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 .
Response to Amendment
The amendment filed 08/17/2026 has been entered. Claim 22 is added, claims 5-6 and 13-14 are cancelled, and claims 2-4, 7-12, and 15-22 remain pending in the application. Applicant’s amendments to the Claims have overcome each and every objection and 112(b) rejections previously set forth in the Non-Final Office Action mailed 05/15/2026.
The applicant submitted a terminal disclaimer over U.S. Patent No. 12370383 on 08/17/2026, and the terminal disclaimer is acknowledged and approved; thus, the Double Patenting Rejection is withdrawn.
Response to Arguments
Applicant’s arguments filed 08/17/2026 with respect to claim(s) 2, 11, and 18 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 2-3, 7-9, 11, 15-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Foley et al. (US 20110040171 A1, published February 17, 2011) in view of Tracey et al. (US 20200046992 A1, published February 13, 2020) and Behar et al. (US 20150223877 A1, August 13, 2015), hereinafter referred to as Behar, respectively.
Regarding claims 2, and similarly for claims 11 and 18, Foley teaches a system (Fig. 5A), comprising:
an ultrasound probe configured to apply focused ultrasound energy to a region of interest (see para. 0084 "In FIG. 5A, a block diagram is illustrated for a system 200 that enables imaging of a target area [region of interest] in 3D and storing of the locations of treatment sites to which the HIFU [high intensity focused ultrasound] therapy has been administered in the 3D image as a HIFU therapy session proceeds combined imaging and HIFU therapy probe 212..."); and
a controller (see para. 0084 "An ultrasound imaging machine 216 provides the synchronization signal to a HIFU control and electrical energy generating system 218 [controller]...") configured to:
acquire image data of the subject from the ultrasound probe operating in an imaging mode (see para. 0084 "In FIG. 5A, a block diagram is illustrated for a system 200that enables imaging of a target area in 3D [imaging mode] and storing of the locations of treatment sites to which the HIFU therapy has been administered in the 3D image as a HIFU therapy session proceeds.");
identify the region of interest in the image data, wherein the region of interest is selected based on anatomical landmarks identified in the image data (see para. 0084 "With information derived from calibrating system 200 with the imaging probe, the position of the target area [identify ROI in image data] and the HIFU transducer focal point can be related to a 3D spatial point, so long as magnetic field sensor 206 is within the range of the magnetic field produced by magnetic field generator 208. 3D image data processor and display 202 also receive ultrasound image information from an ultrasound imaging machine 216 through image acquisition section 204. It uses this information to develop and display 3D information."),
control the ultrasound probe to apply the focused ultrasound energy to the region of interest (see para. 0084 "In FIG. 5A, a block diagram is illustrated for a system 200that enables imaging of a target area in 3D and storing of the locations of treatment sites to which the HIFU therapy has been administered in the 3D image as a HIFU therapy session proceeds An ultrasound imaging machine 216 provides the synchronization signal to a HIFU control and electrical energy generating system 218, as discussed above.").
Foley teaches applying focused ultrasound energy to a region of interest, but does not explicitly teach applying ultrasound energy to a region of interest comprising at least a portion of a celiac plexus in a subject to treat inflammatory bowel diseases in the subject.
Whereas, Tracey, in an analogous field of endeavor, teaches applying ultrasound energy to a region of interest comprising at least a portion of a celiac plexus in a subject to treat inflammatory bowel diseases in the subject (Fig. 1; see para. 0039 "Contemplated modulation targets may include local sites within a mesenteric plexus controlling inflammation and macrophage function in gut." Where mesenteric plexus inherently includes celiac plexus; see para. 0040 "The depicted system includes a pulse generator 14 coupled to an energy application device 12 (e.g., an ultrasound transducer, or a magnetic coil).'").
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified applying focused ultrasound energy to a region of interest, as disclosed in Foley, by applying ultrasound energy to a region of interest comprising at least a portion of a celiac plexus in a subject to treat inflammatory bowel diseases in the subject, as disclosed in Tracey. One of ordinary skill in the art would have been motivated to make this modification in order to target internal tissues or organs that are difficult to access using electrical stimulation techniques, as taught in Tracey (see para. 0039).
Foley in view of Tracey teaches the region of interest is selected based on anatomical landmarks identified in the image data, but does not explicitly teach the anatomical landmarks comprise a junction of at least one of a hepatic artery or splenic artery with an abdominal aorta.
Whereas, Behar, in an analogous field of endeavor, teaches wherein the anatomical landmarks comprise a junction of at least one of a hepatic artery or splenic artery with an abdominal aorta (junction is the celiac trunk, so identify celiac plexus based on celiac trunk; see para. 0169 – “The location of the neural structure may be estimated based on relative location to structures visible on images, for example, the location of the celiac ganglion may be estimated to be at the junction of the celiac artery and the aorta.”; see para. 0175 – “For example, image recognition is performed based on ultrasound images containing one or more of: the aorta, the celiac ganglion (or other target ganglia), branches of the aorta, branches of the celiac artery, or other anatomical landmarks. The location of the target neural structure may be estimated based on the identified structural landmarks within the images.” where the junction of a hepatic artery or splenic artery with an abdominal aorta is the celiac trunk, so it is possible to identify the celiac plexus based on the celiac trunk).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the region of interest is selected based on anatomical landmarks identified in the image data, as disclosed in Foley in view of Tracey, by having the anatomical landmarks comprise a junction of at least one of a hepatic artery or splenic artery with an abdominal aorta, as disclosed in Behar. One of ordinary skill in the art would have been motivated to make this modification in order to perform beam adjustment during treatment, based on images acquired during treatment and/or based on images acquired before treatment with estimated compensation for motion, as taught in Behar (see para. 0175).
Furthermore, regarding claims 3 and 19, Tracey further teaches wherein the region of interest comprises a peripheral ganglion, a superior mesenteric ganglion, celiac ganglion, inferior mesenteric ganglion, or dorsal root ganglion, of the subject (Fig. 1; see para. 0039 "Contemplated modulation targets may include.. local sites within a mesenteric plexus controlling inflammation and macrophage function in gut." Where mesenteric plexus inherently includes peripheral ganglion, a superior mesenteric ganglion, celiac ganglion, inferior mesenteric ganglion, and dorsal root ganglion).
Furthermore, regarding claim 7, Foley further teaches performing one or more assessments to determine a response to the applied focused ultrasound energy; and adjusting one or more modulation parameters of the ultrasound probe based on the one or more assessments (see para. 0092 “…(2) the focal point of the HIFU wave can be observed in the image due to changes in the echogenicity of the tissue at the focal point, which are apparent in the images of the target area, providing an instant feedback [assessment] that can enable a clinician to adjust the focal point [adjust modulation parameter] onto a desired treatment site...").
Furthermore, regarding claim 8, Foley further teaches wherein the one or more assessments comprises determining a change in concentration of one or more molecules relative to a baseline concentration, a change in a disease activity index (DAI) score relative to a baseline DAI score, a change in a stool characteristic relative to a baseline stool characteristic, or a combination thereof (see para. 0105 0106 "In a decision block 400, the treatment site and/or patient are evaluated to determine whether the desired therapeutic effect has been achieved Such an evaluation may also be based on monitoring the patient's physiological responses. For example, if HIFU therapy is being used to alleviate pain, the patient can be questioned to determine if the level of pain has decreased [a change in a disease activity index (DAI) score relative to a baseline DAI score].").
Furthermore, regarding claim 9, Foley further teaches wherein the one or more modulation parameters comprise pulse repetition frequency, pulse width, pulse shape, stimulation pattern, amplitude, frequency, or a combination thereof (see para. 0153 "Specifying different frequencies, focal widths, focal lengths, diameters, and acoustic lenses, the resulting HIFU beam patterns will be determined using both theoretical analysis and computer simulation. The parameters of the HIFU transducer chosen will be those that produce the most optimal beam pattern. Output intensities preferably will range from about 50-2000 W/cm².")
Furthermore, regarding claim 15, Tracey further teaches applying the focused ultrasound energy to cause a change in concentration of one or more molecules of interest in the subject relative to a baseline concentration; and detecting the change in concentration of the one or more molecules of interest (see para. 0050 "In one embodiment, the imaging device 38 may be integrated with the energy application device 12 such that different ultrasound energies are applied for targeting and subsequently neuromodulation."; see para. 0059 "The successful modulation may be assessed via a measured clinical outcome, such as...a change in concentration of released molecules e.g., relative to the baseline concentration before the neuromodulation).").
Furthermore, regarding claim 16, Tracey further teaches wherein the one or more molecules of interest comprises one or more of interleukin (IL)-1, tumor necrosis factor (TNF-a), or interferon- gamma (IFN-y) (see para. 0067 "The cytokine can be, for example, one or more of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1)...").
Furthermore, regarding claim 17, Foley further teaches wherein applying the focused ultrasound energy to the region of interest results in an improvement of a disease activity index (DAI) score of the subject relative to a baseline DAI score, wherein the baseline DAI score is determined prior to the applying (see para. 0105-0106 "In a decision block 400, the treatment site and/or patient are evaluated to determine whether the desired therapeutic effect has been achieved Such an evaluation may also be based on monitoring the patient's physiological responses. For example, if HIFU therapy is being used to alleviate pain, the patient can be questioned to determine if the level of pain has decreased [improvement of DAI score relative to a baseline DAI score].").
Furthermore, regarding claim 20, Foley further teaches applying the focused ultrasound energy as an adjuvant for pharmaceutical or surgical interventions (see para.0010 "Most current treatment options for severe spasticity are primarily used for patients with no preserved voluntary function, because these treatments (BTX, chemical nerve blocks, and the extreme case of nerve transection surgeries) have a non-selective effect on the local nerves and/or muscles. The result will be suppression of voluntary function in the treated region, either temporarily or permanently. Another treatment option, intrathecal baclofen infusion via a subcutaneous pump, has been used to treat patients who retain limited voluntary function.").
Furthermore, regarding claim 22, Behar further teaches wherein the region of interest is spaced 1-10 mm apart from the junction (see para. 0175 – “For example, image recognition is performed based on ultrasound images containing one or more of: the aorta, the celiac ganglion (or other target ganglia), branches of the aorta, branches of the celiac artery, or other anatomical landmarks. The location of the target neural structure may be estimated based on the identified structural landmarks within the images.” where the junction of a hepatic artery or splenic artery with an abdominal aorta is the celiac trunk, so it is possible to identify the celiac plexus based on the celiac trunk. The distance between the ROI (celiac plexus) and junction (celiac trunk) is inherent and known in the art (within 10mm)).
The motivation for claims 3, 15-16, 19, and 22 was shown previously in claim 1, 11, and 18.
Claims 4 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Foley in view of Tracey and Behar, as applied to claims 2 and 11 above, and in further view of Bright et al. (US 20200085809 A1, published March 19, 2020), hereinafter referred to as Bright.
Regarding claims 4 and 12, Foley in view of Tracey and Behar teaches all of the elements disclosed in claim 2 and 11 above.
Foley in view of Tracey and Behar teaches imaging and applying energy to a region of interest including celiac plexus, and it is inherent and known in the art that the vagus nerve is associated with and proximal to the celiac plexus, but does not explicitly teach where the region of interest includes an anterior vagal trunk.
Whereas, Bright, in an analogous field of endeavor, teaches wherein the region of interest comprises an anterior vagal trunk proximal to a superior mesenteric ganglion and a left and right celiac ganglion (Fig. 2A; see para. 0055 "Vagal afferent signals terminate in the celiac ganglion and interact with the adrenergic nerve cell bodies that project distally via the splenic nerve. Sympathetic pre-ganglionic nerves also connect at the celiac superior mesenteric plexus ganglion and innervate the spleen, liver, stomach, pancreas, adrenal glands and intestines.").
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified imaging and applying energy to a region of interest including celiac plexus, as disclosed in Foley in view of Tracey and Behar, by having the region of interest include an anterior vagal trunk, as disclosed in Bright. One of ordinary skill in the art would have been motivated to make this modification in order to trigger the splenic CAP (cholinergic anti-inflammatory pathway) mechanism, attenuate PIC (Pro-inflammatory cytokines) levels and treat sepsis and other inflammatory disorders, as taught in Bright (see para. 0072).
Claims 10 and 21 are rejected under35U.S.C. 103 as being unpatentable over Foley in view of Tracey and Behar, as applied to claim 2 and 18 above, and in further view of Errico et al. (US 20200230408 A1, published July 23, 2020 with a priority date of December 21, 2018), hereinafter referred to as Errico.
Regarding claim 10, Foley in view of Tracey and Behar teaches all of the elements disclosed in claim 2 above.
Foley in view of Tracey and Behar teaches applying the focused ultrasound energy to the region of interest to stimulate an anti-inflammatory response (Tracey: see para. 0082 "The invention further provides a method of treating an infection and/or an inflammation in a subject comprising applying ultrasound and/or electromagnetic stimulation to one or more of lymph nodes and/or spleen of the subject in an amount effective to increase the number of lymphocytes in a tissue and/or decrease serum levels of one or more proinflammatory cytokines in a subject, thereby treating an infection and/or an inflammation in the subject..."), but does not explicitly teach causing enteric cholinergic anti-inflammatory pathway(CAP) stimulation.
Whereas, Errico, in an analogous field of endeavor, teaches wherein applying the focused ultrasound energy to the region of interest causes enteric cholinergic anti-inflammatory pathway (CAP) stimulation (see para. 0216 "The CAP is believed to be the efferent vagus nerve-based arm of the inflammatory reflex, mediated through vagal efferent fibers that synapse onto enteric neurons, which release acetylcholine (Ach) at the synaptic junction with macrophages.").
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified applying the focused ultrasound energy to the region of interest to stimulate an anti-inflammatory response, as disclosed in Foley in view of Tracey and Behar, by also causing enteric cholinergic anti-inflammatory pathway (CAP) stimulation, as disclosed in Errico. One of ordinary skill in the art would have been motivated to make this modification in order to decrease the production of inflammatory cytokines and consequently mitigate the inflammatory response, as taught in Errico (see para. 0216).
Furthermore, regarding claim 21, Errico further teaches wherein applying the focused ultrasound energy to the region of interest does not cause splenic CAP stimulation or causes relatively less splenic CAP stimulation relative to enteric CAP stimulation (see para. 0216 "The CAP is believed to be the efferent vagus nerve-based arm of the inflammatory reflex, mediated through vagal efferent fibers that synapse onto enteric neurons, which release acetylcholine (Ach) at the synaptic junction with macrophages.").
The motivation for claim 21 was shown previously in claim 10.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Sobotka et al. (US 20180117363 A1, published May 3, 2018) discloses treating the splenic artery at its trunk, where it meets the celiac artery, and it is possible to achieve the desired denervation by targeting the celiac artery, but in such a case one would need to demonstrate that modulating the nerves did not cause significant adverse consequences in other structures receiving innervation from nerves proximate to the celiac trunk.
Pilcher et al. (US 20170312021 A1, published November 2, 2017) discloses treatment for a patient diagnosed with pancreatic cancer can include modulating nerves (e.g., celiac plexus) associated with a target vessel (e.g., a celiac artery).
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 Nyrobi Celestine whose telephone number is 571-272-0129. The examiner can normally be reached on Monday - Thursday, 7:00AM - 5:00PM EST.
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/N.C./Examiner, Art Unit 3798
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