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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 13, 2026 has been entered.
Applicants' arguments, filed August 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 § 112 Indefiniteness
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 2, 5, 7-9, and 11-13 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.
Regarding claims 2, 5, and 7, the last step recites “wherein the renal injury is a reversible renal injury such that the glomerular filtration barrier (GFB) integrity of the test subject physiologically recovers to baseline within 24 hours of the bolus administration.” The phrase “such that” appears to be used in a non-limiting, exemplary manner similar to “such as,” rendering the boundaries of the claim indefinite. It is unclear whether the subsequent clause is a required limitation or merely an illustrative embodiment.
The dependent claims fall therewith.
Clarification and/or amendment is required.
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), Shock-Kusch et al. (Kidney International, 2011), and Königshausen et al. (Scientific Reports, 2016; cited on PTO-892).
Regarding claims 2 and 11, Zhong discloses a method for creating a renal injury model induced by infusing angiotensin (Ang) II (renal injury inducer) into mice (test subject) (page 314 Experimental Animals and Protocols).
Zhong does not disclose the administration of a bolus of a renal injury inducer subcutaneously and/or intravenously. Zhong does not disclose the administration of fluorescent molecule to determine the degree of renal injury from the development of the transcutaneous fluorescence (TF). Zhong does not disclose that the renal injury is a reversible renal injury such that the glomerular filtration barrier (GFB) integrity of the test subject physiologically recovers to baseline within 24 hours of the bolus administration.
Byrom discloses a method comprising a single intravenous (IV) injection (bolus) of Ang (renal injury inducer) into rats (test subject) to evaluate its toxic effect on the kidney (renal injury) (page 7, The experiment; page 11, SUMMARY). Byrom discloses that the physiological changes such as vascular blanching and dilation following angiotensin administration can disappear 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).
Schock-Kusch discloses a method comprising the administration of fluorescein isothiocyanate (FITC)-sinistrin (pharmaceutically suitable fluorescent molecule) as a biomarker and the measurement of the development of the TF to analyze renal function in renal injury mouse models (page 1254, abstract; page 1255, PROOF OF PRINCIPLE; page 1256, Table 1). The molecular weight of FITC-sinistrin is ≤ 15 kDa.
Königshausen discloses that Ang II can weaken the structural integrity of the slit diaphragm (component of GFB), which leads to an increased glomerular permeability (abstract). Königshausen discloses that Ang II can induce a “transient” increase in glomerular permeability (page 1, ¶ 2) and that the glomerular permeability can return to normal after 120 minutes of Ang II stimulation or after 60 minutes of Ang II discontinuation washout (page 2, Figure 1 a). This indicates that Ang II-induced disruption of the GFB can naturally recover over time, meaning it is transient and reversible.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Zhong by administering the renal injury inducer such as Ang II as an IV bolus injection to induce reversible renal injury and administering the FITC-sinistrin to determine the degree of renal injury by determining the development of the TF. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Byrom teaches that a single bolus of Ang can induce renal damage; Schock-Kusch teaches that FITC-sinistrin can be used to determine the development of the TF as a biomarker in a renal injury model; and Königshausen teaches that the renal injury induced and increased glomerular permeability induced by Ang II can be reversible. 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. A person of ordinary skill in the art would have been motivated to utilize FITC-sinistrin combined with TF measurement to allow for non-invasive, real-time, and continuous monitoring of kidney function. A person of ordinary skill in the art would have been motivated to establish a reversible renal injury model in order to study both the active phase of kidney damage and the natural biological mechanisms of tissue repair and regeneration, as well as to reuse the same subjects across serial and crossover experimental protocols. A person of ordinary skill in the art would have been motivated to adjust the dose and administration method of the renal injury inducer according to the specific requirements of the intended application. The dosing regimen is 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 dosing regimen for achieving the desired renal injury model, such as a reversible renal injury model recovering GFB integrity and baseline function within 24 hours. Because prior art confirms that Ang II-induced GFB disruption and permeability changes are inherently transient and spontaneously resolve over short timeframes, achieving complete recovery within 24 hours is a predictable result of routine optimization rather than an unexpected technical effect. Selecting or adjusting a specific bolus dosage to achieve a reversible injury profile that recovers within 24 hours is a matter of routine optimization of result-effective parameters. Modifying a known parameter (dosage regimen) to achieve an expected biological timeline represents ordinary skill in the art rather than patentable invention. Moreover, because the cited prior art teaches all the structural and procedural method steps of the claimed invention, the functional recitation that the GFB integrity physiologically recovers to baseline within 24 hours is an inherent result or functional property arising from practicing those known steps. Merely discovering or reciting an inherent property, results, or optimization timeframe of a process already rendered obvious by the prior art does not render the claimed method patentable. See MPEP § 2112.
Regarding claims 5, 9, 12, and 13, in addition to the teachings of Zhong discussed above, Zhong discloses that the renal injury mouse model can be used to identify, test, or characterize a candidate molecule for the treatment of renal injury. Zhong discloses a method for testing a candidate molecule comprising administration of angiotensin-converting enzyme 2 (ACE2) (candidate molecule) intraperitoneally and deduction of its therapeutic effect on Ang II-induced renal disease in the renal injury mouse model (page 314, Abstract; page 315, Experimental Animals and Protocols).
Zhong does not disclose the administration of a bolus of a renal injury inducer subcutaneously and/or intravenously. Zhong does not disclose the administration of fluorescent molecule to determine the degree of renal injury from the development of the TF. Zhong does not disclose that the renal injury is a reversible renal injury such that the GFB integrity of the test subject physiologically recovers to baseline within 24 hours of the bolus administration. Zhong does not disclose further IV administration of a second bolus of renal injury inducer.
In addition to the teachings of Byrom discussed above, Byrom discloses a method comprising two (IV) injections (boli) of Ang (same renal injury inducer), separated by an interval of 10 minutes (administered in sequence), into rats (test subject) to evaluate its toxic effect on the kidney (renal injury) (page 7, The experiment; page 11, SUMMARY).
Schock-Kusch and Königshausen are discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Zhong by administering the renal injury inducer such as Ang II as a bolus or two boli of injection to induce reversible renal injury and administering the FITC-sinistrin to determine the effect of a candidate molecule such as ACE2 on renal injury. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Byrom teaches one bolus or two separate boli of Ang can induce renal damage; Schock-Kusch teaches FITC-sinistrin can be used to assess the renal function; and Königshausen teaches that the renal injury induced and increased glomerular permeability induced by Ang II can be reversible. A person of ordinary skill in the art would have been motivated to utilize FITC-sinistrin combined with TF measurement to allow for non-invasive, real-time, and continuous monitoring of kidney function. A person of ordinary skill in the art would have been motivated to establish a reversible renal injury model in order to study both the active phase of kidney damage and the natural biological mechanisms of tissue repair and regeneration, as well as to reuse the same subjects across serial and crossover experimental protocols such as for screening drug candidates. A person of ordinary skill in the art would have been motivated to adjust the dose and administration method of the renal injury inducer according to the specific requirements of the intended application. The dosing regimen is 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 dosing regimen for achieving the desired renal injury model, such as a reversible renal injury model recovering GFB integrity and baseline function within 24 hours. Because prior art confirms that Ang II-induced GFB disruption and permeability changes are inherently transient and spontaneously resolve over short timeframes, achieving complete recovery within 24 hours is a predictable result of routine optimization rather than an unexpected technical effect. Moreover, because the cited prior art teaches all the structural and procedural metho steps of the claimed invention, the functional recitation that the GFB integrity physiologically recovers to baseline within 24 hours is an inherent result or functional property arising from practicing those known steps. Merely discovering or reciting an inherent property, results, or optimization timeframe of a process already rendered obvious by the prior art does not render the claimed method patentable. See MPEP § 2112. Further, a person of ordinary skill in the art would have been motivated to use two boli of injection to induce a reversible renal injury model by avoiding high mortality and to isolate mechanisms of cellular repair and priming interventions.
Applicant argues that the independent claim 2 has been amended to explicitly incorporate the element of the GFB recovery within 24 hours, and that the inherency of reversible recovery within 24 hours is insufficient from the prior art because Byrom does not teach GFB filtration integrity recovers to baseline. Applicant argues that the prior art does not identify 24-hour restoration of GFB integrity to baseline as a result-effective variable because Byrom does not disclose monitoring such recovery or restoration. Applicant argues that the amended claims reciting 24-hour recovery are biologically distinguished from the prior art because the prior are does not teach or suggest restoration of GFB integrity to baseline within 24 hours after bolus administration. Applicant argues that combining Zhong's chronic model with Byrom's acute bolus method would induce acute vascular shock and tissue necrosis, thereby destroying the very renal tissue viability necessary to monitor GFR.
These arguments are unpersuasive. As discussed above, Königshausen teaches that Ang II-induced disruption of the GFB can be naturally recover over time, demonstrating that Ang II-induced GFB impairment is inherently transient and reversible. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. As discussed above, Byrom explicitly discloses dose-dependent hemodynamic responses to Ang II. Byrom provides a clear teaching of a naturally reversible physiological response. It would have been obvious to a POSITA 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 and Königshausen teach 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 POSITA 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. A POSITA would have been motivated to use reversible renal injury model because establishing a reversible model provides technical advantages including maximizing test subject survival, ensuring high data reproducibility, and creating an optimized time window to evaluate therapeutic agents against transient acute kidney injury. A POSITA would recognize that necrosis occurs only under excessive, toxic dosages, whereas administering a non-lethal IV bolus dose of Ang II is a routine parameter optimization to induce transient renal dysfunction without causing permanent tissue destruction. Determining an optimal dosing regimen to extend or fit this transient recovery profile within a standard 24-hour experimental window is a matter of routine optimization of result-effective parameters. Modifying a known parameter to achieve a predictable recovery timeframe yields no unexpected technical effect. Thus, combining the acute bolus administration method of Byrom with the teachings of Königshausen and Zhong does not destroy renal viability, but rather provides a controlled ,reversible injury model. Further, because all procedural steps of the claimed method are fully rendered obvious by the combination of the prior art, the functional recitation that GFB integrity recovers to baseline within 24 hours represents merely an inherent biological result or functional optimization of practicing those known steps. Reciting an inherent property or expected result of an otherwise obvious combination does not render the claimed process patentable.
Claims 7 and 8 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), Shock-Kusch et al. (Kidney International, 2011), Königshausen et al. (Scientific Reports, 2016; cited on PTO-892), and Cyanagen SRL (EP 2944326 A1; cited on IDS filed Jul 8, 2022).
As discussed above, Zhong discloses a method for creating a renal injury model induced by infusing Ang II (renal injury inducer) into mice (test subject) (page 314 Experimental Animals and Protocols). Zhong also discloses a method for testing a candidate molecule by comparing the subjects treated with ACE2 (candidate molecule) with control subjects treated with placebo (administration of a placebo instead) ( page 315, Experimental Animals and Protocols; page 317, Figure 2).
Zhong does not disclose the administration of a bolus of a renal injury inducer subcutaneously and/or intravenously. Zhong does not disclose the administration of fluorescent molecule to determine the degree of renal injury from the development of the TF. Zhong does not disclose that the renal injury is a reversible renal injury such that the GFB integrity of the test subject physiologically recovers to baseline within 24 hours of the bolus administration. Zhong does not disclose a method for screening a population of candidate molecules.
As discussed above, Byrom discloses a method comprising a single IV injection (bolus) of Ang (renal injury inducer) into rats (test subject) to evaluate its toxic effect on the kidney (renal injury) (page 7, The experiment; page 11, SUMMARY). Byrom discloses that the physiological changes such as vascular blanching and dilation following angiotensin administration can disappear 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).
As discussed above, Schock-Kusch discloses a method comprising the administration of FITC-sinistrin (pharmaceutically suitable fluorescent molecule) as a biomarker and the measurement of the development of the TF to analyze renal function in renal injury mouse models (page 1254, abstract; page 1255, PROOF OF PRINCIPLE; page 1256, Table 1). The molecular weight of FITC-sinistrin is ≤ 15 kDa.
As discussed above, Königshausen discloses that Ang II can weaken the structural integrity of the slit diaphragm (component of GFB), which leads to an increased glomerular permeability (abstract). Königshausen discloses that Ang II can induce a “transient” increase in glomerular permeability (page 1, ¶ 2) and that the glomerular permeability can return to normal after 120 minutes of Ang II stimulation or after 60 minutes of Ang II discontinuation washout (page 2, Figure 1 a). This indicates that Ang II-induced disruption of the GFB can naturally recover over time, meaning it is transient and reversible.
Cyanagen SRL discloses a method for screening pharmaceutical compounds (candidate molecules) suitable for treatment of chronic kidney diseases (renal injury) in a mammal (test subject) (¶ 61; ¶ 62; claim 17).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Zhong by administering the renal injury inducer such as Ang II as an IV bolus injection to induce reversible renal injury and administering the FITC-sinistrin to determine the degree of renal injury by determining the development of the TF in order to develop a method for screening candidate molecules for treatment of renal injury. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Byrom teaches that a single bolus of Ang can induce renal damage; Schock-Kusch teaches that FITC-sinistrin can be used to determine the development of the TF as a biomarker in a renal injury model; Königshausen teaches that the renal injury induced and increased glomerular permeability induced by Ang II can be reversible; and Cyanagen SRL teaches such renal injury models can be used for screening candidate molecules. A person of ordinary skill in the art would have been motivated to utilize FITC-sinistrin combined with TF measurement to allow for non-invasive, real-time, and continuous monitoring of kidney function. A person of ordinary skill in the art would have been motivated to establish a reversible renal injury model in order to study both the active phase of kidney damage and the natural biological mechanisms of tissue repair and regeneration, as well as to reuse the same subjects across serial and crossover experimental protocols such as for screening drug candidates. A person of ordinary skill in the art would have been motivated to adjust the dose and administration method of the renal injury inducer according to the specific requirements of the intended application. The dosing regimen is 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 dosing regimen for achieving the desired renal injury model, such as a reversible renal injury model recovering GFB integrity and baseline function within 24 hours. Because prior art confirms that Ang II-induced GFB disruption and permeability changes are inherently transient and spontaneously resolve over short timeframes, achieving complete recovery within 24 hours is a predictable result of routine optimization rather than an unexpected technical effect. Moreover, because the cited prior art teaches all the structural and procedural metho steps of the claimed invention, the functional recitation that the GFB integrity physiologically recovers to baseline within 24 hours is an inherent result or functional property arising from practicing those known steps. Merely discovering or reciting an inherent property, results, or optimization timeframe of a process already rendered obvious by the prior art does not render the claimed method patentable. See MPEP § 2112. Further, a person of ordinary skill in the art would have been motivated to utilize the renal injury model of Zhong, Byrom, Schock-Kusch, and Königshausen for drug screening in order to expand the practical applications of the model. This allows performing multiple experiments of this setting in the same batch of animals, but with different concentrations of the same candidate molecule, with different administration modalities or with different candidate molecules, thereby allowing multiple screening cycles in the same batch of animals.
Applicant argues that applying Byrom’s acute, toxic bolus method to the screening framework of Cyanagen would destroy the tissue viability necessary to conduct the screening, thereby causing functional incompatibility. Applicant argues that the cited references whether considered alone or in any combination fail to disclose, teach, or suggest a screening method where the induced GFB injury is physiologically repaired and restored to baseline within 24 hours.
This argument is unpersuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. As discussed above, Byrom teaches dose-dependent physiological responses to Ang. 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 POSITA would not blindly apply a lethal dose but would instead calibrate the bolus to induce a non-terminal, transient injury suitable for monitoring. A POSITA would readily understand that tissue necrosis and loss of viability occur only under extreme, toxic doses. The amount of angiotensin administered to induce damage can be appropriately adjusted and optimized depending on the intended applications. A POSITA would recognize that inducing a non-lethal, transient, and reversible injury, rather than terminal necrosis, is a matter of routine dose-response optimization. Therefore, combining the IV bolus administration method of Byrom with the screening framework of Cyanagen does not render the system functionally incompatible or destroy tissue viability, but instead provides a controlled, reversible screening method. As discussed above, Königshausen explicitly teaches that Ang II-induced disruption of the GFB integrity is inherently transient and spontaneously recovers over time. Thus, a POSITA would have been motivated to combine the teachings of the prior art to arrive at the claimed method as discussed above. Establishing a dosing regimen that allows recovery within a 24-hour window represents routine experimentation to adjust result-effective parameters. Reciting an inherent biological recovery timeline resulting from an otherwise obvious combination of process steps does not render the claimed method patentable.
Applicant argues that a specific bolus administration can induce a transient, measurable GFB injury that fully recovers within 24 hours is an unexpected, highly advantageous biological result.
This argument is unpersuasive. While Applicant asserts that a 24-hour recovery model provides highly advantageous experimental utility, an advantageous effect or commercial convenience does not conger patentability where the claimed methos steps are already rendered obvious by the prior art. Establishing an expected, advantageous result arising from an obvious combination of process steps fails to overcome a rejection. Applicant’s assertions of unexpected results fail to satisfy the requisite legal criteria established under MPEP § 716.02. Objective evidence of unexpected results must be supported by an appropriate evidentiary showing, direct comparative data, and must be commensurate in scope with the claims. Applicant has failed to meet this burden based on the following criteria.
First, the alleged results are predictable, not truly unexpected. To establish unexpected results, the improvement or enhancement must significantly exceed what a person having ordinary skill in the art would have reasonably anticipated. The observed 24-hour recovery is not an unexpected result, but rather a predictable, inherent physiological property of Ang II-induced GFB disruption. As discussed above, Königshausen teaches that Ang II-induced GFB disruption is inherently reversible and recovers over time. Because the prior art explicitly demonstrates that the biological system naturally recovers from Ang II challenge once the stimulus subsides or is cleared, observing fully physiological recovery within a standard 24-hour timeframe is an expected biological outcome, not an unexpected result.
Second, Applicant fails to provide a direct comparison with the closest prior art. The evidence of unexpected results must involve a direct, side-by-side comparison between the claimed invention and the closest prior art. Without a direct comparison showing that the actual recovery performance of the claimed method is significantly better than what would be predicted from a simple additive effect of Zhong, Byrom, Shock-Kusch, and Königshausen, the showing is insufficient to rebut the prima facie case of obviousness. Applicant cannot establish unexpected results merely by comparing the claimed formulation against inferior or no-prior art control formulations.
Third, the results are not commensurate in scope of the claims. To effectively rebut a rejection of obviousness, the disclosure or evidence of unexpected results must be commensurate in scope with the claims to which the evidence is applied. Claims 2, 5, and 7 encompass various genera such as subjects, inducers, and dosing regimens. However, Applicant’s arguments rely on narrow, specific example with a specific amount of Ang II in a specific subject. Applicant fails to provide examples of more combinations among various dosing regimens, inducers, and subjects. The limited experimental data does not establish that the entire claimed genus would exhibit the same allegedly unexpected properties.
Further, arguments or conclusory statements in the remarks section of a response do not take the place of evidence in the record. Allegations of unexpected results must be explicitly set forth in the originally filed specification or presented in a formal, signed declaration/affidavit accompanied by actual data. Absent the submission of such proper objective evidence, Applicant’s remarks remain mere unsubstantiated allegations that cannot overcome the rejection. Attorney arguments cannot serve as a substitute for comparative test data showing unexpected results.
Accordingly, because the combination of teachings would have been obvious to one of ordinary skill in the art, and because the Applicant has not provided sufficient objective evidence to demonstrate unexpected results, the rejection is maintained.
Conclusion
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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