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
This office action is responsive to the amendment filed on 07/25/2025. As directed by the amendment: no amendment was made to the claims. Thus, claims 2 – 16, and 21 – 26 are presently pending in this application.
Response to Arguments
Applicant’s arguments with respect to claim(s) 2 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. Specifically, Applicant’s arguments and remarks as filed on 07/25/2025 are directed toward Coe (U.S. 9,265,575), which is not relied on in the new ground of rejections in this Office Action.
See rejections below for more details.
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 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.
Claim(s) 2, 6 – 9, 11 – 13, and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kelly (U.S. 2014/0088581) in view of Rajagopalan (U.S. 11,185,367).
Regarding claim 2, Kelly teaches (see FIG. 4): a method of treating hepatic insulin resistance in a patient (“A method of ablationally treating tissue at a target area in a gastrointestinal tract of a patient with a pathophysiological metabolic condition,” see Abstract and Claim 69), comprising: determining a first level of a pathophysiological metabolic condition of the patient (i.e., high levels of serum insulin, which indicates the pathological condition of insulin resistance, see p. [0109]); and performing an intestinal treatment procedure comprising ablating mucosal tissue of the patient’s duodenum (“delivering radiofrequency energy from a non-penetrating electrode pattern on an ablation structure to the tissue surface within the target area, the target area being a contiguous radial portion of the gastrointestinal tract,” see p. [0009]; “Energy is delivered inwardly from the surface, thus with modulated increases in energy delivery, the level of ablation can be controlled such that, for example, the ablated tissue may consist only of tissue in the epithelial layer, or it may consist of tissue in the epithelial layer and the lamina propria layers, or it may consist of tissue in the epithelial, lamina propria and muscularis mucosal layers, or it may consist of tissue in the epithelial, lamina propria, muscularis mucosa, and submucosal layers, or it may consist of tissue in the epithelial layer, the lamina propria, the muscularis mucosae, the submucosa, and the muscularis propria layers” see p. [0129]) under conditions which achieves a reduction in the pathophysiological metabolic condition (“Any reduction in serum insulin levels that are significant and repeatable compared to insulin levels prior to treatment per embodiments of this invention would be considered an indication of therapeutic benefit,” see p. [0109]); wherein the target mucosal lies distal to the patient’s ampulla of Vater (Figure 2D shows the ablative device working within the jejunum 11 which is distal to the duodenum 10 where the patient’s ampulla of Vater is located); and wherein the intestinal treatment procedure reduces insulin resistance (“Any reduction in the level of insulin resistance, as measured these methods or similar methods, that is significant and reproducible in a patient after ablational therapy as provided by embodiments of the invention may be considered an indication of therapeutic benefit,” see p. [0109]).
Examiner notes that Kelly suggests that the target tissue can be in the duodenum as discussed in paragraph [0017] but does not specify the precise target location within the duodenum.
Kelly also does not explicitly disclose: determining a first level of an insulin sensitivity marker of the patient, and performing an intestinal treatment procedure comprising ablating target tissue comprising a mucosal layer of the selected patient’s duodenum to achieve a reduction in the insulin sensitivity marker, wherein the target tissue lies proximal to the patient’s ligament of Treitz and within 5 cm distal to the patient’s ampulla of Vater.
However, Kelly discloses several methods for measuring insulin resistance in a patient prior to performing an intestinal treatment procedure, including the hyperinsulinemic euglycemic clamp, the modified insulin suppression test, the homeostatic model assessment, and the quantitative insulin sensitivity check index methods (see p. [0109]), which are methods well known in the art that use a variety of biomarkers (i.e., steady- state and/or fasting blood glucose and/or insulin levels) to indicate the insulin sensitivity level of a patient.
One of ordinary skill in the art will note that insulin sensitivity and insulin resistance are inversely related, meaning a measured change in an insulin sensitivity biomarker level is necessarily indicative of a change in insulin resistance of a patient. Thus, the Examiner finds that Kelly necessarily teaches the method step of determining a first level of an insulin sensitivity marker of the patient, and performing an intestinal treatment procedure [[under conditions]] which achieve a reduction in the insulin sensitivity marker. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use one of the methods for measuring insulin resistance taught by Kelly to determine a first level of an insulin sensitivity biomarker of the patient to establish a baseline level / “control” before an intestinal treatment procedure, in order to compare the insulin sensitivity biomarker baseline level to an insulin sensitivity biomarker level post-operation, wherein a reduction in the insulin sensitivity biomarker level is indicative of a desired reduction in insulin resistance after an intestinal treatment procedure. The method step of comparing an insulin sensitivity biomarker level to its baseline level is taught by the methods disclosed by Kelly and listed above and would be obvious to one of ordinary skill in the art to perform for the purpose of preventing over-treatment (i.e., over-ablation) of a target tissue area.
Rajagopalan teaches a method similar to Kelly, further including that tissue targeted in the Rajagopalan reference lies proximal to the patient’s ligament of Treitz and within 5 cm distal to the patient’s ampulla of Vater, specifically a full tissue treatment comprises multiple sequential ablations (usually about 5) performed from immediately beyond the ampulla of Vater to locations proximate (e.g. proximal to) the ligament of Treitz (Col. 170, lines 64 – 67). It would have been obvious for one having ordinary skill in the art at the time the invention was made to make the target tissue lie within 5 cm distal to the patient’s ampulla of Vater, since such modification is the result of choosing from a finite number of identified, predictable solutions (choosing the target tissues within a finite distance from the area immediately beyond the ampulla of Vater) with a reasonable expectation of success. MPEP 2143 (E).
Further, combining the features of Rajagopalan with the method of Kelly would have predictably led to elimination or at least reduction in the use of insulin; improved glycemic control; reduced insulin-associated hypoglycemia, weight gain and/or cardiovascular risks; and/or improved quality of life (Rajagopalan, Col. 172, lines 9 – 12).
Examiner notes the limitation “the intestinal treatment procedure reduces hepatic insulin resistance”. Since the combination of Kelly and Rajagopalan discloses every features of claim 2, the claimed property of “the intestinal treatment procedure reduces hepatic insulin resistance is presumed to be inherent. (MPEP 2112.01 (I))
Further, since the combined system of Kelly and Rajagopalan performs the steps as recited in claim 2 during normal operation, the combined disclosure of Kelly and Rajagopalan anticipates the claimed process of claim 2. (MPEP 2112.02 (I))
Regarding claim 6, Kelly further teaches that the intestinal treatment procedure comprises inserting a treatment device into the patient (“The method continues with insertion of the instrument and the movement of the ablational structure to the locale of the target tissue to be ablated,” see p. [0100]).
Regarding claim 7, Kelly further teaches that the intestinal treatment procedure further comprises expanding submucosa of the intestine (see p. [0117] discussing how the method includes expanding a balloon to occlude the vasculature of the submucosa of the intestine; “The pressure to be exerted to do so should therefore be greater than the pressure exerted by such vessels”; the Examiner notes this teaching indicates at least the inner portion of the submucosa layer must expand).
Regarding claim 8, Kelly further teaches that the ablative procedure comprises delivering an ablative fluid to the treatment device (“the distending or expandable balloon member may have means for carrying or transmitting a heatable fluid within one or more portions of the member so that the thermal energy of the heatable fluid may be used as the ablation energy source,” see p. [0112]).
Regarding claim 9, Kelly further teaches that the treatment device comprises an expandable balloon, and wherein the ablative fluid is delivered to the expandable balloon (“...the inflation member is a balloon. Inflation of the inflation member 105 can be achieved through the inflation line 113 using, for example, controlled delivery of fluid or gas expansion medium,” see p. [0155]; see also p. [0112]).
Regarding claim 11, Kelly further teaches that the ablative procedure further comprises delivering a neutralizing fluid to the treatment device to cool the mucosa of the intestine (see p. [0013] discussing layers of GI tract affected by ablation procedure—includes epithelial layer, which is part of the mucosa layer of the intestine).
Kelly teaches “...the ablation system may include an apparatus to circulate the heating/cool medium from outside the patient to the heating/cooling balloon or other element and then back outside the patient again,” see p. [0148], wherein a cooling medium (i.e. a neutralizing fluid) is delivered to the treatment device to cool the mucosa of the intestine, see p. [0092], [0110], and [0147-0148].
Regarding claims 12-13, the combined method of Kelly and Rajagopalan discloses the claimed invention substantially as claimed, as set forth above in claim 11.
However, the combined method of Kelly and Rajagopalan does not explicitly disclose: the neutralizing fluid being delivered to the treatment device after the ablative fluid is delivered or before and after the ablative fluid is delivered.
The Examiner notes that since the claim does not structurally limit the ablation system to have any specific limitations, structures, or elements to thereby deliver a cooling fluid to the treatment device to cool the target tissue and then subsequently deliver a heated fluid to the expandable treatment element to ablate the target tissue, by having an apparatus connected to the ablation system to circulate the heating/cooling medium from outside the patient to the treatment device and then back outside the patient again, see p. [0148], the device of Kelly is structurally arranged and configured for an operator to provide any means of fluid cooling and/or heating to the device in any order required by the procedure.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the apparatus connected to the ablation system to deliver a neutralizing or cooling fluid to the treatment device before and after the ablative fluid is delivered, or in any order required by the ablation procedure, for the purpose of making the ablation system safer for the patient and preventing over-ablation of the target tissue area.
Regarding claim 21, Kelly teaches that the intestinal treatment procedure comprises treating at least 6cm of an axial length of duodenal mucosa.
Kelly teaches (“The length of the electrode member associated with the balloon member can vary in length from 1 to 10 cm,” see p. [0115]). Additionally, Kelly teaches that the length of the gastrointestinal tract surface that requires ablation corresponds to the length of the electrode member that will be chosen for ablation in a 1:1 ratio. Therefore, Kelly teaches treating at least 6cm of an axial length of the duodenal mucosa (see p. [0017-0018] discussing the ablation target area is in the epithelial layer [i.e., the mucosa layer] of the small intestine, such as in the duodenum).
Claim(s) 3 – 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kelly (U.S. 2014/0088581) in view of Rajagopalan (U.S. 11,185,367), and in view of Walter et al. (“α-Hydroxybutyrate Is an Early Biomarker of Insulin Resistance and Glucose Intolerance in a Nondiabetic Population,” 2010).
Regarding claim 3, the combined method of Kelly, and Rajagopalan discloses the claimed invention substantially as claimed, as set forth above in claim 2.
However, the combined method of Kelly and Rajagopalan does not explicitly disclose: the insulin sensitivity marker comprises α- hydroxybutyrate.
Walter, in a similar field of endeavor, teaches of the many insulin sensitivity biomarkers that can be used in a patient to detect insulin resistance (i.e., instead of commonly used glycemic indicators, such as blood glucose concentration, that have limitations in the early detection of insulin resistant individuals, see Background and Introduction, Par. 3), and the methods for measuring and analyzing said insulin sensitivity markers (see Methods, specifically Par. 4 [Research protocol] — Par. 5 [Metabolomic analysis]). Walter concludes from the study that α-hydroxybutyrate (α-HB) is the most accurate (~76% accurate) early biomarker for insulin resistance and glucose intolerance in a nondiabetic population, see Results, Par. 2 (α-HB is inversely associated with insulin sensitivity).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined method of Kelly and Rajagopalan by incorporating the teachings of Walter of using α-HB as the chosen insulin sensitivity biomarker to accurately determine when an intestinal treatment procedure has decreased hepatic insulin resistance in a patient to a desired baseline level, for the purpose of preventing over-ablation and damage of the target tissue area when treating a patient with the physiological condition of hepatic insulin resistance.
Regarding claims 4-5, the combined device of Kelly, Rajagopalan, and Walter discloses the claimed invention substantially as claimed, as set forth above in claim 3.
Kelly, when combined with the method of Rajagopalan, teaches, wherein restoring normal metabolic conditions (i.e., a reduction in hepatic insulin resistance) after an intestinal treatment procedure can be indicated by a reduction in hepatic glucose levels in the patient (see Coe, FIG. 23A). In combination with the teachings of Walter, as shown above, the restoration of normal metabolic conditions (i.e., a reduction in hepatic insulin resistance) after an intestinal treatment procedure can be indicated by a reduction in o-HB from the first level determined by the operator (see Walter, Results, Par. 2). However, the combined device of Kelly, Rajagopalan, and Walter does not explicitly disclose: the reduction in insulin sensitivity marker is at least a 5% (or 10%) reduction in a- hydroxybutyrate from the first level.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined method of Kelly and Rajagopalan by incorporating the teachings of Walter of using a reduction in the biomarker a-HB to accurately indicate the success of an intestinal treatment procedure (see motivation to combine above in claim 3). The favorable percent reduction in the a-HB level could be determined by one of ordinary skill in the art, since it has been held that “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,” see Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382, and since it has been held that, “[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," see Jn re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05 subsection IA.
Claim(s) 10, and 14 – 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kelly (U.S. 2014/0088581) in view of Rajagopalan (U.S. 11,185,367), and in view of Wang (U.S. 2016/0310200).
Regarding claim 10, the combined method of Kelly and Rajagopalan discloses the claimed invention substantially as claimed, as set forth above in claim 8. Kelly teaches “...an expandable balloon is connected to a power source that provides radio frequency power having the desired characteristics to selectively heat the target tissue to a desired temperature,” see p. [0112]. However, the combined method of Kelly and Rajagopalan does not explicitly disclose: the ablative fluid comprising fluid at a temperature above 75°C.
Wang, in the same field of endeavor, teaches a device and a method for treating diabetes, digestive disease, pain, etc. in the digestive tract by delivering an effective amount of formulation (i.e., ablative fluid) to a tissue, see p. [0148], [0150]. Wang further teaches delivering a vapor or liquid formulation to the segment of the body lumen at a specific delivery rate for a pre-determined duration, wherein the formulation may be heated to at least 80°C prior to delivery, see p. [0134]; therefore this device and method is well configured to control the temperature of an ablative fluid above 75°C.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined method of Kelly and Rajagopalan, which is already configured to selectively heat an expandable balloon to a desired temperature, by incorporating the teachings of Wang to heat the ablative fluid applied to the expandable balloon above 75°C prior to delivery, for the purpose of effectively injuring/damaging the surface, tissue, and nerves of the gastrointestinal lumen to lower insulin resistance levels (Wang, paragraph [0150]).
Regarding claims 14-16, the combined method of Kelly and Rajagopalan discloses the claimed invention substantially as claimed, as set forth above in claim 11.
However, the combined method of Kelly and Rajagopalan does not explicitly disclose: the neutralizing fluid comprising: fluid at a temperature below the body temperature of the patient, between the body temperature of the patient and room temperature, or below room temperature.
Wang, in the same field of endeavor, teaches a device and a method for treating diabetes, digestive disease, pain, etc. in the digestive tract by delivering an effective amount of formulation (i.e., cooling or neutralizing fluid) to a tissue (“If the formulation comprises liquids or solutions, the cooling or heat can be generated from formulation temperatures that fall below or exceed body temperature. The liquid formulation temperature may range from —40°C to 140°C, from —30°C to 100°C, or from —20°C to 80°C. In one embodiment, the formulation temperature may equal that of room temperature. In one embodiment, the formulation temperature may range from —40°C to —20°C In another embodiment, the formulation temperature may range from 15°C to 80°C. In one embodiment, the formulation temperature may equal that of body temperature. In another embodiment, the formulation temperature may range from 50°C to 80°C,” see p. [0024]); therefore, this device and method is well configured to control the temperature of a fluid below the body temperature of the patient, between the body temperature of the patient and room temperature, and/or below room temperature.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined method of Kelly and Rajagopalan by incorporating the teachings of Wang to provide a neutralizing fluid to the expandable balloon at a temperature below the body temperature of the patient, between the body temperature of the patient and room temperature, and/or below room temperature, for the purpose of effectively injuring/damaging the surface, tissue, and nerves of the gastrointestinal lumen to lower insulin resistance levels while preventing the target tissue area from being over-ablated (Wang, paragraph [0150]).
Claim(s) 22 and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kelly (U.S. 2014/0088581) in view of Rajagopalan (U.S. 11,185,367), and in view of Coe (U.S. 9,265,575).
Regarding claims 22-23, the combined method of Kelly and Rajagopalan discloses the claimed invention substantially as claimed, as set forth above in claim 2. However, Kelly does not explicitly disclose: the intestinal treatment procedure is configured to treat NAFLD and/or NASH; or the intestinal treatment procedure improves liver fat content.
Coe, in a similar field of endeavor as Kelly, Rajagopalan, and the current application, teaches a method of treating a patient (i.e., via modulation of nervous tissue that innervates the liver) that is configured to treat NAFLD and/or NASH (see Col. 2, Lines 22-27). Therefore, the treatment procedure taught by Coe necessarily improves liver fat content, since it is taught to be able to treat NAFLD.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Kelly and Rajagopalan by incorporating the teachings of Coe of using the ablative intestinal treatment procedure to treat NAFLD and/or NASH, or to improve liver fat content, by modulating nervous tissue within the GI tract that innervates the liver, for the purpose of allowing the invention to treat a broader range of metabolic conditions (Coe, Col. 2, lines 22-27).
Claim(s) 24 – 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kelly (U.S. 2014/0088581) in view of Rajagopalan (U.S. 11,185,367), and in view of Venn-Watson (WO 2016111843).
Regarding claim 24, the combined method of Kelly and Rajagopalan discloses the claimed invention substantially as claimed, as set forth above in claim 2.
However, the combined method of Kelly and Rajagopalan does not explicitly disclose: determining the level of an iron overload marker comprising ferritin.
Venn-Watson, in a similar field of endeavor, teaches compositions and methods for the diagnosis, treatment, and monitoring of metabolic syndrome (see Abstract), which can be characterized by elevated insulin and/or elevated fasting plasma glucose concentrations (paragraph [0004]), wherein one embodiment of the composition is configured to modulate a marker (i.e., serum ferritin) of metabolic syndrome or a symptom of metabolic symptom (paragraph [0020]). Venn- Watson further teaches that high ferritin in the blood (i.e., hyperferritinemia) can be indicative of iron overload (paragraph [0005]), and that metabolic syndrome is correlated with hyperferritinemia, which is itself associated with impaired production of the insulin sensitizing hormone adiponectin, wherein increased adiponectin levels are associated with better glycemic control (paragraph [0107]).
One of ordinary skill in the art would recognize that an iron overload marker level, such as a measure of serum ferritin level in a patient, is indicative of a patient’s overall glycemic control. Thus, the Examiner finds that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined method of Kelly and Rajagopalan to incorporate the teachings of Venn-Watson by including a method step of determining a level of an iron overload marker comprising ferritin in a patient, for the purpose of using the iron overload marker comprising ferritin to indicate when an ablative procedure has been successful (i.e., when serum ferritin levels have reduced to a desired baseline level, indicating that adiponectin levels have increased to a desired level and normal glycemic control has been achieved), thereby preventing over-ablation and damage of the target tissue (Venn-Watson, paragraph [0107]).
Regarding claims 25-26, the combined method of Kelly, Rajagopalan, and Venn-Watson discloses the claimed invention substantially as claimed, as set forth above in claim 24.
However, the combined method of Kelly, Rajagopalan, and Venn-Watson does not explicitly disclose: the intestinal treatment procedure achieves an at least 5% (and/or at least 10%) reduction in ferritin from a first level determined prior to performing the treatment procedure.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined method of Kelly, Rajagopalan, and Venn-Watson by incorporating the teachings of Venn-Watson of using a reduction in an iron overload marker comprising ferritin to indicate the success of an intestinal treatment procedure (see motivation for combining above in Claim 24). The favorable percent reduction in the serum ferritin level could be determined by one of ordinary skill in the art, since it has been held that “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,” see Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382, and since it has been held that, “[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,” see Jn re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) and MPEP § 2144.05 subsection II.A.
Conclusion
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ANH T. BUI
Examiner
Art Unit 3783
/Anh Bui/ Examiner, Art Unit 3783
/SCOTT J MEDWAY/ Primary Examiner, Art Unit 3783