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 Arguments
Applicant's arguments, filed April 13, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2, 5, 9, and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (Hypertension 2011) in view of Byrom (British Journal of Experimental Pathology 1963) and Shock-Kusch et al. (Kidney International, 2011).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed December 12, 2025 and those set forth herein.
Applicant argues that Zhong and Byrom are incompatible because they employ fundamentally different biological models of different medical conditions. Applicant argues that Zhong is directed to the study of chronic kidney disease (CKD) and the progression to end-stage renal disease, whereas Byrom investigates the acute toxic effects of massive bolus doses of angiotensin to study malignant hypertension. Applicant argues that a PHOSITA seeking to improve or replicate Zhong's chronic disease model would not be motivated to adopt Byrom's bolus method because Byrom discloses that a single intravenous bolus injection causes violent vasoconstriction and results in medial necrosis. Applicant argues that the modification would render Zhong's primary model unsatisfactory for its intended purpose.
This argument is unpersuasive. The Applicant’s reliance on the terminal nature of medial necrosis in Byrom is a narrow interpretation that ignores the broader teachings of the reference. Byrom discloses that the degree of renal damage depends on the angiotensin dosage (page 7, ¶ 3). For example, Bytom discloses that the effect can be observed with as little as 0.002 µg of angiotensin and visible damage occurs at 1-10 µg or more (page 7, ¶ 3). Bytom discloses that very large doses of angiotensin can cause acute medical necrosis of large renal arteries (page 11, ¶ 6). Bytom also discloses that the enormous amount of angiotensin caused remarkably little damage to the kidney apart from hilar arterial necrosis and angiotensin may be incapable of causing renal cortical necrosis (page 10, ¶ 2). As Byrom explicitly provides a dosage-response gradient, a person of ordinary skill in the art would not blindly apply a lethal dose, but would instead calibrate the bolus to induce a non-terminal, transient injury suitable for monitoring. The angiotensin dosage is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of angiotensin to administer in order to create a renal injury model consistent with Zhong. Further, a person of ordinary skill in the art would have been motivated to use a bolus administration instead of continuous infusion in order to achieve rapid onset of action, and a more convenient, simple set up. Accordingly, applying the teachings of Byrom to use bolus doses of angiotensin instead of the continuous infusion in order to achieve the chronic effects desired in Zhong constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering claims obvious.
Applicant argues that there is no suggestion in Schock-Kusch to use its readout to monitor the recovery of an acute, transient injury. Applicant argues that if a PHOSITA were to follow the Examiner's suggestion and combine Schock-Kusch's readout with Byrom's bolus induction, they would find the measurement tool useless for screening, as the medial necrosis taught by Byrom represents terminal tissue damage from which there is no recovery to measure. Applicant argues that Schock-Kusch provides a tool for monitoring stability or chronic decay, not the rapid, 24-hour physiological rebound discovered by the Applicant.
This argument is unpersuasive. As discussed above, a person of ordinary skill in the art would have been adjusted and optimized the amount of bolus induction for creating renal injury model which does not result in an acute, medical necrosis condition when optimized. The choice of dosage is a matter of routine experimentation within the scope of a person of ordinary skill in the art’s skill set. The Applicant’s contention that Schock-Kusch is limited to chronic decay is unsupported by the prior art’s broader technical disclosure. Schock-Kusch teaches transcutaneous fluorescence (TF) can be measured and used to assess renal injury function (abstract). Schock-Kush teaches a general methodology for assessing renal function via TF. Whether the change in function is chronic decay or rapid rebound is merely a matter of the temporal window in which the measurement tool is applied. Further, a person of ordinary skill in the art would have been motivated to use TF measurement for determining the injury in the renal injury model in order to achieve a non-invasive, real-time assessment of renal function. The use of known measurement tool (Schock-Kush) to monitor a known physiological process (renal function) in a known injury model (Zhong and Byrom) is the result of ordinary creativity, not an inventive leap. Accordingly, applying the teachings of Schock-Kusch to the renal injury model of Zhong and Byrom constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering claims obvious. The “rapid, 24-hour physiological rebound” described by the Applicant does not impart patentability to the claim. This rebound is an inherent property of the biological system’s response to the optimized bolus induction. Discovering the specific timing or rate of a recovery that naturally occurs in a non-lethal injury model does not render the method non-obvious, as the tools and the model to observe this phenomenon were already available in the combined teachings of Zhong, Byrom, and Schock-Kusch. Further, the instant claims do not recite that the rapid, 24-hour physiological rebound nor that the injury should be reversible.
Applicant argues that the presently claimed invention represents a significant technical advance over the combined prior art by providing a short-term renal injury model that is unexpectedly fast and reversible. Applicant argues that neither Zhong, Byrom, nor Schock-Kusch-alone or in combination-discloses or suggests a model where renal injury is induced in a reversible manner suitable for high- throughput screening.
This argument is unpersuasive. Byrom discloses that the physiological changes such as vascular blanching and dilation following angiotensin administration can be disappeared as the blood pressure returned to normal within minutes (page 7, ¶ 3). Byrom discloses that angiotensin can cause only partial renal damage because angiotensin is very quickly inactivated (page 10, ¶ 2). This provides a clear teaching of a naturally reversible physiological response. It would have been obvious to a person of ordinary skill in the art that any biological system subjected to a non-lethal, transient stimulus will inherently undergo a natural recovery process once the stimulus is removed or inactivated. Since Byrom teaches that angiotensin can be very quickly inactivated, a person of ordinary skill in the art would have reasonably expected the induced injury to be reversible, when the dosage was optimized. Adjusting the angiotensin amount to induce a level of dagame that is proper (non-terminal) yet reversible is a matter of routine optimization. Since Byrom teaches that the degree of damage is dose-dependent and that the system inherently recovers as the drug is inactivated, the reversible and fast nature of the model of instant application is an inherent property of the prior art combination. Further, a person of ordinary skill in the art would have been motivated to use reversible renal injury model in order to perform several consecutive experiments with the tested animals for high-throughput screening. Further, the instant claims do not recite that the renal injury model is a short-term renal injury model nor that the injury should be reversible.
Claims 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong, Byrom, and Shock-Kusch as applied to claims 2, 5, 9, 11-13, and 17, and further in view of Cyanagen SRL (EP 2944326 A1; cited on IDS filed Jul 8, 2022).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed December 12, 2025 and those set forth herein.
Applicant argues that the bolus induction method of Byrom is foundationally incompatible with the study of chronic kidney condition because the bolus of angiotensin causes medial necrosis. Applicant argues that the proposed modification-applying Byrom's bolus method to the screening framework of Cyanagen would destroy the tissue viability necessary to conduct the screening, thereby rendering the prior art unsatisfactory for its intended purpose. Applicant argues that Cyanagen does not suggest that a bolus induction could be performed in a reversible manner. Applicant argues that the addition of Cyanagen does not rectify the foundational incompatibility between the acute-necrotic model of Byrom and the chronic-fibrotic models of Zhong and Cyanagen.
This argument is unpersuasive. As discussed above, the amount of angiotensin administered to induce damage can be appropriately adjusted and optimized depending on the intended applications. A person of ordinary skill in the art would recognize that inducing a non-lethal, transient, and reversible injury, rather than terminal necrosis, is a matter of routine dose-response optimization. Further, Applicant does not recite “reversible” or “short-term” renal injury model as a limitation in instant claims. As discussed in the Office Action mailed December 12, 2025, Cyanagen teaches that renal injury models can be effectively used for screening candidate molecules (¶ 61; ¶ 62; claim 17). Further, a person of ordinary skill in the art would have been motivated to utilize the renal injury model of Zhong, Byrom, and Schock-Kusch for drug screening in order to expand the practical applications of the model. Accordingly, applying the teachings of Cyanagen to the renal injury model of Zhong, Byrom, and Schock-Kusch, which involves reversible conditions rather than acute medical necrosis when properly optimized, constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering instant claims obvious.
Conclusion
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 JONG HWAN BAEK whose telephone number is (571)272-0670. The examiner can normally be reached Mon - Thu, 9 am - 3 pm ET.
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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