.2 Mhz because it appears to be an arbitrary design consideration based on “"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); … For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").” MPEP 2144.05 II A.; therefore, the claimed feature fails to patentable distinguish over the cited references. One of ordinary skill in the art would be able to obtain bandwidth through routine experimentation.
Claim 39: Shames discloses: A method for monitoring of a blood glucose level in a patient, comprising: ([0001]: “The present invention is generally in the field of medical applications and relates to an apparatus and method for non-invasive assessment of living blood parameters, … using pulsed nuclear magnetic resonance (NMR) relaxometry techniques.”)
providing a static magnetic field to a portion of tissue under a skin of the patient, the portion of tissue comprising blood vessels and tissue surrounding the blood vessels; ([0054]: “the permanent magnet assembly 1 is configured to apply a magnetostatic field 1 f”) (FIG. 1 shows the tissue under the skin of the finger 9 being the portion of tissue, [0049]: “For example, in some embodiments an in vivo blood test is carried out by placing a finger phalange in the test volume of the probehead (i.e., where the magnetostatic field is generated), applying electromagnetic energy pulses (also referred to herein as excitation signals) by a coil of the probehead to excite nuclear spin echoes from protons (or other nuclei) in the living liquids, tissues and bones of the finger, and using the probehead coil to acquire electromagnetic relaxation signals from the finger phalange in response to the applied excitation signals. The acquired relaxation signals are then analyzed and processed to obtain NMR signals (e.g., spin-lattice and/or spin-spin relaxation signals) of the excited nuclei, and the blood parameters of the examined organ are determined based on the NMR signals obtained.”; [0054]: “… FIG. 1 the finger 9 is introduced into the test volume 2 v such that the magnetic field 1 f from the magnet assembly 1 is applied over a portion of the finger 9 placed between the “N” and “S” poles of the magnet assembly 1…the permanent magnet assembly 1 is configured to apply a magnetostatic field 1 f being substantially perpendicular to the length of the finger 9 and the coil 2 c is adapted to apply the electromagnetic excitation signals 1 e substantially along the length of the examined finger, such that the direction of the magnetic field 1 f is substantially perpendicular to the direction of the excitation signals 1 e.”)
delivering at least one pulse of radiofrequency (RF) energy to the portion of tissue to excite proton nuclear spins in the portion of tissue, (FIG. 1, RF transmitter 3 includes inductive coil 2c, [0062]: “…a pulsed RF transmitter 3 electrically connected to the probehead 2 and configured and operable to apply radio frequency excitation signals through the inductive coil 2 c of the probehead.”) (FIG. 1; [0014]: “… Blood parameters of the examined subject are determined using nuclear spin echo signals received from the test organ in response to specific (e.g., short hard off-resonance) electromagnetic pulse sequences having relatively low radiofrequencies (RF). …”; [0049]: “applying electromagnetic energy pulses (also referred to herein as excitation signals) by a coil of the probehead to excite nuclear spin echoes from protons (or other nuclei) in the living liquids, tissues and bones of the finger,”) wherein at least a portion of a transmitter (inductive coil 2c of RF transmitter 3) of a device (FIG. 1) is positioned between a magnet of the device and the skin (skin of finger 9: FIG. 1; [0062]; “a pulsed RF transmitter 3 electrically connected to the probehead 2 and configured and operable to apply radio frequency excitation signals through the inductive coil 2 c of the probehead.”);
generating signal data corresponding to an RF signal detected by a sensor (FIG. 4, RF receiver 4) of the device from the excited proton nuclear spins in the portion of tissue; (FIG. 1; [0001], ‘The present invention is generally in the field of medical applications and relates to an apparatus and method for non-invasive assessment of living blood parameters, such as, for example, blood glucose content, blood viscosity, haematocrit, oxygen saturation and pH, using pulsed nuclear magnetic resonance (NMR) relaxometry techniques.’; [Claim 19], ‘The method according to claim 14 wherein the blood related parameters comprise one or more of the following: blood glucose content, blood viscosity, blood haematocrit, blood oxygen saturation, and blood pH.’; [0062]: “The probehead 2 is further connected to an RF receiver 4 configured and operable to receive through the coil 2 c radio frequency electromagnetic relaxation signals from the examined finger 9 responsive to the radio frequency excitation signals applied by the RF transmitter 3.”; [0049]: “applying electromagnetic energy pulses (also referred to herein as excitation signals) by a coil of the probehead to excite nuclear spin echoes from protons (or other nuclei) in the living liquids, tissues and bones of the finger, and using the probehead coil to acquire electromagnetic relaxation signals from the finger phalange in response to the applied excitation signals.”; [0073], ‘The copper coil in this example is part of a tuned tank circuit (i.e., resonant circuit e.g., LC circuit), placed between the poles of an electromagnet of a commercial Varian E-12 EPR spectrometer. In vivo measurements were carried out in a fixed magnetic field B0=0.273 Tesla at radiofrequency ƒ0=11.62 MHz.’; [0082], ‘1H spin-lattice relaxation times measurements were carried out in vivo on a series of living forefinger phalanges of individuals having different blood glucose levels using the instrumental setup used in Example 1 (ƒo=11.62 MHz) and saturation comb sequence combined with phase cycled spin-echo detection as used in Example 2 (see FIG. 4). Thermal stabilization of the examined finger phalanges was maintained by internal body temperature at normal physiological conditions (36.6±0.5° C.). All individuals under the tests did not suffer from diseases affecting blood viscosity (like polycythemia, hydraemia etc.). Parallel assessment of the blood glucose level was done using a commercial Abbot FreeStyle Lite invasive strip-type glucose meter. Results of the series of tests are shown in FIG. 6, showing dependence of the 1H spin-lattice relaxation time T11 measured on the series of forefinger phalanges as a function of the blood glucose content.’; [0083], ‘FIG. 6 demonstrates clear dependence of the 1H spin-lattice relaxation time T11 on the blood glucose content. Within the normal physiological range of blood glucose levels, and above the normal level the relaxation time T11 shows a tendency to increase.’)
analyzing the signal data to generate a quantitative value corresponding to a level of blood glucose in the patient. (FIG. 1, control unit 7, [0062]: “As exemplified in FIG. 1, the control unit 7 may be configured and operable to provide the demodulator unit 5 control signal for adjusting the gain of the IF receiver. For example, when operating with different materials (changing the nuclei under examination e.g., from 1H to 19F) unit 5 adjusts the frequency of signals generated by its local oscillator 5 a, to obtain the same intermediate frequency (IF), and also adjusts the gain of the IF receiver.”) ([0049]: “The acquired relaxation signals are then analyzed and processed to obtain NMR signals (e.g., spin-lattice and/or spin-spin relaxation signals) of the excited nuclei, and the blood parameters of the examined organ are determined based on the NMR signals obtained.”, FIG. 6; [0082], ‘1H spin-lattice relaxation times measurements were carried out in vivo on a series of living forefinger phalanges of individuals having different blood glucose levels using the instrumental setup used in Example 1 (ƒo=11.62 MHz) and saturation comb sequence combined with phase cycled spin-echo detection as used in Example 2 (see FIG. 4). Thermal stabilization of the examined finger phalanges was maintained by internal body temperature at normal physiological conditions (36.6±0.5° C.). All individuals under the tests did not suffer from diseases affecting blood viscosity (like polycythemia, hydraemia etc.). Parallel assessment of the blood glucose level was done using a commercial Abbot FreeStyle Lite invasive strip-type glucose meter. Results of the series of tests are shown in FIG. 6, showing dependence of the 1H spin-lattice relaxation time T11 measured on the series of forefinger phalanges as a function of the blood glucose content.’; [0083], ‘FIG. 6 demonstrates clear dependence of the 1H spin-lattice relaxation time T11 on the blood glucose content. Within the normal physiological range of blood glucose levels, and above the normal level the relaxation time T11 shows a tendency to increase.’)
Shames fails to disclose:
controlling the transmitter so that parameters of the pulse of RF energy including an average RF frequency and bandwidth select static magnetic field in the portion of tissue
at a depth and thickness controlled to ensure that the portion of tissue includes blood vessels and tissue surrounding the blood vessels; and
However, Blank in the context of magnetic and coil configurations for MRI probes discloses:
controlling the transmitter so that parameters of the pulse of RF energy including an average RF frequency and bandwidth select static magnetic field in the portion of tissue
-The controller 122 controls operating parameters of the transmitter including an RF frequency and bandwidth to select in the portion of tissue a locally uniform static magnetic field.
-The controller (e.g., a PC), ¶0190 overseas an RF power supply, which dictates the transmission of RF power in the form of pulse sequences, ¶0190-0191. The system of Blank features a tuning mechanism, such a variable capacitor, which allows for the adjustment of the RF circuit to a “desired range of frequencies” by applying a DC voltage, ¶0194-0195, ¶0236. Hence the controller has direct control over the RF power supply and tuning mechanisms means for the controller to actively set the RF frequency. The “field of view”, the region from which substantial NMR signals are received, is defined as the region where static magnetic field process magnetic frequency within the bandwidth of the transmitted RF frequency, ¶0185. This establishes that the RF frequency acts as a center point, and the bandwidth defines the ranges of frequencies (and thus magnetic field strengths) over which signals are collected, thereby spatially selecting the region of interest, ¶0185, ¶0196.
Note; based on the Applicants specification at ¶0056, the average RF frequency, f0 is used to adjust a depth (d) of the target area. In the Application’s specification the phrase “average RF frequency (f0)” is described as adjusting the depth and “span of the bandwidth range” is described as adjusting the thickness implies that the (f0) function as the center frequency. Hence, under the broadest reasonably interpretation, the average RF frequency constitutes the center frequency. Further note, the Applicant’s specification does not provide any further detail regarding the average RF frequency other than ¶0056.
-Accordingly, in further detail the RF frequency is used to provide a radial resolution by sequentially exciting different radial regions, ¶0196, by a method which is analogous to “slice selection” in conventional MRI, ¶0196. By changing the RF frequency, the system of Blank can selectively excite nuclei shown in the wall of blood vessel 136 at different magnetic field strengths, which correspond to different radial distances (depths) from the probe, ¶0196, ¶0225-0226. Hence, the RF frequency is indeed used to adjust the depth of the tissue being imaged. To select a specific depth, the system of Blank adjust the transmitted RF frequency, ¶0185, ¶0196. This adjusted RF frequency acts as the center frequency for the excitation of nuclei at that particular depth, where the magnetic field strength matches that frequency, ¶0185, ¶0225-0226. Hence, in view of the broadest reasonable interpretation, when the system of Blank adjust the RF frequency to change depth, its is performing a adjustment of the RF center frequency (f0) to target specific spatial locations.
-The Field of View is defined as the area where the static magnetic field produces the NMR Frequency within the bandwidth of the transmitted RF frequency, ¶0185. This principle ties the RF parameters directly the magnetic field strength in the tissue.
at a depth and thickness controlled to ensure that the portion of tissue includes blood vessels and tissue surrounding the blood vessels; and
-Blank indicates that the RF frequency and bandwidth are selected and controlled to define the depth and thickness of the portion of tissue from which NMR signals are acquires, ¶0185, ¶0196, ¶0198. This spatial selection is a fundamental aspect of how MRI probes operate.
-RF frequency is used to provide a radial resolution by sequentially exciting different radial regions, ¶0196, by a method which is analogous to “slice selection” in conventional MRI, ¶0196. By changing the RF frequency, the system of Blank can selectively excite nuclei shown in the wall of blood vessel 136 at different magnetic field strengths, which correspond to different radial distances (depths) from the probe, ¶0196, ¶0225-0226.
-The RF bandwidth directly determines the radial thickness of the “slice” or portion of tissue being excited, ¶0198. For example, a 1 MHz bandwidth corresponding to a magnetic field range of 0.024 tesla.
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the control of the processing arrangement of Shames to includes controlling operating parameters operating parameters of the transmitter including an average RF frequency and bandwidth to select in the portion of tissue a locally uniform static magnetic field, wherein the operating parameters of the transmitter are selected to define a depth and thickness of the portion of tissue ensuring that the portion of tissue includes blood vessels and tissue surrounding the blood vessels as taught by Blank. The motivation to do this yields predictable results such as “improved properties compared to the prior art. Improved properties may include one or more of: higher static magnetic field in the imaging region for a given strength magnet; greater radial penetration of the static magnetic field and the RF field into the region surrounding the probe; a field of view with greater axial extent; and the ability to image regions in more than one azimuthal direction, and/or at one more than one axial position, simultaneously, without any need to rotate the probe or to move the probe axially.”, as suggested by Blank, ¶0014.
Shames in view of Blank fail to disclose: a locally unfirm static magnetic field.
However, Den Boef in the context of magnetic resonance imaging discloses, a locally uniform static magnetic field; (Col. 1 lines 60-64, ‘An RF coil generates a locally homogeneous RF magnetic field in the examination area, the frequency of this field corresponding to the Larmor frequency of the precissional motion of the nuclear spins about the z-axis in the examination area.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify radiofrequency coil of modified Shames to provide a locally uniform RF field to the portion of tissue as taught by Den Boef. The motivation to do this yields predictable results such as improve locally the homogeneity of a special region of interest within the examination zone, Col 4 of Den Boef.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061), as applied to claim 29, in further view of Iannello (US 2016/0011290 A).
Claim 30: Shames as modified discloses all the elements above in claim 29, Shames fails to disclose: wherein the depth and the thickness of the portion of tissue is further controlled by selecting further operating parameters of the transmitter including a flip angle and phase.
However, Iannello in the context of blood measurements using a portable NMR device discloses, wherein the depth and the thickness of the portion of tissue is further controlled by selecting further operating parameters of the transmitter including a flip angle (¶0028, ‘By varying the strength and duration of the radio frequency (RF) pulse, the tip angle can be controlled. Commonly, the strength of a pulse is described by the tip angle, e.g., a 90-degree pulse, or a 180-degree pulse.’) and phase (¶0038, ‘After each 180-degree pulse is applied, the direction of precession of the hydrogen nuclei is reversed such that the phase spread of the nuclei begins to reverse, reaching coherence (focus) at a time τ after the pulse.’).
-Iannello (¶0028) states that varying the strength and duration of the RF pulse controls the tip angle (flip angle), such that different angles (e.g., 90-degree or 180-degree) affect the excitation profile. Because the flip angle determines how much magnetization is rotated into the transverse plane, it influences signal strength from different depths (i.e., a larger flip angle increases signal contribution from deeper tissue layers, while a smaller flip angle limit excitation to more superficial regions). Iannello (¶0038) discloses further that phase coherence is manipulated through the application of 180-degree pulses, reversing the direction of precession of hydrogen nuclei and refocusing the signal. The phase of RF pulses affects signal localization and refocusing, which influences which tissue layers contribute to the received signal. By adjusting phase parameters, Iannello enables more precise selection of the region of interest in terms of both depth and thickness. Thus, in addition to RF frequency and bandwidth, Iannello teaches that flip angle and phase are further parameters that control the selection of the portion of tissue, ensuring that blood vessels (capillaries) and surrounding tissue are included within a specific depth and thickness range. Iannello explicitly defines its depth and thickness of the portion of tissue, FIG. 9.
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify control of the depth and thickness of modified Shames such that the control further includes selecting operating parameters of the transmitter that includes a flip angle and a phrase as taught by Iannello. The motivation to do this yields predictable results such as increasing the signal-to-noise ratio and the ability to discriminate components of blood can be improved, ¶0049 of Iannello.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061), as applied to claim 29, in further view of Ehman et al (US 2012/0010497 A1).
Claim 32: Shames as modified discloses all the elements above in claim 29, Shames fails to disclose: wherein the magnet is a unilateral magnet
However, Ehman in the context of single-sided magnetic resonance imaging systems discloses, wherein the magnet is a unilateral magnet ([Title], ‘Single-Sided Magnetic Resonance Imaging System Suitable for Performing Magnetic Resonance Elastography’; [Abstract], ‘The unilateral MRI device includes a magnet assembly (110) that produces a static, polarizing magnetic field extending longitudinally outward from a pole face of the magnet,’) ([Abstract], ‘The unilateral MRI device includes a magnet assembly (110) that produces a static, polarizing magnetic field extending longitudinally outward from a pole face of the magnet, substantially homogeneous in a transverse plane in the near-field, and varying quasi-linearly along the longitudinal direction away from the pole face. An imaging assembly is fastened over the pole face of the magnet assembly and includes a radiofrequency (“RF”) coil (202) and a magnetic field gradient (206, 208, 210) coil that produces a magnetic field gradient in the near-field along a gradient axis.’; ¶0011, ‘both the RF and the gradient coils are designed to produce uniform fields as efficiently as possible, thereby maximizing signal-to-noise ratio and gradient switching speeds, and minimizing power consumption’; ¶0038, ‘At any distance along the longitudinal axis 130 from the forward pole face 124, this “near” magnetic field 126, or “near-field”, is relatively uniform, or homogenous, at any radial direction and distance from the longitudinal axis 130.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the magnetic of modified Shames such that it is a unilateral magnet and the portion of tissue comprises an area in which the static magnetic field is locally uniform as taught by Ehman. The motivation to do this yields predictable results such as producing uniform fields as efficiently as possible, thereby maximizing signal-to-noise ratio and minimizing power consumption, ¶0011 Ehman.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061) in view of Ehman et al (US 2012/0010497 A1), as applied to claim 32, in further view of Prado (US 20190076080A1).
Claim 33: Shames as modified discloses all the elements above in claim 32, Shame fails to disclose: wherein the magnet provides the static magnetic field at a strength ranging from 0.05 Tesla to 0.1 Tesla.
However, Prado in the context of single-sided magnetic resonance spectroscopy data obtaining discloses, wherein the magnet provides the static magnetic field at a strength ranging from 0.05 Tesla to 0.1 Tesla. (¶0081, ‘the magnet may generate a magnetic field with a maximum strength ranging from about 0.03 to about 1.0 Tesla. In some examples, field strengths between about 0.05 and about 0.5 Tesla may be used, which correspond to about 2 MHz to about 20 MHz range of operation’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the range of the static magnetic field strength of modified Shames to be ranging from 0.05 Tesla to 0.1 Tesla as taught by Prado because it has been held that "in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art a prima facie case of obviousness exists" (see MPEP 2144.05 subsection I), no criticality is given for the claimed ranges, one of ordinary skill in the art could have made the modification with known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of the invention. Accordingly, one of ordinary skill in the art would be able to obtain the claimed ranges through routine experimentation.
Claim 34 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061), as applied to claim 29, in further view of Prado (US 20190076080A1).
Claim 34: Shames as modified discloses all the elements above in claim 29, Shames fails to disclose: wherein the device is configured to be wearable on a body of the patient.
However, Prado is relied upon above further discloses: wherein the device is configured to be wearable on a body of the patient. (FIG. 5, ¶0012, ‘“unilateral” NMR probe means that the probe is open. There is no need to fully enclose the sensitive volume with the scanning probe, as is the case with conventional MRI magnets. The scanning probe is placed in the proximity of the body or on the body. The probe may generate a sensitive volume outside or inside of the boundaries of the probe, as explained hereafter. Other terms sometimes used to describe unilateral NMR probes may be, for example, “single sided” and “open.” The term “single sided” may be used to refer to magnets that generate sensitive volumes only outside of the boundaries of the magnet. For clarification, in the present disclosure, the sensitive volume may be beyond or within the outer boundaries of the scanning probe.’; ¶0069, ‘The magnet array may have an open and long geometry, to accommodate placing the probe on the body or in the proximity of the body of a patient or animal’;)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the device of modified Shames such that it is configured to be wearable (i.e., capable of being worn) on a body of the patient as taught by Prado for the advantage of providing an improved apparatus being able to inspect multiple body parts without utilizing large and expensive MRI devices, ¶0013 of Prado.
Claim 35 are rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061), as applied to claim 29, in further view of Rapoport et al (US 4,875,486).
Claim 35: Shames as modified discloses all the elements above in claim 29, Shames fails to disclose, wherein the processing arrangement is further configured to demodulate the signal data and apply a Fast Fourier Transform (FFT) to the signal data to extract a magnetic resonance (MR) spectrum corresponding to a component of the signal data contributed solely by blood circulating through the blood vessels within the portion of tissue.
However, Rapoport as disclosed by Shames, is in the context of non-invasive testing of body fluid constitutes discloses, wherein the processing arrangement is further configured to demodulate the signal data (FIG. 4A-4C; [Col. 5 lines 40-42], ‘Those signals are received by receiver/gate 48, converted from analog signals to digital signals by the A/D converter 50 and fed to the microprocessor 44’; [Col. 6 lines 38-41], ‘A five microsecond sample pulse is taken, and the free induction decay output from the A/D converter is noted. Next, the data points are stored in the memory 45 and the process is repeated (i.e., looped) perhaps one hundred times’) and apply a Fast Fourier Transform (FFT) to the signal data to extract a magnetic resonance (MR) spectrum corresponding to a component of the signal data (FIG. 4A-4C; Claim 23: ‘transforming the multiplied data with a fast Fourier transform;’; [Abstract], ‘Specifically, predetermined water and glucose peaks are compared with the measured water and glucose peaks for determining the measured glucose concentration.’; [Col. 6 lines 43-51], ‘there is shown a series of diagrams representing the one second homodecoupling pulse, the five microsecond sampling pulse, the decay, and a Fourier transformation of the decay data points. The amplitude (Amp.) of the response is recorded along the Y-axis. After the samplings, the read lamp is deactivated, the accumulated responses are multiplied by an exponential decay to provide line broadening, a Fourier transformation is run, and a spectrum is stored as the chemical shifts versus the peak height as patient data’; [Col. 7 lines 1-12], ‘the next step is an operational check where the spectrum of chemical shifts versus peak height data for the standard sample is recalled and compared to the standard data previously taken within allowable tolerances. If the error is not within an acceptable tolerance, the error display lamp 66 is lit and the operator notified. If the data is within an allowable error, the system proceeds to the next step. It is noted that on the right-hand side of FIG. 4c that a comparison is shown between the standard sample data and standard sample spectrum showing the allowable shifts, peak height and frequency with amplitude plotted along the Y-axis.’; [Col. 7 lines 13-18], ‘The next step is to normalize the patient data and standard sample data for equal water heights. Here the patient data is recalled and the standard sample data is recalled. Next, the patient data water peak height is scaled to match the standard sample data water peak height.’; [Col. 7 lines 19-29], ‘The system then executes the next step which is to calculate the glucose level. To do this a ratio is obtained of the patient data glucose peak height and the standard sample data peak height. This ratio is then multiplied by the known standard sample glucose to water ratio to obtain the patient reading and multiplied by a concentration factor (K) from the standard sample and expressed in milligrams per deciliter or some other convenient unit. Then the patient glucose level is displayed in relation to plasma level. Normal glucose concentration is ninety milligrams per deciliter.’) contributed solely by blood circulating through the blood vessels within the portion of tissue. ([Col. 5 lines 9-19], ‘It will be noted that the finger is positioned so that the fingernail is located adjacent the surface coil. This positioning is chosen as the fingernail is dead tissue but has a bed of active blood vessels positioned just below the nail. These vessels are believed to provide an accurate testing site. In many other test sites, live body tissue or bone must be penetrated in order to test blood in a vessel, which means that the tissue or bone will emit signals due to testing which act as noise and may interfere with analysis of the blood for glucose concentration.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the processing arrangement of modified Shames to demodulate the signal data and apply a Fast Fourier Transform (FFT) to the signal data to extract a magnetic resonance (MR) spectrum corresponding to a component of the signal data contributed solely by blood circulating through the blood vessels within the portion of tissue as taught by Rapoport for the advantage of providing an improved apparatus being able to differentiate between peak values corresponding to glucose and water to improve glucose concentration calculations, Col 7 of Rapoport.
Claims 36 are rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061) in view of Rapoport et al (US 4,875,486), as applied to claim 35, in further view of Siegle Jr et al (US 5,521,502).
Claim 36: Shames as modified discloses all the elements above in claim 35, Shames discloses the processing arrangement (FIG. 1, control unit 7, [0062]: “As exemplified in FIG. 1, the control unit 7 may be configured and operable to provide the demodulator unit 5 control signal for adjusting the gain of the IF receiver. For example, when operating with different materials (changing the nuclei under examination e.g., from 1H to 19F) unit 5 adjusts the frequency of signals generated by its local oscillator 5 a, to obtain the same intermediate frequency (IF), and also adjusts the gain of the IF receiver.”)
Shames fails to disclose that the processing arrangement is further configured to remove contributions to the signal data from static tissue including fat within the portion of tissue.
However, Siegel in the context of MRI imaging processing and analysis discloses, remove contributions to the signal data from static tissue including fat within the portion of tissue. (FIG. 5. [Col 5 lines 28-32], ‘Generally, the signal level in a region of disturbed flow is less than the signal level of static material for substances such as water, muscle, fat, or tissue, and therefore, this signal is perceived to be lost.’; [Col. 3 lines 19-21], ‘Another object of the present invention is to provide a process and system having the improved ability in MRI to suppress the signal of the static material.’; [Col 8 lines 12-16], ‘the flow differentiation process provides excellent suppression of the signal from static tissue, and thereby creating angiograms where flow is clearly differentiated from static tissue.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the processing arrangement of modified Shame such that it is further configured to remove contributions to the signal data from static tissue and fat within the portion of tissue as taught by Siegel Jr. The motivation to do this yields predictable results such as eliminating artifacts or signal loss caused by turbulence, [Col 1 lines 6-9] of Siegel Jr.
Claims 37 are rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061) in view of Rapoport et al (US 4,875,486) in view of Siegle Jr et al (US 5,521,502), as applied to claim 36, in further view of Iannello (US 2016/0011290 A1).
Claim 37 Shames as modified discloses all the elements above in claim 36, Shames fails to disclose: wherein the processing arrangement is further configured to determine an area, AGlu, under the MR spectrum corresponding to glucose and an area, Aw, under the MR spectrum corresponding to water.
However, Iannello is relied upon above further discloses, wherein the processing arrangement is further configured to determine an area, AGlu , under the MR spectrum corresponding to glucose and an area, Aw , under the MR spectrum corresponding to water. (¶0033, ‘The glucose level in the blood then can be determined by calculating the area under the glucose peak relative to the area under the water peak. This ratio then can be compared against a standard to obtain the actual glucose level.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify processing arrangement of modified Shames such that it is further configured to determine an area under the MR spectrum corresponding to glucose and an area under the MR spectrum corresponding to water as taught by Iannello for the advantage of providing an improved apparatus being able to obtain the actual glucose level, Iannello ¶0033.
Claims 38 are rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061) in view of Rapoport et al (US 4,875,486) in further view of Siegle Jr et al (US 5,521,502) in view of Iannello (US 2016/0011290 A1), as applied to claim 37, in further view Uibel et al (US 7,973,926 B1).
Claim 38: Shames as modified discloses all the elements above in claim 37, Shames fails to disclose: wherein the quantitative value is calculated as an absolute glucose concentration in blood plasma, CGlu, based on pre-set calibration parameters a and b according to CGlu= a* ( AGlu / Aw )+b.
However, Iannello discloses wherein the quantitative value is calculated as an absolute glucose concentration in blood plasma, CGlu, according to CGlu= ( AGlu / Aw ). (¶0033, ‘The glucose level in the blood then can be determined by calculating the area under the glucose peak relative to the area under the water peak. This ratio then can be compared against a standard to obtain the actual glucose level.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the quantitative value of modified Shames such that the quantitative value is calculated as an absolute glucose concentration in blood plasma, CGlu, according to CGlu= ( AGlu / Aw ) as taught by Iannello for the advantage of providing an improved apparatus being able to obtain the actual glucose level, Iannello ¶0033.
Modified Shames fails to disclose: based on pre-set calibration parameters a and b according to CGlu= a* ( AGlu / Aw )+b.
However, Uibel in the context of Raman spectrum from a linear calibration reference discloses, wherein the quantitative value is calculated as an absolute olefin concentration, Olefin vol %, based on pre-set calibration parameters a and b according to Olefin vol %= M* (area ratio)+ B. ([Abstract], ‘Generally, a Raman spectrum from a linear-calibration reference sample (e.g., a pure hydrocarbon, such as toluene) and Raman spectra from multiple simulated fuel samples having known olefin concentrations are obtained. An area ratio for each simulated fuel sample is created by dividing the area in the olefin region of each fuel sample by the area in the chemical spectral region of the linear-calibration reference sample. The area ratio and the known olefin concentration for each simulated sample are used to create a linear olefin calibration. The olefin concentration of a fuel sample with an unknown olefin concentration is calculated by determining the area ratio between the olefin spectral region in the unknown sample and the chemical spectral region in a concentration-calculation reference sample (e.g., toluene) and placing the new area ratio into the linear olefin calibration.’; [Claim 1], ‘obtaining a linear calibration curve described by an equation: Olefin vol %=M(area ratio)+B wherein: Olefin vol % comprises an actual olefin concentration, by volume percent; M comprises a slope of the linear calibration curve; "area ratio" comprises a ratio of a first area in an olefin spectral region compared to a second area in a first chemical spectral region of a Raman spectrum of a first chemical in a linear-calibration reference sample; and B comprises a Y-intercept of the linear calibration curve’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify concentration equation of modified Shames to include pre-set calibration parameters (i.e., linear calibration) with respect to an area ratio as taught by Uibel. The motivation to do this yields predictable results such as eliminating problems that arise from spectral variation between different mixtures, [Col 12] Uibel. The modified combination above would disclose pre-set calibration parameters (i.e., linear calibration) akin to ‘a’ and ‘b’ as taught by Uibel with respect to the area ratio of Iannello to arrive at the claimed absolute glucose concentration equation: CGlu= a* ( AGlu / Aw )+b .
Claims 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061), as applied to claim 39, in further view of Iannello (US 2016/0011290 A).
Claim 40: Shames as modified discloses all the elements above in claim 39, Shames fails to disclose: wherein the depth and the thickness of the portion of tissue is further controlled by selecting further operating parameters of the transmitter including a flip angle and phase.
However, Iannello in the context of blood measurements using a portable NMR device discloses, wherein the depth and the thickness of the portion of tissue is further controlled by selecting further operating parameters of the transmitter including a flip angle (¶0028, ‘By varying the strength and duration of the radio frequency (RF) pulse, the tip angle can be controlled. Commonly, the strength of a pulse is described by the tip angle, e.g., a 90-degree pulse, or a 180-degree pulse.’) and phase (¶0038, ‘After each 180-degree pulse is applied, the direction of precession of the hydrogen nuclei is reversed such that the phase spread of the nuclei begins to reverse, reaching coherence (focus) at a time τ after the pulse.’).
-Iannello (¶0028) states that varying the strength and duration of the RF pulse controls the tip angle (flip angle), such that different angles (e.g., 90-degree or 180-degree) affect the excitation profile. Because the flip angle determines how much magnetization is rotated into the transverse plane, it influences signal strength from different depths (i.e., a larger flip angle increases signal contribution from deeper tissue layers, while a smaller flip angle limit excitation to more superficial regions). Iannello (¶0038) discloses further that phase coherence is manipulated through the application of 180-degree pulses, reversing the direction of precession of hydrogen nuclei and refocusing the signal. The phase of RF pulses affects signal localization and refocusing, which influences which tissue layers contribute to the received signal. By adjusting phase parameters, Iannello enables more precise selection of the region of interest in terms of both depth and thickness. Thus, in addition to RF frequency and bandwidth, Iannello teaches that flip angle and phase are further parameters that control the selection of the portion of tissue, ensuring that blood vessels (capillaries) and surrounding tissue are included within a specific depth and thickness range. Iannello explicitly defines its depth and thickness of the portion of tissue, FIG. 9.
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify control of the depth and thickness of modified Shames such that the control further includes selecting operating parameters of the transmitter that includes a flip angle and a phrase as taught by Iannello. The motivation to do this yields predictable results such as increasing the signal-to-noise ratio and the ability to discriminate components of blood can be improved, ¶0049 of Iannello.
Claim 41: Shames as modified discloses all the elements above in claim 40, Shames discloses: wherein the transmitter delivers the RF energy at a frequency in between a bandwidth from 2.1 megahertz (MHz) and 4.2 MHz. (¶0012, ‘and electromagnetic excitation signals of relatively low radiofrequencies, i.e., in the range of 1 to 20 MHz.’)
Claim 43 & 44 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061) in view of Iannello (US 2016/0011290 A), as applied to claim 41, in further view of Prado (US 20190076080A1).
Claim 43: Shames as modified discloses all the elements above in claim 41, Shame fails to disclose: wherein the RF frequency matches the static magnetic field at a strength ranging from 0.05 Tesla to 0.1 Tesla.
However, Prado in the context of single-sided magnetic resonance spectroscopy data obtaining discloses, wherein the RF frequency matches the static magnetic field at a strength ranging from 0.05 Tesla to 0.1 Tesla. (¶0081, ‘the magnet may generate a magnetic field with a maximum strength ranging from about 0.03 to about 1.0 Tesla. In some examples, field strengths between about 0.05 and about 0.5 Tesla may be used, which correspond to about 2 MHz to about 20 MHz range of operation’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the range of the static magnetic field strength of modified Shames to be ranging from 0.05 Tesla to 0.1 Tesla as taught by Prado because it has been held that "in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art a prima facie case of obviousness exists" (see MPEP 2144.05 subsection I), no criticality is given for the claimed ranges, one of ordinary skill in the art could have made the modification with known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of the invention. Accordingly, one of ordinary skill in the art would be able to obtain the claimed ranges through routine experimentation.
Claim 44: Shames as modified discloses all the elements above in claim 43, Shames fails to disclose: wherein the magnet is configured to be wearable on a body of the patient.
However, Prado is relied upon above further discloses: wherein the magnet is configured to be wearable on a body of the patient. (FIG. 5, ¶0012, ‘“unilateral” NMR probe means that the probe is open. There is no need to fully enclose the sensitive volume with the scanning probe, as is the case with conventional MRI magnets. The scanning probe is placed in the proximity of the body or on the body. The probe may generate a sensitive volume outside or inside of the boundaries of the probe, as explained hereafter. Other terms sometimes used to describe unilateral NMR probes may be, for example, “single sided” and “open.” The term “single sided” may be used to refer to magnets that generate sensitive volumes only outside of the boundaries of the magnet. For clarification, in the present disclosure, the sensitive volume may be beyond or within the outer boundaries of the scanning probe.’; ¶0069, ‘The magnet array may have an open and long geometry, to accommodate placing the probe on the body or in the proximity of the body of a patient or animal’;)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the device of modified Shames such that it is configured to be wearable (i.e., capable of being worn) on a body of the patient as taught by Prado for the advantage of providing an improved apparatus being able to inspect multiple body parts without utilizing large and expensive MRI devices, ¶0013 of Prado.
Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061) in view of Iannello (US 2016/0011290 A) in view of Prado (US 20190076080A1) as applied to claim 43, in further view of Ehman et al (US 2012/0010497 A1).
Claim 42: Shames as modified discloses all the elements above in claim 43, Shames fails to disclose: wherein the statis magnetic field is generated by a unilateral magnet
However, Ehman in the context of single-sided magnetic resonance imaging systems discloses, wherein the statis magnetic field is generated by a unilateral magnet ([Title], ‘Single-Sided Magnetic Resonance Imaging System Suitable for Performing Magnetic Resonance Elastography’; [Abstract], ‘The unilateral MRI device includes a magnet assembly (110) that produces a static, polarizing magnetic field extending longitudinally outward from a pole face of the magnet,’) ([Abstract], ‘The unilateral MRI device includes a magnet assembly (110) that produces a static, polarizing magnetic field extending longitudinally outward from a pole face of the magnet, substantially homogeneous in a transverse plane in the near-field, and varying quasi-linearly along the longitudinal direction away from the pole face. An imaging assembly is fastened over the pole face of the magnet assembly and includes a radiofrequency (“RF”) coil (202) and a magnetic field gradient (206, 208, 210) coil that produces a magnetic field gradient in the near-field along a gradient axis.’; ¶0011, ‘both the RF and the gradient coils are designed to produce uniform fields as efficiently as possible, thereby maximizing signal-to-noise ratio and gradient switching speeds, and minimizing power consumption’; ¶0038, ‘At any distance along the longitudinal axis 130 from the forward pole face 124, this “near” magnetic field 126, or “near-field”, is relatively uniform, or homogenous, at any radial direction and distance from the longitudinal axis 130.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the magnetic of modified Shames such that the statis magnetic field is generated by a unilateral magnet as taught by Ehman. The motivation to do this yields predictable results such as producing uniform fields as efficiently as possible, thereby maximizing signal-to-noise ratio and minimizing power consumption, ¶0011 Ehman.
Claim 45 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061), as applied to claim 39, in further view of Rapoport et al (US 4,875,486).
Claim 45: Shames as modified discloses all the elements above in claim 39, Shames fails to disclose, further comprising demodulating the signal data and applying a Fast Fourier Transform (FFT) to the signal data to extract a magnetic resonance (MR) spectrum corresponding to a component of the signal data contributed solely by blood circulating through the blood vessels within the portion of tissue.
However, Rapoport as disclosed by Shames, is in the context of non-invasive testing of body fluid constitutes discloses, demodulating the signal data (FIG. 4A-4C; [Col. 5 lines 40-42], ‘Those signals are received by receiver/gate 48, converted from analog signals to digital signals by the A/D converter 50 and fed to the microprocessor 44’; [Col. 6 lines 38-41], ‘A five microsecond sample pulse is taken, and the free induction decay output from the A/D converter is noted. Next, the data points are stored in the memory 45 and the process is repeated (i.e., looped) perhaps one hundred times’) and applying a Fast Fourier Transform (FFT) to the signal data to extract a magnetic resonance (MR) spectrum corresponding to a component of the signal data (FIG. 4A-4C; Claim 23: ‘transforming the multiplied data with a fast Fourier transform;’; [Abstract], ‘Specifically, predetermined water and glucose peaks are compared with the measured water and glucose peaks for determining the measured glucose concentration.’; [Col. 6 lines 43-51], ‘there is shown a series of diagrams representing the one second homodecoupling pulse, the five microsecond sampling pulse, the decay, and a Fourier transformation of the decay data points. The amplitude (Amp.) of the response is recorded along the Y-axis. After the samplings, the read lamp is deactivated, the accumulated responses are multiplied by an exponential decay to provide line broadening, a Fourier transformation is run, and a spectrum is stored as the chemical shifts versus the peak height as patient data’; [Col. 7 lines 1-12], ‘the next step is an operational check where the spectrum of chemical shifts versus peak height data for the standard sample is recalled and compared to the standard data previously taken within allowable tolerances. If the error is not within an acceptable tolerance, the error display lamp 66 is lit and the operator notified. If the data is within an allowable error, the system proceeds to the next step. It is noted that on the right-hand side of FIG. 4c that a comparison is shown between the standard sample data and standard sample spectrum showing the allowable shifts, peak height and frequency with amplitude plotted along the Y-axis.’; [Col. 7 lines 13-18], ‘The next step is to normalize the patient data and standard sample data for equal water heights. Here the patient data is recalled and the standard sample data is recalled. Next, the patient data water peak height is scaled to match the standard sample data water peak height.’; [Col. 7 lines 19-29], ‘The system then executes the next step which is to calculate the glucose level. To do this a ratio is obtained of the patient data glucose peak height and the standard sample data peak height. This ratio is then multiplied by the known standard sample glucose to water ratio to obtain the patient reading and multiplied by a concentration factor (K) from the standard sample and expressed in milligrams per deciliter or some other convenient unit. Then the patient glucose level is displayed in relation to plasma level. Normal glucose concentration is ninety milligrams per deciliter.’) contributed solely by blood circulating through the blood vessels within the portion of tissue. ([Col. 5 lines 9-19], ‘It will be noted that the finger is positioned so that the fingernail is located adjacent the surface coil. This positioning is chosen as the fingernail is dead tissue but has a bed of active blood vessels positioned just below the nail. These vessels are believed to provide an accurate testing site. In many other test sites, live body tissue or bone must be penetrated in order to test blood in a vessel, which means that the tissue or bone will emit signals due to testing which act as noise and may interfere with analysis of the blood for glucose concentration.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the analyzing of modified Shames to further comprise demodulating the signal data and applying a Fast Fourier Transform (FFT) to the signal data to extract a magnetic resonance (MR) spectrum corresponding to a component of the signal data contributed solely by blood circulating through the blood vessels within the portion of tissue as taught by Rapoport for the advantage of providing an improved apparatus being able to differentiate between peak values corresponding to glucose and water to improve glucose concentration calculations, Col 7 of Rapoport.
Claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061) in view of Rapoport et al (US 4,875,486), as applied to claim 45, in further view of Siegle Jr et al (US 5,521,502).
Claim 46: Shames as modified discloses all the elements above in claim 45,
Shames fails to disclose further comprising: removing contributions to the signal data from static tissue including fat within the portion of tissue.
However, Siegel in the context of MRI imaging processing and analysis discloses, removing contributions to the signal data from static tissue including fat within the portion of tissue. (FIG. 5. [Col 5 lines 28-32], ‘Generally, the signal level in a region of disturbed flow is less than the signal level of static material for substances such as water, muscle, fat, or tissue, and therefore, this signal is perceived to be lost.’; [Col. 3 lines 19-21], ‘Another object of the present invention is to provide a process and system having the improved ability in MRI to suppress the signal of the static material.’; [Col 8 lines 12-16], ‘the flow differentiation process provides excellent suppression of the signal from static tissue, and thereby creating angiograms where flow is clearly differentiated from static tissue.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the analyzing of modified Shame such that it is further configured to remove contributions to the signal data from static tissue and fat within the portion of tissue as taught by Siegel Jr. The motivation to do this yields predictable results such as eliminating artifacts or signal loss caused by turbulence, [Col 1 lines 6-9] of Siegel Jr.
Claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061) in view of Rapoport et al (US 4,875,486) in view of Siegle Jr et al (US 5,521,502), as applied to claim 45, in further view of Iannello (US 2016/0011290 A1).
Claim 47 Shames as modified discloses all the elements above in claim 45, Shames fails to disclose: further comprising determining an area, AGlu, under the MR spectrum corresponding to glucose and an area, Aw, under the MR spectrum corresponding to water.
However, Iannello is relied upon above further discloses, determining an area, AGlu , under the MR spectrum corresponding to glucose and an area, Aw , under the MR spectrum corresponding to water. (¶0033, ‘The glucose level in the blood then can be determined by calculating the area under the glucose peak relative to the area under the water peak. This ratio then can be compared against a standard to obtain the actual glucose level.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the analyzing of modified Shames such that it is further configured to determine an area under the MR spectrum corresponding to glucose and an area under the MR spectrum corresponding to water as taught by Iannello for the advantage of providing an improved apparatus being able to obtain the actual glucose level, Iannello ¶0033.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Shames et al (US 2015/0018638 A1) in view of Blank et al (US 2006/0084861 A1) in view of Den Boef (US 4,890,061) in view of Rapoport et al (US 4,875,486) in further view of Siegle Jr et al (US 5,521,502) in view of Iannello (US 2016/0011290 A1), as applied to claim 47, in further view Uibel et al (US 7,973,926 B1).
Claim 48: Shames as modified discloses all the elements above in claim 47, Shames fails to disclose: wherein the quantitative value is calculated as an absolute glucose concentration in blood plasma, CGlu, based on pre-set calibration parameters a and b according to CGlu= a* ( AGlu / Aw )+b.
However, Iannello discloses wherein the quantitative value is calculated as an absolute glucose concentration in blood plasma, CGlu, according to CGlu= ( AGlu / Aw ). (¶0033, ‘The glucose level in the blood then can be determined by calculating the area under the glucose peak relative to the area under the water peak. This ratio then can be compared against a standard to obtain the actual glucose level.’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify the quantitative value of modified Shames such that the quantitative value is calculated as an absolute glucose concentration in blood plasma, CGlu, according to CGlu= ( AGlu / Aw ) as taught by Iannello for the advantage of providing an improved apparatus being able to obtain the actual glucose level, Iannello ¶0033.
Modified Shames fails to disclose: based on pre-set calibration parameters a and b according to CGlu= a* ( AGlu / Aw )+b.
However, Uibel in the context of Raman spectrum from a linear calibration reference discloses, wherein the quantitative value is calculated as an absolute olefin concentration, Olefin vol %, based on pre-set calibration parameters a and b according to Olefin vol %= M* (area ratio)+ B. ([Abstract], ‘Generally, a Raman spectrum from a linear-calibration reference sample (e.g., a pure hydrocarbon, such as toluene) and Raman spectra from multiple simulated fuel samples having known olefin concentrations are obtained. An area ratio for each simulated fuel sample is created by dividing the area in the olefin region of each fuel sample by the area in the chemical spectral region of the linear-calibration reference sample. The area ratio and the known olefin concentration for each simulated sample are used to create a linear olefin calibration. The olefin concentration of a fuel sample with an unknown olefin concentration is calculated by determining the area ratio between the olefin spectral region in the unknown sample and the chemical spectral region in a concentration-calculation reference sample (e.g., toluene) and placing the new area ratio into the linear olefin calibration.’; [Claim 1], ‘obtaining a linear calibration curve described by an equation: Olefin vol %=M(area ratio)+B wherein: Olefin vol % comprises an actual olefin concentration, by volume percent; M comprises a slope of the linear calibration curve; "area ratio" comprises a ratio of a first area in an olefin spectral region compared to a second area in a first chemical spectral region of a Raman spectrum of a first chemical in a linear-calibration reference sample; and B comprises a Y-intercept of the linear calibration curve’)
It would have been obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to modify concentration equation of modified Shames to include pre-set calibration parameters (i.e., linear calibration) with respect to an area ratio as taught by Uibel. The motivation to do this yields predictable results such as eliminating problems that arise from spectral variation between different mixtures, [Col 12] Uibel. The modified combination above would disclose pre-set calibration parameters (i.e., linear calibration) akin to ‘a’ and ‘b’ as taught by Uibel with respect to the area ratio of Iannello to arrive at the claimed absolute glucose concentration equation: CGlu= a* ( AGlu / Aw )+b .
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 Nicholas Robinson whose telephone number is (571)272-9019. The examiner can normally be reached M-F 9:00AM-5:00PM EST.
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, Pascal Bui-Pho can be reached at (571) 272-2714. 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.
/N.A.R./Examiner, Art Unit 3798
/PASCAL M BUI PHO/Supervisory Patent Examiner, Art Unit 3798
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