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 .
Election/Restrictions and Claim Status
Applicant’s election without traverse of Group 1 in the reply filed on 9/15/25 is acknowledged.
Applicant’s election of the species of hypotension and acute kidney injury in the reply filed on 9/15/25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 70 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/15/25.
Claims to the elected species are rejected as set forth below. Any relevant art that was uncovered during the search for the elected species is cited herein in order to advance prosecution.
Claims 3-6, 8-13, 15-17, 19-22, 24-29, 32, 35, 37-39, 41-46, 48-51, 55-60, 63-66, 68-69 and 71-147 have been canceled.
Claims 1-2, 7, 14, 18, 23, 30-31, 33-34, 36, 40, 47, 52-54, 61-62 and 67 are being examined.
Priority
The priority information is found in the filing receipt of 2/25/25.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/19/22 and 12/10/21 have been considered by the examiner.
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 1-2, 7, 14, 18, 23, 30-31, 33-34, 36, 40, 47, 52-54, 61-62 and 67 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 1 recites ‘of treating hypertension’ and ‘administering’ if a certain condition is met. If the condition is not met, it would seem that the administering step is not necessary. If the administering step is not required, it is unclear if the measuring step alone would be considered ‘treating’. None of the dependent claims clarify the claim scope.
Claim 30 recites ‘of suppressing a renin level’ and ‘administering’ if a certain condition is met. If the condition is not met, it would seem that the administering step is not necessary. If the administering step is not required, it is unclear if the measuring step alone would be considered ‘suppressing’. None of the dependent claims clarify the claim scope.
Claims 1 and 30 refer to ‘a threshold value’. In this context it is unclear what the value is a threshold for. It is unclear if the threshold is in relation to what quantity is detectable via the measuring step or if the threshold is in relation to something else. As such, the scope of claims 1, 7, 14, 18, 23, 30-31, 33-34, 40, 47, 52-53, 61-62 and 67 are unclear.
Although unclear, the claims have been given the broadest reasonable interpretation consistent with the specification and the claims have been interpreted as being 101 compliant.
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.
Claim(s) 1, 7, 18, 23, 30-31, 33-34, 40 and 67 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2017/120440 (07-2017 ‘Chawla’).
Chawla teach a method of treating hypotension in a human patient (claim 1) in which the blood plasma renin activity is measured and angiotensin II is administered at an initial rate of at least 20 ng/kg/min if the blood plasma renin activity is at least 1.2 µIU/ml (claim 53).
In relation to the patient of claim 1, Chawla teach a method of treating hypotension in a human patient (claim 1).
In relation to the measuring of claim 1, Chawla teach that the blood plasma renin activity is measured (claim 53).
In relation to the administering of claims 1 and 7, Chawla teach angiotensin II is administered at an initial rate of at least 20 ng/kg/min if the blood plasma renin activity is at least 1.2 µIU/ml (claim 53).
In relation to claim 18, Chawla teach a patient with acute respiratory distress syndrome (claim 73).
In relation to claim 23, Chawla teach a method of treating hypotension in a human patient (claim 1) which does not require a subject with sepsis.
In relation to the measuring of claim 30, Chawla teach that the blood plasma renin activity is measured (claim 53).
In relation to the administering of claims 30 and 40, Chawla teach angiotensin II is administered at an initial rate of at least 20 ng/kg/min if the blood plasma renin activity is at least 1.2 µIU/ml (claim 53). Since an agent as claimed is administered it would function as claimed.
In relation to claim 31, Chawla teach a MAP above 75 mm HG (claim 1).
In relation to claim 33, Chawla teach a method of treating hypotension in a human patient (claim 1) which does not require a subject with sepsis.
In relation to claim 34, Chawla teach a method of treating hypotension in a human patient (claim 1).
In relation to claim 67, Chawla teach angiotensin II is administered at an initial rate of at least 20 ng/kg/min if the blood plasma renin activity is at least 1.2 µIU/ml (claim 53). Since an agent as claimed is administered it would function as claimed.
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) 1-2, 7, 14, 18, 23, 30-31, 33-34, 36, 40, 47, 52-54, 61-62 and 67 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/120440 (07-2017 ‘Chawla’) in view of Volpe et al. (‘Renin as a biomarker of cardiovascular disease in clinical practice’ Nutrition, Metabolism & Cardiovascular Diseases v22 2012 pages 312-317; ‘Volpe’) in view of Gleeson et al. (‘Renin as a marker of tissue-perfusion and prognosis in critically ill patients’ Critical Care Medicine v47(2) February 2019 pages 152-158; ‘Gleeson’) in view of Bussard et al. (cited with IDS 12/20/21; ‘Bussard’).
Chawla teach that hypotension can occur as the result of various conditions such as septic shock (page 1 first paragraph of background). Chawla recognizes that the patient may have sepsis or septic shock or ARDS or may not have ARDS (page 18 lines 1-6). Chawla teach that the hemodynamic effects of angiotensin II have been studied in numerous clinical trials and that it mediates the effect on vasculature by inducing vasoconstriction (pages 28-29 connecting paragraph). Chawla teach that angiotensin II can be administered at various rates including 5 ng/kg/min or 20 ng/kg/min (page 9 lines 14-19) and that the rate of administration can be optimized (page 10 lines 3-30). Chawla teach that if the mean arterial pressure is below 75 mm Hg then the rate of administration of the angiotensin is increased (page 2 lines 28-30). Chawla teach that the rate of the angiotensin therapeutic agent may be decreased if a measured mean arterial pressure meets or exceeds a target value (page 7 lines 16-21). Chawla recognizes that the mean arterial pressure value can be 65 mm Hg (pages 7-8 connecting paragraph). Chawla teach that the invention provides a method of assessing the response of a subject with hypotension to therapy by testing the patient for a change in a therapeutic parameter (page 18 last paragraph). Chawla teach measuring a feature in a patient prior to administering the composition, specifically measuring the blood plasma renin activity (page 19 last paragraph and claims 51-55). Chawla specifically teach administering the angiotensin therapeutic agent (for example angiotensin II) if the blood plasma renin activity is at least at a predetermined threshold value which can range from at least 50 – 0.01 µIU/ml (page 22 lines 30 – page 23 line 8). Chawla teach a method of treating hypotension in a human patient (claim 1) in which the blood plasma renin activity is measured and angiotensin II is administered at an initial rate of at least 20 ng/kg/min if the blood plasma renin activity is at least 1.2 µIU/ml (claim 53).
Chawla teach not recite a specific threshold value as in claim 2 nor does Chawla specifically recite acute kidney injury.
Volpe teach that plasma renin can be reported as either IU/L or pg/ml (page 313 5th paragraph). Volpe teach that several studies have shown that elevated plasma renin activity is associated with increased morbidity and mortality (abstract and Table 1).
Gleeson teach a study in which maximum renin achieved significant prognostic value for ICU mortality (page 152 section ‘Measurement and Main Results’ and figure 3). Gleeson teach that 55% of the patients had acute kidney injury (page 154 last paragraph). Gleeson teach that all patients who had a normal renin level survived their ICU stay (100% negative predictive value), and all patients who died in the ICU had elevated renin levels (100% sensitivity) (page 157 last paragraph before conclusions). Gleeson teach that they have validated arterial direct plasma renin as a biomarker of circulatory function in critically ill patients (page 157 conclusion section).
Bussard teach that angiotensin II (Ang II) has been shown to increase blood pressure in patients with hypotension (page 1287 introduction paragraph). Bussard teach that evidence suggests that angiotensin II may preferentially be of benefit in acute kidney injury (abstract). Bussard teach that downregulation of renin synthesis can occur in the presence of exogenous angiotensin II (page 1289 first complete paragraph). Bussard teach that during hypotension that RAS is activated and angiotensin II acts to restore blood pressure (page 1288 last complete paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Chawla based on the specific teachings and suggestions of Chawla. Since Chawla teach methods of treating hypotension in a human patient (claim 1) and Chawla teach that hypotension can occur as the result of various conditions such as septic shock (page 1 first paragraph of background) and recognizes that the patient may have sepsis or septic shock or ARDS or may not have ARDS (page 18 lines 1-6) one would have been motivated to administer to such subjects. Since Chawla teach administering an angiotensin therapeutic agent and teach that the hemodynamic effects of angiotensin II have been studied in numerous clinical trials and that it mediates the effect on vasculature by inducing vasoconstriction (pages 28-29 connecting paragraph) and teach that angiotensin II can be administered at various rates including 5 ng/kg/min or 20 ng/kg/min (page 9 lines 14-19) and that the rate of administration can be optimized (page lines 3-30) one would have been motivated to administer angiotensin II.
Since Chawla teach measuring a feature in a patient prior to administering the composition, specifically measuring the blood plasma renin activity (page 19 last paragraph and claims 51-55) one would have been motivated to do such. Chawla specifically teach administering the angiotensin therapeutic agent (for example angiotensin II) if the blood plasma renin activity is at least at a predetermined threshold value which can range from at least 20 – 0.01 µIU/ml (page 22 lines 30 – page 23 line 8). Since Volpe teach that plasma renin can be reported as either IU/L or pg/ml (page 313 5th paragraph) and teach that several studies have shown that elevated plasma renin activity is associated with increased morbidity and mortality (abstract and Table 1) one would have been motivated to measure the renin activity level.
Since Gleeson teach a study in which maximum renin achieved significant prognostic value for ICU mortality (page 152 section ‘Measurement and Main Results’ and figure 3) and teach that 55% of the patients had acute kidney injury (page 154 last paragraph) and teach that all patients who had a normal renin level survived their ICU stay (100% negative predictive value), and all patients who died in the ICU had elevated renin levels (100% sensitivity) (page 157 last paragraph before conclusions) one would have been motivated to administer to a patient with acute kidney injury and specifically target those with elevated renin. With respect to the specific threshold value, Chawla specifically teach administering the angiotensin therapeutic agent (for example angiotensin II) if the blood plasma renin activity is at least at a predetermined threshold value which can range from at least 20 – 0.01 µIU/ml (page 22 lines 30 – page 23 line 8) so one would have been motivated to find the optimal amount. Further, Bussard teach that evidence suggests that angiotensin II may preferentially be of benefit in acute kidney injury (abstract). In the instant case, the agent administered (angiotensin II) and its function (inducing vasoconstriction) were known. Further, the art expressly teach and suggest that elevated plasma renin activity is associated with increased morbidity and mortality (abstract and Table 1 of Volpe). Bussard teach that downregulation of renin synthesis can occur in the presence of exogenous angiotensin II (page 1289 first complete paragraph). Thus one would have been motivated to administer to patients with elevated plasma renin activity. Since Chawla teach that angiotensin II can be administered at various rates including 5 ng/kg/min or 20 ng/kg/min (page 9 lines 14-19) and that the rate of administration can be optimized (page lines 3-30) one would have been motivated to do such. Since Chawla teach that if the mean arterial pressure is below 75 mm Hg then the rate of administration of the angiotensin is increased (page 2 lines 28-30) and Chawla teach that the rate of the angiotensin therapeutic agent may be decreased if a measured mean arterial pressure meets or exceeds a target value (page 7 lines 16-21) one would have been motivated to do such. One would have had a reasonable expectation of success since Bussard teach that angiotensin II (Ang II) has been shown to increase blood pressure in patients with hypotension (page 1287 introduction paragraph). Bussard teach that downregulation of renin synthesis can occur in the presence of exogenous angiotensin II (page 1289 first complete paragraph).
In relation to the patient of claim 1, Chawla teach a method of treating hypotension in a human patient (claim 1).
In relation to the measuring of claim 1, Chawla teach that the blood plasma renin activity is measured (claim 53). Chawla teach that the invention provides a method of assessing the response of a subject with hypotension to therapy by testing the patient for a change in a therapeutic parameter (page 18 last paragraph). Chawla teach measuring a feature in a patient prior to administering the composition, specifically measuring the blood plasma renin activity (page 19 last paragraph and claims 51-55).
In relation to the administering of claims 1 and 7, Chawla teach angiotensin II is administered at an initial rate of at least 20 ng/kg/min if the blood plasma renin activity is at least 1.2 µIU/ml (claim 53).
In relation to claim 2, Chawla specifically teach administering the angiotensin therapeutic agent (for example angiotensin II) if the blood plasma renin activity is at least at a predetermined threshold value which can range from at least 20 – 0.01 µIU/ml (page 22 lines 30 – page 23 line 8). Volpe teach that plasma renin can be reported as either IU/L or pg/ml (page 313 5th paragraph). Volpe teach that several studies have shown that elevated plasma renin activity is associated with increased morbidity and mortality (abstract and Table 1).
In relation to claim 14, Chawla teach that angiotensin II can be administered at various rates including 5 ng/kg/min (page 9 lines 14-19) and that the rate of administration can be optimized (page lines 3-30).
In relation to claim 18, Chawla teach a patient with acute respiratory distress syndrome (claim 73). Chawla teach that hypotension can occur as the result of various conditions such as septic shock (page 1 first paragraph of background). Chawla recognizes that the patient may have sepsis or septic shock or ARDS (page 18 lines 1-6).
In relation to claim 23, Chawla teach a method of treating hypotension in a human patient (claim 1) which does not require a subject with sepsis.
In relation to the measuring of claim 30, Chawla teach that the blood plasma renin activity is measured (claim 53).
In relation to the administering of claims 30 and 40, Chawla teach angiotensin II is administered at an initial rate of at least 20 ng/kg/min if the blood plasma renin activity is at least 1.2 µIU/ml (claim 53). Since an agent as claimed is administered it would function as claimed.
In relation to claim 31, Chawla teach a MAP above 75 mm HG (claim 1).
In relation to claim 33, Chawla teach a method of treating hypotension in a human patient (claim 1) which does not require a subject with sepsis. Chawla recognizes that the patient may not have ARDS (page 18 lines 1-6).
In relation to claim 34, Chawla teach a method of treating hypotension in a human patient (claim 1). Bussard teach that evidence suggests that angiotensin II may preferentially be of benefit in acute kidney injury (abstract).
In relation to claims 36 and 54, Chawla specifically teach administering the angiotensin therapeutic agent (for example angiotensin II) if the blood plasma renin activity is at least at a predetermined threshold value which can range from at least 20 – 0.01 µIU/ml (page 22 lines 30 – page 23 line 8). Volpe teach that plasma renin can be reported as either IU/L or pg/ml (page 313 5th paragraph). Volpe teach that several studies have shown that elevated plasma renin activity is associated with increased morbidity and mortality (abstract and Table 1).
In relation to claims 40 and 47, Chawla teach that angiotensin II can be administered at various rates including 5 ng/kg/min (page 9 lines 14-19) and that the rate of administration can be optimized (page lines 3-30).
In relation to claim 52, Chawla teach that the invention provides a method of assessing the response of a subject with hypotension to therapy by testing the patient for a change in a therapeutic parameter (page 18 last paragraph). Chawla teach that the rate of administration may be optimized for different patients and the therapeutic agent rate can be decreased (page 10 first complete paragraph). Chawla recognizes decreasing the rate at which the angiotensin is administered (claim 31). Volpe teach that several studies have shown that elevated plasma renin activity is associated with increased morbidity and mortality (abstract and Table 1) so if such goal is being met one would have been motivated to decrease the rate of administration.
In relation to claim 53, Chawla teach that the invention provides a method of assessing the response of a subject with hypotension to therapy by testing the patient for a change in a therapeutic parameter (page 18 last paragraph). Chawla teach that the rate of administration may be optimized for different patients and the therapeutic agent rate can be increased (page 10 first complete paragraph). Volpe teach that several studies have shown that elevated plasma renin activity is associated with increased morbidity and mortality (abstract and Table 1) so if such goal is not being met one would have been motivated to increase the rate of administration.
In relation to claim 61, Chawla teach that the invention provides a method of assessing the response of a subject with hypotension to therapy by testing the patient for a change in a therapeutic parameter (page 18 last paragraph). Chawla teach that the rate of the angiotensin therapeutic agent may be decreased if a measured mean arterial pressure meets or exceeds a target value (page 7 lines 16-21). Chawla recognizes that the mean arterial pressure value can be 65 mm Hg (pages 7-8 connecting paragraph).
In relation to claim 62, Chawla teach that the invention provides a method of assessing the response of a subject with hypotension to therapy by testing the patient for a change in a therapeutic parameter (page 18 last paragraph). Chawla teach that mean arterial pressure is below 75 mm Hg that the rate of administration of the angiotensin is increased (page 2 lines 28-30). Chawla recognizes that the mean arterial pressure value can be 65 mm Hg (pages 7-8 connecting paragraph).
In relation to claim 67, Chawla teach angiotensin II is administered at an initial rate of at least 20 ng/kg/min if the blood plasma renin activity is at least 1.2 µIU/ml (claim 53). Since an agent as claimed is administered it would function as claimed.
Conclusion
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658