DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-25, 27, and 29-32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception in the form of an abstract idea without significantly more.
In a test for patent subject matter eligibility, the claims pass Step 1 (see 2019 Revised Patent Subject Matter Eligibility), as they are related to a process, machine, manufacture, or composition of matter.
When assessed under Step2A, Prong I, Independent claim 1 are found to recite a judicial exception (i.e. abstract idea). In this instance, claim 1 recite the limitations “receiving imaging data obtained from imaging the region of the body of the subject comprising data representative of a distribution of a marker within the region administered to the subject prior to the imaging”, “processing the imaging data to obtain a measure of marker signal in the region”, “correcting the measure of marker signal for an effect on the marker signal of tissue structure within the region”, and “determining the measure of the disease for the region using the corrected measure of the marker signal”. The cited limitations, under their broadest reasonable interpretation, encompass a mental process (i.e. abstract idea) of receiving imaging data, processing imaging data, correcting the measure of marker signal, determining a measure of the disease, which can be performed in the mind or by a human using a pen and a paper (e.g. observation, evaluation, judgment, opinion). In other words, a person could reasonably receive imaging data through observation, process the imaging data via observation/evaluation, correct the measure of the marker signal by evaluation/judgment (e.g. excluding/removing data mentally), determine the measure of the disease through observation/evaluation. Examiner notes that there is nothing in the claims that preclude the limitation from being performed by a human, mentally or with pen and paper, thus the cited limitation(s) recites a judicial exception (MPEP 2106.04(a)) and the claim must be reviewed under Step 2A, Prong II to determine patent eligibility.
Step 2A, Prong II determines whether any claim recites an additional element that integrates the judicial exception into a practical application. Independent claims recites the following additional element(s):
Receiving imaging data obtained from the imaging the region of the body of the subject comprising data representative of a distribution of a marker within the region administered to the subject prior to the imaging, wherein the marker binds to a biological target related to the disease;
Processing the imaging data to obtain a measure of marker to obtain a measure of marker signal in the region
Correcting the measure of marker signal for an effect on the marker signal of tissue structure within the region
The additional elements in the cited independent claim are not found to integrate the judicial exception into a practical application. In this case, receiving imaging data, processing the imaging data, and correcting the measure of the marker are alternatively considered as additional elements which are seen mere pre-solution activity of data gathering and generic processing where correcting the measure of the marker signal is broadly recited and includes interpretations of filtering, gain correction, etc. which are well understood routine and conventional methods of processing data. These elements are seen as adding insignificant extra-solution activity to the judicial exception. Examiner further notes the data representative of a distribution of a marker where the marker binds to a biological target is considered to merely tie to judicial exception to a particular technological environment or field of use of diagnostic imaging with a tracer. Such limitations do no more than link the judicial exception to a particular technological environment or field of use. Therefore, under step 2A Prong II the Judicial exception is not integrated into a practical application by additional elements of independent claim 1 and the claims must be reviewed under Step 2B to determine patent eligibility.
Step 2B determines where a claim amounts to significantly more.
The additional element(s) listed above do not amount to significantly more than the judicial exception. In this instance, as noted above the additional elements under the alternative interpretation amount to merely insignificant pre-solution activity of data gathering/processing. Additionally there is no improvement in the functioning of the computer or technological field, and there is no transformation of subject matter into a different state. Therefore, under Step 2B in a test for patent subject matter eligibility, the judicial exception of the independent claim(s) do not amount to significantly more and the independent claim(s) remain patent ineligible.
Dependent claims 2-25, 27, and 29-32 further limit the abstract idea of independent claim 1. When analyzed as a whole, these claims are held to be patent ineligible under 35 U.S.C. 101 because the additional recited limitations fail to establish that the claims are not directed towards an abstract idea and do not sufficiently integrate the subject matter into a practical application or recite elements which constitute significantly more than the abstract ideas identified. The dependent claims are directed toward additional elements which encompass abstract ideas
In this instance, dependent claims recite the following limitations:
Determining a vascular density in the region (claim 5)
Determining the total volume of blood vessels in the region (claim 6)
Identifying blood vessels in the region using the data representative of tissue structure (claim 7)
Determining a background marker signal corresponding to marker signal from unbound marker in blood (claim 9)
Identifying sub-regions of reduced tissue density in the region using the data representative of tissue structure (claim 11)
Wherein the measure of marker signal is normalized by a background marker signal corresponding to marker signal from unbound marker in blood (claim 17)
The cited limitation(s), under their broadest reasonable interpretation, encompass mental processes (i.e. abstract idea) which can be performed in the mind or by a human using a pen and a paper (e.g. observation, evaluation, judgment, opinion). In other words, a human could reasonably determine a vascular density, determine a total volume of blood vessels, identify blood vessels, determine a background marker signal, identify sub-regions via observation/evaluation, normalize a measure of marker signal. Examiner notes that there is nothing in the claims that preclude the limitation from being performed by a human, mentally or with pen and paper, thus the claimed limitation is considered to be directed towards a judicial exception (MPEP 2106.04(a)).
Under Step 2A, Prong II for dependent claims 2-25, 27, and 29-32, present additional elements which only further narrow the judicial exceptions (e.g. claim 2 which further narrows the nature of the corrected measure of marker signal, claim 3 which further narrows the nature of the disease and the biological target, claim 4 which further narrows the nature of the correcting of the measure of the marker signal such that it is “for marker signal due to vascular flow”, claims 7 and 11 which further narrows the nature of the imaging data such that it comprises data representative of tissue structure in the region, claims 8 and 12 which further narrows the nature of the data representative of tissue structure and how it is obtained which amounts to mere data gathering using well-understood routine and conventional imaging techniques in the medical field, claim 10 which further narrows the nature of the correcting such that it is “for tissue density in the region”, claim 13 which further narrows the data representative of tissue structure and sub-region identification, claim 14, which further narrows the correcting for tissue density such that it is “based on a proportion of tissue in the region having reduced density”, claim 15 which further narrows the nature of the correction of the measure of marker such that it is determined using measurements of marker signal in a plurality of individuals, claim 16 which further narrows the nature of the measure of the marker signal, claim 17 which further narrows the nature of the measure of marker signal such that it is normalized by a background marker signal which amounts to mere insignificant data processing, claims 18 and 19 which further narrow the background marker signal, claim 20 which further narrows the biological target, claim 21 which further narrows the marker, claim 22 which further narrows how the data representative of the distribution within the region of the marker is obtained which amounts to mere data gathering using well-understood, routine, and conventional imaging techniques in the medical field and specifically tracer imaging, claim 24 which merely further narrows the imaging data such that it comprises data representative of a distribution of each of a plurality of markers and further narrows the processing, the correcting and the determining accordingly where a person having ordinary skill in the art would remain to be able to process, correct, and determine in the mind or with the aid of pen and paper, claims 25, 27, and 32 which merely further narrow the nature of the data representative of tissue structure and data representative of the distribution of the marker and recite alignment/deforming of data which amount to merely insignificant pre-solution activity of data registration, claim 29-30 which merely introduce a computer/processor for performing the steps of claim 1 which amount to merely applying the judicial exception with a generic computer, and claim 31 which further narrows the background marker signal) and provide no additional element which are found to integrate the judicial exception into a practical application.
These dependent claims include no additional claims that are sufficient to amount to significantly more than the judicial exception. Additionally, there is no improvement in the functioning of the computer or technological field, and there is no transformation of subject matter into a different state. As discussed above with respect to integration of the abstract idea into a practical application, the additional claims do not provide any additional elements that would amount to significantly more than the judicial exception. Under Step 2B, these claims are not patent eligible.
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 2, 7-8, 11-13, 17, 20, 23, 25, and 31-32 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 recites the limitation “tissue within the region”. It is unclear if the tissue within the region is or corresponds with the biological target, if the tissue is the same as or corresponds with the tissue structure, or if this is some other tissue which is different from any of the previously recited elements which may be considered a tissue. For examination purposes, it has been interpreted to mean any tissue, however, clarification is required.
Claims 7 and 11 recite the limitation “tissue structure”. It is unclear if the tissue structure is the same as the tissue structure recited previously or if this is different tissue structure. For examination purposes, it has been interpreted to mean any tissue structure, however, clarification is required.
Claim 11 recites the limitation “identifying sub-regions of reduced tissue density” and claim 14 recites the limitation “a proportion of tissue in the region having reduced density”. It is unclear what is considered “reduced density” and what the reduced density is with respect to. In other words, it is unclear if reduced tissue density is with respect to surrounding tissue density, with respect to normal tissue density, with respect to other tissues densities, etc. For examination purposes, it has been interpreted that any tissue density which is less than another is considered to have a reduced density, however, clarification is required.
Claim 13 recites the limitation “the data representative of tissue structure is obtained using x-rays”. The limitation is unclear as claim 12 previously recites “the data representative of tissue structure is obtained by one or more of low-dose computed tomography, high-resolution computed tomography, multi-slice computed tomography, magnetic resonance imaging, plain radiography, and ultrasound” and it is unclear if the limitation is intending to further define the data representative of tissue structure is obtained by one or more of low-dose computed tomography, high-resolution computed tomography, multi-slice computed tomography, or plain radiography which are understood to use x-rays, if the data is obtained using x-rays other than one of the imaging types listed in claim 12 or if the data is obtained using one or more of the imaging types listed in claim 12 in addition to x-rays. For examination purposes, it has been interpreted that the data representative of tissue structure is obtained using x-rays and may be the same as any of the previously recited imaging types or a different obtaining of the data representative of tissue structure.
Claim 17 recites the limitation “wherein the measure of marker signal is normalized by a background marker signal”. It is unclear if the normalization of the measure of the marker signal is the same as correcting or if this is a different processing performed on the measure of marker signal as normalization of data may be interpreted as correction/correcting of the measure of the marker signal. In other words, it is unclear if the claim is attempting to further narrow the correcting to be or include normalizing by the background marker signal or if this is a different/additional step performed on the measure of the marker signal and/or the corrected marker signal. For examination purposes, it has been interpreted that the correcting may include or be different from normalizing, however, clarification is required.
Regarding claims 20, 23, 25, and 32, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For examination purposes, it has been interpreted that the elements recited after “for example” are not required of the claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 9-14, 16-24, and 29-32 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ben Haim (US 20150366523 A1), hereinafter Ben Haim.
Regarding claims 1, 29, and 30,
Ben-Haim discloses an apparatus comprising a non-transitory computer-readable medium and a computer/processor ([0125] which discloses the data processor includes a volatile memory for storing instructions and/or data and/or a non-volatile storage, for example, a magnetic hard-disk and/or removable media, for storing instructions and/or data), the non-transitory computer-readable medium comprising instructions which, when executed by the computer/processor, causes the computer/processor to carry out a method for determining a measure of a disease in a region of the body of a subject selected tasks according to embodiments of the invention could be implemented as a plurality of software instructions being executed by a computer using any suitable operating system), the method comprising:
receiving imaging data (at least fig. 1 (101 and 103) and corresponding disclosure in at least [0597]-[0599] and/or at least fig. 4 (4802 and 4808) and corresponding disclosure in at least [0512] and [0516]) obtained from imaging the region of the body of the subject comprising data representative of a distribution of a marker within the region ([0599] which discloses a SPECT image, describing a distribution of radioactive tracer according to any one of the embodiments described herein relating to SPECT data acquisition and [0512] which discloses optionally, the functional images includes regions of relatively high concentration of radioactive tracer (e.g., as described herein), that denote synaptic centers.) administered to the subject prior to the imaging (at least fig. 1 (102) and corresponding disclosure in at least [0598]); wherein the marker binds to a biological target related to the disease (abstract which discloses the radioactive tracer binds to automatic nervous system synapses and see also [0224]-[0225] which discloses in some embodiments, the radioactive tracer is a radio-ligand. the term “radio-ligand” refers to a radiolabeled compound which selectively binds a target (e.g., a protein), that is, the radiolabeled compound serves as a ligand of the target and [0228]-[0229])
processing the imaging data to obtain a measure of marker signal in the region ([0033] which discloses processing the anatomical image to generate at least one image mask corresponding to dimensions of the at least one internal body part; and correlating the at least one generated image mask with the data describing a distribution of the radioactive tracer in the body, for guiding a reconstruction of an image depicting the at least one synaptic center and [0502] which discloses for processing functional images acquired using a radioactive tracer, for examples, images of a distribution of radioactive tracer such as described herein, to identify and/or locate synaptic centers (may correspond to method 300, and particularly to blocks 308, 310, 312 and/or 314 in FIG. 3), in accordance with some embodiments of the present invention. See also [0418] which discloses data is used in a format wherein a signal for a region in the body is correlated to a concentration of radioactive tracer in the region (e.g., the signal simply represents the amount of detected radioactivity emitted from the region in the body). See also fig. 4 (4824 or 4830) and corresponding disclosure in at least [0559]);
correcting the measure of marker signal for an effect on the marker signal of tissue structure within the region ([0035] which discloses the method further comprises removing data describing a presence of the radioactive tracer from anatomical regions that do not contain synaptic centers based on the anatomical data of the anatomical regions and [0513] which discloses Optionally, the noise is removed from the functional data based on the corresponding anatomical image (e.g., after image registration). Optionally, emission intensity readings associated with noise within blood (or other fluid) filled chambers and/or vessels is removed. For example, emission intensity readings of the radioactive tracer data corresponding to heart chambers and/or surrounding blood vessels are removed. Examiner notes that such removal of data/noise is considered to correct the measure of marker signal for an effect on the marker signal of tissue structure within the region. See also [0563] disclosing normalization of parameters (i.e. a measure). See also at least fig. 4 (4832) and corresponding disclosure in at least [0563]);
and determining the measure of the disease for the region using the corrected measure of marker signal ([0041] which discloses the method further comprises diagnosing a disease or disorder associated with an abnormal autonomic nervous system activity based on the imaging and [0571] which discloses the calculated results and/or reconstructed images are provided for presentation. For example, presented on a monitor to a physician. The calculated results may help in diagnosing the patient (e.g., as described herein) and/or in guiding treatment (e.g., as described herein))
Regarding claim 2,
Ben-Haim further discloses wherein the corrected measure of marker signal is representative of a level of binding of the marker to tissue within the region ([0513] which discloses the noise is removed from the functional data based on the corresponding anatomical image (e.g., after image registration). Optionally, emission intensity readings associated with noise within blood (or other fluid) filled chambers and/or vessels is removed. For example, emission intensity readings of the radioactive tracer data corresponding to heart chambers and/or surrounding blood vessels are removed. [0615] which discloses the method further comprises filtering at least part of a representation of the intrabody area or volume in the radioactive tracer data based on a match with a reference value (e.g., by removing noise from regions other than a ROI and [0559] which discloses one or more parameters are calculated for the identified synaptic centers parameters include specific radioactive tracer level (e.g., counts per voxel of synaptic center divided by average counts in the corresponding image mask volume). Examiner notes that the corrected measure of marker signal including the marker signal after removal of noise/data from other regions and normalization are considered to be representative of a level of binding of the marker to tissue within the region in its broadest reasonable interpretation).
Regarding claim 3,
Ben-Haim further discloses wherein the disease is an inflammatory disease ([0648] which discloses medical conditions and/or diseases which may be treated diagnosed and/or monitored include… chronic obstructive pulmonary disease and rheumatoid arthritis), and the biological target is a component of an inflammatory pathway (abstract which discloses the radioactive tracer binds to automatic nervous system synapses and see also [0224]-[0225] which discloses in some embodiments, the radioactive tracer is a radio-ligand. the term “radio-ligand” refers to a radiolabeled compound which selectively binds a target (e.g., a protein), that is, the radiolabeled compound serves as a ligand of the target and [0228]-[0229]. Examiner notes that a protein and synapses are considered components of an inflammatory pathway).
Regarding claim 4,
Ben-Haim further discloses wherein the correcting of the measure of the marker signal comprises correcting for marker signal due to vascular flow in the region ([0513] which discloses Optionally, emission intensity readings associated with noise within blood (or other fluid) filled chambers and/or vessels is removed. For example, emission intensity readings of the radioactive tracer data corresponding to heart chambers and/or surrounding blood vessels are removed. Examiner notes that such removal of data corresponding to blood vessels or blood filled chambers necessarily corrects for marker signal due to vascular flow in the region).
Regarding claim 9,
Ben-Haim further discloses wherein correcting for marker signal due to vascular flow in the region comprises determining a background marker signal corresponding to marker signal from unbound marker in blood ([0513] which discloses emission intensity readings associated with noise within blood (or other fluid) filled chambers and/or vessels is removed. For example, emission intensity readings (i.e. a background marker signal) of the radioactive tracer data corresponding to heart chambers and/or surrounding blood vessels are removed. Examiner notes that removal of such readings requires determining the background marker signal and that such readings are understood to correspond to noise/marker signals in the blood and thus corresponds to marker signal from unbound marker in blood in its broadest reasonable interpretation. Additionally/alternatively [0565] discloses level of a radioactive tracer at a local region compared to an average value and/or a standard deviation across the organ volume, within the image mask space and/or relative to a predefined threshold. Where it is noted that the average value across the organ volume corresponds to all marker signals including any unbound marker in blood).
Regarding claim 10,
Ben-Haim further discloses wherein the correcting of the marker signal comprises correcting for tissue density in the region ([0513] which discloses no nervous system activity is expected from inside the hollow chambers (containing blood). Noise may be received from areas corresponding to the inside of the heart chamber, even though no nervous system activity is expected. Optionally, the noise is removed from the functional data based on the corresponding anatomical image (e.g., after image registration). Optionally, emission intensity readings associated with noise within blood (or other fluid) filled chambers and/or vessels is removed. For example, emission intensity readings of the radioactive tracer data corresponding to heart chambers and/or surrounding blood vessels are removed).
Regarding claim 11,
Ben-Haim further discloses wherein the imaging data further comprises data representative of tissue structure in the region, and the correcting for tissue density comprises identifying sub-regions of reduced tissue density in the region using the data representative of tissue structure ([0513] which discloses the noise is removed from the functional data based on the corresponding anatomical image (e.g., after image registration). Optionally, emission intensity readings associated with noise within blood (or other fluid) filled chambers and/or vessels is removed. For example, emission intensity readings of the radioactive tracer data corresponding to heart chambers and/or surrounding blood vessels are removed and [0528] which discloses the anatomical images are processed to generate the image mask corresponding to dimensions of at least one internal body part, for example, the walls of the chambers of the heart and [0529] which discloses the image masks are selected and/or defined for tissue surrounding a hollow chamber, for example, the image masks are defined based on the shape of the heart chamber walls and do not include the hollow region within the chambers, the image masks are based on the shape of the arterial wall and do not include the hollow region within the artery, the image masks are based on the shape of the bladder wall and do not include the hollow region within the bladder. It is noted that synaptic centers may exist within the tissues defined by the image masks, but may not exist within the hollow spaces (which may be filled with fluid such as blood, urine or other fluids). The image masks may include tissue surrounding the organ of interest. Examiner notes that the areas corresponding to the heart chamber or tissue surrounding the heart chamber are considered identifying sub-regions of reduced tissue density in the region using the data representative of the structure (i.e. the anatomical image)).
Regarding claim 12,
Ben-Haim further teaches wherein the data representative of tissue structure is obtained by one or more magnetic resonance imaging and ultrasound ([0032] which discloses the image of at least a portion of a body is obtained using an imaging modality selected from the group consisting of a positron emission tomography (PET) modality, a computerized tomography (CT) modality, a magnetic resonance imaging (MRI) modality and an ultrasound modality).
Regarding claim 13,
Ben-Haim further discloses wherein the data representative of tissue structure is obtained using x-rays ([0516] which discloses anatomical data and/or images are received from a CT thus obtained using x-rays), and a sub-region is identified as a sub-region of reduced tissue density if the attenuation of x-rays in the sub-region is below a predetermined threshold (Examiner notes that the sub-region is identified as a sub-region of reduced tissue intensity and would be identified in any case including if the attenuation of x-rays in the sub-region is below a predetermined threshold).
Regarding claim 14,
Ben-Haim further discloses wherein the correcting for tissue density comprises correcting the measure of marker signal based on a proportion of tissue in the region having reduced density ([0513] which discloses no nervous system activity is expected from inside the hollow chambers (containing blood). Noise may be received from areas corresponding to the inside of the heart chamber, even though no nervous system activity is expected. Optionally, the noise is removed from the functional data based on the corresponding anatomical image (e.g., after image registration). Optionally, emission intensity readings associated with noise within blood (or other fluid) filled chambers and/or vessels is removed. For example, emission intensity readings of the radioactive tracer data corresponding to heart chambers and/or surrounding blood vessels are removed and examiner notes that such correcting is necessarily based on a proportion of tissue in the region having reduced density (i.e. chambers/blood vessels)).
Regarding claim 16,
Ben-Haim further discloses wherein the measure of marker signal is an average marker signal in the region ([0540] the average functional activity (e.g., average radioactive tracer emission and/or concentration) is calculated)
Regarding claim 17,
Ben-Haim further discloses wherein the measure of the marker signal is normalized by a background marker signal corresponding to marker signal from unbound marker in blood ([0565] which discloses level of a radioactive tracer at a local region compared to an average value and/or a standard deviation across the organ volume, within the image mask space and/or relative to a predefined threshold. Where it is noted that the average value across the organ volume corresponds to all marker signals including any unbound marker in blood).
Regarding claim 18,
Ben-Haim further discloses wherein the background marker signal is identified from marker signal in a major blood vessel, optionally the aortic arch ([0565] which discloses level of a radioactive tracer (e.g., as described herein, optionally mIBG) at a local region is compared to an average value and/or standard deviation across the organ volume, within the image mask space and/or relative to a predefined threshold. [0160] which discloses nervous tissue include, without limitation, synaptic centers (as defined herein), ganglia, neural fibers, neural synapses, neural sub-systems (e.g., an autonomic sub-system (such as the sympathetic and the parasympathetic autonomic sub-systems), a peripheral sub system), and organ-specific nervous tissues, such as a carotid body, aortic arch, pulmonary, renal, splenic, hepatic, inferior mesenteric, superior mesenteric, muscular and/or penile nervous tissue and [0539] which discloses the generated image mask is correlated with the functional data for guiding the reconstruction of a functional image depicting the target nervous tissue.).
Regarding claim 19,
Ben-Haim wherein the background marker signal is an average marker signal in the major blood vessel ([0565] which discloses which discloses level of a radioactive tracer (e.g., as described herein, optionally mIBG) at a local region is compared to an average value and/or standard deviation across the organ volume, within the image mask space (thus when the image mask depicts the nervous tissue such as aortic arch [0160]) the background marker signal is an average marker signal therein).
Regarding claim 20,
Ben-Haim further discloses wherein the biological target comprises an immune and/or inflammatory signaling protein, for example a cytokine, a chemokine, a cell surface receptor, or an extra-cellular matrix component ([0225] which discloses the radiolabeled compound which selectively binds a target (e.g. a protein) and [0226] which discloses the radio-ligand selectively binds a target (e.g. a receptor, a molecular transporter) characteristic of certain cell types. See [0300] which discloses the radio-ligand selectively finds to M1 muscarinic receptors, M2 muscarinic receptors, or M3 muscarinic receptors).
Regarding claim 21,
Ben-Haim further discloses wherein the marker comprises a radioactive marker ([0171] which discloses a radioactive tracer)
Regarding claim 22,
Ben-Haim further discloses wherein the data representative of the distribution within the region of the marker is obtained using single-photon emission computed tomography SPECT or positron emission tomography ([0171] which discloses measuring radioactive emission (e.g., via single-photon emission computed tomography (SPECT) and/or positron emission tomography (PET)) of the radioactive tracer to obtain data describing a distribution of the radioactive tracer in the body, thereby imaging the radioactive tracer in the body (e.g., imaging a distribution of radioactive tracer in the body)).
Regarding claim 23,
Ben-Haim further discloses wherein the region of the body of the subject comprises an organ of the subject ([0635] which discloses the diagnosis comprises estimating an effect of an autonomic nervous system on an organ (e.g., an organ affected by a medical condition and/or disease described herein).
Regarding claim 24,
Ben-Haim further teaches wherein the imaging data comprises data representative of a distribution with the region of each of a plurality of markers administered to the subject prior to the imaging, wherein each of the plurality of markers binds to a different biological target ([0158] which discloses in some embodiments, at least two radioactive tracers (e.g., as described herein) which selectively bind to synapses are used. For example, the radioactive tracers may optionally bind to different synapse types (e.g., adrenergic vs. cholinergic, parasympathetic vs. sympathetic and [0183] which discloses In some embodiments according to any one of the aspects described herein, imaging is performed using more than one radioactive tracer. In some embodiments, two radioactive tracers are used (e.g., as described herein));
The processing of the imaging data comprises processing the imaging data to obtain a measure of marker signal for each of the plurality of markers (at least fig. 4 and [0508] which discloses the method according to fig. 4 may be used to detect different types of synaptic centers, at different locations in the body. Thus a person having ordinary skill in the art would have recognized that the processing of the imaging data is to obtain a measure of marker for each of the plurality of markers as disclosed in at least [0158] and [0183]. See also [0493] which discloses In some embodiments, sympathetic and parasympathetic synaptic centers may uptake different tracers, and can generate different images, for example, if a multi-energy imager is used to acquire radiation data);
The correcting of the measure of marker signal comprises correcting each of the measures of marker signal ([0035] which discloses further comprises removing data describing a presence of the radioactive tracer from anatomical regions that do not contain synaptic centers based on the anatomical data of the anatomical regions); and
The determining of the measure of the disease uses the plurality of corrected measures of marker ([0508] which discloses the method according to fig. 4 may be used to detect different types of synaptic centers, at different locations in the body. [0041] which discloses the method further comprises diagnosing a disease or disorder associated with an abnormal autonomic nervous system activity based on the imaging and [0571] which discloses the calculated results and/or reconstructed images are provided for presentation. For example, presented on a monitor to a physician. The calculated results may help in diagnosing the patient (e.g., as described herein) and/or in guiding treatment (e.g., as described herein) and [0151] which discloses emission of radioactive tracers in the body may be measured by nuclear imaging techniques (e.g., PET, SPECT), and the obtained data can be analyzed in a manner designed to identify the synaptic centers in an image, thereby revealing the distribution, location and/or activity the synaptic centers. The inventor has further envisioned that such information can be of great importance in the diagnosis and/or treatment of a wide variety of conditions associated with abnormal ANS activity. See also [0190] which discloses emission of radioactive tracers in the body may be measured by nuclear imaging techniques (e.g., PET, SPECT), and the obtained data can be analyzed in a manner designed to identify the synaptic centers in an image, thereby revealing the distribution, location and/or activity the synaptic centers. The inventor has further envisioned that such information can be of great importance in the diagnosis and/or treatment of a wide variety of conditions associated with abnormal ANS activity. See also [0201] and [0631]. Examiner thus notes that the determining of the measuring the disease uses the plurality of corrected measures of the marker signal when using two tracers for measuring multiple synaptic centers).
Regarding claim 31,
Ben-Haim further discloses wherein the background marker signal is identified from marker signal in a major blood vessel, optionally the aortic arch ([0565] which discloses level of a radioactive tracer (e.g., as described herein, optionally mIBG) at a local region is compared to an average value and/or standard deviation across the organ volume, within the image mask space and/or relative to a predefined threshold. [0160] which discloses nervous tissue include, without limitation, synaptic centers (as defined herein), ganglia, neural fibers, neural synapses, neural sub-systems (e.g., an autonomic sub-system (such as the sympathetic and the parasympathetic autonomic sub-systems), a peripheral sub system), and organ-specific nervous tissues, such as a carotid body, aortic arch, pulmonary, renal, splenic, hepatic, inferior mesenteric, superior mesenteric, muscular and/or penile nervous tissue and [0539] which discloses the generated image mask is correlated with the functional data for guiding the reconstruction of a functional image depicting the target nervous tissue.).
Regarding claim 32,
Ben-Haim further teaches wherein the data representative of tissue structure and the data representative of the distribution of the marker are measured with the body of the subject in different states and are measured at different times ([0622] which discloses the radioactive tracer data and anatomical data are obtained by measuring each radiolabeled agent (e.g., an I-123 labeled radioactive tracer and a Tc-99m labeled imaging agent) one after the other, for example, by first injecting the radioactive (e.g., I-123 labeled) tracer (e.g., I-123-mIBG), image the radioactive tracer, then inject Tc-99m imaging agent and image the imaging agent);
And the method further comprises aligning the data representative of tissue structure and the data representative of the distribution of the marker ([0525] which discloses optionally, at 4818, the functional images and the anatomical images are registered. Optionally, the images are registered based on alignment of the extracted anatomical regions of blocks 4804 and 4814. [0526] Optionally, the registration is performed to take into account the dynamics of an organ, for example, movement of the heart)
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 5-8 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Ben-Haim in view of Kang et al. (US 20120150048 A1), hereinafter Kang.
Regarding claim 5,
Ben-Haim teaches the elements of claim 4 as previously stated. Ben-Haim further teaches wherein the correcting for marker signal due to vascular flow comprises identifying at least one blood vessel (see [0513] which discloses functional data is collected from a body part that has regions where nervous system (e.g. ANS activity) is expected and regions where nervous system (e.g. ANS) activity is not expected. For example, during imaging of the heart, data denoting nervous system activity is expected from the heart wall and/or surrounding tissues, and no nervous system activity is expected from inside the hollow chambers (containing blood). Noise may be received from areas corresponding to the inside of the heart chamber, even though no nervous system activity is expected. Optionally, the noise is removed from the functional data based on the corresponding anatomical image (e.g., after image registration). Optionally, emission intensity readings associated with noise within blood (or other fluid) filled chambers and/or vessels is removed. For example, emission intensity readings of the radioactive tracer data corresponding to heart chambers and/or surrounding blood vessels are removed. See also [0590] which discloses providing data regarding the location of at least one blood vessel)
Ben-Haim fails to explicitly teach determining a vascular density in the region
Kang, in a similar field of endeavor involving medical imaging, teaches determining a vascular density in a region of a body ([0208] which discloses the Poker chip representation may be used to compute vessel density)
It would have been obvious to a person having ordinary skill in the art before the effective filing date to have modified Ben-Haim to include determining a vascular density as taught by Kang in order to provide a vessel geometry capable of distinguishing a boundary of a portion of the vasculature. Such a modification would allow for facilitation of boundary identification of the vasculature (Kang [0208]) which would enhance the correcting of the measure of the marker signal of Ben-Haim by ensuring that the removal of noise is contained within the boundaries of the vasculature accordingly as desired by Ben-Haim in at least [0513].
Regarding claim 6,
Ben-Haim, as modified, teaches the elements of claim 5 as previously stated. Kang, as applied to claim 6 above, further teaches wherein the determining of the vascular density comprises determining the total volume of blood vessels in the region ([0010] which discloses the vasculature (e.g., measured by total vascular volume, total vascular density, total vascular surface, etc., or any other metric, or any combination thereof within a 2D or 3D region) may be provided as a value or an average for a region of interest. See also [0013] and [0303] which discloses total vessel volume density (number of voxels belonging to a vessel within a given volume).
Regarding claim 7,
Ben-Haim teaches the elements of claim 5 as previously stated. Ben-Haim further teaches wherein the image data further comprises data representative of a tissue structure in the region (at least fig. 4 (4802) and corresponding disclosure in at least [0512] and [0513] and/or least fig. 4 (4808) and corresponding disclosure in at least [0516]), and the identifying blood vessels in the region using the data representative of tissue structure ([0514] which discloses optionally, the tissue (which may contain nervous tissue) is separated from hollow spaces (which do not contain nervous tissue, but may contain fluid). For example, to image the heart, the wall of the left ventricle (LV) may be extracted. Alternatively or additionally, the hollow space within the LV may be extracted. It is noted that the extracted region may be a layer of tissue, such as the tissue layers forming the LV wall, instead of, for example, the LV including the hollow chamber inside the LV. For example, to image the kidney, the walls of the renal artery may be extracted and/or the inside of the artery may be extracted. When imaging other organs, dominant portions of the organ may be selected. [0513] which discloses Optionally, the noise is removed from the functional data based on the corresponding anatomical image (e.g., after image registration) and [0590] which discloses some embodiments, an imaging agent is localized primarily to the bloodstream (e.g., following injection of the imaging agent into the bloodstream), thereby providing data regarding the location of at least one blood vessel and/or a blood-rich organ (e.g., heart))
Kang further teaches wherein the determining of the vascular density comprises identifying blood vessels in the region using data representative of tissue structure ([0207] which discloses In act 1410, regions of the geometric representation are evaluated and those regions that meet a selected criteria are identified. The criteria may be any measure(s) corresponding to one or more features of the geometric representation of the vascular network and [0206] which discloses the geometric representation may be obtained from images or generated by other means, as the aspects of the invention are not limited in this respect).
Examiner therefore notes that in the modified system determining the vascular density comprises identifying blood vessels in the region using the data representative of tissue structure.
Regarding claim 8,
Ben-Haim further teaches wherein the data representative of tissue structure (4808) is obtained by one or more of magnetic resonance imaging and ultrasound ([0116] which discloses the anatomical data is generated by an imaging modality selected from a group consisting of a positron emission tomography (PET) modality, a computerized tomography (CT) modality, a magnetic resonance imaging (MRI) modality, and an ultrasound modality).
Kang, as applied to claim 7 above, also teaches wherein the data representative of tissue structure is obtained by one or more of magnetic resonance imaging and ultrasound ([0091])
Regarding claim 25,
Ben-Haim further teaches wherein the data representative of tissue structure and the data representative of the distribution of the marker have different volume segmentations ([0527] which discloses one or more image masks are generated based on the anatomical image and/or data. Optionally, the image masks direct processing and/or visual display of the nerve tissue to specific locations of the image located within the image masks. For example, synaptic centers are displayed and/or processed within the volume of an applied image mask. Synaptic centers outside the volume of the image mask may optionally not be processed and/or displayed. Synaptic centers outside the volume of the image mask may optionally be processed and/or displayed differently than those synaptic centers inside the image mask and [0530] which discloses The image masks are defined, for example, based on image segmentation (e.g., according to the ability of the system to segment the image), based on tissue types (e.g., muscle vs. connective tissue), based on organ size, based on sub-structures within the organ (e.g., heart chambers, liver lobes, kidney parts), or other methods, where the original functional data (i.e. data representative of the distribution of the marker) is not considered to have a volume segmentation and thus is different) are measured with the body of the subject in different states and are measured at different times ([0622] which discloses the radioactive tracer data and anatomical data are obtained by measuring each radiolabeled agent (e.g., an I-123 labeled radioactive tracer and a Tc-99m labeled imaging agent) one after the other, for example, by first injecting the radioactive (e.g., I-123 labeled) tracer (e.g., I-123-mIBG), image the radioactive tracer, then inject Tc-99m imaging agent and image the imaging agent);
And the method further comprises aligning the data representative of tissue structure and the data representative of the distribution of the marker ([0525] which discloses optionally, at 4818, the functional images and the anatomical images are registered. Optionally, the images are registered based on alignment of the extracted anatomical regions of blocks 4804 and 4814. [0526] Optionally, the registration is performed to take into account the dynamics of an organ, for example, movement of the heart. See also [0501] which discloses the anatomical information, in the form of the mask, is used for guiding the processing to certain regions of the functional image and [0539] which discloses the generated image mask is correlated with the functional data for guiding the reconstruction of a functional image depicting the target nervous tissue.).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Ben-Haim.
Regarding claim 15,
Ben-Haim teaches the elements of claim 14 as previously stated. Ben-Haim further teaches wherein the correction of the measure of the marker signal based on a proportion of tissue in the region having reduced density is determined using measurements of marker signal of a normal patient data set ([0564]). Examiner notes that it is understood that the normal patient data set includes at least one individual (i.e. a normal patient) having varying portions of tissue in a region having reduced density.
Ben-Haim fails to explicitly teach a plurality of individuals.
Nonetheless, it would have been obvious to a person having ordinary skill in the art before the effective filing date to have modified the normal patient data set to be of plurality of individuals (which would have varying portions of tissue in a region having reduced density) in order to provide a normalization which is with respect to a number of individuals (e.g. an average value of marker signal) such that the normal patient data is not merely with respect to one normal individual which may not be reflective of the general population. Such a modification would enhance the accuracy of the normalization of Ben-Haim by ensuring that the normal patient data set reflects a plurality of normal patients.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Ben-Haim in view of Kang or in the alternative Ben-Haim in view of Kang and further in view of Schaefferkoetter (US 20230260141 A1), hereinafter Shaefferkoetter.
Regarding claim 27,
Ben-Haim teaches the elements of claim 25 as previously stated. Ben-Haim further teaches wherein the alignment comprises deforming the data representative of tissue structure to match the data representative of the distribution of the marker ([0515] which discloses at 4806, one or more registration cues are extracted from the image (i.e. functional modality image of 4802) and [0524] which discloses at 4816 one or more registration cues are extracted from the image (i.e. anatomical) and [0525] which discloses the functional images are registered based on alignment of the extracted anatomical regions of blocks 4804 and 4814. Examiner notes that such alignment of extracted anatomical regions is considered a deformation in its broadest reasonable interpretation. Additionally/alternatively [0527] which discloses one or more image masks are generated based on the anatomical image and/or data. Optionally, the image masks direct processing and/or visual display of the nerve tissue to specific locations of the image located within the image masks. For example, synaptic centers are displayed and/or processed within the volume of an applied image mask. Synaptic centers outside the volume of the image mask may optionally not be processed and/or displayed. Synaptic centers outside the volume of the image mask may optionally be processed and/or displayed differently than those synaptic centers inside the image mask. [0539] which discloses the generated image mask is correlated with the functional data for guiding the reconstruction of a functional image depicting the target nervous tissue. Where generation of the image mask is considered a deformation of the data representing the tissue structure and is used to match the data representing the distribution of the marker).
However, if it is believed that such alignment of features and generation of an image mask do not constitute deforming the data representative of the tissue structure, Schaefferkoetter, in a similar field of endeavor involving anatomical and function imaging, teaches deforming data representing a tissue structure to match data representing a distribution of a maker ([0024] which discloses the deformation field may be represented by a dense finely sampled displacement matrix that can be used to warp (thus deform) the anatomical image to match the spatial distribution of the functional tracer and [0041]).
It would have been obvious to a person having ordinary skill in the art before the effective filing date to have modified been Ben-Haim, as currently modified, to include deforming the anatomical image as taught by Schaeffer in order to accurately correct spatial alignment at every point in the field of view. Such a modification provides for a less tedious, less time-consuming, and more accurate alignment between the tissue structure data and the marker data (Schaefferkoetter [0022]). Such a modification would further improve misregistration artifacts at various sites such that morphological boundaries are aligned with the distribution of the tracer data which would be beneficial for removing any misalignment artifacts due to gross involuntary motion (Schaefferkoetter [0026]), thereby enhancing the accuracy of the alignment between data sets. Furthermore, such a modification amounts to merely a simple substitution of one known alignment method for another yielding predictable results with respect to multi-modality image alignment thereby rendering the claim obvious (MPEP 2143).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lee (EP 2693401 A1) teaches correcting a measure of a marker signal ([0089]-[0090]) and determining a measure of a disease using the corrected measure of marker signal ([0041] which discloses the vessel segmentation method may provide a simulation based, high-precision, personalized medical service including high-precision, computerized diagnosis, treatment, and prediction)
Solf (US 20110299747 A1) teaches correcting a measure of a marker signal and normalizing a marker signal with respect to background marker signal in at least [0097].
Jerebko (US 20110229007 A1) teaches differentiating denser tissue from less dense tissue using attenuation of X-rays in at least [0039]
Kubassova (US 20160035091 A1) teaches correcting a measure of a marker signal (at least figs 1 and 2 (1-2) and corresponding disclosure in at least [0077] and [0106]) and determining a measure of a disease using the corrected measure of the marker (at least fig. s 1 and 2 (4 and 4A) and corresponding disclosure in at least [0106])
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BROOKE L KLEIN whose telephone number is (571)270-5204. The examiner can normally be reached Mon-Fri 7:30-4.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Kozak can be reached at 5712700552. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BROOKE LYN KLEIN/Primary Examiner, Art Unit 3797
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