DETAILED ACTION
The examiner notes that in the printed publication (US 2024/0032801), two instances of “Müller's” is incorrectly printed: [0022] – “Milner’s”, and [0061] – “Milller’s”. Should the application be allowed, the applicant is advised to be alert to the same misprint and request a correction. No such mistake is found in applicant’s submitted specifications.
Claim Objections
Claim 24 is objected to because of the following informalities: “wherein the blood vessel is one or more a renal artery” should be “wherein the blood vessel is one or more of a renal artery”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 17 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 17 recites “comparing the calculated stiffness and measured blood pressure of the blood vessel to known tissue properties at a reference blood pressure to determine the normalized stiffness of the blood vessel.” The sole disclosure directed to this subject matter is a single sentence found in the specifications: “the index value can be determined computationally based on known tissue properties of the blood vessel and calculating distensibility at a reference pressure given measured distensibility at actual pressure” ([0054] of the pgpub). It is noted that the recitation in ([0022]) is merely a verbatim restatement of the claim limitation itself.
Consider the following Wands factors:
The breadth of the claims: the claim reads on any tissue property and at any reference pressure, and on any computational relationship between them;
The nature of the invention: the transformation of a measurement taken at one pressure into a value at a difference pressure requires knowledge of the relationship between pressure and vessel properties;
The level of predictability in the art: [0027] of the instant specifications note that arterial wall stiffness is a result of multiple factors including the mechanical properties and tone of the smooth muscle, collage, and elastin content of the arterial wall and the adventitia, along with other factors such as arterial disease, plaque, fibromuscular dysplasia and is thus a complex attribute having many components
The amount of direction provided by the inventor: no direction is provided at all – not a single property is named, no model is identified, no reference pressure is specified, and no equation is given
The existence of working examples: none provided
The quantity of experimentation needed: because the specifications lack any disclosure of a property, model, or reference pressure, one of ordinary skill in the art would be required to start blind.
The above factors weigh in the favor of undue experimentation. Thus claim 17 is not enabled by the disclosure.
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 15-18 and 20-25 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.
As to claim 15, the claim recites two independent predicates for the same conclusion; it recites “determining that the patient is likely to experience a positive response to a denervation when the normalized stiffness is greater than a predetermined value” while the wherein clause also recites “a response to the stimulus is indicative of a likelihood of a patient experiencing a positive response to a denervation of the blood vessel”. It is unclear whether the stimulus response is the input from which the normalized stiffness is determined, the after-stimulus stiffness is the normalized stimulus that is compared to the predetermined value, or the stimulus response is a second, parallel determination. It seems likely that one of the first two interpretations is correct, as [0062] states that the “use of the two different measurements before and after stimulation provide a basis for normalizing the stiffness of the blood vessel based on the relative change in the distension of the blood vessel pre- and post-perturbation”, but the claim itself remains unclear. Clarification and/or amendments are required.
In addition, claim 15 also recites “calculating an after-stimulus stiffness of the blood vessel” that has no further ties to the claim. Applicant is advised to recite the relationship between the after-stimulus stiffness and the normalized stiffness that is compared to the predetermined value.
As to claim 17, the claim recites comparing to “known tissue properties at a reference blood pressure”. The scope of “known tissue properties” is not ascertainable from the specifications.
As to claim 23, the claim recites “a reduction in stiffness in excess of a predetermined value”. It is unclear which of the several stiffness values recited in claim 15 the reduction is measured. It is further unclear whether the post-denervation “stiffness of the blood vessel” in claim 23 is itself normalized, to allow for an apples-to-apples comparison if the stiffness is referring to a normalized stiffness.
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.
Claim(s) 15-18, 22, and 24-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over van der Horst (US 2019/0090856) in view of Robinson et al. (US 2019/0029532) and Foin (US 2021/0383908).
As to claim 15, van der Horst teaches a method comprising: measuring a blood pressure of a patient ([0012] - pressure sensor to monitor a pressure in a vessel); calculating a stiffness of a blood vessel identified for receiving denervation therapy ([0010] – Lurz is characterized as teaching PWV as a marker of arterial stiffness which predicts outcomes of renal sympathetic denervation); [0011] – PWV measurement used to predict efficacy of renal denervation; [0039] – “embodiments of the present disclosure are configured to perform pulse wave velocity measurements of the renal artery for stratification of patients for renal artery denervation”), normalizing the calculated pulse wave measurement relative to the measured blood pressure of the patient ([0013-0015], claim 2 – shown equation reflects a measured change in vessel dimension expressed relative (i.e. normalized) to the concurrently measured blood pressure change), determining that the patient is likely to experience a positive response to a denervation when the normalized pulse wave measurement is greater than a predetermined value ([0011], [0045-0047]).
van der Horst fails to expressly teach the use of a stiffness measurement directly, but as noted previously, recognizes PWV to be a marker of arterial stiffness). Robinson teaches a direct equation which defines the relationship between PWV and the compliance (i.e. stiffness) of the artery ([0016]). In addition, Robinson states that it is important to note that PWV is influenced by both arterial stiffness and the blood pressure in the vessel ([0015]) and teaches that stiffness can be determined via an index that is pressure insensitive (i.e. normalized) ([0127]) and that the standard use of arterial stiffness refers to a characteristic of the vessel without regard for the conditions of the measurement, specifically the blood pressure or transmural pressure at the time of measurement ([0130]). It would have been obvious to modify van der Horst with Robinson to specifically utilize a measurement of stiffness to normalize relative to the patient’s measured blood pressure as it would allow for a direct adjustment of the stiffness value itself.
The above combination does not expressly teach normalizing the calculated stiffness further includes applying a stimulus to the patient and calculating an after-stimulus stiffness of the blood vessel, wherein a response to the stimulus is indicative of a likelihood of a patient experiencing a positive response to a denervation of the blood vessel. Foin teaches receiving a first measurement of the renal vasculature under a first condition and a second measurement of the renal vasculature under a second condition, the first condition being non-stimulated and the second condition being the provision of a pre-determined stimulation ([0005]), the measured parameter being at least one of vessel blood pressure and pulse wave velocity ([0082]) and teaches the PWV is a measure of vessel stiffness ([0134]). Foin further teaches that resulting index is used to determine suitability for renal denervation ([0021]), specifically that for those suitable for renal denervation, the increase in stiffness and therefore PWV after stimulation is not that big and therefore the ratio will be smaller than those who are not suitable for renal denervation ([0197]). As such, it would have been obvious to modify the above combination with Foin to apply a stimulus and calculate an after-stimulus stiffness, and to treat the response to that stimulus as indicative of the likelihood of a positive response to denervation, as taught by Foin, to allow the differentiation of those whose increase in stiffness is unrelated to sympathetic overdrive, as those patients will be the ones to benefit from the procedure.
As to claim 16, van der Horst fails to expressly teach measuring a mean aortic pressure (MAP) of the patient and comparing the measured MAP and calculated stiffness to a database of MAP and stiffness data to determine the normalized stiffness of the blood vessel. Robinson teaches that the normalization of measured stiffness value is performed by reference to stored population data ([0196]), and that the patient-specific parameters used include the patient’s mean arterial pressure ([0197]). Moreover, Foin teaches that physiological parameters such as vessel blood pressure can be applied in the specific context of predicting renal denervation response ([0078], [0082]). Accordingly, it would have been obvious to further modify the above combination to perform the normalization against a stored data set of pressure and stiffness values to increase the accuracy of the resulting determination.
As to claim 17, Robinson teaches comparing ([0129]) the calculated stiffness and measured blood pressure of the blood vessel to known tissue properties ([0136]) at a reference blood pressure ([0130]) to determine the normalized stiffness of the blood vessel ([0129]). It would have been obvious to further modify the above combination with Robinson to utilize known arterial tissue properties evaluated at a defined reference pressure to increase the accuracy of the normalization.
As to claim 18, Foin teaches measuring a blood pressure of a plurality of patients; calculating a stiffness of a blood vessel for the plurality of patients; and correlating the measured blood pressure and calculated blood vessel stiffness of the plurality of patients to an expected outcome of denervation of the blood vessel ([0018], [0022], [0082], [0093], [0134]). It would have been obvious to further modify the above combination with Foin to utilize data from population data to eliminate any individual outliers which may affect the result.
As to claim 22, van der Horst teaches denervating at the blood vessel ([0040]).
As to claim 24, van der Horst teaches the blood vessel is one or more a renal artery, a hepatic artery, a splanchnic artery, a celiac artery, a superior mesenteric artery, or an inferior mesenteric artery ([0037], [0048]).
As to claim 25, van der Horst teaches the blood vessel is a renal artery of a patient ([0037], [0048]).
Claim(s) 20-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over van der Horst (US 2019/0090856), Robinson et al. (US 2019/0029532), and Foin (US 2021/0383908), and further in view of Toth (US 2017/0231490).
As to claim 20, the above combination fails to expressly teach the stimulus is a non- invasive stimulus including one or more of a Valsalva maneuver, Müller's maneuver, cold pressor, or a mental stress test. Toth teaches a device for measuring vascular stiffness ([0180]) and determining suitability for a denervation procedure ([0235]) in which the applied stress test is a Valsalva maneuver ([0116]). It would have been obvious to modify the above combination with Toth to enable the use of a specific procedure to obtain the measurements, as Foin already teaches the application of a general physical maneuver.
As to claim 21, the above combination fails to expressly teach the stimulus is an invasive stimulus including one or more of an application of a vasodilator or a vasoconstrictor. Toth teaches a device for measuring vascular stiffness ([0180]) and determining suitability for a denervation procedure ([0235]) in which the applied stress test is a vasodilator or a vasoconstrictor ([0116]). It would have been obvious to modify the above combination with Toth to enable the use of a specific procedure to obtain the measurements, as Foin already teaches the application of a general pharmaceutical stimulus.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over van der Horst (US 2019/0090856), Robinson et al. (US 2019/0029532), and Foin (US 2021/0383908), and further in view of Sverdlik (US 2014/0012133).
As to claim 23, the above combination fails to expressly teach calculating a stiffness of the blood vessel following denervation, wherein a reduction in stiffness in excess of a predetermined value is indicative of a successful denervation. Sverdlik teaches a device for determining effectiveness of a renal denervation treatment ([0005]) in which measurements are made before and after the denervation procedure ([0033]) and determining a reduction by measuring various parameters including arterial stiffness ([0066], [0108], [0110]). It would have been obvious to modify the above combination with Sverdlik to assess whether the treatment was successful to determine whether further intervention is necessary.
Response to Arguments
Applicant’s arguments 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.
It is noted that the enablement rejection has been re-iterated with the Wands analysis articulated.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTIAN JANG whose telephone number is (571)270-3820. The examiner can normally be reached Monday-Friday (7-3:30 EST).
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CHRISTIAN JANG
Primary Examiner
Art Unit 3791
/CHRISTIAN JANG/Primary Examiner, Art Unit 3791 9/29/26
